Natural polymorphism in the thrombospondin-related adhesive protein of Plasmodium falciparum

We have developed a typing system using natural sequence variation in the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum. This method permits a haplotype to be assigned to any particular TRAP gene. We have applied this method to a hospital-based, case control-study in Mali. Previous sequence variation and conservation in TRAP has been confirmed. Particular TRAP haplotypes can be used as geographic hallmarks. Because of the high level of conflict between characters, we have examined the phylogenetic relationships between parasites using a network approach. Having received patient samples from urban and periurban areas of Bamako, the majority of haplotypes were closely related and distinct from TRAP sequences present in other continents. This suggests that the structure of TRAP can only tolerate a limited number of sequence variations to preserve its function but that this is sufficient to allow the parasite to evade the host's immune system until a long-lived immune response can be maintained. It may also reflect host genetics in that certain variants may escape the host immune response more efficiently than others. For vaccine design, sequences from the major regional variants may need to be considered in the production of effective subunit vaccines

Résultats fonctionnels de la chirurgie de la cataracte par phacoalternative avec implantation en chambre postérieure: à propos de 300 cas à Bobo Dioulasso (Burkina Faso)

La cataracte est la première cause de cécité curable dans le monde. Son traitement est chirurgical. Le but de notre travail a été d'évaluer les résultats de la phacoalternative ou la chirurgie de la cataracte à petite incision. Il s'est agi d'une étude transversale descriptive à collecte prospective allant du 1er janvier au 31 septembre 2014, chez des patients âgés d'au moins 40 ans. Les données socio-démographiques, l'acuitévisuelle, l'astigmatisme et les complications ont été évalués.Nous avons inclus 300 yeux de 286 patients. L'âge moyen était de 66 ans (écart type9,93) avec une prédominance masculine de 57,7%. Les co-morbidités étaient dominées par l'hypertension artérielle 30,33% des cas. L'acuitévisuelle pré-opératoire était de moins de 1/20è dans 70, 7% des cas. En biométrie, la puissance moyenne était de 21,50 dioptries. L'implant posé aété adéquat dans 60%. Les principales complications per-opératoires  étaient le chémosis post-anesthésie 4,67% et l'issue de vitrée moins de 2% des cas. Les complications post opératoires précoces ont été dominées par l'oedème de cornée 26,33%, et les complications tardives par la cataracte secondaire. L'astigmatisme induit était de 1, 12 dioptrie en  moyenne (écart type 1,26). Sans correction, les résultats visuels étaientmauvais dans moins de 1%, limites dans 31%, et bons 68% suivants les normes de l'Organisation Mondiale de la Santé. La phacoalternative donne des résultats satisfaisants, avec peu de complications. L'amélioration du plateau technique et la disponibilité d'implants adéquats pourraient les améliorer

Biotransformations of bisphenol A in a mammalian model: answers and new questions raised by low-dose metabolic fate studies in pregnant CD1 mice.

We investigated the metabolic fate of a low dose (25 micro g/kg) of bisphenol A [2,2-bis(4-hydroxy-phenyl)propane] (BPA) injected subcutaneously in CD1 pregnant mice using a tritium-labeled molecule. Analytic methods were developed to allow a radio-chromatographic profiling of BPA residues in excreta and tissues, as well as in mothers' reproductive tracts and fetuses, that contained more than 4% of the administered radioactivity. BPA was extensively metabolized by CD1 mice. Identified metabolite structures included the glucuronic acid conjugate of BPA, several double conjugates, and conjugated methoxylated compounds, demonstrating the formation of potentially reactive intermediates. Fetal radioactivity was associated with unchanged BPA, BPA glucuronide, and a disaccharide conjugate. The latter structure, as well as that of a dehydrated glucuronide conjugate of BPA (a major metabolite isolated from the digestive tract), showed that BPA metabolic routes were far more complex than previously thought. The estrogenicity of the metabolites that were identified but not tested for hormonal activity cannot be ruled out; however, in general, conjugated BPA metabolites have significantly lower potency than that of the parent compound. Thus, these data suggest the parental compound is responsible for the estrogenic effects observed in fetuses exposed to BPA during gestation in this mammalian model

Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens

Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection

Serological Evaluation of Onchocerciasis and Lymphatic Filariasis Elimination in the Bakoye and Falémé foci, Mali

In Mali, ivermectin-based onchocerciasis elimination from the Bakoye and Falémé foci, reported in 2009–2012, was a beacon leading to policy shifting from morbidity control to elimination of transmission (EOT). These foci are also endemic for lymphatic filariasis (LF). In 2007–2016 mass ivermectin plus albendazole administration was implemented. We report Ov16 (onchocerciasis) and Wb123 (LF) seroprevalence after 24–25 years of treatment to evaluate if onchocerciasis EOT and LF elimination as a public health problem (EPHP) have been achieved

Mosaic Genome Architecture of the Anopheles gambiae Species Complex

Attempts over the last three decades to reconstruct the phylogenetic history of the Anopheles gambiae species complex have been important for developing better strategies to control malaria transmission.We used fingerprint genotyping data from 414 field-collected female mosquitoes at 42 microsatellite loci to infer the evolutionary relationships of four species in the A. gambiae complex, the two major malaria vectors A. gambiae sensu stricto (A. gambiae s.s.) and A. arabiensis, as well as two minor vectors, A. merus and A. melas.We identify six taxonomic units, including a clear separation of West and East Africa A. gambiae s.s. S molecular forms. We show that the phylogenetic relationships vary widely between different genomic regions, thus demonstrating the mosaic nature of the genome of these species. The two major malaria vectors are closely related and closer to A. merus than to A. melas at the genome-wide level, which is also true if only autosomes are considered. However, within the Xag inversion region of the X chromosome, the M and two S molecular forms are most similar to A. merus. Near the X centromere, outside the Xag region, the two S forms are highly dissimilar to the other taxa. Furthermore, our data suggest that the centromeric region of chromosome 3 is a strong discriminator between the major and minor malaria vectors.Although further studies are needed to elucidate the basis of the phylogenetic variation among the different regions of the genome, the preponderance of sympatric admixtures among taxa strongly favor introgression of different genomic regions between species, rather than lineage sorting of ancestral polymorphism, as a possible mechanism

Tofacitinib May Inhibit Myofibroblast Differentiation from Rheumatoid-Fibroblast-like Synoviocytes Induced by TGF-β and IL-6

During rheumatoid arthritis (RA), the pathogenic role of resident cells within the synovial membrane is suggested, especially for a population frequently referred to as fibroblast-like synoviocytes (FLSs). In this study, we assess the markers of myofibroblast differentiation of RA-FLSs by ex vivo observations and in vitro evaluations following the stimulation with both TGF-β and IL-6. Furthermore, we investigated the possible inhibiting role of tofacitinib, a JAK inhibitor, in this context. Myofibroblast differentiation markers were evaluated on RA synovial tissues by immune-fluorescence or immune-histochemistry. RA-FLSs, stimulated with transforming growth factor (TGF-β) and interleukin-6 (IL-6) with/without tofacitinib, were assessed for myofibroblast differentiation markers expression by qRT-PCR and Western blot. The same markers were evaluated following JAK-1 silencing by siRNA assay. The presence of myofibroblast differentiation markers in RA synovial tissue was significantly higher than healthy controls. Ex vivo, α-SMA was increased, whereas E-Cadherin decreased. In vitro, TGF-β and IL-6 stimulation of RA-FLSs promoted a significant increased mRNA expression of collagen I and α-SMA, whereas E-Cadherin mRNA expression was decreased. In the same conditions, the stimulation with tofacitinib significantly reduced the mRNA expression of collagen I and α-SMA, even if the Western blot did not confirm this finding. JAK-1 gene silencing did not fully prevent the effects of stimulation with TGF-β and IL-6 on these features. TGF-β and IL-6 stimulation may play a role in mediating myofibroblast differentiation from RA-FLSs, promoting collagen I and α-SMA while decreasing E-Cadherin. Following the same stimulation, tofacitinib reduced the increases of both collagen I and α-SMA on RA-FLSs, although further studies are needed to fully evaluate this issue and confirm our results

The Critical Care Society of Southern Africa guidelines on the allocation of scarce critical care resources during the COVID-19 public health emergency in South Africa

Letter by Gopalan et al. on article by Singh and Moodley (Singh JA, Moodley K. Critical care triaging in the shadow of COVID-19: Ethics considerations. S Afr Med J 2020;110(5):355-359. https://doi.org/10.7196/SAMJ.2020.v110i5.14778); and response by Singh and Moodle

Knowledge/Attitude/Practices of HPV & Cervical Cancer, Willingness to Participate in Vaccine Trial in Preparation for HIV & HPV Vaccine Trials in Mali

Oral Presentation from AIDS Vaccine 2012 Boston, MA, USA. 9-12 September 201