The angiotensin II AT(1), receptor structure-activity correlations in the light of rhodopsin structure

The most prevalent physiological effects of ANG II, the main product of the renin-angiotensin system, are mediated by the AT(1) receptor, a rhodopsin-like AGPCR. Numerous studies of the cardiovascular effects of synthetic peptide analogs allowed a detailed mapping of ANG II's structural requirements for receptor binding and activation, which were complemented by site-directed mutagenesis studies on the AT(1) receptor to investigate the role of its structure in ligand binding, signal transduction, phosphorylation, binding to arrestins, internalization, desensitization, tachyphylaxis, and other properties. the knowledge of the high-resolution structure of rhodopsin allowed homology modeling of the AT(1) receptor. the models thus built and mutagenesis data indicate that physiological (agonist binding) or constitutive (mutated receptor) activation may involve different degrees of expansion of the receptor's central cavity. Residues in ANG II structure seem to control these conformational changes and to dictate the type of cytosolic event elicited during the activation. 1) Agonist aromatic residues (Phe(8) and Tyr(4)) favor the coupling to G protein, and 2) absence of these residues can favor a mechanism leading directly to receptor internalization via phosphorylation by specific kinases of the receptor's COOH-terminal Ser and Thr residues, arrestin binding, and clathrin-dependent coated-pit vesicles. On the other hand, the NH2-terminal residues of the agonists ANG II and [Sar(1)]-ANG II were found to bind by two distinct modes to the AT(1) receptor extracellular site flanked by the COOH-terminal segments of the EC-3 loop and the NH2-terminal domain. Since the [Sar(1)]-ligand is the most potent molecule to trigger tachyphylaxis in AT(1) receptors, it was suggested that its corresponding binding mode might be associated with this special condition of receptors.Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilUniv São Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, BrazilUniv São Paulo, Inst Chem, Dept Biochem, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilWeb of Scienc

The State of the ReCLes. pt CLIL training project

Content and Language Integrated Learning (CLIL), an area that has only recently been more thoroughly explored for appropriate use at higher levels of education, has been one of the research areas identified by the Association of Language Centers in Higher Education in Portugal (ReCLes.pt). ReCLes.pt members – administration and research professors are striving to make a difference in the paucity of scientific publications in this area with the creation of their national program for training content teachers in Portuguese higher education. To best learn from each other in a collaborative network and apply well-informed teaching and learning methodology to English-taught classrooms, the underlying concepts range from classroom management and scaffolding to learner autonomy and from Web 2.0 tools to terminology-based learning. As an update of the current state of the art as interpreted in this project, the outreach and reception will be described in full with attention to some detailed examples of the more successful aspects as well as others where we have found room for improvement. Recommendations will be made for other networks and individual schools aiming to effectively prepare their students for the market by using an integrated approach to content and language learning. This paper reports on the current state of the ongoing ReCLes.pt CLIL Training Project, financed in part by the FCT (the Portuguese Foundation for Science and Technology), with project members from a number of universities and polytechnics across Portugal.info:eu-repo/semantics/publishedVersio

Nursing Diagnosis Risk for falls: prevalence and clinical profile of hospitalized patients

Objectives: to identify the prevalence of the Nursing Diagnosis (ND) Risk for falls in the hospitalizations of adult patients in clinical and surgical units, to characterize the clinical profile and to identify the risk factors of the patients with this ND. Method: a cross-sectional study with 174 patients. The data was collected from the computerized nursing care prescriptions system and on-line hospital records, and analyzed statistically. Results: the prevalence of the ND Risk for falls was 4%. The patients’ profile indicated older adults, males (57%), those hospitalized in the clinical units (63.2%), with a median length of hospitalization of 20 (10-24) days, with neurological illnesses (26%), cardio-vascular illnesses (74.1%) and various co-morbidities (3±1.8). The prevalent risk factors were neurological alterations (43.1%), impaired mobility (35.6%) and extremes of age (10.3%). Conclusion: the findings contributed to evidencing the profile of the patients with a risk of falling hospitalized in clinical and surgical wards, which favors the planning of interventions for preventing this adverse event

Applying the Maternal Near Miss Approach for the Evaluation of Quality of Obstetric Care: A Worked Example from a Multicenter Surveillance Study

Objective. To assess quality of care of women with severe maternal morbidity and to identify associated factors. Method. This is a national multicenter cross-sectional study performing surveillance for severe maternal morbidity, using the World Health Organization criteria. the expected number of maternal deaths was calculated with the maternal severity index (MSI) based on the severity of complication, and the standardized mortality ratio (SMR) for each center was estimated. Analyses on the adequacy of care were performed. Results. 17 hospitals were classified as providing adequate and 10 as nonadequate care. Besides almost twofold increase in maternal mortality ratio, the main factors associated with nonadequate performance were geographic difficulty in accessing health services (P < 0.001), delays related to quality of medical care (P = 0.012), absence of blood derivatives (P = 0.013), difficulties of communication between health services (P = 0.004), and any delay during the whole process (P = 0.039). Conclusions. This is an example of how evaluation of the performance of health services is possible, using a benchmarking tool specific to Obstetrics. in this study the MSI was a useful tool for identifying differences in maternal mortality ratios and factors associated with nonadequate performance of care.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Campinas UNICAMP, Sch Med Sci, Dept Obstet & Gynaecol, BR-13083881 Campinas, SP, BrazilCtr Res Reprod Hlth Campinas Cemicamp, BR-13083888 Campinas, SP, BrazilUniv Fed Amazonas, Manaus, Amazonas, BrazilSch Med Sci, CISAM, Recife, PE, BrazilUniv Fed Ceara, Fortaleza, Ceara, BrazilUniv Fed Bahia, Salvador, BA, BrazilHosp Geral Cesar Cals, Fortaleza, Ceara, BrazilHosp Geral Fortaleza, Fortaleza, Ceara, BrazilMaternidade Odete Valadares, Belo Horizonte, MG, BrazilHosp Materno Infantil, Goiania, Go, BrazilInst Materno Infantil Pernambuco, Recife, PE, BrazilUniv Fed Pernambuco, Recife, PE, BrazilUniv Fed Campina Grande, Campina Grande, PB, BrazilUniv Fed Maranhao, Sao Luis, MA, BrazilUniv Fed Parana, BR-80060000 Curitiba, Parana, BrazilUniv Fed Paraiba, BR-58059900 Joao Pessoa, Paraiba, BrazilHosp Maternidade Fernando Magalhaes, Rio de Janeiro, RJ, BrazilUniv Fed Rio Grande do Sul, Porto Alegre, RS, BrazilHosp Maternidade Celso Pierro, Campinas, SP, BrazilInst Fernandes Figueira Fiocruz, Rio de Janeiro, RJ, BrazilHosp Israelita Albert Einstein, São Paulo, BrazilUniv State São Paulo, Botucatu, SP, BrazilJundiai Sch Med, Jundiai, SP, BrazilUniv São Paulo, BR-14049 Ribeirao Preto, SP, BrazilSanta Casa Limeira, Limeira, SP, BrazilSanta Casa Sao Carlos, Sao Carlos, SP, BrazilMaternidade Leonor Mendes de Barros, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilCNPq: 402702/2008-5Web of Scienc

Microsatellite analysis supports clonal propagation and reduced divergence of Trypanosoma vivax from asymptomatic to fatally infected livestock in South America compared to West Africa

Background: Mechanical transmission of the major livestock pathogen Trypanosoma vivax by other biting flies than\ud tsetse allows its spread from Africa to the New World. Genetic studies are restricted to a small number of isolates\ud and based on molecular markers that evolve too slowly to resolve the relationships between American and West\ud African populations and, thus, unable us to uncover the recent history of T. vivax in the New World.\ud Methods: T. vivax genetic diversity, population structure and the source of outbreaks was investigated through the\ud microsatellite multiloci (7 loci) genotype (MLGs) analysis in South America (47isolates from Brazil, Venezuela and\ud French Guiana) and West Africa (12 isolates from The Gambia, Burkina Faso, Ghana, Benin and Nigeria).\ud Relationships among MLGs were explored using phylogenetic, principal component and STRUCTURE analyses.\ud Results: Although closely phylogenetically related, for the first time, genetic differences were detected between\ud T. vivax isolates from South America (11 genotypes/47 isolates) and West Africa (12 genotypes/12 isolates) with no\ud MLGs in common. Diversity was far greater across West Africa than in South America, where genotypes from Brazil\ud (MLG1-6), Venezuela (MLG7-10) and French Guiana (MLG11) shared similar but not identical allele composition. No\ud MLG was exclusive to asymptomatic (endemic areas) or sick (outbreaks in non-endemic areas) animals, but only\ud MLGs1, 2 and 3 were responsible for severe haematological and neurological disorders.\ud Conclusions: Our results revealed closely related genotypes of T. vivax in Brazil and Venezuela, regardless of\ud endemicity and clinical conditions of the infected livestock. The MLGs analysis from T. vivax across SA and WA\ud support clonal propagation, and is consistent with the hypothesis that the SA populations examined here derived\ud from common ancestors recently introduced from West Africa. The molecular markers defined here are valuable to\ud assess the genetic diversity, to track the source and dispersion of outbreaks, and to explore the epidemiological\ud and pathological significance of T. vivax genotypes.This work was funded through projects within the PROAFRICA and PROSUL programs from the Brazilian agency CNPq. We are grateful to Professor Erney P. Camargo for the joint coordination of these projects and helpful commentaries on the manuscript. HAG was funded by a CDCH-UCV studentship from Venezuela; ACR is a postdoctoral fellow of PNPD-CAPES and CMFR is recipient of PhD scholarships from CNPq-PROTAX. The authors would like to acknowledge for clinical and epidemiological information, blood samples of T. vivax infected livestock and valuable help in the fieldwork several colleagues Garcia et al. Parasites & Vectors 2014, 7:210 Page 11 of 13\ud http://www.parasitesandvectors.com/content/7/1/210 from African countries, Venezuela and Brazil (Galiza GF, Da Silva A and Cadioli L\ud also for previous joint studies). We are grateful to The Wellcome Trust for making available sequences from the genome of T. vivax from Sanger Institute. We are deeply in debt to Wendy Gibson (Bristol University, UK) for helpful discussions and suggestions that much improved our manuscript

Automated database-guided expert-supervised orientation for immunophenotypic diagnosis and classification of acute leukemia

Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications