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Com aporte teórico-metodológico nos estudos foucaultianos, neste artigo, analisamos os enquadramentos que ora possibilitaram que educação sexual aparecesse e/ou desaparecesse do currículo escolar brasileiro, ora permitiram que a temática do sexo fosse mostrada de modos mais ou menos explícitos no cinema. Tomamos, para tanto, as movimentações em prol de uma abordagem médico-científica do sexo, ao modo como desenvolvidas no campo da educação e do cinema, especialmente na primeira metade do século XX. A partir de uma espécie de genealogia dos discursos “anti-ideológicos” e "anti-pornográficos" nesses campos (educação sexual e cinema), queremos apontar como, no Brasil da atualidade, tais discursos impulsionam tentativas de retirada da educação sexual do currículo escolar.

T cells are endowed with the capacity to sense their environment including other T cells around them. They do so to set their numbers and activation thresholds. This form of regulation has been well-studied within a given T cell population – i.e., within the naïve or memory pool; however, less is known about the cross-talk between T cell subsets. Here, we tested whether memory T cells interact with and influence surrounding naïve T cells. We report that human naïve CD8 T cells (TN) undergo phenotypic and transcriptional changes in the presence of autologous activated-memory CD8 T cells (TMem). Following in vitro co-culture with activated central memory cells (TCM), ~3% of the TN acquired activation/memory canonical markers (CD45RO and CD95) in an MHC-I dependent-fashion. Using scRNA-seq, we also observed that ~3% of the TN acquired an activated/memory signature, while ~84% developed a unique activated transcriptional profile hybrid between naïve and activated memory. Pseudotime trajectory analysis provided further evidence that TN with an activated/memory or hybrid phenotype were derived from TN. Our data reveal a non-cytotoxic function of TMem with potential to activate autologous TN into the activated/memory pool. These findings may have implications for host-protection and autoimmunity that arises after vaccination, infection or transplantation.

T cells are endowed with the capacity to sense their environment including other T cells around them. They do so to set their numbers and activation thresholds. This form of regulation has been well-studied within a given T cell population – i.e., within the naïve or memory pool; however, less is known about the cross-talk between T cell subsets. Here, we tested whether memory T cells interact with and influence surrounding naïve T cells. We report that human naïve CD8 T cells (TN) undergo phenotypic and transcriptional changes in the presence of autologous activated-memory CD8 T cells (TMem). Following in vitro co-culture with activated central memory cells (TCM), ~3% of the TN acquired activation/memory canonical markers (CD45RO and CD95) in an MHC-I dependent-fashion. Using scRNA-seq, we also observed that ~3% of the TN acquired an activated/memory signature, while ~84% developed a unique activated transcriptional profile hybrid between naïve and activated memory. Pseudotime trajectory analysis provided further evidence that TN with an activated/memory or hybrid phenotype were derived from TN. Our data reveal a non-cytotoxic function of TMem with potential to activate autologous TN into the activated/memory pool. These findings may have implications for host-protection and autoimmunity that arises after vaccination, infection or transplantation.

BACKGROUND AND AIMS Although considerable advances have been made in understanding the cellular effector mechanisms responsible for donor-specific antibody (DSA) generation leading to antibody-mediated rejection (ABMR), the identification of cellular regulators of such immune responses is lacking. METHOD In a cohort of 96 kidney transplant recipients, we used high-dimensional flow cytometry to concomitantly profile and track the two major subsets of regulatory lymphocytes in the blood: T regulatory (TREG) and transitional B (TrB) cells. Additionally, we established co-culture assays to address their respective capacities to suppress antibody responses in vitro. RESULTS TREG and TrB were potent suppressors of T follicular helper-mediated B cell differentiation into plasmablast and antibody generation. While TREG and TrB were both durably expanded in patients who did not develop DSA post-transplant, patients who manifested DSA and progressed to ABMR displayed a marked and persistent numerical reduction in TREG and TrB cells. Strikingly, specific cell clusters expressing the transcription factor T-bet were selectively depleted in both TREG and TrB compartments in patients with ABMR. Importantly, the coordinated loss of these T-bet + CXCR5+ TREG and T-bet+CD21–TrB cell clusters was correlated with increased and inflammatory DSA responses, more extensive microvascular inflammation and a higher rate of kidney allograft loss. CONCLUSION Our study identified coordinated and persistent defects in the regulatory T and B cell responses in patients undergoing ABMR, which may contribute to their loss of humoral immune regulation and thus warranting timely therapeutic interventions to replenish and sustain TREG and TrB cells in these patients.

Tratou-se de um relato de experiência vivenciado no projeto PET-Saúde cujo objeto de intervenção foi o desenvolvimento de práticas de educação popular em saúde para ações de prevenção e controle da dengue, tendo como cenário os Conselhos Locais de Saúde (CLS). O objetivo desse estudo é descrever a experiência e a sua contribuição para o processo de formação dos futuros profissionais de saúde. As atividades foram desenvolvidas durante o ano de 2014 e ao final foram visitados 19 CLS. Identificou limitação na participação dos usuários nas instâncias de controle social; a necessidade de (re) significar as práticas de educação popular em saúde; e a importância de se intensificar a articulação ensino-serviço-comunidade a partir de experiências pautadas em novas abordagens pedagógicas, como forma de possibilitar a construção da aprendizagem que possibilite o exercí­cio crí­tico do trabalho em saúde.

The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development and mobilization against SARS-CoV-2 (the etiologic agent of COVID-19) has been rapid. However, novel strategies are still necessary to slow the pandemic, and this includes new approaches to vaccine development and/or delivery, which improve vaccination compliance and demonstrate efficacy against emerging variants. Here we report on the immunogenicity and efficacy of a SARS-CoV-2 vaccine comprised of stabilized, pre-fusion Spike protein trimers displayed on a ferritin nanoparticle (SpFN) adjuvanted with either conventional aluminum hydroxide or the Army Liposomal Formulation QS-21 (ALFQ) in a cynomolgus macaque COVID-19 model. Vaccination resulted in robust cell-mediated and humoral responses and a significant reduction of lung lesions following SARS-CoV-2 infection. The strength of the immune response suggests that dose sparing through reduced or single dosing in primates may be possible with this vaccine. Overall, the data support further evaluation of SpFN as a SARS-CoV-2 protein-based vaccine candidate with attention to fractional dosing and schedule optimization.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019. We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50-μg) SpFN vaccine, given twice 28 days apart, induced a T helper cell 1 (TH1)–biased CD4 THresponse and elicited neutralizing antibodies against SARS-CoV-2 wild type and variants of concern, as well as against SARS-CoV-1. These potent humoral and cell-mediated immune responses translated into rapid elimination of replicating virus in the upper and lower airways and lung parenchyma of nonhuman primates after high-dose SARS-CoV-2 respiratory challenge. The immune response elicited by SpFN vaccination and resulting efficacy in nonhuman primates support the utility of SpFN as a vaccine candidate for SARS-causing betacoronaviruses.

Humoral alloimmunity of organ transplant recipient to donor can lead to antibody-mediated rejection (ABMR), causing thousands of organ transplants to fail each year worldwide. However, the mechanisms of adaptive immune cell responses at the basis of humoral alloimmunity have not been entirely understood. In this review, we discuss how recent investigations have allowed to uncover the key contributions of T follicular helper and B cells, and their coordinated actions in driving donor-specific antibody generation and the immune progression towards ABMR. We show how recognition of the role of T follicular helper-B cell interactions may allow to elaborate improved clinical strategies for immune monitoring and to identify novel therapeutic targets to tackle ABMR that will ultimately allow to improve organ transplant survival.

Although considerable advances have been made in understanding the cellular effector mechanisms responsible for donor-specific antibody generation leading to antibody-mediated rejection (ABMR), the identification of cellular regulators of such immune responses is lacking. To clarify this, we used high dimensional flow cytometry to concomitantly profile and track the two major subsets of regulatory lymphocytes in blood: T regulatory (T

Background: Chronic exposure to stress may dysregulate the hypothalamic-pituitary-adrenal axis and brain monoamine levels, contributing to the development of ethanol dependence. Exposure to chronic social defeat stress may impact ethanol-related effects, neural, and endocrine functions. Aim: This study assessed ethanol-induced locomotor activity, corticosterone responses, and brain monoamine levels in Swiss albino mice 10 days post-exposure to chronic social defeat stress. Methods: During a period of 10 days, male Swiss mice were exposed to daily defeat episodes, followed by housing with an aggressive mouse for 24 h. Control mice were housed in pairs and rotated every 24 h. Ten days post-stress, locomotor behavior was recorded after a challenge with ethanol (2.2 g/kg; intraperitoneal) or saline. After the test, blood and brain samples were collected for determination of plasma corticosterone and brain monoamines across different brain areas through high-performance liquid chromatography. Results: Defeated mice failed to show a stimulant locomotor response to ethanol, while controls displayed the expected ethanol-induced stimulation. Ethanol increased plasma corticosterone levels, with lower corticosterone secretion in defeated mice. Brain monoamines were affected by social defeat and ethanol, varying in different brain regions. Social stress reduced levels of dopamine, noradrenaline, and serotonin in the hypothalamus. Defeated mice presented reduced serotonin and dopamine levels in the frontal cortex. In the striatum, ethanol treatment increased dopamine levels in controls, but failed to do so in defeated mice. Conclusions: Our results suggest that chronic exposure to social defeat blunted ethanol-induced locomotor stimulation, and reduced ethanol-induced corticosterone secretion. Social stress promoted differential reductions in brain monoamine levels in the hypothalamus and frontal cortex and blunted ethanol-induced dopamine increases in the striatum.

Significance The emergence of SARS-CoV-2 variants of concern (VOCs) that reduce the efficacy of current COVID-19 vaccines is a major threat to pandemic control. We evaluate a SARS-CoV-2 spike receptor-binding domain ferritin nanoparticle protein vaccine (RFN) in a nonhuman primate challenge model that addresses the need for a next-generation vaccine with increased pan-SARS breadth of coverage. RFN, adjuvanted with a liposomal-QS21 formulation (ALFQ), elicits humoral and cellular immune responses with excellent breadth and potency against SARS-CoV-2 VOCs and SARS-CoV-1, and protects against high-dose respiratory tract challenge with SARS-CoV-2. Our results support consideration of RFN for vaccine development against multiple concerning members of the Sarbecovirus subgenus of Betacoronaviruses., Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 µg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV−like Sarbecovirus vaccine development.

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates (NHPs). High-dose (50µg) SpFN vaccine, given twice within a 28 day interval, induced a Th1-biased CD4 T cell helper response and a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and minimal decrement against variants of concern. Vaccinated animals mounted an anamnestic response upon high-dose SARS-CoV-2 respiratory challenge that translated into rapid elimination of replicating virus in their upper and lower airways and lung parenchyma. SpFN’s potent and broad immunogenicity profile and resulting efficacy in NHPs supports its utility as a candidate platform for SARS-like betacoronaviruses.One-Sentence SummaryA SARS-CoV-2 Spike protein ferritin nanoparticle vaccine, co-formulated with a liposomal adjuvant, elicits broad neutralizing antibody responses that exceed those observed for other major vaccines and rapidly protects against respiratory infection and disease in the upper and lower airways and lung tissue of nonhuman primates.

Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets.

Population-based net survival is an important tool for assessing prognostic advances. The unbiased Pohar Perme Estimator (PPE) was suggested in 2012 and soon established itself as the gold standard for estimating net survival. This scoping review aims to know in which context this estimator is being used in the oncology area, what the authors point out as a justification for its use, and the limitations found. We searched PubMed, and the grey literature to answer the question: Have studies involving patients diagnosed with cancer used the PPE to estimate cancer-specific survival? How do they justify the use of the PPE and what are the limitations pointed out? Out of 295 screened, 85 studies were included in this review. The two main characteristics of the PPE mentioned by the studies as justification were the fact that it is an unbiased estimator (83.5%) and that it produces comparable estimates among populations with different mortality rates from causes other than cancer (36.47%). No study pointed to a limitation due to the use of PPE. As a conclusion, the Pohar Perme Estimator is the gold standard for estimating net survival and should be more used in oncology, especially when dealing with population-based studies where the follow-up time is long, making high the probability of death from causes other than cancer.

Cell invasion by Trypanosoma cruzi extracellular amastigotes (EAs) relies significantly upon the host cell actin cytoskeleton. In past decades EAs have been established as a reliable model for phagocytosis inducer in non-phagocytic cells. Our current hypothesis is that EAs engage a phagocytosis-like mechanism in non-professional phagocytic cells; however, the molecular mechanisms in professional phagocytes still remain unexplored. In this work, we evaluated the involvement of Rac1 and Cdc42 in the actin-dependent internalization of EAs in RAW 246.7 macrophages. Kinetic assays showed similar internalization of EAs in unstimulated RAW and non-phagocytic HeLa cells but increased in LPS/IFN-γ stimulated RAW cells. However, depletion of Rac1, Cdc42 or RhoA inhibited EA internalization similarly in both unstimulated and stimulated RAW cells. Overexpression of active, but not the dominant-negative, construct of Rac1 increased EA internalization. Remarkably, for Cdc42, both the active and the inactive mutants decreased EA internalization when compared to wild type groups. Despite that both Rac1 and Cdc42 activation mutants were similarly recruited to and colocalized with actin at the EA-macrophage contact sites when compared to their native isoforms. Altogether, these results corroborate that EAs engage phagocytic processes to invade both professional and non-professional phagocytic cells providing evidences of converging actin mediated mechanisms induced by intracellular pathogens in both cell types.

Com aporte teorico-metodologico nos estudos de genero de perspectiva pos-estruturalista, propomos uma aproximacao entre a pornografia audiovisual e a educacao sexual escolar medico-cientifica. Para tanto, tomamos como objetos de analise o filme Garganta Profunda (1972) e a coletânea Enciclopedia da Vida Sexual: da Fisiologia a Psicologia (1973). Nessa proposicao de acercamento entre artefatos culturais entendidos, aparentemente, como discordantes, perseguimos as seguintes perguntas: O que os filmes pornograficos ensinam sobre o sexo? Em que medida as pedagogias de genero e sexualidade exercidas pelo cinema porno se aproximam das exercidas pela educacao sexual escolar? Estariam esses multiplos discursos sobre a egide de uma mesma norma?

O objetivo deste artigo foi investigar o potencial educativo do Ensino Híbrido como uma prática educativa em um colégio da rede particular de Belo Horizonte – Minas Gerais. Para tal, foi realizada uma pesquisa de natureza qualitativa, descritiva. Quanto ao procedimento técnico, escolheu-se o estudo de caso. O instrumento de coleta de dados utilizado foi a observação não participativa. Os dados observados foram registrados em um diário de campo. Os resultados encontrados permitiram concluir que as práticas pedagógicas que fazem parte do Ensino Híbrido têm proporcionado um ensino que desperta o interesse nos alunos da Geração Internet, devido ao uso das tecnologias digitais, as quais dinamizou as aulas e motivou os alunos, que tiveram a oportunidade de vivenciar diferentes experimentos e novos conhecimentos. Ao usar as tecnologias digitais, pôde-se observar que as atuações dos alunos foram mais ativas. Além disso, o Ensino Híbrido favoreceu a colaboração entre aos alunos durante as atividades práticas e, mostrou sua potencialidade em favorecer a personalização do ensino. Também, pôde-se verificar o engajamento de todos os profissionais envolvidos nesse projeto de implementação do Ensino Híbrido no colégio, avaliando positivamente suas práticas. Os principais motivos que permitiram essa avalição foram: a escola envolveu toda a equipe para a realização do projeto sobre o Ensino Híbrido, ofereceu condições físicas, tecnológicas e pedagógicas e, começou a implementação gradativamente, dando tempo para que todos fossem se adaptando ao novo modelo. ensino.

Regulatory dendritic cells (DCreg) promote transplant tolerance following their adoptive transfer in experimental animals. We investigated the feasibility, safety, fate, and impact on host T cells of donor monocyte-derived DCreg infused into prospective, living donor liver transplant patients, 7 days before transplantation. The DCreg expressed a tolerogenic gene transcriptional profile, high cell surface programed death ligand-1 (PD-L1):CD86 ratios, high IL-10/no IL-12 productivity and poor ability to stimulate allogeneic T cell proliferation. Target DCreg doses (range 2.5-10 × 106 cells/kg) were achieved in all but 1 of 15 recipients, with no infusion reactions. Following DCreg infusion, transiently elevated levels of donor HLA and immunoregulatory PD-L1, CD39, and CD73 were detected in circulating small extracellular vesicles. At the same time, flow and advanced image stream analysis revealed intact DCreg and "cross-dressing" of host DCs in blood and lymph nodes. PD-L1 co-localization with donor HLA was observed at higher levels than with recipient HLA. Between DCreg infusion and transplantation, T-bethi Eomeshi memory CD8+ T cells decreased, whereas regulatory (CD25hi CD127- Foxp3+ ): T-bethi Eomeshi CD8+ T cell ratios increased. Thus, donor-derived DCreg infusion may induce systemic changes in host antigen-presenting cells and T cells potentially conducive to modulated anti-donor immune reactivity at the time of transplant.

Introduction: The heterogeneous nature and intrinsically aggressive tumor pathology of the triple negative breast cancer subtype results in an unfavorable prognosis and limited clinical success. The use of hematological components of the systemic inflammatory response for patients with triple-negative breast cancer can add important prognostic information to the criteria traditionally used for cancer patients, since inflammation can promote tumor progression support by affecting the stages of tumorigenesis. Objectives: The aim of this study was to evaluate the hematological parameters neutrophil/lymphocyte, monocyte/lymphocyte and platelet/lymphocyte ratios as prognostic indicators in patients with triple-negative breast cancer. Methods: This was a singlecenter retrospective observational study in an oncology referral hospital in the South region of Brazil. Electronic medical records of patients diagnosed with triple-negative breast cancer from 2012 to 2016 were reviewed and analyzed using SPSS. Results: The low blood cell ratio groups had significantly higher overall survival than the high blood cell ratio groups. Univariate analysis also confirmed the correlation of patients in the high blood cell ratio groups with unfavorable results. Conclusions: Hematological components of the systemic inflammatory response are promising prognostic indicators. More studies on the subject should be carried out to assist in future medical decision-making so these parameters of easy assessment and low cost can be introduced in clinical practice.

Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression. Whereas LPS-stimulated control iDC (mature DC; matDC) secreted pro-inflammatory tumor necrosis factor but no IL-10, the converse was observed for LPS-stimulated DCreg. DCreg weakly stimulated naive and memory allogeneic CD4+ and CD8+ T cell proliferation and IFNγ, IL-17A and perforin/granzyme B production in MLR. Their stimulatory function was enhanced however, by blocking PD-1 ligation. High-throughput T cell receptor (TCR) sequencing revealed that, among circulating T cell subsets, memory CD8+ T cells contained the most alloreactive TCR clonotypes and that, while matDC expanded these alloreactive memory CD8 TCR clonotypes, DCreg induced more attenuated responses. These findings demonstrate the feasibility of generating highly-purified GMP-grade DCreg for systemic infusion, their influence on the alloreactive T cell response, and a key mechanistic role of the PD1 pathway.

Este texto faz o movimento de tomar como problemática de análise as seguintes perguntas, disparadas a partir de um debate realizado no festival Colors: Cinema + Diversidade (Curitiba, 2017): Quais as instâncias de resistência e de captura presentes em diferentes modos de representar personagens LGBT no cinema? Qual o alcance de filmes voltados às discussões das temáticas das diversidades sexuais e de gêneros, a depender da abordagem - mais ou menos desafiadora à norma heterossexual - por eles adotada? A fim de relançar estas perguntas no contexto do cinema contemporâneo, apresentamos um breve panorama de diferentes movimentações realizadas tanto no campo das produções teóricas quanto audiovisuais, através das quais, desde os anos 1970, esboçam-se dúvidas e também respostas que operam tais questionamentos. Com este propósito, recuperamos as reflexões de autores e autoras como D.A. Miller, Christine Holmlund e B. Ruby Rich e tecemos algumas considerações acerca da representação da homossexualidade nos filmes Festim Diabólico (Alfred Hitchcock, 1948), Filadélfia (Jonathan Demme, 1993) e Viver Até o Fim (Gregg Araki, 1992).

The use of biomass resources to generate energy has been growing as renewable alternative, foremost because of their promising properties. Nowadays, one of the newest alternative resources under study is the biomass from short-rotation forests. However, such process lacks development to be used in commercial scale in Brazil, despite its positive perspectives. The aim of the present study is to chemically characterize Eucalyptus sp. residues, in order to find their applicability potential as sustainable fuel. The material was collected in short-rotation forests in Taiobeiras, Minas Gerais State. Two treatments were tested, namely: residues collected in the harvester (T1) and 40-day-dried soil residues (T2). Firstly, the volatile matter and the ash content were analyzed in triplicate to determine the fixed carbon content. The results were 1.35%, 79.35% and 19.3%, in T1; and 1.30%, 80.60% and 19.2%, in T2, respectively. The extractive levels were 15.88%, in T1; and 12.37%, in T2. The lignin values reached 17.12% and 20%, in T1 and T2, respectively. The holocellulose and ?-cellulose levels were recorded and the hemicellulose level was found using the difference between the holocellulose and ?-cellulose values. The holocellulose reached 65.94%, in T1; and 61.34%, in T2; whereas the ?-cellulose presented values such as 40.64%, in T1; and 36.22%, in T2. Therefore, the hemicellulose content was 25.30% and 25.12%, in T1 and T2, respectively. Lastly, the calorific power levels were 18132.5 J/g and 18175.0 J/g, in T1 and T2, results that may be related to the chemical composition of short rotation timber.

Introduction: With aging, the sensory systems suffer an accumulation of degenerative, infectious and/or traumatic processes that may hinder the body balance maintenance. Objective: To assess the influence of sensory information on static body balance of elderly individuals with vestibular disorders. Methods: Cross-sectional study of elderly individuals with vestibular disorders. The Clinical Test of Sensory Interaction and Balance and posturography integrated with virtual reality (Balance Rehabilitation UnitTM) were used. Posturography parameters analyzed included center of pressure and velocity of body sway. Results: 123 individuals with mean age of 73.11 were assessed. Worst performance was observed in the Clinical Test of Sensory Interaction and Balance condition of visual dome-unstable surface. Differences between conditions were: firm surface-open eyes/firm surface-closed eyes, unstable surface-open eyes/unstable surface-closed eyes (p < 0.001), and unstable surface-closed eyes/unstable surface-visual dome. Considering center of pressure and velocity of body sway, significant differences were observed between the following conditions: firm surface-open eyes/firm surface-closed eyes: firm surface-saccadic stimulus/firm surfacevertical optokinetic stimulus; firm surface-optokinetic stimuli/firm surface-visual-vestibular interaction; and firm surface-visual-vestibular interaction/unstable surface. Worse performances were observed in conditions firm surface-closed eyes, firm surface-vertical optokinetic stimulus, F-visual-vestibular interaction, and unstable surface-closed eyes. There was a difference in the center of pressure between firm surface-closed eyes/firm surface-saccadic stimulus, with a worse performance in the condition of firm surface-closed eyes, and of velocity of body sway, between firm surface-saccadic stimulus/firm surface-horizontal optokinetic stimulus (p < 0.001). Conclusion: Static body balance in elderly individuals with vestibular disorders is worse when the sensory conditions are more challenging, i.e. stable and unstable surfaces, visual stimuli, such as optokinetic and visual-vestibular interaction, and with the eyes closed. Introdução: Com o envelhecimento, o sistema sensorial sofre um acúmulo de processos degenerativos, infecciosos e/ou traumáticas que podem dificultar a manutenção do equilíbrio corporal. Objetivo: Avaliar a influência das informações sensoriais no equilíbrio corporal estático de idosos vestibulopatas. Método: Estudo transversal, cuja amostra foi constituída por idosos vestibulopatas. Empregaram-se o Clinical Test of Sensory Interaction and Balance (CTSIB) e a posturografia integrada à realidade virtual (Balance Rehabilitation Unit.). Os parâmetros avaliados à posturografia foram: área do centro de pressão (COP) e velocidade de oscilação (VOC). Resultados: Foram avaliados 123 idosos, com média etária de 73,11 anos. O pior desempenho ocorreu na condição cúpula visual-superfície instável (SI) do CTSIB. As diferenças entre as condições foram: superfície firme (SF)-olhos abertos (OA)/SF-olhos fechados (OF) e SI-OA/SI-OF (p < 0,001); SI-OF/SI-cúpula visual. Observou-se diferença da área do COP e da VOC entre as condições: SF-OA/SF-OF; SF-estímulo sacádico/SF-estímulo optocinético vertical; SF-estímulos optocinéticos/SF-interação visuo-vestibular (IVV); SF-IVV/SI, com pior desempenho nas condições SF-OF, SF-estímulo optocinético vertical, SF-IVV e SI-OF. Observou-se diferençado COP entre as condições SF-OF/SF-estímulo sacádico, com pior desempenho na condição SF-OF, e da VOC entre as condições SF-estímulo sacádico e SF-estímulo optocinético horizontal (p < 0,001). Conclusão: O equilíbrio corporal estático de idosos vestibulopatas é pior à medida que as condições sensoriais são mais desafiadoras, ou seja, em SI e SE, estímulos visuais como os optocinéticos e interação visuovestibular e OF.

We investigated in vitro whether HLA highly sensitized patients with end-stage renal disease will be disadvantaged immunologically after a genetically engineered pig kidney transplant.Blood was drawn from patients with a calculated panel-reactive antibody (cPRA) 99% to 100% (Gp1, n = 10) or cPRA 0% (Gp2, n = 12), and from healthy volunteers (Gp3, n = 10). Serum IgM and IgG binding was measured (i) to galactose-α1-3 galactose and N-glycolylneuraminic acid glycans by enzyme-linked immunosorbent assay, and (ii) to pig red blood cell, pig aortic endothelial cells, and pig peripheral blood mononuclear cell from α1,3-galactosyltransferase gene-knockout (GTKO)/CD46 and GTKO/CD46/cytidine monophosphate-N-acetylneuraminic acid hydroxylase-knockout (CMAHKO) pigs by flow cytometry. (iii) T-cell and B-cell phenotypes were determined by flow cytometry, and (iv) proliferation of T-cell and B-cell carboxyfluorescein diacetate succinimidyl ester-mixed lymphocyte reaction.(i) By enzyme-linked immunosorbent assay, there was no difference in IgM or IgG binding to galactose-α1-3 galactose or N-glycolylneuraminic acid between Gps1 and 2, but binding was significantly reduced in both groups compared to Gp3. (ii) IgM and IgG binding in Gps1 and 2 was also significantly lower to GTKO/CD46 pig cells than in healthy controls, but there were no differences between the 3 groups in binding to GTKO/CD46/CMAHKO cells. (iii and iv) Gp1 patients had more memory T cells than Gp2, but there was no difference in T or B cell proliferation when stimulated by any pig cells. The proliferative responses in all 3 groups were weakest when stimulated by GTKO/CD46/CMAHKO pig peripheral blood mononuclear cell.(i) End-stage renal disease was associated with low antipig antibody levels. (ii) Xenoreactivity decreased with increased genetic engineering of pig cells. (iii) High cPRA status had no significant effect on antibody binding or T-cell and B-cell response.

International audience; Background. The human regulatory macrophage (Mreg) has emerged as a promising cell type for use as a cell-based adjunct immunosuppressive therapy in solid organ transplant recipients. In this brief report, dehydrogenase/reductase 9 (DHRS9) is identified as a robust marker of human Mregs.Methods. The cognate antigen of a mouse monoclonal antibody raised against human Mregs was identified as DHRS9 by immunoprecipitation and MALDI-MS sequencing. Expression of DHRS9 within a panel of monocyte-derived macrophages was investigated by quantitative PCR, immunoblotting and flow cytometry.Results. DHRS9 expression discriminated human Mregs from a panel of in vitro derived macrophages in other polarisation states. Likewise, DHRS9 expression distinguished Mregs from a variety of human monocyte-derived tolerogenic antigen-presenting cells in current development as cell-based immunotherapies, including Tol-DC, Rapa-DC, DC-10, and PGE 2-induced myeloid-derived suppressor cells. A subpopulation of DHRS9-expressing human splenic macrophages was identified by immunohistochemistry. Expression of DHRS9 was acquired gradually during in vitro development of human Mregs from CD14 + monocytes and was further enhanced by IFN-γ treatment on day 6 of culture. Stimulating Mregs with 100 ng/mL lipopolysaccharide for 24 hours did not extinguish DHRS9 expression. Dhrs9 was not an informative marker of mouse Mregs. Conclusion. DHRS9 is a specific and stable marker of human Mregs.

This study employed the intruder-resident paradigm to evaluate the effects of continuous social defeat on depressive- and anxiety-like behaviors and the reinforcing and motivational actions of ethanol in male Swiss mice. Male Swiss mice were exposed to a 10-day social defeat protocol, while control mice cohabitated with a non-aggressive animal. Continuous defeat stress consisted of episodes of defeat, followed by 24h or 48h cohabitation with the aggressor until the following defeat. Mice were assessed for sucrose drinking (anhedonia), social investigation test, elevated plus-maze, conditioned place preference to ethanol, and locomotor response to ethanol. Plasma corticosterone was measured prior to, after the first and the final defeat, and 10days after the end of defeat. Defeated mice exhibited a depressive-like phenotype as indicated by social inhibition and reduced sucrose preference, relative to non-defeated controls. Defeated mice also displayed anxiety-like behavior when tested in the elevated plus-maze. Stressed animals failed to present ethanol-induced locomotor stimulation, but showed increased sensitivity for ethanol-induced conditioned place preference. Corticosterone response to defeat was the highest after the first defeat, but was still elevated after the last defeat (day 10) when compared to non-stressed controls. Baseline corticosterone levels were unchanged 10days after the final defeat. These data suggest that social defeat stress increased depressive- and anxiety-like behavior as well increased vulnerability to ethanol reward in mice.

Resumo: Os conteúdos de estatística e probabilidade possuem grande relevância na educação básica possibilitando ao aluno recursos para uma leitura de sua sociedade e exercício consciente de sua cidadania. Como o livro didático possui um papel de destaque na atuação do professor, analisamos como um livro didático do 7º ano aborda os conteúdos de estatística e probabilidade. Tivemos como aporte metodológico a pesquisa qualitativa. Nosso objetivo foi analisar o livro didático particularizando a análise global, regional e local. Do qual identificamos fragilidades no que tange a definições, conteúdos e habilidades. Esperamos contribuir no sentido de trazer reflexões sobre como vêm sendo apresentado o “Tratamento da Informação” nos livros didáticos evidenciando suas potencialidades e fragilidades. Palavras-chave: Livro Didático; Ensino; Educação Estatística; Tratamento da Informação. An analysis of contents of the block information treatment in a teaching book of the 7th year of fundamental education Abstract: The contents of statistics and probability have great relevance in basic education allowing the student resources for a reading of their society and conscious exercise of their citizenship. As the textbook has a prominent role in the teacher's performance, we analyze how a 7th grade textbook addresses the contents of statistics and probability. We had as methodological contribution the qualitative research. Our goal was to analyze the textbook, particularizing the global, regional and local analysis. Of which we identified weaknesses regarding definitions, content and skills. We hope to contribute to bring reflections on how the "Treatment of Information" has been presented in textbooks highlighting its potentialities and weaknesses. Keywords: Textbook; Teaching; Statistical Education; Information Processing.

Recent evidence indicates the involvement of orexin in reward circuitry and drug addiction. In the present study we evaluated the role of orexin in ethanol-induced behavioral sensitization. In the first experiment, Swiss male mice received seven administrations of saline or ethanol (2.2 g/kg, i.p., chronic), every other day. On the last day of treatment, half of saline-treated mice received a saline injection (saline) whereas the other half received 2.2 g/kg of ethanol (i.p., acute). Behavioral sensitization was assessed by locomotor activity tests and after the last one, immunoreactivity for orexin and Fos (ORX + Fos-ir) was assessed in the lateral hypothalamic area. Chronic ethanol treatment produced behavioral sensitization and a trend for greater ORX + Fos-ir. In the second experiment, mice were treated as in Experiment 1 and type 1 orexin receptor antagonist, SB334867 (20 mg/kg), was administered before the ethanol challenge successfully blocking the expression of sensitization in mice chronically treated with EtOH. These results indicate that orexin plays a role in ethanol-induced behavioral sensitization.

To minimize maintenance immunosuppression in upper-extremity transplantation to favor the risk-benefit balance of this procedure.Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the risks and side effects of multidrug immunosuppression. We present our experience with upper-extremity transplantation under a novel, donor bone marrow (BM) cell-based treatment protocol ("Pittsburgh protocol").Between March 2009 and September 2010, 5 patients received a bilateral hand (n = 2), a bilateral hand/forearm (n = 1), or a unilateral (n = 2) hand transplant. Patients were treated with alemtuzumab and methylprednisolone for induction, followed by tacrolimus monotherapy. On day 14, patients received an infusion of donor BM cells isolated from 9 vertebral bodies. Comprehensive follow-up included functional evaluation, imaging, and immunomonitoring.All patients are maintained on tacrolimus monotherapy with trough levels ranging between 4 and 12 ng/mL. Skin rejections were infrequent and reversible. Patients demonstrated sustained improvements in motor function and sensory return correlating with time after transplantation and level of amputation. Side effects included transient increase in serum creatinine, hyperglycemia managed with oral hypoglycemics, minor wound infection, and hyperuricemia but no infections. Immunomonitoring revealed transient moderate levels of donor-specific antibodies, adequate immunocompetence, and no peripheral blood chimerism. Imaging demonstrated patent vessels with only mild luminal narrowing/occlusion in 1 case. Protocol skin biopsies showed absent or minimal perivascular cellular infiltrates.Our data suggest that this BM cell-based treatment protocol is safe, is well tolerated, and allows upper-extremity transplantation using low-dose tacrolimus monotherapy.

In rodents, chronic social defeat stress promotes deficits in social interest and social interaction. We further explored these antisocial effects by comparing the consequences of two different defeat stress protocols (episodic vs. continuous stress) in a social investigation test. We expected that continuous, but not episodic, stress would induce social deficits in this model. Furthermore, we tested whether a potentially anxiolytic dose of ethanol reverses social deficits induced by defeat stress. Male Swiss mice were exposed to a 10-day social defeat protocol, using daily confrontations with an aggressive resident mouse. Episodic stress consisted of brief defeat episodes, after which the defeated mouse was returned to its home cage, until the next defeat 24 h later (n = 7-11/group). For continuous stress, similar defeat episodes were followed by cohabitation with the aggressive resident for 24 h, separated by a perforated divider, until the following defeat (n = 8-14/group). Eight days after stress termination, defeated and control mice were assessed in a social investigation test, after treatment with ethanol (1.0 g/kg, i.p.) or 0.9% saline. Considering the time spent investigating a social target, mice exposed to episodic or continuous social stress showed less social investigation than controls (p

Serial EBV load monitoring of clinically asymptomatic pediatric thoracic organ transplant patients has identified three groups of children who exhibit undetectable (16,000 copies/ml) EBV loads in peripheral blood. Chronic high EBV load patients have a 45% rate of progression to late-onset posttransplant lymphoproliferative disorders. In this article, we report that asymptomatic patients carrying EBV loads (low and high) expressed increased frequencies of EBV-specific CD8+ T cells, as compared with patients with undetectable EBV loads. Although patients with low viral load displayed EBV-specific CD8+ T cells with moderate signs of activation (CD38+/−/CD127+/−), programmed death 1 upregulation and effective IFN-γ secretion, high EBV load carriers showed significant CD38+ upregulation, features of cellular exhaustion (programmed death 1+/CD127−) accompanied by a decline in IFN-γ release. Immunopolarization of EBV-specific CD8+ T cells was skewed from the expected type 1 (IFN-γ) toward type 0 (IFN-γ/IL-5) in patients, and Tr1 (IL-10) in high load carriers. These results indicate the importance of chronic EBV load and of the levels of antigenic pressure in shaping EBV-specific memory CD8+ T cells. Concomitant phenotypic and functional EBV monitoring is critical for identifying the complex “functional” versus “exhausted” signature of EBV-specific CD8+ T cells, with implications for immunologic monitoring in the clinic.

BK virus (BKV) nephropathy and hemorrhagic cystitis are increasingly recognized causes of disease in renal and hematopoietic stem cell transplant recipients, respectively. Functional characterization of the immune response to BKV is important for clinical diagnosis, prognosis, and vaccine design. A peptide mix (PepMix) and overlapping (OPP) or random (RPP) peptide pools derived from BKV large T antigen (LTA) were used to restimulate 14-day-expanded peripheral blood mononuclear cells (PBMC) from 27 healthy control subjects in gamma interferon (IFN-γ)-specific enzyme-linked immunospot (ELISPOT) assays. A T-cell response to LTA PepMix was detected in 15/27 subjects. A response was frequently observed with peptides derived from the helicase domain (9/15 subjects), while the DNA binding and host range domains were immunologically inert (0/15 subjects). For all nine subjects who responded to LTA peptide pools, the immune response could be explained largely by a 15-mer peptide designated P313. P313-specific CD4+T-cell clones demonstrated (i) stringent LTA peptide specificity; (ii) promiscuous recognition in the context of HLA-DR alleles; (iii) cross recognition of homologous peptides from the polyomavirus simian virus 40 (SV40); (iv) an effector memory phenotype, CD107a expression, and intracellular production of IFN-γ and tumor necrosis factor alpha (TNF-α); (v) cytotoxic activity in a chromium release assay; and (vi) the ability to directly present cognate antigen to autologous T cells. In conclusion, T-cell-mediated immunity to BKV in healthy subjects is associated with a polyfunctional population of CD4+T cells with dual T-helper and T-cytotoxic properties. HLA class II promiscuity in antigen presentation makes the targeted LTA peptide sequence a suitable candidate for inclusion in immunotherapy protocols.

Prolonged inhibition of the kinase, mammalian target of rapamycin (mTOR), during myeloid dendritic cell (DC) generation confers resistance to maturation. Recently, however, mTOR inhibition immediately before Toll-like receptor ligation has been found to exert proinflammatory effects on myeloid cells, notably enhanced IL-12p40/p70 production. We show, for the first time, that mouse or human DCs generated under mTOR inhibition exhibit markedly enhanced IL-12p70 production after lipopolysaccharide (LPS) stimulation, despite impaired costimulatory molecule expression and poor T-cell stimulatory ability. Consistent with this finding, we reveal that increased IL-12p40 production occurs predominantly in CD86lo immature DCs. High IL-12p40/p70 production by CD86lo DC resulted from failed down-regulation of glycogen synthase kinase-3 (GSK-3) activity and could not be ascribed to enhanced Akt function. Despite high IL-12p70 secretion, rapamycin-conditioned, LPS-stimulated DCs remained poor T-cell stimulators, failing to enhance allogeneic Th1 cell responses. We also report that inhibition of GSK-3 impedes the ability of LPS-stimulated DCs to induce forkhead box p3 in CD4+CD25− T cells, as does the absence of IL-12p40/p70. Thus, GSK-3 activity in DC is regulated via signaling linked to mTOR and modulates their capacity both to produce IL-12p40/p70 and induce forkhead box p3 in CD4+ T cells under inflammatory conditions.

As the target CD52 molecule is expressed on erythrocytes of most nonhuman primate strains, using alemtuzumab in these species would cause massive hemolysis. Six cynomolgus monkeys of Indonesian origin, screened by agglutination assay for absence of CD52 on erythrocytes, were administered alemtuzumab in a cumulative dose to a maximum of 60 mg/kg. In two monkeys, mycophenolate mofetil (MMF) was added as maintenance therapy. Complete depletion of T and B lymphocytes (99.5%) was achieved with 20 mg/kg alemtuzumab and was more profound than in monkeys treated with antithymocyte globulin (n = 5), as quantified by flow cytometry. Repopulation was suppressed by weekly injections of 10 mg/kg. Without MMF, repopulation of CD20(+)B cells and CD8(+)T cells was complete within 2 and 3 months, respectively, and repopulation of CD4(+)T cells was 67% after 1 year. MMF significantly delayed CD4(+)T-cell repopulation. Among repopulating CD4(+) and CD8(+) T cells, a phenotypic shift was observed from CD45RA(hi)CD62L(hi) naïve cells toward CD45RA(lo)CD62L(lo) effector memory cells. In lymph nodes, the depletion of naïve cells was more profound than of memory cells, which may have initiated a proliferation of memory cells. This model offers opportunities to investigate lymphocyte depletion/repopulation phenomena, as well as the efficacy of alemtuzumab in preclinical transplantation models.

BACKGROUND Immunologic monitoring of pediatric transplant (Tx) recipients, who are at increased risk of Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disease, is an important goal in clinical transplantation. Here, we investigated the impact of EBV load on T-cell immunity from pediatric Tx recipients, using clinically applicable tests for improved assessment of T-cell immune competence. METHODS Thirty-five asymptomatic pediatric thoracic Tx patients were categorized into three groups according to their EBV load levels as follows: undetectable viral load (UVL), chronic low viral load (LVL) and chronic high viral load (HVL). Global and EBV-specific T-cell immunity were assessed by ATP release using Cylex Immuknow and T Cell Memory assays. RESULTS UVL patients exhibited normal ATP release to Concanavalin A (ConA) and phytohemagglutinin (PHA; 190+/-86 ng/mL, 328+/-163 ng/mL) and detectable EBV-specific (37+/-34 ng/mL) ATP responses. LVL patients displayed significantly stronger responses to ConA (373+/-174 ng/mL), PHA (498+/-196 ng/mL) and EBV (152+/-179 ng/mL), when compared with UVL or to HVL patients (ConA 185+/-114 ng/mL, PHA 318+/-173 ng/mL, and EBV 33+/-42 ng/mL). Moreover, HVL patients displayed significant inverse correlation between CD4+ T-cell ATP levels and EBV loads. CONCLUSIONS Evaluation of global and EBV-specific T-cell immunity provides a rapid assessment of patients' immune competence. It is still unclear whether selective oversuppressed ATP release by CD4+ T cells reflects HVL patients at risk of posttransplant lymphoproliferative disease. Further longitudinal studies will determine the importance of Immuknow test in identifying asymptomatic HVL patients vulnerable to EBV complications.

OBJECTIVE: To identify factors relating to depressive symptoms among elderly people with chronic vestibular dysfunction. METHOD: This was a cross-sectional study in which 120 elderly people with chronic vestibular dysfunction answered the Geriatric Depression Scale questionnaire. Multivariate linear regression analysis was performed (p

INTRODUCTION: There are positive influences of religious and spiritual beliefs in the face of diseases such as cancer. OBJECTIVE: To analyse the influence of spirituality and religiosity in cancer in the perspective of cancer patients. METHODS: It is a qualitative, descriptive and exploratory research, carried out with 10 patients in cancer treatment, aged between 37 and 75 years. Data were collected through interviews, containing guiding questions about the theme and treated according to the Content Analysis. RESULTS: The results are summarized into three categories: (1) perceptions / conceptions of patients in the discovery of cancer; (2) vision and experience of spirituality / religiosity of cancer patients and (3) the influence of spirituality / religiosity in the treatment of cancer. They were discussed in the light of the relevant literature to the subject. CONCLUSION: Cancer brings a new life meaning for patients. Religion and spirituality have a strong relationship between the disease and faith in the possibilities of healing, which makes the religious coping a stress reduction strategy and improves quality of life of people.

Immune responses to EBV in immunosuppressed (IS) solid organ transplant (SOTx) recipients have not been well characterized. Here we evaluate the phenotype and function of EBV-specific CD8+ T cells in peripheral blood isolated from "stable" IS SOTx recipients. The EBV-specific CD8+ T cell memory subset distribution in the peripheral blood of patients was examined by flow cytometric analysis using HLA-A2 tetramers incorporating BMLF1 (lytic), and LMP2 and EBNA3A (latent)-derived peptides, in conjunction with mAbs against the CD45RO, CD45RA, and CD62L markers. The ability of CD8+ T cells to produce IFN-gamma in response to the same EBV-derived peptides was measured by ELISPOT assay. Patients and healthy normal donors exhibited similar anti-EBV CD8+ T cell frequencies and specificities against the EBV epitopes evaluated. When compared to healthy normal donors, an overall significant expansion of the CD8+ T cell "effector memory" (CD45RO+/CD62L-) pool, including that of EBV "latent" (LMP2 and EBNA3A)-specific CD8+ T cells was detected in IS SOTx patients. However, the patients' EBV-specific CD8+ T cells showed decreased IFN-gamma production to the EBV-peptide stimulation. These results indicate that the impairment of EBV-specific CD8+ T cell activity is not due to clonal depletion, but is mainly due to impaired functional activation.