Endothelial transcriptomic analysis identifies biomarkers of severe and cerebral malaria.

Malaria can quickly progress from an uncomplicated infection into a life-threatening severe disease. However, the unspecificity of early symptoms often makes it difficult to identify patients at high risk of developing severe disease. Additionally, one of the most feared malaria complications - cerebral malaria - is challenging to diagnose, often resulting in treatment delays that can lead to adverse outcomes. To identify candidate biomarkers for the prognosis and/or diagnosis of severe and cerebral malaria, we have analyzed the transcriptomic response of human brain microvascular endothelial cells to erythrocytes infected with Plasmodium falciparum. Candidates were validated in plasma samples from a cohort of pediatric patients with malaria from Mozambique, resulting in the identification of several markers with capacity to distinguish uncomplicated from severe malaria, the most potent being the metallopeptidase ADAMTS18. Two other biomarkers, Angiopoietin-like-4 and Inhibin-ßE were able to differentiate children with cerebral malaria within the severe malaria group, showing increased sensitivity after combination in a biomarker signature. The validation of the predicted candidate biomarkers in plasma of children with severe and cerebral malaria underscores the power of this transcriptomic approach and indicates that a specific endothelial response to P. falciparum-infected erythrocytes is linked to the pathophysiology of severe malaria.

Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil.

Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical-immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Pará State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical-immunological (symptomatic and asymptomatic) profiles of human L. (L.) chagasi-infection in the Brazilian Amazon.

Role of antigen-presenting cells in non-ulcerated skin lesions caused by Leishmania (Leishmania) infantum chagasi.

In Central America, infection by Leishmania (Leishmania) infantum chagasi causes visceral leishmaniasis and non-ulcerated cutaneous leishmaniasis (NUCL). This work aimed to evaluate the participation of subpopulations of antigen-presenting cells in skin lesions of patients affected by NUCL through double-staining immunohistochemistry using cellular and intracellular markers. Twenty-three skin biopsies from patients affected by NUCL were used. Histological sections stained by HE were used for histopathological study. Immunohistochemical studies were performed using primary antibodies against Langerhans cells, dermal dendritic cells, T lymphocytes, and the cytokines IL-12, IFN-γ, TNF-α, iNOS, and IL-10. The histopathological lesions were characterized by an inflammatory infiltrate, predominantly lymphohistiocytic, of variable intensity, with a diffuse arrangement associated with epithelioid granulomas and discreet parasitism. Double-staining immunohistochemistry showed higher participation of dendritic cells producing the proinflammatory cytokine IL-12 in relation to the other evaluated cytokines. Activation of the cellular immune response was marked by a higher density of CD8 Tc1-lymphocytes followed by CD4 Th1-lymphocytes producing mainly IFN-γ. The data obtained in the present study suggest that antigen-presenting cells play an important role in the in situ immune response through the production of proinflammatory cytokines, directing the cellular immune response preferentially to the Th1 and Tc1 types in NUCL caused by L. (L.) infantum chagasi.

Saúde e queixa escolar: registros de conserv(ação) na conduta de psicólogos / Salud y queja escolar: registros de conserv(acción) en la conducta de los psicólogos / Health and school complaint: records of conserv(action) in the conduct of psychologists

RESUMO. Este artigo expõe a temática da conduta de profissionais da psicologia no campo da saúde, diante das demandas escolares. Resulta de uma pesquisa de Mestrado, cujo objetivo principal foi, com base na Psicologia Histórico-Cultural, identificar de que forma as práticas contemporâneas da psicologia na saúde explicitam a concepção dos profissionais ante os encaminhamentos e a função da escola para a constituição da subjetividade. Para tanto, foram analisados prontuários de crianças e adolescentes entre quatro e dezessete anos, encaminhados por queixa escolar a dois serviços públicos de saúde em um município de pequeno porte do interior paulista, durante o biênio 2014-2015, e efetivadas entrevistas com as/os psicólogas/os responsáveis nos diferentes serviços. Os resultados indicaram que a atividade da/o psicóloga/o, ao receber a demanda escolar, encontra-se pouco alterada em relação às condutas que vêm sendo adotadas no país, desde os anos de 1990. As práticas aderidas consistem, em grande maioria, no atendimento clínico individual ou grupal, que não envolve o ambiente escolar. Também se mantém o perfil das crianças encaminhadas e, no contexto da ciência psicológica aplicada à saúde, um distanciamento quanto ao conhecimento das implicações da educação escolar para a aprendizagem e o desenvolvimento humano, tanto quanto a importância do acesso aos bens culturais humanos, o que pode ser decisivo para as circunstâncias e para a qualidade do processo de humanização.

RESUMEN. Este artículo expone el tema de la conducta de los profesionales de la psicología en el campo de la salud, delante de las demandas escolares. Es el resultado de una investigación de maestría, cuyo objetivo principal era, basado en la psicología histórico-cultural, identificar cómo las prácticas contemporáneas de psicologia, en la salud, hacen explícito la concepción de los profesionales delante de las derivaciones y el papel de la escuela para el constitución de subjetividad. Con este fin, se analizaron los registros de salud de niños y adolescentes entre cuatro y diecisiete años, reenviados por queja escolar a dos servicios de salud pública en una pequeña ciudad del interior de São Paulo, durante el bienio 2014-2015, y efectivadas entrevistas con los psicólogos responsables em los diferentes servicios. Los resultados indicaron que la actividad del psicólogo, al recibir la demanda escolar, cambia poco en relación a las conductas que se han adoptado en el país, desde la década de los noventa. Las prácticas adheridas consisten, en su gran mayoría, en el cuidado clínico individual o grupal, que no involucra el ambiente escolar. El perfil de los niños referidos también se mantiene y, en el contexto de la ciencia psicológica aplicada a la salud, una distancia en cuanto al conocimiento de las implicaciones de la educación escolar para el aprendizaje y el desarrollo humano, así como la importancia del acceso a los bienes culturales humanos, que puede ser decisivo para las circunstancias y la calidad del proceso de humanización.

ABSTRACT. This article exposes the theme of the conduct of psychology professionals in the field of health, in view of school demands. It results from a Master's research, mainly aimed to, based on Historical-Cultural Psychology, identify how contemporary Psychology practices in health may explain the professionals' understanding about the referrals and the role of the school in building subjectivity. To this end, medical records of children and adolescents of four to seventeen years old were analyzed. Participants had been referred due to school complaint to two public healthcare services in a small municipality in São Paulo, in the biennium 2014-2015, and participated in interviews with the responsible psychologists in the services. The results indicated that the psychologist's activity when receiving the school demand has changed a little in relation to the conducts being adopted in the country since the 1990s. The practices adopted mainly consist in individual or group clinical care, disregarding the school environment. The profile of the children referred is also maintained and, in the context of psychological science applied to health, there is a distancing regarding the knowledge of the implications of school education on human learning and development, as well as the importance of accessing human cultural assets. This could be decisive for the circumstances and the quality of the humanization process.

Visceral Leishmaniasis Urbanization in the Brazilian Amazon Is Supported by Significantly Higher Infection Transmission Rates Than in Rural Area.

This was an open cohort prospective study (2016−2018) that analyzed the prevalence and incidence rates of human Leishmania (L.) infantum chagasi-infection and the evolution of their clinical-immunological profiles in distinct urban and rural scenarios of American visceral leishmaniasis (AVL) in Pará State, in the Brazilian Amazon. These infection profiles were based on species-specific DTH/IFAT-IgG assays and clinical evaluation of infected individuals, comprising five profiles: three asymptomatic, Asymptomatic Infection [AI], Subclinical Resistant Infection [SRI], and Indeterminate Initial Infection [III]; and two symptomatic, Subclinical Oligosymptomatic Infection [SOI] and Symptomatic Infection [SI = AVL]. The two distinct scenarios (900 km away) were the urban area of Conceição do Araguaia municipality and the rural area of Bujaru municipality in the southeast and northeast of Pará State. Human populations were chosen based on a simple convenience sampling design (5−10% in each setting), with 1723 individuals (5.3%) of the population (32,464) in the urban area and 1568 individuals (8.9%) of the population (17,596) in the rural one. A serological survey (IFAT-IgG) of canine infection was also performed in both scenarios: 195 dogs in the urban area and 381 in the rural one. Prevalence and incidence rates of human infection were higher in the urban area (20.3% and 13.6/100 person-years [py]) than in the rural setting (14.1% and 6.8/100-py). The AI profile was the most prevalent and incident in both urban (13.4% and 8.1/100-py) and rural (8.3% and 4.2/100-py) scenarios, but with higher rates in the former. An III profile case evolved to SOI profile after four weeks of incubation and another to SI (=AVL) after six. The prevalence of canine infection in an urban setting (39.2%) was also higher (p < 0.05) than that (32%) in the rural zone. AVL urbanization in Pará State, in the Brazilian Amazon, has led to infection rates significantly higher than those in rural sites, requiring more intense control measures.

Plasmodium falciparum and TNF-α Differentially Regulate Inflammatory and Barrier Integrity Pathways in Human Brain Endothelial Cells.

Cerebral malaria is a severe complication of Plasmodium falciparum infection characterized by the loss of blood-brain barrier (BBB) integrity, which is associated with brain swelling and mortality in patients. P. falciparum-infected red blood cells and inflammatory cytokines, like tumor necrosis factor alpha (TNF-α), have been implicated in the development of cerebral malaria, but it is still unclear how they contribute to the loss of BBB integrity. Here, a combination of transcriptomic analysis and cellular assays detecting changes in barrier integrity and endothelial activation were used to distinguish between the effects of P. falciparum and TNF-α on a human brain microvascular endothelial cell (HBMEC) line and in primary human brain microvascular endothelial cells. We observed that while TNF-α induced high levels of endothelial activation, it only caused a small increase in HBMEC permeability. Conversely, P. falciparum-infected red blood cells (iRBCs) led to a strong increase in HBMEC permeability that was not mediated by cell death. Distinct transcriptomic profiles of TNF-α and P. falciparum in HBMECs confirm the differential effects of these stimuli, with the parasite preferentially inducing an endoplasmic reticulum stress response. Our results establish that there are fundamental differences in the responses induced by TNF-α and P. falciparum on brain endothelial cells and suggest that parasite-induced signaling is a major component driving the disruption of the BBB during cerebral malaria, proposing a potential target for much needed therapeutics. IMPORTANCE Cerebral malaria is a severe complication of Plasmodium falciparum infection that causes the loss of blood-brain barrier integrity and frequently results in death. Here, we compared the effect of P. falciparum-infected red blood cells and inflammatory cytokines, like TNF-α, in the loss of BBB integrity. We observed that while TNF-α induced a small increase in barrier permeability, P. falciparum-infected red blood cells led to a severe loss of barrier integrity. Our results establish that there are fundamental differences in the responses induced by TNF-α and P. falciparum on brain endothelial cells and suggest that parasite-induced signaling is a major component driving the disruption of the BBB during cerebral malaria, proposing a potential target for much needed therapeutics.

Selênio, um elemento essencial à vida humana

Introdução: O Selênio ao mesmo tempo em que é tóxico se ingerido em grandes quantidades, é, também, micronutriente essencial em diversos processos metabólicos de animais e humanos. A deficiência de selênio vem sendo relacionada à predisposição em desenvolver doenças como o câncer, a diabetes, doenças cardiovasculares, entre outras. Na química medicinal, o selênio vem ganhando importância a partir da descoberta do ebselen, do ethaselen e do disseleneto de difenila. Objetivo: Essa revisão tem como objetivo compilar as principais informações disponíveis na literatura sobre a importância do selênio para a vida humana, proporcionando ao leitor uma visão geral do papel biológico desse elemento, das principais doenças relacionadas à deficiência de selênio, e da química medicinal dos três principais compostos de organoselênio. Metodologia: Foram recuperados artigos e teses acadêmicas que contemplassem o papel do selênio na bioquímica e na química medicinal, publicados em português e inglês, utilizando-se as bases de dados SciFinder, PubMed e Google Acadêmico. Resultados: Até o momento, foram identificadas 25 selenoproteínas que desempenham funções biológicas essenciais em animais e humanos. Sabe-se que a deficiência de selênio está diretamente relacionada à predisposição no desenvolvimento de diversas doenças. No campo da química medicinal, foi provado que é possível desenvolver moléculas bioativas, com baixa toxidez, contendo átomos de selênio em sua estrutura. Conclusão: O selênio é um elemento essencial à vida, sendo o componente-chave das selenoproteínas. O entendimento dos processos bioquímicos modulados por elas é imperativo para que os químicos medicinais possam desenvolver fármacos potentes contendo átomos de selênio em sua estrutura.

SUMMARY Introduction: Selenium is, at the same time, toxic if ingested in great amounts and an essential micronutrient to several metabolic processes in both animals and humans. Selenium deficiency is being related to an increased chance to develop diseases such as cancer, diabetes, cardiovascular diseases, among others. In medicinal chemistry, selenium has gained in importance since the discovery of ebselen, ethaselen, and diphenyl disselenide. Objectives: This review aims to compile the main data avail-able on the literature on the importance of selenium to human life, providing an overview of its biological role, the main diseases related to its deficiency, as well as the medicinal chemistry of the three most prominent organoselenium compounds. Methodology: Articles and academic thesis, published in English and Portuguese, showing the role of selenium in biochemistry and medicinal chemistry were recov-ered from SciFinder, PubMed, and Google Scholar. Results: So far, 25 selenopro-teins that play a biological role in humans and animals were identified. It is known that selenium deficiency is directly related not only to a predisposition to developing some diseases but is also the main cause of illnesses such as Keshan and Kashin-Beck. In the medicinal chemistry field, the development of selenium-containing bioactive compounds with low toxicity was proved possible. Conclusion: Selenium is an essential element to life, being the core component of selenoproteins. The under-standing of the biochemical processes modulated by those proteins is mandatory to medicinal chemists willing to develop potent organoselenium drugs.

Introducción: El selenioa la par que tóxico si se ingiere en grandes cantidades, es también un micronutriente esencial en varios procesos metabólicos en animales y humanos. La deficiencia de selenio se ha relacionado con una predisposición a desarrollar enfermedades como cáncer, diabetes, enfermedades cardiovasculares, entre otras. Em química médica, el selenio ha ganado importancia desde el descubrimiento del ebselen, etaselen y difenil diselenide. Objetivo: Esta revisión tiene como objetivo recopilar los principales datos disponibles en la literatura sobre la importancia del selenio para la vida humana, y proporcionar al lector una descripción general del papel biológico de este elemento, las principales enfermedades relacionadas con la deficiencia de este elemento, así como los compuestos de organoselenio más destacados. Metodología: Se recuperaron artículos y tesis académicas que contemplaban el papel del selenio en la bioquímica y la química médica, publicados en portugués e inglés, utilizando las bases de datos SciFinder, PubMed y Google Scholar. Resultados: Hasta el momento, se han identificado 25 selenoproteínas que realizan funciones biológicas esenciales en animales y humanos. Se sabe que la deficiencia de selenio está directamente relacionada con la predisposición en el desarrollo de varias dolencias, y también es la principal causa de enfermedades como las de Keshan y Kashin-Beck. En el campo de la química médica se ha comprobado que es posible desarrollar moléculas bioactivas, de baja toxicidad, que contengan átomos de selenio en su estructura. Conclusión: El selenio es un elemento esencial en la vida, siendo un componente central de las selenoproteínas. Comprender los procesos bioquímicos modulados por ellos es imperativo para que los químicos médicos puedan desarrollar fármacos potentes que contengan átomos de selenio en su estructura.

Aplicação da Avaliação Geriátrica Ampla (AGA) em pacientes cardiopatas / Application of the Comprehensive Geriatric Assessment (AGA) in patients with heart disease

INTRODUÇÃO: A avaliação geriátrica ampla (AGA), também chamada de avaliação global do idoso, é um instrumento que permite ampliar a avaliação clínica, contribuindo para a predição de desfechos adversos e a decisão da melhor abordagem terapêutica. Seus principais domínios são funcionalidade, cognição, humor, mobilidade / equilíbrio / quedas, visão / audição, estado nutricional e suporte social. Este estudo tem como objetivo avaliar a aplicação da AGA em pacientes cardiopatas idosos acompanhados por ambulatório de cardiogeriatria de serviço terciário do estado de São Paulo. MÉTODOS: Estudo retrospectivo, descritivo e observacional, a partir de dados de prontuário, de outubro de 2018 a dezembro de 2021. Foram incluídos pacientes com 70 anos ou mais, portadores de doença valvar grave, acompanhados em ambulatório e para os quais a AGA havia sido aplicada durante avaliação de rotina. A AGA realizada era composta por exame clínico, avaliação de comorbidades, fragilidade (escala de Frail), funcionalidade (escalas de Katz e Lawton), risco de depressão, função cognitiva (miniexame do estado mental - MEEM), suporte social (apgar familiar) e estado nutricional. As variáveis quantitativas foram apresentadas em forma de média e desvio padrão, com valores expressos em percentuais. RESULTADOS: Foram avaliados 50 pacientes com doença valvar grave. Observou-se idade média de 78,8 anos (+ 6,1) e predomínio do sexo masculino (60%). As comorbidades mais prevalentes, além da estenose valvar aórtica grave, foram hipertensão arterial sistêmica (80%), dislipidemia (58%), diabetes melitos (42%) e insuficiência cardíaca (42%). A polifarmácia estava presente em 60% dos casos e as medicações mais utilizadas foram: inibidores da enzima conversora da angiotensina ou bloqueadores do receptor de angiotensina (80%), estatinas (74%) e ácido acetilsalicílico (54%). Fragilidade foi identificada em 50% dos pacientes, sendo 20% pré-frágeis e 20% frágeis. Comprometimento de funcionalidade foi observado em 28% dos casos, provável déficit cognitivo em 26%, risco nutricional em 20%, humor deprimido em 28% e risco de quedas em 36%. Disfunção familiar acentuada foi identificada em 6%, caracterizando risco social. CONCLUSÃO: A AGA mostra-se como ferramenta adicional importante na avaliação clínica do paciente idoso com doença valvar grave, podendo fornecer elementos novos e fundamentais para uma melhor decisão terapêutica, especialmente no que se refere à procedimentos invasivos.

Development of genomic predictions for Angus cattle in Brazil incorporating genotypes from related American sires.

Genomic prediction has become the new standard for genetic improvement programs, and currently, there is a desire to implement this technology for the evaluation of Angus cattle in Brazil. Thus, the main objective of this study was to assess the feasibility of evaluating young Brazilian Angus (BA) bulls and heifers for 12 routinely recorded traits using single-step genomic BLUP (ssGBLUP) with and without genotypes from American Angus (AA) sires. The second objective was to obtain estimates of effective population size (Ne) and linkage disequilibrium (LD) in the Brazilian Angus population. The dataset contained phenotypic information for up to 277,661 animals belonging to the Promebo breeding program, pedigree for 362,900, of which 1,386 were genotyped for 50k, 77k, and 150k single nucleotide polymorphism (SNP) panels. After imputation and quality control, 61,666 SNPs were available for the analyses. In addition, genotypes from 332 American Angus (AA) sires widely used in Brazil were retrieved from the AA Association database to be used for genomic predictions. Bivariate animal models were used to estimate variance components, traditional EBV, and genomic EBV (GEBV). Validation was carried out with the linear regression method (LR) using young-genotyped animals born between 2013 and 2015 without phenotypes in the reduced dataset and with records in the complete dataset. Validation animals were further split into progeny of BA and AA sires to evaluate if their progenies would benefit by including genotypes from AA sires. The Ne was 254 based on pedigree and 197 based on LD, and the average LD (±SD) and distance between adjacent single nucleotide polymorphisms (SNPs) across all chromosomes were 0.27 (±0.27) and 40743.68 bp, respectively. Prediction accuracies with ssGBLUP outperformed BLUP for all traits, improving accuracies by, on average, 16% for BA young bulls and heifers. The GEBV prediction accuracies ranged from 0.37 (total maternal for weaning weight and tick count) to 0.54 (yearling precocity) across all traits, and dispersion (LR coefficients) fluctuated between 0.92 and 1.06. Inclusion of genotyped sires from the AA improved GEBV accuracies by 2%, on average, compared to using only the BA reference population. Our study indicated that genomic information could help us to improve GEBV accuracies and hence genetic progress in the Brazilian Angus population. The inclusion of genotypes from American Angus sires heavily used in Brazil just marginally increased the GEBV accuracies for selection candidates.

There was a desire to implement genomic selection for Angus cattle in Brazil since the technology has been proved to increase genetic gain in animal breeding programs. Single-step genomic best linear unbiased prediction (ssGBLUP), which simultaneously combines pedigree and genomic information, was used to estimate individuals' genomic breeding values (GEBV) or genetic merit. Genomic selection can accelerate genetic progress by increasing accuracy, especially in young animals without progeny. The accuracy of GEBV can also be improved by combing data from other countries to increase the reference population (i.e., genotyped and phenotyped animals) in small, genotyped populations. Thus, the main objective of this study was to evaluate the accuracy of GEBV for young Brazilian Angus (BA) bulls and heifers with ssGBLUP, including or not the genotypes from American Angus sires. The accuracies with ssGBLUP were higher than those from traditional BLUP (EBV calculated from pedigree), improving accuracies by, on average, 16% for young bulls and heifers. Including genotypes from American Angus sires heavily used in Brazil just marginally increased the GEBV accuracies for selection candidates.

Comparative Genomic Analyses of New and Old World Viscerotropic Leishmanine Parasites: Further Insights into the Origins of Visceral Leishmaniasis Agents.

Visceral leishmaniasis (VL), also known as kala-azar, is an anthropozoonotic disease affecting human populations on five continents. Aetiologic agents belong to the Leishmania (L.) donovani complex. Until the 1990s, three leishmanine parasites comprised this complex: L. (L.) donovani Laveran & Mesnil 1903, L. (L.) infantum Nicolle 1908, and L. (L.) chagasi Lainson & Shaw 1987 (=L. chagasi Cunha & Chagas 1937). The VL causal agent in the New World (NW) was previously identified as L. (L.) chagasi. After the development of molecular characterization, however, comparisons between L. (L.) chagasi and L. (L.) infantum showed high similarity, and L. (L.) chagasi was then regarded as synonymous with L. (L.) infantum. It was, therefore, suggested that L. (L.) chagasi was not native to the NW but had been introduced from the Old World by Iberian colonizers. However, in light of ecological evidence from the NW parasite's enzootic cycle involving a wild phlebotomine vector (Lutzomyia longipalpis) and a wild mammal reservoir (the fox, Cerdocyon thous), we have recently analyzed by molecular clock comparisons of the DNA polymerase alpha subunit gene the whole-genome sequence of L. (L.) infantum chagasi of the most prevalent clinical form, atypical dermal leishmaniasis (ADL), from Honduras (Central America) with that of the same parasite from Brazil (South America), as well as those of L. (L.) donovani (India) and L. (L.) infantum (Europe), which revealed that the Honduran parasite is older ancestry (382,800 ya) than the parasite from Brazil (143,300 ya), L. (L.) donovani (33,776 ya), or L. (L.) infantum (13,000 ya). In the present work, we have now amplified the genomic comparisons among these leishmanine parasites, exploring mainly the variations in the genome for each chromosome, and the number of genomic SNPs for each chromosome. Although the results of this new analysis have confirmed a high genomic similarity (~99%) among these parasites [except L. (L.) donovani], the Honduran parasite revealed a single structural variation on chromosome 17, and the highest frequency of genomic SNPs (more than twice the number seen in the Brazilian one), which together to its extraordinary ancestry (382,800 ya) represent strong evidence that L. (L.) chagasi/L. (L.) infantum chagasi is, in fact, native to the NW, and therefore with valid taxonomic status. Furthermore, the Honduran parasite, the most ancestral viscerotropic leishmanine parasite, showed genomic and clinical taxonomic characteristics compatible with a new Leishmania species causing ADL in Central America.

Imaginando, criando, construindo juntos: práticas do psicólogo escolar em tempos de pandemia / Imagining, creating, building together: school psychologist practices in times of pandemic

Este artigo apresenta reflexões sobre práticas para a atuação do psicólogo escolar, bem como seus impactos no fortalecimento de coletivos no compromisso com a transformação de contextos educacionais durante o período da pandemia do novo coronavírus (COVID-19). Assume-se como perspectiva teórico-metodológica as proposições desenvolvidas por Lev Vygotsky e outros estudiosos da Psicologia Histórico-Cultural. Como enfoque das discussões lançadas, destacam-se o relato e a análise de duas práticas desenvolvidas por psicólogos-pesquisadores, inseridos nos campos da Educação Básica e da Educação Superior, durante o período de isolamento social ocasionado pela pandemia. Em ambos os contextos, e como eixo norteador das discussões, a arte é tomada como instrumento mediador, ou seja, como uma forma de linguagem potente que possibilita a ressignificação de si e do mundo. Ressalta-se a importância de o psicólogo escolar reconhecer-se como profissional cujo papel fundamental é o investimento na construção, na manutenção e na transformação dos vínculos estabelecidos entre os diferentes atores inseridos nesses contextos educacionais.

This article is intended to spur reflections on school psychologist's remote practices and its impacts on the strengthening of collectives in the commitment for the transformation of educational frameworks during the pandemic period caused by the new coronavirus (COVID-19). The propositions of Lev Vygotsky and other scholars from the Cultural-Historical Theory set the theoretical-methodological grounds for the discussions and analysis presented. The data derived from two online interventions - one in Basic Education and another in Higher Education - developed by the authors of this paper during the period of social isolation caused by the pandemic. In both contexts, and as the guiding axis of our discussions, art was used as a mediating tool, a cultural instrument that through aesthetic experience promotes the creation of new meanings and senses of oneself, of others and the world. The importance of the school psychologist to recognize him/herself as a professional whose main role is to invest in the construction, maintenance, and transformation of the bonds established among the different actors inserted in educational contexts was emphasized.

Whole-Genome Sequencing of Leishmania infantum chagasi Isolates from Honduras and Brazil.

This work reports on the whole-genome sequencing of Leishmania infantum chagasi from Honduras (Central America) and Brazil (South America).

Produções sobre neuropsicologia e suas contribuições para a (DES) patologização da educação / Productions on Neuropsychology and their contributions to the (de)pathologization of education

INTRODUÇÃO: Esse artigo lança como objetivo geral analisar a vinculação temática entre Neuropsicologia, Educação e Educação Inclusiva, a fim de mapear as contribuições teóricas e desafios metodológicos para a atualização sistemática de repertórios que promovam novas construções epistemológicas para a Educação Inclusiva. MÉTODO: O estudo baseou-se em uma busca de artigos científicos publicados no SciELO entre os anos de 2009 e 2019, a partir dos descritivos de busca "neuropsicologia e educação" e "neuropsicologia e educação inclusiva". A partir da seleção de 21 artigos, empreendeu-se uma análise textual que possibilitou a categorizações temáticas, a partir dos seguintes descritores de análise: "Favorecendo novos/outros contextos sociais", "Uso x abuso de medicamentos", "Empenho/Desempenho Cognitivo: do que estamos falando"; "Funções executivas: avanços necessários"; "Testagem x estereotipagem social". RESULTADOS: Como resultado, evidenciamos que, quantitativamente, a maioria dos estudos ocupam os domínios das ciências da saúde, provenientes de pesquisas experimentais de enfoque cognitivista, enquanto uma minoria ocupa periódicos de ciências sociais/humanas e educação. Não obstante aos limites teóricos e conceituais que reproduzem uma leitura fragmentada de desenvolvimento humano, reforçando um enfoque diagnóstico que acarreta abuso de medicamentos como técnica de ajustamento, há proposições pautadas na Psicologia Histórico-Cultural que, qualitativamente, constituem-se como possibilidade de alinhamento da Neuropsicologia a ações educacionais inclusivas. CONCLUSÃO: Concluímos que, para o desafio de anúncio na democratização de oportunidades educacionais, é preciso avançar no desvelamento das condições materiais que sustentam os pilares de uma sociedade capitalista periférica, bem como os impactos psicossociais implicados nesta, na determinação de nossas funções psíquicas superiores.

INTRODUCTION: This article aims to analyze the thematic link between Neuropsychology, Education and Inclusive Education, in order to map the theoretical contributions and methodological challenges for the systematic updating of repertoires that promote new constructions for inclusive education. METHODS: The study was based on a search for scientific articles published in SciELO between the years 2009 and 2019 based on the search descriptions "neuropsychology and education" and "neuropsychology and inclusive education". Based on the selection of 21 articles, a textual analysis was carried out that enabled the thematic categorization, based on the following analysis descriptors: "Favoring new / other social contexts", "Use x abuse of medicines", "Commitment / Cognitive Performance: what are we talking about"; "Executive functions: necessary advances"; "Testing vs. social stereotyping". RESULTS: As a result, we show that quantitatively, most studies occupy the domains of health sciences, derived from experimental research with a cognitive focus, while a minority occupies journals in the social / human sciences and education. Despite the theoretical and conceptual limits that reproduce a fragmented reading of human development, reinforcing a diagnostic focus that leads to drug abuse as an attempt to adjust, there are propositions based on Historical-Cultural Psychology that, qualitatively, constitute a possibility of aligning the Neuropsychology to inclusive educational actions. CONCLUSION: We conclude that for the advertising challenge in the democratization of educational opportunities, it is necessary to advance in the unveiling of the perverse material conditions that support the pillars of a peripheral capitalist society, as well as the psychosocial impacts implied in this, in the determination of our higher psychic functions.

The expression of FOXP3 in lesions of several forms of leprosy in patients co-infected with HIV.

BACKGROUND: Brazil remains endemic for infection by the human immunodeficiency virus (HIV) and leprosy, having a major impact on public health and the life quality of affected patients. Although the relevance of this co-infection is recognized, several aspects, such as the immune response, are not yet fully understood. The objective of this study was to investigate the expression of FOXP3+ Treg cells in leprosy skin lesions and to correlate their clinical forms, laboratory characteristics (CD4, CD8, and CV), and the immune reconstitution syndrome in HIV-leprosy co-infection. METHODOLOGY/PRINCIPAL FINDINGS: An observational, cross-sectional, and analytical study was carried out comparing four groups of patients: those with concomitant diagnosis of leprosy and HIV infection without a leprosy reaction, those with leprosy and HIV co-infection patients with a reverse reaction (RR), those with leprosy without HIV and without reaction, and those with leprosywithout HIV and with RR. The patients were diagnosed at a dermatology outpatient clinic located in Belém, Pará, Brazil, from 2003 to 2017. In the sample studied, there was a positive correlation between FOXP3+ cell density and viral load, negative correlation with blood CD4+ (not statistically significant), significant positive correlation in CD8 count in patients with leprosy reaction, and positive relationship in patients with IRIS. The density of cells expressing FOXP3 was higher in the BL/LL forms in patients without HIV, although the difference was not statistically significant. However, the cell mean was higher in the TT/BT forms in patients co-infected with leprosy and HIV, showing contradictory results. CONCLUSIONS/SIGNIFICANCE: These findings support that higher activity of the HIV may stimulate or result in a higher expression of FOXP3-Tregs and that they may be involved in active immunosuppression observed at the infection site at the tissue level. This supports the need to expand studies on FOXP3+ Treg cells in co-infected patients.

Immunomodulatory Properties of Umbilical Cord Blood-Derived Small Extracellular Vesicles and Their Therapeutic Potential for Inflammatory Skin Disorders.

Umbilical cord blood (UCB) has long been seen as a rich source of naïve cells with strong regenerative potential, likely mediated by paracrine signals. More recently, small extracellular vesicles (sEV), such as exosomes, have been shown to play essential roles in cell-to-cell communication, via the transport of numerous molecules, including small RNAs. Often explored for their potential as biomarkers, sEV are now known to have regenerative and immunomodulating characteristics, particularly if isolated from stem cell-rich tissues. In this study, we aim to characterize the immunomodulating properties of umbilical cord blood mononuclear cell-derived sEV (UCB-MNC-sEV) and explore their therapeutic potential for inflammatory skin diseases. UCB-MNC-sEV were shown to shift macrophages toward an anti-inflammatory phenotype, which in turn exert paracrine effects on fibroblasts, despite previous inflammatory stimuli. Additionally, the incubation of PBMC with UCB-MNC-sEV resulted in a reduction of total CD4+ and CD8+ T-cell proliferation and cytokine release, while specifically supporting the development of regulatory T-cells (Treg), by influencing FOXP3 expression. In a 3D model of psoriatic skin, UCB-MNC-sEV reduced the expression of inflammatory and psoriatic markers IL6, IL8, CXCL10, COX2, S100A7, and DEFB4. In vivo, UCB-MNC-sEV significantly prevented or reversed acanthosis in imiquimod-induced psoriasis, and tendentially increased the number of Treg in skin, without having an overall impact on disease burden. This work provides evidence for the anti-inflammatory and tolerogenic effect of UCB-MNC-sEV, which may be harnessed for the treatment of Th17-driven inflammatory skin diseases, such as psoriasis.

Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19.

High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.

Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles.

The development and adoption of cell therapies has been largely limited by difficulties associated with their safety, handling, and storage. Extracellular vesicles (EV) have recently emerged as a likely mediator for the therapeutic effect of cells, offering several advantages over cell therapies. Due to their small size and inability to expand and metastasize, EV are generally considered safer than cell transplantation. Nevertheless, few studies have scrutinized the toxicity profile of EV, particularly after repeated high-dose administration. The present study aimed to evaluate a preparation of small EV obtained from umbilical cord blood mononuclear cells (UCB-MNC-sEV) for its cytotoxicity in different cell lines, as well as its differential accumulation, distribution, and toxicity following repeated intravenous (IV) administrations in a rodent model. In vitro, repeated sEV exposure in concentrations up to 1 × 1011 particles/mL had no deleterious impact on the viability or metabolic activity of peripheral blood mononuclear cells, THP-1 monocytes, THP-1-derived macrophages, normal dermal human fibroblasts, or human umbilical vein endothelial cells. DiR-labelled sEV, injected intravenously for four weeks in healthy rats, were detected in clearance organs, particularly the kidneys, spleen, and liver, similarly to control dye. Moreover, repeated administrations for six and twelve weeks of up to 1 × 1010 total particles of sEV dye were well-tolerated, with no changes in general haematological cell counts, or kidney and liver toxicity markers. More importantly, unlabelled sEV likewise did not induce significant alterations in cellular and biochemical blood parameters, nor any morphological changes in the heart, kidney, lung, spleen, or liver tissue. In sum, our data show that UCB-MNC-sEV have no significant toxicity in vitro or in vivo, even when administered repeatedly at high concentrations, therefore confirming their safety profile and potential suitability for future clinical use.

Immunogenic Peptides from Pap31 and SCS-α of Bartonella bacilliformis: One Step Closer to a Rapid Diagnostic Tool for Carrion's Disease.

Bartonella bacilliformis is the causal agent of Carrion's disease, an overlooked illness endemic in the Andean Mountains with Peru being the most affected country. The diagnostic of this illness is a challenge due to the limited resources and the common symptomatology with other infectious diseases. The goal of this study was to identify immunogenic peptides from Pap31 and succinyl-CoA synthetase α (SCS-α) of B. bacilliformis that might be suitable for developing a serologic tool. The immunodominant character of Pap31 and SCS-α was determined by Western blotting and in-silico analysis. Subsequently, 35 peptides were selected for epitope mapping and their immunoreactivity was tested by enzyme-linked immunosorbent assay (ELISA). A total of 30 sera were tested including pre-exposed people with high IgM levels for Pap31/SCS-α (23 sera), patients (2 sera) as well as 5 sera with no reactivity to Pap31/SCS-α. The results indicate that Pap31-8 (187QAIGSAILKGTKDTGT202) and SCS-α-12 (59IFASVAEGKEKTGANA74) are the most immunogenic peptides, with Pap31-8 showing potential to discriminate between B. bacilliformis and the remaining Bartonella spp., and SCS-α-12 differentiating Bartonella spp. from other microorganisms.

Multiple Country and Breed Genomic Prediction of Tick Resistance in Beef Cattle.

Ticks cause substantial production losses for beef and dairy cattle. Cattle resistance to ticks is one of the most important factors affecting tick control, but largely neglected due to the challenge of phenotyping. In this study, we evaluate the pooling of tick resistance phenotyped reference populations from multi-country beef cattle breeds to assess the possibility of improving host resistance through multi-trait genomic selection. Data consisted of tick counts or scores assessing the number of female ticks at least 4.5 mm length and derived from seven populations, with breed, country, number of records and genotyped/phenotyped animals being respectively: Angus (AN), Brazil, 2,263, 921/1,156, Hereford (HH), Brazil, 6,615, 1,910/2,802, Brangus (BN), Brazil, 2,441, 851/851, Braford (BO), Brazil, 9,523, 3,062/4,095, Tropical Composite (TC), Australia, 229, 229/229, Brahman (BR), Australia, 675, 675/675, and Nguni (NG), South Africa, 490, 490/490. All populations were genotyped using medium density Illumina SNP BeadChips and imputed to a common high-density panel of 332,468 markers. The mean linkage disequilibrium (LD) between adjacent SNPs varied from 0.24 to 0.37 across populations and so was sufficient to allow genomic breeding values (GEBV) prediction. Correlations of LD phase between breeds were higher between composites and their founder breeds (0.81 to 0.95) and lower between NG and the other breeds (0.27 and 0.35). There was wide range of estimated heritability (0.05 and 0.42) and genetic correlation (-0.01 and 0.87) for tick resistance across the studied populations, with the largest genetic correlation observed between BN and BO. Predictive ability was improved under the old-young validation for three of the seven populations using a multi-trait approach compared to a single trait within-population prediction, while whole and partial data GEBV correlations increased in all cases, with relative improvements ranging from 3% for BO to 64% for TC. Moreover, the multi-trait analysis was useful to correct typical over-dispersion of the GEBV. Results from this study indicate that a joint genomic evaluation of AN, HH, BN, BO and BR can be readily implemented to improve tick resistance of these populations using selection on GEBV. For NG and TC additional phenotyping will be required to obtain accurate GEBV.