Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service.

Several studies have demonstrated the cost-effectiveness of genetic testing for surveillance and treatment of carriers of germline pathogenic variants associated with hereditary breast/ovarian cancer syndrome (HBOC). In Brazil, seventy percent of the population is assisted by the public Unified Health System (SUS), where genetic testing is still unavailable. And few studies were performed regarding the prevalence of HBOC pathogenic variants in this context. Here, we estimated the prevalence of germline pathogenic variants in BRCA1, BRCA2 and TP53 genes in Brazilian patients suspected of HBOC and referred to public healthcare service. Predictive power of risk prediction models for detecting mutation carriers was also evaluated. We found that 41 out of 257 tested patients (15.9%) were carriers of pathogenic variants in the analyzed genes. Most frequent pathogenic variant was the founder Brazilian mutation TP53 c.1010G > A (p.Arg337His), adding to the accumulated evidence that supports inclusion of TP53 in routine testing of Brazilian HBOC patients. Surprisingly, BRCA1 c.5266dupC (p.Gln1756fs), a frequently reported pathogenic variant in Brazilian HBOC patients, was not observed. Regarding the use of predictive models, we found that familial history of cancer might be used to improve selection or prioritization of patients for genetic testing, especially in a context of limited resources.

New SHH and Known SIX3 Variants in a Series of Latin American Patients with Holoprosencephaly.

Holoprosencephaly (HPE) is the failure of the embryonic forebrain to develop into 2 hemispheres promoting midline cerebral and facial defects. The wide phenotypic variability and causal heterogeneity make genetic counseling difficult. Heterozygous variants with incomplete penetrance and variable expressivity in the SHH, SIX3, ZIC2, and TGIF1 genes explain ∼25% of the known causes of nonchromosomal HPE. We studied these 4 genes and clinically described 27 Latin American families presenting with nonchromosomal HPE. Three new SHH variants and a third known SIX3 likely pathogenic variant found by Sanger sequencing explained 15% of our cases. Genotype-phenotype correlation in these 4 families and published families with identical or similar driver gene, mutated domain, conservation of residue in other species, and the type of variant explain the pathogenicity but not the phenotypic variability. Nine patients, including 2 with SHH pathogenic variants, presented benign variants of the SHH, SIX3, ZIC2, and TGIF1 genes with potential alteration of splicing, a causal proposition in need of further studies. Finding more families with the same SIX3 variant may allow further identification of genetic or environmental modifiers explaining its variable phenotypic expression.

Maternal ingestion of cocoa causes constriction of fetal ductus arteriosus in rats.

Maternal consumption of polyphenol-rich foods has been associated with fetal ductus arteriosus constriction (DAC), but safety of chocolate exposure in fetal life has not been studied. This experimental study tested the hypothesis that maternal cocoa consumption in late pregnancy causes fetal DAC, with possible associated antioxidant effects. Pregnant Wistar rats, at the 21st gestational day, received by orogastric tube cocoa (720 mg/Kg) for 12 h, indomethacin (10 mg/Kg), for 8 h, or only water, before cesaren section. Immediately after withdrawal, every thorax was obtained and tissues were fixed and stained for histological analysis. The ratio of the narrowest part of the pulmonary artery to the fetal ductus inner diameter and increased ductal inner wall thickness characterized ductal constriction. Substances reactive to thiobarbituric acid were quantified. Statistical analysis used ANOVA and Tukey test. Cocoa (n = 33) and indomethacin (n = 7) reduced fetal internal ductus diameter when compared to control (water, n = 25) (p < 0.001) and cocoa alone increased ductus wall thickness (p < 0.001), but no change was noted in enzymes activity. This pharmacological study shows supporting evidences that there is a cause and effect relationship between maternal consumption of cocoa and fetal ductus arteriosus constriction. Habitual widespread use of chocolate during gestation could account for undetected ductus constriction and its potentially severe consequences, such as perinatal pulmonary hypertension, cardiac failure and even death. For this reason, dietary guidance in late pregnancy to avoid high chocolate intake, to prevent fetal ductal constriction, may represent the main translational aspect of this study.

Implementation of a rapid response team in a large nonprofit Brazilian hospital: improving the quality of emergency care through Plan-Do-Study-Act. / Implantação de um time de resposta rápida em um grande hospital filantrópico brasileiro: melhora na qualidade dos cuidados de emergência por meio do ciclo Planejar-Fazer-Estudar-Agir.

OBJECTIVE: To describe the implementation of a rapid response team in a large nonprofit hospital, indicating relevant issues for other initiatives in similar contexts, particularly in Latin America. METHODS: In general terms, the intervention consisted of three major components: (1) a tool to detect aggravation of clinical conditions in general wards; (2) the structuring of a rapid response team to attend to all patients at risk; and (3) the monitoring of indicators regarding the intervention. This work employed four half-year Plan-Do-Study-Act cycles to test and adjust the intervention from January 2013 to December 2014. RESULTS: Between 2013 and 2014, the rapid response team attended to 2,296 patients. This study showed a nonsignificant reduction in mortality from 8.3% in cycle 1 to 5.0% in cycle 4; however, death rates remained stable in cycles 3 and 4, with frequencies of 5.2% and 5.0%, respectively. Regarding patient flow and continuum of critical care, which is a premise of the rapid response system, there was a reduction in waiting time for intensive care unit beds with a decrease from 45.9% to 19.0% in the frequency of inpatients who could not be admitted immediately after indication (p < 0.001), representing improved patient flow in the hospital. In addition, an increase in the recognition of palliative care patients from 2.8% to 10.3% was noted (p = 0.005). CONCLUSION: Implementing a rapid response team in contexts where there are structural restrictions, such as lack of intensive care unit beds, may be very beneficial, but a strategy of adjustment is needed.

OBJETIVO: Descrever a implantação de um time de resposta rápida em um grande hospital filantrópico, indicando as questões relevantes para as iniciativas em contextos similares, particularmente na América Latina. MÉTODOS: Em termos gerais, a intervenção consistiu em três componentes principais: (1) uma ferramenta para detecção de agravamento das condições clínicas nas enfermarias gerais; (2) estruturação de time de resposta rápida capaz de atender a todos os pacientes em risco; e (3) monitoramento dos indicadores relacionados à intervenção. Este trabalho empregou quatro ciclos semestrais (Planejar-Fazer-Estudar-Agir), com a finalidade de testar e ajustar a intervenção, entre janeiro de 2013 e dezembro de 2014. RESULTADOS: Entre 2013 e 2014, o time de resposta rápida atendeu 2.296 pacientes. Houve redução não significante da mortalidade de 8,3% no ciclo 1, para 5,0% no ciclo 4; contudo, o número de óbitos permaneceu estável nos ciclos 3 e 4, com frequência de 5,2% e 5,0%, respectivamente. Com relação ao fluxo de pacientes e cuidados críticos continuados − uma premissa do time de resposta rápida −, houve decréscimo no tempo de espera por um leito na unidade de terapia intensiva, com diminuição de 45,9% para 19,0% na frequência de pacientes hospitalizados que não puderam ser imediatamente admitidos após a indicação (p < 0,001), representando melhora no fluxo de pacientes do hospital; ocorreu também aumento no reconhecimento de pacientes para cuidados paliativos, de 2,8% para 10,3% (p = 0,005). CONCLUSÃO: A implantação de um time de resposta rápida pode trazer benefícios nos contextos em que ocorrem restrições estruturais, como falta de leitos em unidades de terapia intensiva, porém há necessidade de alguns ajustes.

Implantação de um time de resposta rápida em um grande hospital filantrópico brasileiro: melhora na qualidade dos cuidados de emergência por meio do ciclo Planejar-Fazer-Estudar-Agir / Implementation of a rapid response team in a large nonprofit Brazilian hospital: improving the quality of emergency care through Plan-Do-Study-Act

RESUMO Objetivo: Descrever a implantação de um time de resposta rápida em um grande hospital filantrópico, indicando as questões relevantes para as iniciativas em contextos similares, particularmente na América Latina. Métodos: Em termos gerais, a intervenção consistiu em três componentes principais: (1) uma ferramenta para detecção de agravamento das condições clínicas nas enfermarias gerais; (2) estruturação de time de resposta rápida capaz de atender a todos os pacientes em risco; e (3) monitoramento dos indicadores relacionados à intervenção. Este trabalho empregou quatro ciclos semestrais (Planejar-Fazer-Estudar-Agir), com a finalidade de testar e ajustar a intervenção, entre janeiro de 2013 e dezembro de 2014. Resultados: Entre 2013 e 2014, o time de resposta rápida atendeu 2.296 pacientes. Houve redução não significante da mortalidade de 8,3% no ciclo 1, para 5,0% no ciclo 4; contudo, o número de óbitos permaneceu estável nos ciclos 3 e 4, com frequência de 5,2% e 5,0%, respectivamente. Com relação ao fluxo de pacientes e cuidados críticos continuados − uma premissa do time de resposta rápida −, houve decréscimo no tempo de espera por um leito na unidade de terapia intensiva, com diminuição de 45,9% para 19,0% na frequência de pacientes hospitalizados que não puderam ser imediatamente admitidos após a indicação (p < 0,001), representando melhora no fluxo de pacientes do hospital; ocorreu também aumento no reconhecimento de pacientes para cuidados paliativos, de 2,8% para 10,3% (p = 0,005). Conclusão: A implantação de um time de resposta rápida pode trazer benefícios nos contextos em que ocorrem restrições estruturais, como falta de leitos em unidades de terapia intensiva, porém há necessidade de alguns ajustes.

ABSTRACT Objective: To describe the implementation of a rapid response team in a large nonprofit hospital, indicating relevant issues for other initiatives in similar contexts, particularly in Latin America. Methods: In general terms, the intervention consisted of three major components: (1) a tool to detect aggravation of clinical conditions in general wards; (2) the structuring of a rapid response team to attend to all patients at risk; and (3) the monitoring of indicators regarding the intervention. This work employed four half-year Plan-Do-Study-Act cycles to test and adjust the intervention from January 2013 to December 2014. Results: Between 2013 and 2014, the rapid response team attended to 2,296 patients. This study showed a nonsignificant reduction in mortality from 8.3% in cycle 1 to 5.0% in cycle 4; however, death rates remained stable in cycles 3 and 4, with frequencies of 5.2% and 5.0%, respectively. Regarding patient flow and continuum of critical care, which is a premise of the rapid response system, there was a reduction in waiting time for intensive care unit beds with a decrease from 45.9% to 19.0% in the frequency of inpatients who could not be admitted immediately after indication (p < 0.001), representing improved patient flow in the hospital. In addition, an increase in the recognition of palliative care patients from 2.8% to 10.3% was noted (p = 0.005). Conclusion: Implementing a rapid response team in contexts where there are structural restrictions, such as lack of intensive care unit beds, may be very beneficial, but a strategy of adjustment is needed.

Prevalence and clinical profile of microcephaly in South America pre-Zika, 2005-14: prevalence and case-control study.

Objective To describe the prevalence and clinical spectrum of microcephaly in South America for the period 2005-14, before the start of the Zika epidemic in 2015, as a baseline for future surveillance as the Zika epidemic spreads and as other infectious causes may emerge in future.Design Prevalence and case-control study.Data sources ECLAMC (Latin American Collaborative Study of Congenital Malformations) database derived from 107 hospitals in 10 South American countries, 2005 to 2014. Data on microcephaly cases, four non-malformed controls per case, and all hospital births (all births for hospital based prevalence, resident within municipality for population based prevalence). For 2010-14, head circumference data were available and compared with Intergrowth charts.Results 552 microcephaly cases were registered, giving a hospital based prevalence of 4.4 (95% confidence interval 4.1 to 4.9) per 10 000 births and a population based prevalence of 3.0 (2.7 to 3.4) per 10 000. Prevalence varied significantly between countries and between regions and hospitals within countries. Thirty two per cent (n=175) of cases were prenatally diagnosed; 29% (n=159) were perinatal deaths. Twenty three per cent (n=128) were associated with a diagnosed genetic syndrome, 34% (n=189) polymalformed without a syndrome diagnosis, 12% (n=65) with associated neural malformations, and 26% (n=145) microcephaly only. In addition, 3.8% (n=21) had a STORCH (syphilis, toxoplasmosis, other including HIV, rubella, cytomegalovirus, and herpes simplex) infection diagnosis and 2.0% (n=11) had consanguineous parents. Head circumference measurements available for 184/235 cases in 2010-14 showed 45% (n=82) more than 3 SD below the mean, 24% (n=44) between 3 SD and 2 SD below the mean, and 32% (n=58) larger than -2 SD.Conclusion Extrapolated to the nearly 7 million annual births in South America, an estimated 2000-2500 microcephaly cases were diagnosed among births each year before the Zika epidemic began in 2015. Clinicians are using more than simple metrics to make microcephaly diagnoses. Endemic infections are important enduring causes of microcephaly.

Cellular basis of morphological variation and temperature-related plasticity in Drosophila melanogaster strains with divergent wing shapes.

Organ shape evolves through cross-generational changes in developmental patterns at cellular and/or tissue levels that ultimately alter tissue dimensions and final adult proportions. Here, we investigated the cellular basis of an artificially selected divergence in the outline shape of Drosophila melanogaster wings, by comparing flies with elongated or rounded wing shapes but with remarkably similar wing sizes. We also tested whether cellular plasticity in response to developmental temperature was altered by such selection. Results show that variation in cellular traits is associated with wing shape differences, and that cell number may play an important role in wing shape response to selection. Regarding the effects of developmental temperature, a size-related plastic response was observed, in that flies reared at 16 °C developed larger wings with larger and more numerous cells across all intervein regions relative to flies reared at 25 °C. Nevertheless, no conclusive indication of altered phenotypic plasticity was found between selection strains for any wing or cellular trait. We also described how cell area is distributed across different intervein regions. It follows that cell area tends to decrease along the anterior wing compartment and increase along the posterior one. Remarkably, such pattern was observed not only in the selected strains but also in the natural baseline population, suggesting that it might be canalized during development and was not altered by the intense program of artificial selection for divergent wing shapes.

O esporte náutico e a dinâmica da hélice tríplice no projeto Grael: um estudo de caso / The nautical sport and the dynamics of triple helix in the Grael project: a case study

Alguns projetos desenvolvidos no âmbito do esporte têm se destacado por apresentarem modelos inovadores. Este estudo focaliza o Projeto Grael e suas relações com o governo, com a indústria e com a universidade. Tem como objetivo geral promover a reflexão sobre o papel do esporte no desenvolvimento de regiões. O modelo teórico da hélice tríplice é utilizado para analisar a participação de diferentes atores. A conclusão aponta que o principal parceiro do projeto é a prefeitura da cidade de Niterói. A atuação das indústrias, basicamente, situa-se no âmbito do patrocínio. A universidade participa de forma tímida.

Some projects developed within the sport have been known for presenting innovative models. This study focuses on the Grael Project and its relations with government, industry and the university. It aims at promoting reflection on the role of sport in developing regions. The theoretical model of the triple helix is used to analyze the participation of different actors. The conclusion shows that the main project partner is the mayor of the city of Niteroi. The performance of industries, basically, is located in the sponsorship. The University participates in a shy way.

Algunos proyectos desarrollados en el deporte han sido conocidos por la presentación de modelos innovadores. Este estudio se centra en el Proyecto Grael y sus relaciones con el gobierno, la industria y la universidad. Su objetivo es promover la reflexión sobre el papel del deporte en las regiones en desarrollo. El modelo teórico de la triple hélice se utiliza para analizar la participación de diferentes actores. La conclusión muestra que el socio principal del proyecto es el alcalde de la ciudad de Niterói. El rendimiento de las industrias, básicamente, se encuentra en el patrocinio. La Universidad participa de una manera tímida.