Red blood cells derived from peripheral blood and bone marrow CD34+ human haematopoietic stem cells are permissive to Plasmodium parasites infection

The production of fully functional human red cells in vitro from haematopoietic stem cells (hHSCs) has been successfully achieved. Recently, the use of hHSCs from cord blood represented a major improvement to develop the continuous culture system for Plasmodium vivax. Here, we demonstrated that CD34+hHSCs from peripheral blood and bone marrow can be expanded and differentiated to reticulocytes using a novel stromal cell. Moreover, these reticulocytes and mature red blood cells express surface markers for entrance of malaria parasites contain adult haemoglobin and are also permissive to invasion by P. vivax and Plasmodium falciparum parasites.

Plasmodium vivax malaria elimination: should innovative ideas from the past be revisited?

In the 1950s, the strategy of adding chloroquine to food salt as a prophylaxis against malaria was considered to be a successful tool. However, with the development of Plasmodium resistance in the Brazilian Amazon, this control strategy was abandoned. More than 50 years later, asexual stage resistance can be avoided by screening for antimalarial drugs that have a selective action against gametocytes, thus old prophylactic measures can be revisited. The efficacy of the old methods should be tested as complementary tools for the elimination of malaria.

Slow clearance of Plasmodium vivax with chloroquine amongst children younger than six months of age in the Brazilian Amazon

Plasmodium vivax is the most widespread parasite causing malaria, being especially prevalent in the Americas and Southeast Asia. Children are one of the most affected populations, especially in highly endemic areas. However, there are few studies evaluating the therapeutic response of infants with vivax malaria. This study retrospectively evaluated the parasitaemia clearance in children diagnosed with vivax malaria during the first five days of exclusive treatment with chloroquine (CQ). Infants aged less than six months old had a significantly slower parasitaemia clearance time compared to the group of infants and children between six months and 12 years old (Kaplan-Meier survival analysis; Wilcoxon test; p = 0.004). The impaired clearance of parasitaemia in younger children with vivax malaria is shown for the first time in Latin America. It is speculated that CQ pharmacokinetics in young children with vivax malaria is distinct, but this specific population may also allow the detection of CQ-resistant parasites during follow-up, due to the lack of previous immunity.

G6PD deficiency in Latin America: systematic review on prevalence and variants

Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available.

Influence of age on the haemoglobin concentration of malaria-infected patients in a reference centre in the Brazilian Amazon

Anaemia is amongst the major complications of malaria, a major public health problem in the Amazon Region in Latin America. We examined the haemoglobin (Hb) concentrations of malaria-infected patients and compared it to that of malaria-negative febrile patients and afebrile controls. The haematological parameters of febrile patients who had a thick-blood-smear performed at an infectious diseases reference centre of the Brazilian Amazon between December 2009-January 2012 were retrieved together with clinical data. An afebrile community control group was composed from a survey performed in a malaria-endemic area. Hb concentrations and anaemia prevalence were analysed according to clinical-epidemiological status and demographic characteristics. In total, 7,831 observations were included. Patients with Plasmodium falciparum infection had lower mean Hb concentrations (10.5 g/dL) followed by P. vivax-infected individuals (12.4 g/dL), community controls (12.8 g/dL) and malaria-negative febrile patients (13.1 g/dL) (p < 0.001). Age, gender and clinical-epidemiological status were strong independent predictors for both outcomes. Amongst malaria-infected individuals, women in the reproductive age had considerably lower Hb concentrations. In this moderate transmission intensity setting, both vivax and falciparum malaria are associated with reduced Hb concentrations and risk of anaemia throughout a wide age range.

Genetic diversity of chloroquine-resistant Plasmodium vivax parasites from the western Brazilian Amazon

The molecular basis of Plasmodium vivax chloroquine (CQ) resistance is still unknown. Elucidating the molecular background of parasites that are sensitive or resistant to CQ will help to identify and monitor the spread of resistance. By genotyping a panel of molecular markers, we demonstrate a similar genetic variability between in vitro CQ-resistant and sensitive phenotypes of P. vivax parasites. However, our studies identified two loci (MS8 and MSP1-B10) that could be used to discriminate between both CQ-susceptible phenotypes among P. vivax isolates in vitro. These preliminary data suggest that microsatellites may be used to identify and to monitor the spread of P. vivax-resistance around the world.

An overview of malaria transmission from the perspective of Amazon Anopheles vectors

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.

Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei

A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP)-expressing Plasmodium bergheistrain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3) inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.

Draft genome of the Leptospira interrogans strains, Acegua, RCA, Prea, and Capivara, obtained from wildlife maintenance hosts and infected domestic animals

In the present paper, we announce new draft genomes of four Leptospira interrogans strains named Acegua, RCA, Prea, and Capivara. These strains were isolated in the state of Rio Grande do Sul, Brazil, from cattle, dog, Brazilian guinea pig, and capybara, respectively.

Ideologia gerencialista e subjetividade do trabalhador no terceiro setor

Neste artigo, trata-se o impacto de reestruturações de cunho gerencialista sobre a subjetividade de trabalhadores em organizações ambientalistas do terceiro setor historicamente ligadas à benemerência, ao humanismo e à luta por direitos. O crescimento dessa população organizacional tem gerado competição por recursos, com a consequente busca por sistemas e modelos gerenciais que possam viabilizar a sobrevivência de cada organização via vantagens comparativas associadas à eficácia, à eficiência, à efetividade e ao posicionamento de marca. Nesse contexto, percebe-se uma crescente adoção de modelos importados do segundo setor - privado de interesse privado. Elementos característicos do gerencialismo, tais como intensificação e aceleração do trabalho, precarização das relações trabalhistas e primazia do determinismo econômico, são também assimilados no processo. Investe-se no culto à excelência e na mobilização psíquica do sujeito como formas de se enquadrar a pessoa como ativo estratégico da organização. As práticas decorrentes chocam-se com os valores humanistas geralmente vigentes no terceiro setor, causando conflitos de racionalidade e intrapsíquicos. Desenvolveu-se pesquisa qualitativa e exploratória, baseada em entrevistas com profissionais de quatro organizações ambientais de relevo no País, para fazer emergir, por meio da análise do discurso, a percepção dos sujeitos sobre o fenômeno em questão. Os resultados mostram que a ideologia gerencialista foi, pelo menos nos casos estudados, assimilada pelo trabalhador, que as relações de trabalho estão se precarizando em nome da rentabilidade financeira dos investimentos na organização, que as estratégias de defesa e adesão implicam sofrimento subjetivo e que o terceiro setor se distancia crescentemente de sua identidade histórica de esfera de agenciamento marcada por uma racionalidade substantiva.

Vitae sanctorum.

Abdo et Sennes (262-263v) ; Acisclus et Victoria (163-165) ; Adrianus (72v-77) ; Affra (45v) ; Amancius (122-125v) ; Andochius (90v-92v) ; Andreas (186-194v) ; Antoninus (68v-70v, 221v) ; Apollinaris (1bis-1bis v); Audardus (254-259) ; Augustinus (231-232v) ; Bartholomeus (55v-59v) ; Bricius Turonensis (162v-163) ; Caprasius (107-108) ; Caprasius et Fides (218-219v) ; Cassianus (48v) ; Cecilia (168v-174v) ; Christina (12-16v) ; Christoforus (22-24) ; Ciricus et Julita (2v-6, 260v-262) ; Cirillus (2-2v) ; Ciprianus (47v-48v) ; Claudius, Asterius, Neo (54v-55v) ; Clemens (174v-176) ; Cosmas et Damianus (97v-98v) ; Crisantus et Daria (179-182v) ; Crucis exaltatio (83-84) ; Cucufas (24-25) ; Dalmacius Rutenae urbis (131-132v) ; Desiderius Caturcensis (207v-217v) ; Dionisius (105-106v) ; Donatus (263v-265v) ; Eleazarus (38-38v) ; Eptadius (59v-61v) ; Eufemia (84-86) ; Eugenia (78-83) ; Eulalia (195v-199) ; Eustachius (125v-129v) ; Fabius (34v-36v) ; Fausta (52-53v) ; Faustus, Januarius et Marcialis (106v-107) ; Felix (36v-38) ; Felix Nolensis ep. (25-27) ; Filibertus (227v-231) ; Genesius Arelatensis (61v-62v) ; Germanus Autissiodorensis (33-34) ; Gervasius et Protasius (259v-260v) ; Gregorius papa (222-224v) ; Grisogonus (176v-178) ; Jacobus major (20v-21v) ; Jeronimus (100-102) ; Johannis Baptistae decollatio (66v-68v) ; Johannes et Paulus (227-227v) ; Julia (11-12) ; Julianus (64-64v) ; Julianus, auct. Gregorio Turonense (265v-272) ; Julius (178-178v) ; Justa et Rufina (6v-7) ; Justina et Ciprianus (92v-97v) ; Justus et Pastor (44v-45) ; Laurianus (167v-168v) ; Leochadia (195-195v) ; Leodegarius (102-104v) ; Licerius (62v-64) ; Longinus (195) ; Lucia (199-200v) ; Machabei (34-34v) ; Mammes (45v-47v) ; Marcellinus et Petrus (259-259v) ; Marcellus (114) ; Marcellus Cavalonis (219v-220) ; Marcellus Kavilonensis (1v-1bis) ; Marcus (224v-225) ; Marciana (129v-131) ; Marcianus (206-206v) ; Margarita (7-11) ; Mariae assumptio (48v-51) ; Martinus, auct. Sulpicio Severo (133-160v) ; Matheus (86-89) ; Mauricius (89-90v) ; Mauricius, Exuperius, Candidus, Innocentius, Victor cum sociis eorum (272-272v) ; Maurinus (245-247v) ; Maximus (241-244v) ; Medardus (225-227) ; Mennas (160v-162v) ; Michael (98v-100) ; Mimius (39v-40) ; Nazarius et Celsus (27-31v) ; Omnes Sancti (118v-122) ; Pantaleo (31v-32v) ; Petri cathedra (220-221v, 249-250) ; Petrus, ep. Alexandriae (248-249) ; Procopius (39-39v) ; Quintinus (114-118v) ; Regina (70v-72v) ; Reparata (104v-105) ; Romanus (165-167) ; Sabina (64v-66v) ; Salvius (77-78) ; Saturninus et Sisinnius (178v) ; Saturninus Tolosanensis (182v-185v, 232v-239) ; Segolena (16v-20v) ; Servandus et Germanus (108-109) ; Sixtus, Laurentius et Ypolitus (40-44v); Symo et Judas (109-112v) ; Symphorianus (53v-54v) ; Teodota (38v-39) ; Terencianus (239-241) ; Theodardus Narbonensis (250-254) ; Thomas (200v-206) ; Valerianus (206v-207) ; Vamnes (51-52) ; Vincentius et Savina (112v-114). Le f. 220v contient un catalogue ancien de la bibliothèque de Moissac.

Genetic variation in LIN28B is associated with the timing of puberty.

The timing of puberty is highly variable. We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 x 10(-8)). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08-0.16; P = 2.8 x 10(-10); combined P = 3.6 x 10(-16)). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 x 10(-7); N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing, as the first genetic determinant regulating the timing of human pubertal growth and development.

Supporting life-long competence development using the TENCompetence infrastructure: a first experiment

This paper describes an experiment to explore the effects of the TENCompetence infrastructure for supporting lifelong competence development which is now in development. This infrastructure provides structured, multi-leveled access to learning materials, based upon competences. People can follow their own learning path, supported by a listing of competences and their components, by competence development plans attached to competences and by the possibility to mark elements as complete. We expected the PCM to have an effect on (1) control of participants of their own learning, and (2) appreciation of their learning route, (3) of the learning resources, (4) of their competence development, and (5) of the possibilities of collaboration. In the experiment, 44 Bulgarian teachers followed a distance learning course on a specific teaching methodology for six weeks. Part of them used the TENCompetence infrastructure, part used an infrastructure which was similar, except for the characterizing elements mentioned above. The results showed that in the experimental condition, more people passed the final competence assess-ment, and people felt more in control of their own learning. No differences between the two groups were found on the amount and appreciation of collaboration and on further measures of competence development.

The achievable region approach to the optimal control of stochastic systems

The achievable region approach seeks solutions to stochastic optimisation problems by: (i) characterising the space of all possible performances(the achievable region) of the system of interest, and (ii) optimisingthe overall system-wide performance objective over this space. This isradically different from conventional formulations based on dynamicprogramming. The approach is explained with reference to a simpletwo-class queueing system. Powerful new methodologies due to the authorsand co-workers are deployed to analyse a general multiclass queueingsystem with parallel servers and then to develop an approach to optimalload distribution across a network of interconnected stations. Finally,the approach is used for the first time to analyse a class of intensitycontrol problems.

Fecundidade e longevidade de Aphis gossypii Glover, 1877 (Hemiptera, Aphididae) em diferentes temperaturas e cultivares comerciais de crisântemo (Dendranthema grandiflora Tzvelev)

Fecundity and longevity of Aphis gossypii Glover, 1877 (Hemiptera, Aphididae) at different temperatures and commercial chrysanthemum cultivars (Dendranthema grandiflora Tzvelev). The aphid A. gossypii is one of the main pests in a number of crops both under field and protected conditions. The objective of the present study was to evaluate the fecundity and longevity of A. gossypii under different temperatures and commercial chrysanthemum cultivars (Yellow Snowdon, White Reagan and Dark Splendid Reagan) with different trichomes densities (11.3; 16.6 and 21.6 trichome/mm² of the leaf, respectively) The trials were carried out in climatic chambers, at four temperatures (15, 20, 25 and 30 ±1 °C), 70 ± 10% RH and photophase 10h. The reproductive period significantly decreased with increase of temperature in the three cultivars. In Yellow Snowdon cultivar average duration of the reproductive period was 14.3 days at 25 °C. The maximum fecundity was obtained at the temperature of 25 ºC with 3,1; 2,8 and 3,6 nymphs/female/day in the Yellow Snowdon, White Reagan and Dark S. Reagan cultivars, respectively. The total fecundity was reduced by extreme temperatures (15 and 30 °C), and was obtained at 25 °C with 35,9 nymphs/female. Females maintained in Yellow Snowdon cultivar significantly showed superiority (30,7 nymphs/female) in total fecundity in relation to White Reagan (22,1 nymphs/female) and Dark S. Reagan (22,9 nymphs/female). The Yellow Snowdon cultivar (with a lower trichome density) had a significant influence in daily and total capacity of nymphs production, showing a higher fecundity of A. gossypii females. The aphid's longevity was affected by cultivars and temperature, and this longevity decreased whit increase of temperature. The results showed that there was an interaction between the temperature and host plant on reproductive parameters of A. gossypii.