Spatial distribution of Schistosoma mansoni infection before and after chemotherapy with two praziquantel doses in a community of Pernambuco, Brazil

Praziquantel chemotherapy has been the focus of the Schistosomiasis Control Program in Brazil for the past two decades. Nevertheless, information on the impact of selective chemotherapy against Schistosoma mansoni infection under the conditions confronted by the health teams in endemic municipalities remains scarce. This paper compares the spatial pattern of infection before and after treatment with either a 40 mg/kg or 60 mg/kg dose of praziquantel by determining the intensity of spatial cluster among patients at 180 and 360 days after treatment. The spatial-temporal distribution of egg-positive patients was analysed in a Geographic Information System using the kernel smoothing technique. While all patients became egg-negative after 21 days, 17.9% and 30.9% reverted to an egg-positive condition after 180 and 360 days, respectively. Both the prevalence and intensity of infection after treatment were significantly lower in the 60 mg/kg than in the 40 mg/kg treatment group. The higher intensity of the kernel in the 40 mg/kg group compared to the 60 mg/kg group, at both 180 and 360 days, reflects the higher number of reverted cases in the lower dose group. Auxiliary, preventive measures to control transmission should be integrated with chemotherapy to achieve a more enduring impact

Angiotensin-(1-7)/MasR axis promotes migration of monocytes/macrophages with a regulatory phenotype to perform phagocytosis and efferocytosis.

Nonphlogistic migration of macrophages contributes to the clearance of pathogens and apoptotic cells, a critical step for the resolution of inflammation and return to homeostasis. Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system that acts through Mas receptor (MasR). Ang-(1-7) has recently emerged as a novel proresolving mediator, yet Ang-(1-7) resolution mechanisms are not fully determined. Herein, Ang-(1-7) stimulated migration of human and murine monocytes/macrophages in a MasR-, CCR2-, and MEK/ERK1/2-dependent manner. Pleural injection of Ang-(1-7) promoted nonphlogistic mononuclear cell influx alongside increased levels of CCL2, IL-10, and macrophage polarization toward a regulatory phenotype. Ang-(1-7) induction of CCL2 and mononuclear cell migration was also dependent on MasR and MEK/ERK. Of note, MasR was upregulated during the resolution phase of inflammation, and its pharmacological inhibition or genetic deficiency impaired mononuclear cell recruitment during self-resolving models of LPS pleurisy and E. coli peritonitis. Inhibition/absence of MasR was associated with reduced CCL2 levels, impaired phagocytosis of bacteria, efferocytosis, and delayed resolution of inflammation. In summary, we have uncovered a potentially novel proresolving feature of Ang-(1-7), namely the recruitment of mononuclear cells favoring efferocytosis, phagocytosis, and resolution of inflammation. Mechanistically, cell migration was dependent on MasR, CCR2, and the MEK/ERK pathway

A Rationale for Schistosomiasis Control in Elementary Schools of the Rainforest Zone of Pernambuco, Brazil

In 2001, a World Health Assembly resolution urged member states to ensure treatment against schistosomiasis and soil-transmitted helminthiasis in endemic areas with the goal of attaining a minimum target of at least 75% of all school-aged children by 2010. In the highly endemic Rainforest Zone of Pernambuco (ZMP), northeast Brazil, the Schistosomiasis Control Program has registered a cumulative coverage of only 20% of the population at risk, which jeopardizes the accomplishment of the minimum target for that area. Demographic and parasitological data from a representative municipality of the ZMP provide evidence that the current, community-based approach to control can be complemented with school-based actions. In the most troubled municipalities, individual diagnosis and treatment could be focused on school-aged children rather than whole populations without compromising the principles of the primary health care system. Local health and education teams should be encouraged to include school-based interventions to scale up coverage and achieve a rapid impact on infection

The prevalence of schistosomiasis in school-aged children as an appropriate indicator of its prevalence in the community

School-aged children (6-15 years) from the endemic area of Pernambuco were evaluated both as a target group for and an indicator of schistosomiasis control in the community. Parasitological data were drawn from baseline stool surveys of whole populations that were obtained to diagnose Schistosoma mansoni infection. Nineteen representative localities were selected for assessing the prevalence of schistosomiasis among individuals in the following age groups: 0-5, 6-15, 16-25, 26-40 and 41-80 years. For each locality, the prevalence in each age group was compared to that of the overall population using contingency table analysis. To select a reference group, the operational difficulties of conducting residential surveys were considered. School-aged children may be considered to be the group of choice as the reference group for the overall population for the following reasons: (i) the prevalence of schistosomiasis in this age group had the highest correlation with the prevalence in the overall population (r = 0.967), (ii) this age group is particularly vulnerable to infection and plays an important role in parasite transmission and (iii) school-aged children are the main target of the World Health Organization in terms of helminth control. The Schistosomiasis Control Program should consider school-aged children both as a reference group for assessing the need for intervention at the community level and as a target group for integrated health care actions of the Unified Health System that are focused on high-risk groups

Intracellular directed evolution of proteins from combinatorial libraries based on conditional phage replication

Directed evolution is a powerful tool to improve the characteristics of biomolecules. Here we present a protocol for the intracellular evolution of proteins with distinct differences and advantages in comparison with established techniques. These include the ability to select for a particular function from a library of protein variants inside cells, minimizing undesired coevolution and propagation of nonfunctional library members, as well as allowing positive and negative selection logics using basally active promoters. A typical evolution experiment comprises the following stages: (i) preparation of a combinatorial M13 phagemid (PM) library expressing variants of the gene of interest (GOI) and preparation of the Escherichia coli host cells; (ii) multiple rounds of an intracellular selection process toward a desired activity; and (iii) the characterization of the evolved target proteins. The system has been developed for the selection of new orthogonal transcription factors (TFs) but is capable of evolving any gene—or gene circuit function—that can be linked to conditional M13 phage replication. Here we demonstrate our approach using as an example the directed evolution of the bacteriophage λ cI TF against two synthetic bidirectional promoters. The evolved TF variants enable simultaneous activation and repression against their engineered promoters and do not cross-react with the wild-type promoter, thus ensuring orthogonality. This protocol requires no special equipment, allowing synthetic biologists and general users to evolve improved biomolecules within ~7 weeks

An application of the Rasch model to reading comprehension measurement

An effective reading comprehension measurement demands robust psychometric tools that allow teachers and researchers to evaluate the educational practices and track changes in students’ performance. In this study, we illustrate how Rasch model can be used to attend such demands and improve reading comprehension measurement. We discuss the construction of two reading comprehension tests: TRC-n, with narrative texts, and TRC-e, with expository texts. Three vertically scaled forms were generated for each test (TRC-n-2, TRC-n-3, TRC-n-4; TRC-e-2, TRC-e-3 and TRC-e-4), each meant to assess Portuguese students in second, third and fourth grade of elementary school. The tests were constructed according to a nonequivalent groups with anchor test design and data were analyzed using the Rasch model. The results provided evidence for good psychometric qualities for each test form, including unidimensionality and local independence and adequate reliability. A critical view of this study and future researches are discussed.CIEC – Research Centre on Child Studies, IE, UMinho (FCT R&D unit 317), PortugalThis research was supported by Grant FCOMP-01-0124-FEDER-010733 from Fundação para a Ciência e Tecnologia (FCT) and the European Regional Development Fund (FEDER) through the European program COMPETE (Operational Program for Competitiveness Factors) under the National Strategic Reference Framework (QREN).info:eu-repo/semantics/publishedVersio