Innate immunity refers to the mechanisms responsible for the first line of defense against pathogens, cancer cells and toxins. The innate immune system is also responsible for the initial activation of the body’s specific immune response (adaptive immunity). Innate immunity was studied and further developed in parallel with adaptive immunity beginning in the first half of the 19th century and has been gaining increasing importance to our understanding of health and disease. In the present overview, we describe the main findings and ideas that contributed to the development of innate immunity as a continually expanding branch of modern immunology. We start with the toxicological studies by Von Haller and Magendie, in the late 18th and early 19th centuries, and continue with the discoveries in invertebrate immunity that supported the discovery and characterization of lipopolysaccharide (LPS) and pattern recognition receptors that led to the development of the pattern recognition and danger theory.

Abstract The impact of high-speed exercise on the musculoskeletal system of young racehorses has been extensively discussed because of concerns regarding animal health and welfare. This study investigated the correlation between age, degree of ossification of the distal radial epiphysis, sex, and career longevity of Thoroughbred racehorses in Brazil from 2012 to 2015. We performed a retrospective evaluation of 286 dorsopalmar radiographs of the left radiocarpal region of young horses and their racing performance. Distal radial epiphyseal closure was classified into three degrees: A, B, or C. Performance data included the number of races raced, athletic career length, and the number of races per month. The variables were subjected to regression analysis. At the time of radiographic examination, male horses were significantly older than females, and horses with epiphyseal closure degrees differed with age. Age at first race was 33.08±3.81 months, the average of races raced was 18.32±15.14 races, athletic career duration was 20.37±13.82 months, and the number of races raced per month was 0.93±0.46 races. Age influenced (P>0.001) the distal radial epiphyseal closure on racehorses, but sex did not (P=0.218 for males and P=0.275 for females). An inverse association was observed between age at the first race, the number of races raced per month, and athletic career duration. The frequency of race and the age at the first race influenced athletic career duration.

Resumo O impacto do exercício de alta velocidade no sistema musculoesquelético de cavalos de corrida jovens tem sido amplamente discutido devido a preocupações com a saúde e o bem-estar animal. Este estudo investigou a correlação entre idade, grau de ossificação da epífise radial distal, sexo e longevidade da carreira de cavalos Puro Sangue Inglês de corrida no Brasil de 2012 a 2015. Realizamos uma avaliação retrospectiva de 286 radiografias dorsopalmar da região radiocarpica esquerda de cavalos jovens e seu desempenho de corrida. O fechamento epifisário radial distal foi classificado em três graus decrescentes: A, B ou C. Os dados de desempenho incluíram o número de corridas disputadas, duração da carreira atlética e o número de corridas por mês. As variáveis foram submetidas à análise de regressão. No momento do exame radiográfico, os cavalos machos eram significativamente mais velhos que as fêmeas, e os cavalos com graus de fechamento epifisário diferiram com a idade. A idade na primeira corrida foi de 33,08±3,81 meses, a média de corridas disputadas foi de 18,32±15,14 corridas, a duração da carreira atlética foi de 20,37±13,82 meses e o número de corridas realizadas por mês foi de 0,93±0,46 corridas. A idade influenciou (P>0,001) o fechamento da epífise radial distal em cavalos de corrida, mas o sexo não (P=0,218 para machos e P=0,275 para fêmeas). Uma associação inversa foi observada entre a idade na primeira corrida, o número de corridas disputadas por mês e a duração da carreira atlética. A frequência de corrida e a idade na primeira corrida influenciaram a duração da carreira atlética.

Abstract The Magnetic separation of ultra-fine ore particles has always posed a challenge to the JONES/WHIMS process. Despite many advances in this technology, no effective improvement has been made to its core component: The Magnetic Matrix. The current approach to separate ultra-fine particles teaches that the gap of the matrix and its teeth size must be smaller than usual in order to accommodate the small size of the particles. However, practice proved this approach to be far from ideal. The closing of the gap between grooved plates, whose teeth are smaller, drastically reduces the flow area, reduces the feed capacity, and makes the matrices prone to clogging. In addition, smaller teeth reduce the magnetic field and its gradient, leading to poor results with ultra-fine ore particles. This research proves that bigger teeth are better suited for high intensity magnetic separation of ultra-fines because they avoid matrix clogging thanks to the larger slurry flow area. Additionally, bigger teeth amplify the magnetic field “Bmax” and increases the magnetic gradient “Grad (∆B /∆X)”. The positive results of this new “BigFLUX Matrix” technology, are being displayed in several mining operations worldwide, increasing metallurgical recovery and producing high quality concentrates and low iron content sand from iron ore tailings.

BACKGROUND Cerebral malaria is a lethal complication of Plasmodium falciparum infections in need of better therapies. Previous work in murine experimental cerebral malaria (ECM) indicated that the combination of artemether plus intraperitoneal whole blood improved vascular integrity and increased survival compared to artemether alone. However, the effects of blood or plasma transfusion administered via the intravenous route have not previously been evaluated in ECM. OBJECTIVES To evaluate the effects of intravenous whole blood compared to intravenous plasma on hematological parameters, vascular integrity, and survival in artemether-treated ECM. METHODS Mice with late-stage ECM received artemether alone or in combination with whole blood or plasma administered via the jugular vein. The outcome measures were hematocrit and platelets; plasma angiopoietin 1, angiopoietin 2, and haptoglobin; blood-brain barrier permeability; and survival. FINDINGS Survival increased from 54% with artemether alone to 90% with the combination of artemether and intravenous whole blood. Intravenous plasma lowered survival to 18%. Intravenous transfusion provided fast and pronounced recoveries of hematocrit, platelets, angiopoietins levels and blood brain barrier integrity. MAIN CONCLUSIONS The outcome of artemether-treated ECM was improved by intravenous whole blood but worsened by intravenous plasma. Compared to prior studies of transfusion via the intraperitoneal route, intravenous administration was more efficacious.

Abstract This article presents a study of the factors that influence the mechanism of soil-structure interaction with a pilot building having concrete walls and their impact on their performance. To illustrate the studies carried out, a numerical modeling of a four-floor concrete wall pilot building was performed, subjected to vertical actions, supported by a slab-on-ground foundation, using the Finite Element Method (FEM), together with specific 3D software for analysis and structural dimensioning in reinforced concrete. For the consideration of the geotechnical and structural system (foundation structure), the discrete spring model (Winkler model) coupled to the superstructure was used and the slab foundation thickness was varied by 16 cm, 25 cm and 40 cm. The local geotechnical formation was represented by a soft clay (SPT = 5) from the Belo Horizonte Metropolitan Region, Brazil. The influential factors of the SSI analyzed in this research were: relative stiffness of the foundation structure, requesting stresses, settlements in the foundation of the building and steel reinforcement bar ratio. For a better visualization of the influence of these various factors, an analysis was made of the distribution of normal stresses and stresses at the base of the walls of this building, in the form of graphs. Finally, it was concluded that the change in slab foundation, stiffness influences the distribution of stresses and stresses in the foundation, with a tendency to uniformity as the slab foundation thickness increases. However, this relationship is not linear.

In the present study, we investigated the genetic diversity of Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain in two municipalities of the main malaria hotspot in Brazil, i.e., the Juruá Valley, and observed complete sequence identity among all P. vivax field isolates and the Sal-1 reference strain. Analysis of PvMCA1 catalytic domain in different P. vivax genomic sequences publicly available also revealed a high degree of conservation worldwide, with very few amino acid substitutions that were not related to putative histidine and cysteine catalytic residues, whose involvement with the active site of protease was herein predicted by molecular modeling. The genetic conservation presented by PvMCA1 may contribute to its eligibility as a druggable target candidate in vivax malaria.

Abstract The present work analyses some particular aspects of Oswaldo Cruz's unique biography, valuing his work, which was built along a successful physician and scientist professional trajectory and also as a courageous and fortunate formulator of public health policies and of fight strategies against the epidemics that seasonally affected the city of Rio de Janeiro at the beginning of the 20th century. The authors also dwell on his legacy as Head scientist and manager of the Institute that bears his name and became the template for experimental research and medicine in Brazil and the bedrock of the Fundação Oswaldo Cruz, one of the most important Brazilian Institutions devoted to teaching, research, development and production in health. This heritage made possible to overcome the existing dissensions between doctors and scientists to build a sanitary movement committed to the major health problems in Brazil. Finally, the paper explores some features of the character and reports some of his moments during his passage, as a Full Academician, at the Brazilian Academia Nacional de Medicina.

Resumo: O artigo examina a história de Louis Pasteur do ponto de vista de um filme clássico que foi projetado durante os Seminários Semanais do Instituto Oswaldo Cruz no final das atividades de 2017. Embora bastante antigo, o filme The Story of Louis Pasteur (Warner Bros., 1936) inspirou os espectadores e deu lugar a um debate animado que levou os autores a decidir publicar os comentários da Coordenadora dos Seminários, do debatedor convidado e do público. O filme incorpora personagens reais e fictícios para comunicar ao público o legado de um dos maiores precursores da história da saúde pública. O artigo destaca os episódios reais da biografia de Pasteur e também os ficcionais, sem desmerecer o trabalho dos criadores cinematográficos. O principal mérito do filme, um dos primeiros passos de uma política de divulgação científica, é de revelar a importância das vacinas e da higiene das mãos na prevenção das doenças infecciosas. Os autores argumentam que o cineasta retratou primorosamente a tenacidade do grande cientista na busca incansável por descobertas, além de sua ideia de que somente o trabalho persistente pode levar a resultados recompensadores, lembrando que o contexto criado por pesquisadores anteriores permitiu que Pasteur estabelecesse paradigmas novos. Finalmente, os autores citam trechos do filme que ilustram realidades que persistem até os dias de hoje: (i) a tendência da ciência de resistir, por inércia, aos paradigmas novos, exemplificada pela oposição da comunidade de ciência médica à proposição de práticas simples como a lavagem de mãos e a fervura de instrumentos e (ii) a confiança excessiva, e até arrogância, de alguns especialistas, em vez da serenidade e da humildade que nascem da pesquisa dedicada e do conhecimento acumulado.

Abstract: This article examines the story of Louis Pasteur from the point of view of a classic movie presented at the Weekly Seminars of the “Oswaldo Cruz Institute”, at the end of the 2017 activities. Although very old, the movie The Story of Louis Pasteur (Warner Bros., 1936) inspired spectators and gave rise to an energetic debate that led the authors to decide for publishing the comments of the Seminar Coordinator, the guest commentator and the audience. The movie communicates to the public the legacy of one of the greatest precursors of the public health history using also fictional characters. The article presents the reliable passages in Pasteur’s biography and the fictional ones, without disrespecting the production of the creators of cinematographic work. The major merit of the movie, one of the first steps towards the policy of scientific diffusion, is to disclose the importance of vaccines and hand hygiene to prevent infectious diseases. The authors argue that the film-maker impeccably captured the scientist’s tenacity in the relentless search for discoveries and Pasteur’s idea that only persistent work can lead to rewarding results, remembering that the context created by previous researchers enabled Pasteur to establish new paradigms. Finally, the authors cite movie passages illustrating realities that are still in force: (i) the inertial resistance of science to new paradigms, illustrated by the medical-scientific community opposing to simple practices proposition, such as washing hands and boiling instruments, and (ii) the excessive confidence, and even arrogance, of some specialists, instead of serenity and humility that arise from committed study and accumulated knowledge.

Resumen: Este artículo examina la historia de Louis Pasteur desde el punto de vista de una película clásica, presentada en los Seminarios Semanales del Instituto Oswaldo Cruz, al final de las actividades de 2017. A pesar de ser muy antigua, la película The Story of Louis Pasteur (Warner Bros., 1936) inspiró a los espectadores y provocó un animado debate que condujo a los autores a la decisión de publicar los comentarios de la Coordinadora de los Seminarios, así como los del comentarista invitado y de la audiencia. Utilizando también personajes de ficción, la película transmitía al público el legado de uno de los más grandes precursores de la historia de la salud pública. El artículo señala pasajes fidedignos en la biografía de Pasteur y ficticios, sin menoscabar el trabajo de los creadores cinematográficos. El mayor mérito de la película, uno de los primeros pasos hacia la política de divulgación científica, es revelar la importancia de las vacunas y de la higiene de las manos para prevenir enfermedades infecciosas. Los autores enfatizan que el director de la película capturó impecablemente la tenacidad del científico en su búsqueda sin descanso de descubrimientos, así como su idea de que solo un trabajo persistente podía conducir a resultados gratificantes, recordando que el contexto creado por investigadores previos permitieron a Pasteur establecer nuevos paradigmas. Finalmente, los autores citan pasajes de la película que ilustran realidades todavía muy vigentes: (i) la resistencia por inercia de la ciencia a nuevos paradigmas, ilustrados por la oposición de la comunidad médico-científica hacia la propuesta de prácticas simples, tales como lavarse las manos y hervir los instrumentos, así como (ii) la excesiva confianza, e incluso arrogancia, de algunos especialistas, en lugar de la serenidad y humildad que surgen del estudio realizado y el conocimiento acumulado.

Resumo: O artigo examina a história de Louis Pasteur do ponto de vista de um filme clássico que foi projetado durante os Seminários Semanais do Instituto Oswaldo Cruz no final das atividades de 2017. Embora bastante antigo, o filme The Story of Louis Pasteur (Warner Bros., 1936) inspirou os espectadores e deu lugar a um debate animado que levou os autores a decidir publicar os comentários da Coordenadora dos Seminários, do debatedor convidado e do público. O filme incorpora personagens reais e fictícios para comunicar ao público o legado de um dos maiores precursores da história da saúde pública. O artigo destaca os episódios reais da biografia de Pasteur e também os ficcionais, sem desmerecer o trabalho dos criadores cinematográficos. O principal mérito do filme, um dos primeiros passos de uma política de divulgação científica, é de revelar a importância das vacinas e da higiene das mãos na prevenção das doenças infecciosas. Os autores argumentam que o cineasta retratou primorosamente a tenacidade do grande cientista na busca incansável por descobertas, além de sua ideia de que somente o trabalho persistente pode levar a resultados recompensadores, lembrando que o contexto criado por pesquisadores anteriores permitiu que Pasteur estabelecesse paradigmas novos. Finalmente, os autores citam trechos do filme que ilustram realidades que persistem até os dias de hoje: (i) a tendência da ciência de resistir, por inércia, aos paradigmas novos, exemplificada pela oposição da comunidade de ciência médica à proposição de práticas simples como a lavagem de mãos e a fervura de instrumentos e (ii) a confiança excessiva, e até arrogância, de alguns especialistas, em vez da serenidade e da humildade que nascem da pesquisa dedicada e do conhecimento acumulado.

Abstract: This article examines the story of Louis Pasteur from the point of view of a classic movie presented at the Weekly Seminars of the “Oswaldo Cruz Institute”, at the end of the 2017 activities. Although very old, the movie The Story of Louis Pasteur (Warner Bros., 1936) inspired spectators and gave rise to an energetic debate that led the authors to decide for publishing the comments of the Seminar Coordinator, the guest commentator and the audience. The movie communicates to the public the legacy of one of the greatest precursors of the public health history using also fictional characters. The article presents the reliable passages in Pasteur’s biography and the fictional ones, without disrespecting the production of the creators of cinematographic work. The major merit of the movie, one of the first steps towards the policy of scientific diffusion, is to disclose the importance of vaccines and hand hygiene to prevent infectious diseases. The authors argue that the film-maker impeccably captured the scientist’s tenacity in the relentless search for discoveries and Pasteur’s idea that only persistent work can lead to rewarding results, remembering that the context created by previous researchers enabled Pasteur to establish new paradigms. Finally, the authors cite movie passages illustrating realities that are still in force: (i) the inertial resistance of science to new paradigms, illustrated by the medical-scientific community opposing to simple practices proposition, such as washing hands and boiling instruments, and (ii) the excessive confidence, and even arrogance, of some specialists, instead of serenity and humility that arise from committed study and accumulated knowledge.

Resumen: Este artículo examina la historia de Louis Pasteur desde el punto de vista de una película clásica, presentada en los Seminarios Semanales del Instituto Oswaldo Cruz, al final de las actividades de 2017. A pesar de ser muy antigua, la película The Story of Louis Pasteur (Warner Bros., 1936) inspiró a los espectadores y provocó un animado debate que condujo a los autores a la decisión de publicar los comentarios de la Coordinadora de los Seminarios, así como los del comentarista invitado y de la audiencia. Utilizando también personajes de ficción, la película transmitía al público el legado de uno de los más grandes precursores de la historia de la salud pública. El artículo señala pasajes fidedignos en la biografía de Pasteur y ficticios, sin menoscabar el trabajo de los creadores cinematográficos. El mayor mérito de la película, uno de los primeros pasos hacia la política de divulgación científica, es revelar la importancia de las vacunas y de la higiene de las manos para prevenir enfermedades infecciosas. Los autores enfatizan que el director de la película capturó impecablemente la tenacidad del científico en su búsqueda sin descanso de descubrimientos, así como su idea de que solo un trabajo persistente podía conducir a resultados gratificantes, recordando que el contexto creado por investigadores previos permitieron a Pasteur establecer nuevos paradigmas. Finalmente, los autores citan pasajes de la película que ilustran realidades todavía muy vigentes: (i) la resistencia por inercia de la ciencia a nuevos paradigmas, ilustrados por la oposición de la comunidad médico-científica hacia la propuesta de prácticas simples, tales como lavarse las manos y hervir los instrumentos, así como (ii) la excesiva confianza, e incluso arrogancia, de algunos especialistas, en lugar de la serenidad y humildad que surgen del estudio realizado y el conocimiento acumulado.

BACKGROUND The central repetitive region (CRR) of the Plasmodium vivax circumsporozoite surface protein (CSP) is composed of a repetitive sequence that is characterised by three variants: VK210, VK247 and P. vivax-like. The most important challenge in the treatment of P. vivax infection is the possibility of differential response based on the parasite genotype. OBJECTIVES To characterise the CSP variants in P. vivax isolates from individuals residing in a malaria-endemic region in Brazil and to profile these variants based on sensitivity to chloroquine and mefloquine. METHODS The CSP variants were determined by sequencing and the sensitivity of the P. vivax isolates to chloroquine and mefloquine was determined by Deli-test. FINDINGS Although five different allele sizes were amplified, the sequencing results showed that all of the isolates belonged to the VK210 variant. However, we observed substantial genetic diversity in the CRR, resulting in the identification of 10 different VK210 subtypes. The frequency of isolates that were resistant to chloroquine and mefloquine was 11.8 and 23.8%, respectively. However, we did not observe any difference in the frequency of the resistant isolates belonging to the VK210 subtypes. MAIN CONCLUSION The VK210 variant is the most frequently observed in the studied region and there is significant genetic variability in the CRR of the P. vivax CSP. Moreover, the antimalarial drug sensitivity profiles of the isolates does not seem to be related to the VK210 subtypes.

BACKGROUND The prompt diagnosis of plasmodial species for effective treatment prevents worsening of individual health and avoids transmission maintenance or even malaria reintroduction in areas where Plasmodium does not exist. Polymerase chain reaction (PCR) allows for the detection of parasites below the threshold of microscopic examination. OBJECTIVE Our aim was to develop a real-time PCR test to reduce diagnostic errors and increase efficacy. METHODS The lower limit of quantification and the linearity/analytical sensitivity to measure sensitivity or limit of detection (LoD) were determined. Intra-assay variations (repeatability) and alterations between assays, operators, and instruments (reproducibility) were also assessed to set precision. FINDINGS The linearity in SYBR™ Green and TaqMan™ systems was 106 and 102 copies and analytical sensitivity 1.13 and 1.17 copies/μL, respectively. Real-time PCR was more sensitive than conventional PCR, showing a LoD of 0.01 parasite (p)/μL. Reproducibility and repeatability (precision) were 100% for up to 0.1 p/μL in SYBR™ Green and 1 p/μL in TaqMan™ and conventional PCR. CONCLUSION Real-time PCR may replace conventional PCR in reference laboratories for P. vivax detection due to its rapidity. The TaqMan™ system is the most indicated when quantification assays are required. Performing tests in triplicate when diagnosing Plasmodium-infected-asymptomatic individuals is recommended to minimise diagnostic errors.

BACKGROUND AND OBJECTIVE Brazil is responsible for a large number of Plasmodium vivax cases in America. Given the emergence of P. vivax parasites resistant to chloroquine and the effectiveness of antifolates in vivax malaria treatment together with a correlation between mutations in P. vivax dhfr and dhps genes and SP treatment failure, the point mutations in these genes were investigated. METHODS Blood samples from 54 patients experiencing vivax malaria symptomatic episodes in the Amazonian Region were investigated. Genomic DNA was extracted using a DNA extraction kit (QIAGENTM). Nested polymerase chain reaction (PCR) amplification was carried out followed by Sanger sequencing to detect single nucleotide polymorphisms (SNPs). FINDINGS All tested isolates showed non-synonymous mutations in pvdhfr gene: 117N (54/54, 100%) and 58R (25/54, 46%). Double mutant allele 58R/117N (FRTNI, 28%) was the most frequent followed by triple mutant alleles (58R/117N/173L, FRTNL, 11%; 58R/61M/117N, FRMNI, 5% 117N/173L, FSTNL, 4%) and quadruple mutant allele (58R/61M/117N/173L, FRMNL, 2%). A single mutation was observed at codon C383G in pvdhps gene (SGKAV, 48%). CONCLUSION No evidence of molecular signatures associated with P. vivax resistance to SP was observed in the Brazilian samples.