From In Vivo to In Vitro: Dynamic Analysis of Plasmodium falciparum var Gene Expression Patterns of Patient Isolates during Adaptation to Culture

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var gene family, plays a crucial role in disease virulence through its involvement in binding to various host cellular receptors during infection. Growing evidence suggests that differential expression of the various var subgroups may be involved in parasite virulence. To further explore this issue, we have collected isolates from symptomatic patients in south China-Myanmar border, and characterized their sequence diversity and transcription profiles over time of var gene family, and cytoadherence properties from the time of their initial collection and extending through a two month period of adaptation to culture. Initially, we established a highly diverse, DBLα (4 cysteines) subtype-enriched, but unique local repertoire of var-DBL1α sequences by cDNA cloning and sequencing. Next we observed a rapid transcriptional decline of upsA- and upsB-subtype var genes at ring stage through qRT-PCR assays, and a switching event from initial ICAM-I binding to the CD36-binding activity during the first week of adaptive cultivation in vitro. Moreover, predominant transcription of upsA var genes was observed to be correlated with those isolates that showed a higher parasitemia at the time of collection and the ICAM-1-binding phenotype in culture. Taken together, these data indicate that the initial stage of adaptive process in vitro significantly influences the transcription of virulence-related var subtypes and expression of PfEMP1 variants. Further, the specific upregulation of the upsA var genes is likely linked to the rapid propagation of the parasite during natural infection due to the A-type PfEMP1 variant-mediated growth advantages

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l’Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems

Persistence and adherence in multiple sclerosis patients starting glatiramer acetate treatment: assessment of relationship with care received from multiple disciplines

Peter Joseph Jongen,1,2 Wim A Lemmens,3 Raymond Hupperts,4 Erwin LJ Hoogervorst,5 Hans M Schrijver,6 Astrid Slettenaar,7 Els L de Schryver,8 Jan Boringa,9 Esther van Noort,10 Rogier Donders3 1Department of Community and Occupational Medicine, University Medical Centre Groningen, University Groningen, Groningen, 2MS4 Research Institute, 3Department for Health Evidence, Radboud university medical center, Nijmegen, 4Department of Neurology, Zuijderland Medisch Centrum Sittard, Sittard, 5Department of Neurology, St Antonius Hospital, Nieuwegein, 6Department of Neurology, Multiple Sclerosis Centre, Westfries Gasthuis, Hoorn, 7Department of Neurology, Medisch Spectrum Twente, Enschede, 8Department of Neurology, Alrijne Ziekenhuis, Leiderdorp, 9Department of Neurology, Meander Medisch Centrum, Amersfoort, 10Curavista BV, Geertruidenberg, the Netherlands Background: In multiple sclerosis patients, the persistence of, and adherence to, disease-modifying treatment are often insufficient. The degree of persistence and adherence may relate to the care received from various disciplines. Methods: In an observational study of 203 patients treated with glatiramer acetate 20 mg subcutaneous daily, we assess the persistence and adherence in relation to the amount of care received in various disciplines. The frequencies and durations of care per discipline were reported by patients online, as were missed doses and eventual treatment discontinuation. The associations between the care provided by neurologists, nurses, psychologists, pharmacists, and rehabilitative doctors and persistence and adherence were the primary outcomes; the associations between care received from general practitioners, occupational therapists, physiotherapists, social workers, dieticians, home caregivers, informal caregivers, other medical specialists, and other caregivers and persistence and adherence were secondary outcomes. Results: It was found that the 12-month persistence rate was 62% and that 85% of the persistent patients were 95% adherent (missed <5% of doses). Patients who discontinued treatment in the fourth quarter (Q) had received less-frequent and shorter psychological care in Q3 than persistent patients (P=0.0018 and P=0.0022). Adherent patients had received more frequent home care and informal care than nonadherent patients (P=0.0074 and P=0.0198), as well as longer home care and informal care (P=0.0074 and P=0.0318). Associations between care in other disciplines and persistence or adherence were not observed. As to the relationship between adherence and persistence, nonadherence in Q2 was related to discontinuation after Q2 (P=0.0001). Conclusion: We obtained no evidence that, in multiple sclerosis patients, persistence of and adherence to disease-modifying treatment are associated with the amount of neurological, nursing, pharmaceutical, or rehabilitative care. However, findings suggest that the treatment of psychological problems in Q3 may relate to persistence and that home care and informal care may relate to adherence. Keywords: home care, informal care, nursing, pharmaceutical, rehabilitative, psychologica