Adherence to a Six-Dose Regimen of Artemether-Lumefantrine for Treatment of Uncomplicated Plasmodium Falciparum Malaria in Uganda.

Measuring baseline levels of adherence and identifying risk factors for non-adherence are important steps before the introduction of new antimalarials. In Mbarara in southwestern Uganda, we assessed adherence to artemether-lumefantrine (Coartem) in its latest World Health Organization blister formulation. Patients with uncomplicated Plasmodium falciparum malaria were prescribed artemether-lumefantrine and received an explanation of how to take the following five doses at home. A tablet count was made and a questionnaire was completed during a home visit. Among 210 analyzable patients, 21 (10.0%) were definitely or probably non-adherent, whereas 189 (90.0%) were probably adherent. Age group was not associated with adherence. Lack of formal education was the only factor associated with non-adherence after controlling for confounders (odds ratio = 3.1, 95% confidence interval [CI] = 1.1-9.7). Mean lumefantrine blood levels were lower among non-adherent (n = 16) (2.76 microg/mL, 95% CI = 1.06-4.45) than among adherent (n = 171) (3.19 microg/mL, 95% CI = 2.84-3.54) patients, but this difference was not statistically significant. The high adherence to artemether-lumefantrine found in our study suggest that this drug is likely to be very effective in Mbarara provided that patients receive clear dosage explanations

3D Bioprinting of Gelatin–Xanthan Gum Composite Hydrogels for Growth of Human Skin Cells

In recent years, bioprinting has attracted much attention as a potential tool for generating complex 3D biological constructs capable of mimicking the native tissue microenvironment and promoting physiologically relevant cell–cell and cell–matrix interactions. The aim of the present study was to develop a crosslinked 3D printable hydrogel based on biocompatible natural polymers, gelatin and xanthan gum at different percentages to be used both as a scaffold for cell growth and as a wound dressing. The CellInk Inkredible 3D printer was used for the 3D printing of hydrogels, and a glutaraldehyde solution was tested for the crosslinking process. We were able to obtain two kinds of printable hydrogels with different porosity, swelling and degradation time. Subsequently, the printed hydrogels were characterized from the point of view of biocompatibility. Our results showed that gelatin/xanthan-gum bioprinted hydrogels were biocompatible materials, as they allowed both human keratinocyte and fibroblast in vitro growth for 14 days. These two bioprintable hydrogels could be also used as a helpful dressing material

Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.

BACKGROUND: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data. METHODS: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa. RESULTS: C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared < 0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p < 0.001). CONCLUSION: Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination

Malvinas-slope water intrusions on the northern Patagonia continental shelf

The Patagonia continental shelf located off southeastern South America is bounded offshore by the Malvinas Current, which extends northward from northern Drake Passage (~55&amp;deg; S) to nearly 38&amp;deg; S. The transition between relatively warm-fresh shelf waters and Subantarctic Waters from the western boundary current is characterized by a thermohaline front extending nearly 2500 km. We use satellite derived sea surface temperature, and chlorophyll-&lt;I&gt;a&lt;/I&gt; data combined with hydrographic and surface drifter data to document the intrusions of slope waters onto the continental shelf near 41&amp;deg; S. These intrusions create vertically coherent localized negative temperature and positive salinity anomalies extending onshore about 150 km from the shelf break. The region is associated with a center of action of the first mode of non-seasonal sea surface temperature variability and also relatively high chlorophyll-&lt;I&gt;a&lt;/I&gt; variability, suggesting that the intrusions are important in promoting the local development of phytoplankton. The generation of slope water penetrations at this location may be triggered by the inshore excursion of the 100 m isobath, which appears to steer the Malvinas Current waters over the outer shelf

Erosional and depositional contourite features at the transition between the western Scotia Sea and southern South Atlantic Ocean: links with regional water-mass circulation since the Middle Miocene

The aim of the present study was to characterise the morpho-sedimentary features and main stratigraphic stacking pattern off the Tierra del Fuego continental margin, the north-western sector of the Scotia Sea abyssal plain (Yaghan Basin) and the Malvinas/Falkland depression, based on single- and multi-channel seismic profiles. Distinct contourite features were identified within the sedimentary record from the Middle Miocene onwards. Each major drift developed in a water depth range coincident with a particular water mass, contourite terraces on top of some of these drifts being associated with interfaces between water masses. Two major palaeoceanographic changes were identified. One took place in the Middle Miocene with the onset of Antarctic Intermediate Water flow and the enhancement of Circumpolar Deep Water (CDW) flow, coevally with the onset of Weddell Sea Deep Water flow in the Scotia Sea. Another palaeoceanographic change occurred on the abyssal plain of the Yaghan Basin in the Late Miocene as a consequence of the onset of Southeast Pacific Deep Water flow and its complex interaction with the lower branch of the CDW. Interestingly, these two periods of change in bottom currents are coincident with regional tectonic episodes, as well as climate and Antarctic ice sheet oscillations. The results convincingly demonstrate that the identification of contourite features on the present-day seafloor and within the sedimentary record is the key for decoding the circulation of water masses in the past. Nevertheless, further detailed studies, especially the recovery of drill cores, are necessary to establish a more robust chronology of the evolutionary stages at the transition between the western Scotia Sea and the southern South Atlantic Ocean.Fil: Pérez, Lara F.. Instituto Andaluz de Ciencias de la Tierra; España. Geological Survey of Denmark and Greenland; DinamarcaFil: Hernández Molina, F. Javier. Royal Holloway University of London; Reino UnidoFil: Esteban, Federico Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Tassone, Alejandro Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; ArgentinaFil: Piola, Alberto Ricardo. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maldonado, Andrés. Instituto Andaluz de Ciencias de la Tierra; EspañaFil: Preu, Benedict. Chevron North Sea; Reino UnidoFil: Violante, Roberto Antonio. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; ArgentinaFil: Lodolo, Emanuele. Istituto Nazionale di Oceanografia e di Geofisica Sperimentale; Itali

Contourite terraces along the Argentine continental margin : morphosedimentary and oceanographic implications

Un enorme Sistema Deposicional Contornítico, compuesto mediante rasgos deposicionales y erosivos, ha sido caracterizado en el margen continental Argentino. El presente trabajo se centra en los rasgos erosivos contorníticos y en concreto en uno de ellos: las terrazas contorníticas. Se identifican a lo largo del talud continental, y a diferentes profundidades, un conjunto de terrazas con una muy buena continuidad lateral. Esta terrazas son elementos morfológicos sub-horizontales sobre el actual fondo submarino desarrolladas durantes sucesivas fases constructivas (deposicionales) y erosivas mediante la acción de las masas de agua antárticas que interaccionan con el talud continental. Regionalmente la ubicación de las terrazas se correlaciona con la posición de las interfases entre las principales masas de agua. La presencia de las terrazas contorníticas implica cambios muy significativos en el perfil morfológico del talud, generando un perfil muy diferente al definido en los modelos conceptuales de los taludes para los márgenes continentalesA significant Contourite Depositional System on the slope of the Argentine margin was characterised, where several depositional and erosive features are well developed. This work is focused on one of these erosive features: the contourite terraces. A set of terraces with good lateral continuity has been described at different depths along the slope. They are sub-horizontal morphologic elements identified at the present sea-floor, which have developed over time in constructional (depositional) and erosive phases caused by the interaction of Antarctic water masses with the seafloor. Their location can be correlated with the main interfaces of water masses. Contourite terraces occurrence has conditioned a remark change in the slope morphologic profile very different to those defined in the conceptual models for continental margin

Transmission of Plasmodium vivax in South-Western Uganda: Report of Three Cases in Pregnant Women

Plasmodium vivax is considered to be rare in the predominantly Duffy negative populations of Sub-Saharan Africa, as this red blood cell surface antigen is essential for invasion by the parasite. However, despite only very few reports of molecularly confirmed P. vivax from tropical Africa, serological evidence indicated that 13% of the persons sampled in Congo had been exposed to P. vivax. We identified P. vivax by microscopy in 8 smears from Ugandan pregnant women who had been enrolled in a longitudinal study of malaria in pregnancy. A nested polymerase chain reaction (PCR) protocol was used to detect and identify the Plasmodium parasites present. PCR analysis confirmed the presence of P. vivax for three of the women and analysis of all available samples from these women revealed clinically silent chronic low-grade vivax infections for two of them. The parasites in one woman carried pyrimethamine resistance-associated double non-synonymous mutations in the P. vivax dihydrofolate reductase gene. The three women found infected with P. vivax were Duffy positive as were nine of 68 women randomly selected from the cohort. The data presented from these three case reports is consistent with stable transmission of malaria in a predominantly Duffy negative African population. Given the substantial morbidity associated with vivax infection in non-African endemic areas, it will be important to investigate whether the distribution and prevalence of P. vivax have been underestimated in Sub-Saharan Africa. This is particularly important in the context of the drive to eliminate malaria and its morbidity

Multiple invasions in urbanized landscapes: interactions between the invasive garden ant Lasius neglectus and Japanese knotweeds (Fallopia spp.)

International audienceUrbanized landscapes are the theater of multiple simultaneous biological invasions likely to affect spread dynamics when co-occurring introduced species interact with each other. Interactions between widespread invaders call for particular atten- tion because they are likely to be common and because non-additive outcomes of such associations might induce negative consequences (e.g., enhanced population growth increasing impacts or resistance to control). We explored the invasions of two widespread invasive taxa: the Japanese knotweed species complex Fallopia spp. and the invasive garden ant Lasius neglectus, in the urban area of Lyon (France). First, we investigated landscape habitat preferences as well as co-occurrence rates of the two species. We showed that Fallopia spp. and L. neglectus had broadly overlapping environmental preferences (measured by seven landscape variables), but their landscape co-occurrence pattern was random, indicating independent spread and non-obligatory association. Second, as Fallopia spp. produce extra-floral nectar, we estimated the amount of nectar L. neglectus used under field conditions without ant competitors. We estimated that L. neglectus collected 150–321 kg of nectar in the month of April (when nectar production is peaking) in a 1162 m2 knotweed patch, an amount likely to boost ant population growth. Finally, at six patches of Fallopia spp. surveyed, herbivory levels were low (1–6% loss of leaf surface area) but no relationship between ant abundance (native and invasive) and loss of leaf surface was found. Co-occurrences of Fallopia spp. and L. neglectus are likely to become more common as both taxa colonize landscapes, which could favor the spread and invasion success of the invasive ant

Understanding the pharmacokinetics of Coartem®

Artemether and lumefantrine (AL), the active constituents of Coartem® exhibit complementary pharmacokinetic profiles. Artemether is absorbed quickly; peak concentrations of artemether and its main active metabolite, dihydroartemisinin (DHA) occur at approximately two hours post-dose, leading to a rapid reduction in asexual parasite mass and a prompt resolution of symptoms. Lumefantrine is absorbed and cleared more slowly (terminal elimination half-life 3-4 days in malaria patients), and accumulates with successive doses, acting to prevent recrudescence by destroying any residual parasites that remain after artemether and DHA have been cleared from the body. Food intake significantly enhances the bioavailability of both artemether and lumefantrine, an effect which is more apparent for the highly lipophilic lumefantrine. However, a meal with only a small amount of fat (1.6 g) is considered sufficient to achieve adequate exposure to lumefantrine. The pharmacokinetics of artemether or lumefantrine are similar in children, when dosed according to their body weight, compared with adults. No randomized study has compared the pharmacokinetics of either agent in pregnant versus non-pregnant women. Studies in healthy volunteers and in children with malaria have confirmed that the pharmacokinetic characteristics of crushed standard AL tablets and the newly-developed Coartem® Dispersible tablet formulation are similar. Studies to date in healthy volunteers have not identified any clinically relevant drug-drug interactions; data relating to concomitant administration of HIV therapies are limited. While dose-response analyses are difficult to undertake because of the low rate of treatment failures under AL, it appears that artemether and DHA exposure impact on parasite clearance time while lumefantrine exposure is associated with cure rate, consistent with their respective modes of action. In conclusion, knowledge of the pharmacokinetic profiles of artemether and lumefantrine is increasing within a range of settings, including infants and children. However, additional data would be warranted to better characterize artemether and lumefantrine pharmacokinetics in patients with hepatic impairment, in pregnant women, and in patients undergoing HIV/AIDS chemotherapy