Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease.

Chagas disease (CD) (American trypanosomiasis caused by Trypanosoma cruzi) is a parasitic disease endemic in 21 countries in South America, with increasing global spread. When administered late in the infection, the current antiparasitic drugs do not prevent the onset of cardiac illness leading to chronic Chagasic cardiomyopathy. Therefore, new therapeutic vaccines or immunotherapies are under development using multiple platforms. In this study, we assessed the feasibility of developing an mRNA-based therapeutic CD vaccine targeting two known T. cruzi vaccine antigens (Tc24─a flagellar antigen and ASP-2─an amastigote antigen). We present the mRNA engineering steps, preparation, and stability of the lipid nanoparticles and evaluation of their uptake by dendritic cells, as well as their biodistribution in c57BL/J mice. Furthermore, we assessed the immunogenicity and efficacy of two mRNA-based candidates as monovalent and bivalent vaccine strategies using an in vivo chronic mouse model of CD. Our results show several therapeutic benefits, including reductions in parasite burdens and cardiac inflammation, with each mRNA antigen, especially with the mRNA encoding Tc24, and Tc24 in combination with ASP-2. Therefore, our findings demonstrate the potential of mRNA-based vaccines as a therapeutic option for CD and highlight the opportunities for developing multivalent vaccines using this approach.

Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease.

Post-infectious conditions present major health burdens but remain poorly understood. In Chagas disease (CD), caused by Trypanosoma cruzi parasites, antiparasitic agents that successfully clear T. cruzi do not always improve clinical outcomes. In this study, we reveal differential small molecule trajectories between cardiac regions during chronic T. cruzi infection, matching with characteristic CD apical aneurysm sites. Incomplete, region-specific, cardiac small molecule restoration is observed in animals treated with the antiparasitic benznidazole. In contrast, superior restoration of the cardiac small molecule profile is observed for a combination treatment of reduced-dose benznidazole plus an immunotherapy, even with less parasite burden reduction. Overall, these results reveal molecular mechanisms of CD treatment based on simultaneous effects on the pathogen and on host small molecule responses, and expand our understanding of clinical treatment failure in CD. This link between infection and subsequent persistent small molecule perturbation broadens our understanding of infectious disease sequelae.

Heterologous mRNA-protein vaccination with Tc24 induces a robust cellular immune response against Trypanosoma cruzi, characterized by an increased level of polyfunctional CD8+ T-cells.

Tc24 is a Trypanosoma cruzi-derived flagellar protein that, when formulated with a TLR-4 agonist adjuvant, induces a balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination with the recombinant Tc24 protein can reduce parasite levels and improve survival during acute infection. Although some mRNA vaccines have been proven to elicit a stronger immune response than some protein vaccines, they have not been used against T. cruzi. This work evaluates the immunogenicity of a heterologous prime/boost vaccination regimen using protein and mRNA-based Tc24 vaccines. Mice (C57BL/6) were vaccinated twice subcutaneously, three weeks apart, with either the Tc24-C4 protein + glucopyranosyl A (GLA)-squalene emulsion, Tc24 mRNA Lipid Nanoparticles, or with heterologous protein/mRNA or mRNA/protein combinations, respectively. Two weeks after the last vaccination, mice were euthanized, spleens were collected to measure antigen-specific T-cell responses, and sera were collected to evaluate IgG titers and isotypes. Heterologous presentation of the Tc24 antigen generated antigen-specific polyfunctional CD8+ T cells, a balanced Th1/Th2/Th17 cytokine profile, and a balanced humoral response with increased serum IgG, IgG1 and IgG2c antibody responses. We conclude that heterologous vaccination using Tc24 mRNA to prime and Tc24-C4 protein to boost induces a broad and robust antigen-specific immune response that was equivalent or superior to two doses of a homologous protein vaccine, the homologous mRNA vaccine and the heterologous Tc24-C4 Protein/mRNA vaccine.

[Addressing HIV/AIDS and syphilis in Venezuelan migrant women from the perspective of health managers in the North of BrazilManejo de la infección por el VIH/sida y la sífilis en mujeres migrantes venezolanas desde la perspectiva de los gestores de salud en el norte de Brasil]. / Enfrentamento de HIV/aids e sífilis em mulheres venezuelanas migrantes na perspectiva de gestores de saúde no Norte do Brasil.

Objective: To identify the perception of health managers regarding the actions taken and the challenges encountered in addressing HIV and syphilis in Venezuelan migrant women in Brazil. Method: This descriptive-exploratory study using a qualitative approach was conducted from January to March 2021 in the municipalities of Boa Vista (state of Roraima) and Manaus (state of Amazonas). Audio interviews with the participants were transcribed in full and examined using thematic content analysis. Results: Ten managers were interviewed (five in Boa Vista and five in Manaus). Content analysis identified the following domains and themes: available infrastructure for diagnosis and treatment of AIDS and syphilis - access, availability of medical appointments /waiting list, training of health teams, and psychosocial support; challenges faced by Venezuelan women - language, documentation issues, and frequent address changes; and strategies and actions adopted and expectations for addressing HIV/AIDS and syphilis in the context of migration. Conclusions: Despite the care provided to Venezuelan women in Brazil - guaranteed by the universal nature of the Brazilian health system - language and lack of documentation remain as barriers. Given the absence of action plans and future planning for the care of migrant women with HIV or syphilis in municipalities, it is important to develop public policies aimed at minimizing the difficulties faced by this population.

Objetivo: Determinar la percepción de los gestores de salud sobre las medidas adoptadas y los desafíos encontrados para manejar la infección por el VIH y la sífilis en mujeres migrantes venezolanas en Brasil. Métodos: Este estudio descriptivo y exploratorio, con enfoque cualitativo, se realizó de enero a marzo del 2021 en los municipios de Boa Vista (estado de Roraima) y Manaos (estado de Amazonas). La grabación de las entrevistas de los participantes se transcribió en su totalidad. El análisis se basó en la técnica de evaluación temática del contenido. Resultados: Se hicieron entrevistas a diez gestores (cinco en Boa Vista y cinco en Manaos). En el análisis del contenido se observaron los siguientes ejes y temas: la estructura disponible para el diagnóstico y tratamiento del sida y de la sífilis, con inclusión de acceso, cupos de atención, filas de espera y formación de equipos de salud y apoyo psicosocial; los desafíos enfrentados por las mujeres venezolanas, como idioma, problemas de documentación y frecuencia de cambio de domicilio; las estrategias y medidas adoptadas y las expectativas para enfrentar la infección por el VIH/sida y la sífilis en el marco de la migración. Conclusiones: A pesar de las medidas de acogida a las mujeres migrantes venezolanas, garantizadas por la universalidad del sistema de salud brasileño, todavía existen algunas barreras como el idioma y la falta de documentación. Ante la falta de planes de acción y planificación futura de la atención a las mujeres migrantes portadoras del VIH o con sífilis en los municipios, es importante formular políticas públicas con el fin de reducir las dificultades enfrentadas por este grupo de la población.

Enfrentamento de HIV/aids e sífilis em mulheres venezuelanas migrantes na perspectiva de gestores de saúde no Norte do Brasil

[RESUMO]. Objetivo. Identificar a percepção dos gestores de saúde sobre as ações adotadas e os desafios encontrados no enfrentamento de HIV e sífilis em mulheres venezuelanas migrantes no Brasil. Métodos. Este estudo descritivo-exploratório, de abordagem qualitativa, foi realizado de janeiro a março de 2021 nos municípios de Boa Vista (estado de Roraima) e Manaus (estado do Amazonas). As entrevistas em áudio realizadas com os participantes foram transcritas na íntegra. A análise foi pautada na técnica de ava- liação de conteúdo temática. Resultados. Foram entrevistados 10 gestores (cinco em Boa Vista e cinco em Manaus). A análise de conteúdo identificou os seguintes eixos e temas: estrutura disponível para diagnóstico e tratamento de aids e sífilis — acesso, vagas para atendimento/fila de espera, formação das equipes de saúde e suporte psicossocial; desafios enfrentados pelas mulheres venezuelanas — idioma, questões de documentação e frequência de alteração de endereço; e estratégias e ações adotadas e expectativas para o enfrentamento de HIV/aids e sífilis no contexto de migração. Conclusões. Apesar das ações de acolhimento das mulheres venezuelanas migrantes — garantido pela universalidade do sistema de saúde brasileiro — aspectos como o idioma e a falta de documentação per- manecem como barreiras. Diante da inexistência de planos de ação e planejamento futuro da atenção a mulheres migrantes portadoras de HIV ou sífilis nos municípios, é importante desenvolver políticas públicas com o objetivo de minimizar as dificuldades enfrentadas por essa população.

[ABSTRACT]. Objective. To identify the perception of health managers regarding the actions taken and the challenges encountered in addressing HIV and syphilis in Venezuelan migrant women in Brazil. Method. This descriptive-exploratory study using a qualitative approach was conducted from January to March 2021 in the municipalities of Boa Vista (state of Roraima) and Manaus (state of Amazonas). Audio inter- views with the participants were transcribed in full and examined using thematic content analysis. Results. Ten managers were interviewed (five in Boa Vista and five in Manaus). Content analysis identified the following domains and themes: available infrastructure for diagnosis and treatment of AIDS and syphilis — access, availability of medical appointments /waiting list, training of health teams, and psychosocial support; challenges faced by Venezuelan women — language, documentation issues, and frequent address changes; and strategies and actions adopted and expectations for addressing HIV/AIDS and syphilis in the context of migration. Conclusions. Despite the care provided to Venezuelan women in Brazil — guaranteed by the universal nature of the Brazilian health system — language and lack of documentation remain as barriers. Given the absence of action plans and future planning for the care of migrant women with HIV or syphilis in municipalities, it is important to develop public policies aimed at minimizing the difficulties faced by this population.

[RESUMEN]. Objetivo. Determinar la percepción de los gestores de salud sobre las medidas adoptadas y los desafíos encontrados para manejar la infección por el VIH y la sífilis en mujeres migrantes venezolanas en Brasil. Métodos. Este estudio descriptivo y exploratorio, con enfoque cualitativo, se realizó de enero a marzo del 2021 en los municipios de Boa Vista (estado de Roraima) y Manaos (estado de Amazonas). La grabación de las entrevistas de los participantes se transcribió en su totalidad. El análisis se basó en la técnica de evalua- ción temática del contenido. Resultados. Se hicieron entrevistas a diez gestores (cinco en Boa Vista y cinco en Manaos). En el análisis del contenido se observaron los siguientes ejes y temas: la estructura disponible para el diagnóstico y tratamiento del sida y de la sífilis, con inclusión de acceso, cupos de atención, filas de espera y formación de equipos de salud y apoyo psicosocial; los desafíos enfrentados por las mujeres venezolanas, como idioma, problemas de documentación y frecuencia de cambio de domicilio; las estrategias y medidas adoptadas y las expectativas para enfrentar la infección por el VIH/sida y la sífilis en el marco de la migración. Conclusiones. A pesar de las medidas de acogida a las mujeres migrantes venezolanas, garantizadas por la universalidad del sistema de salud brasileño, todavía existen algunas barreras como el idioma y la falta de documentación. Ante la falta de planes de acción y planificación futura de la atención a las mujeres migrantes portadoras del VIH o con sífilis en los municipios, es importante formular políticas públicas con el fin de redu- cir las dificultades enfrentadas por este grupo de la población.

Localized cardiac metabolic trajectories and post-infectious metabolic sequelae in experimental Chagas disease.

Post-infectious conditions, where clinical symptoms fail to resolve even after pathogen clearance, present major health burdens. However, the mechanisms involved remain poorly understood. In Chagas disease (CD), caused by the parasite Trypanosoma cruzi, antiparasitic agents can clear T. cruzi but late-stage treatment does not improve clinical cardiac outcomes. In this study, we revealed differential metabolic trajectories of cardiac regions during T. cruzi infection, matching sites of clinical symptoms. Incomplete, region-specific, cardiac metabolic restoration was observed in animals treated with the antiparasitic benznidazole, even though parasites were successfully cleared. In contrast, superior metabolic restoration was observed for a combination treatment of reduced-dose benznidazole plus an immunotherapy (Tc24-C4 T. cruzi flagellar protein and TLR4 agonist adjuvant), even though parasite burden reduction was lower. Overall, these results provide a mechanism to explain prior clinical treatment failures in CD and to test novel candidate treatment regimens. More broadly, our results demonstrate a link between persistent metabolic perturbation and post-infectious conditions, with broad implications for our understanding of post-infectious disease sequelae.

Enfrentamento de HIV/aids e sífilis em mulheres venezuelanas migrantes na perspectiva de gestores de saúde no Norte do Brasil / Addressing HIV/AIDS and syphilis in Venezuelan migrant women from the perspective of health managers in the North of Brazil / Manejo de la infección por el VIH/sida y la sífilis en mujeres migrantes venezolanas desde la perspectiva de los gestores de salud en el norte de Brasil

RESUMO Objetivo. Identificar a percepção dos gestores de saúde sobre as ações adotadas e os desafios encontrados no enfrentamento de HIV e sífilis em mulheres venezuelanas migrantes no Brasil. Métodos. Este estudo descritivo-exploratório, de abordagem qualitativa, foi realizado de janeiro a março de 2021 nos municípios de Boa Vista (estado de Roraima) e Manaus (estado do Amazonas). As entrevistas em áudio realizadas com os participantes foram transcritas na íntegra. A análise foi pautada na técnica de avaliação de conteúdo temática. Resultados. Foram entrevistados 10 gestores (cinco em Boa Vista e cinco em Manaus). A análise de conteúdo identificou os seguintes eixos e temas: estrutura disponível para diagnóstico e tratamento de aids e sífilis — acesso, vagas para atendimento/fila de espera, formação das equipes de saúde e suporte psicossocial; desafios enfrentados pelas mulheres venezuelanas — idioma, questões de documentação e frequência de alteração de endereço; e estratégias e ações adotadas e expectativas para o enfrentamento de HIV/aids e sífilis no contexto de migração. Conclusões. Apesar das ações de acolhimento das mulheres venezuelanas migrantes — garantido pela universalidade do sistema de saúde brasileiro — aspectos como o idioma e a falta de documentação permanecem como barreiras. Diante da inexistência de planos de ação e planejamento futuro da atenção a mulheres migrantes portadoras de HIV ou sífilis nos municípios, é importante desenvolver políticas públicas com o objetivo de minimizar as dificuldades enfrentadas por essa população.

ABSTRACT Objective. To identify the perception of health managers regarding the actions taken and the challenges encountered in addressing HIV and syphilis in Venezuelan migrant women in Brazil. Method. This descriptive-exploratory study using a qualitative approach was conducted from January to March 2021 in the municipalities of Boa Vista (state of Roraima) and Manaus (state of Amazonas). Audio interviews with the participants were transcribed in full and examined using thematic content analysis. Results. Ten managers were interviewed (five in Boa Vista and five in Manaus). Content analysis identified the following domains and themes: available infrastructure for diagnosis and treatment of AIDS and syphilis — access, availability of medical appointments /waiting list, training of health teams, and psychosocial support; challenges faced by Venezuelan women — language, documentation issues, and frequent address changes; and strategies and actions adopted and expectations for addressing HIV/AIDS and syphilis in the context of migration. Conclusions. Despite the care provided to Venezuelan women in Brazil — guaranteed by the universal nature of the Brazilian health system — language and lack of documentation remain as barriers. Given the absence of action plans and future planning for the care of migrant women with HIV or syphilis in municipalities, it is important to develop public policies aimed at minimizing the difficulties faced by this population.

RESUMEN Objetivo. Determinar la percepción de los gestores de salud sobre las medidas adoptadas y los desafíos encontrados para manejar la infección por el VIH y la sífilis en mujeres migrantes venezolanas en Brasil. Métodos. Este estudio descriptivo y exploratorio, con enfoque cualitativo, se realizó de enero a marzo del 2021 en los municipios de Boa Vista (estado de Roraima) y Manaos (estado de Amazonas). La grabación de las entrevistas de los participantes se transcribió en su totalidad. El análisis se basó en la técnica de evaluación temática del contenido. Resultados. Se hicieron entrevistas a diez gestores (cinco en Boa Vista y cinco en Manaos). En el análisis del contenido se observaron los siguientes ejes y temas: la estructura disponible para el diagnóstico y tratamiento del sida y de la sífilis, con inclusión de acceso, cupos de atención, filas de espera y formación de equipos de salud y apoyo psicosocial; los desafíos enfrentados por las mujeres venezolanas, como idioma, problemas de documentación y frecuencia de cambio de domicilio; las estrategias y medidas adoptadas y las expectativas para enfrentar la infección por el VIH/sida y la sífilis en el marco de la migración. Conclusiones. A pesar de las medidas de acogida a las mujeres migrantes venezolanas, garantizadas por la universalidad del sistema de salud brasileño, todavía existen algunas barreras como el idioma y la falta de documentación. Ante la falta de planes de acción y planificación futura de la atención a las mujeres migrantes portadoras del VIH o con sífilis en los municipios, es importante formular políticas públicas con el fin de reducir las dificultades enfrentadas por este grupo de la población.

Antigenic diversity of MASP gene family of Trypanosoma cruzi.

Trypanosoma cruzi, the etiological agent of Chagas disease (CD), is a heterogeneous species with high genetic and phenotypic diversity. MASP is the second largest multigene family of T. cruzi. The high degree of polymorphism of the family associated with its location at the surface of infective forms of T. cruzi suggests that MASP participates in mechanisms of host-parasite interaction. In this work, MASP members were divided into 7 subgroups based on protein sequence similarity, and one representative member from each subgroup was chosen to be expressed recombinantly. Immunogenicity of recombinant MASP proteins (rMASP) was investigated using different sera panels from T. cruzi infected mice. To mimic a natural condition in which different MASP members are expressed at the same time in the parasite population, a multiplex bead-based flow cytometry assay was also standardized. Results showed that rMASPs are poorly recognized by sera from mice infected with Colombiana strain, whereas sera from mice infected with CL Brener and Y display high reactivity against the majority of rMASPs tested. Flow cytometry showed that MASP recognition profile changes 10 days after infection. Also, multiplex assay suggests that MASP M1 and M2 are more immunogenic than the other MASP members evaluated that may play an immunodominant role during infection.

SARS­CoV-2 RBD219-N1C1: A yeast-expressed SARS-CoV-2 recombinant receptor-binding domain candidate vaccine stimulates virus neutralizing antibodies and T-cell immunity in mice.

There is an urgent need for an accessible and low-cost COVID-19 vaccine suitable for low- and middle-income countries. Here, we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed at high levels in yeast (Pichia pastoris), as a suitable vaccine candidate against COVID-19. After introducing two modifications into the wild-type RBD gene to reduce yeast-derived hyperglycosylation and improve stability during protein expression, we show that the recombinant protein, RBD219-N1C1, is equivalent to the wild-type RBD recombinant protein (RBD219-WT) in an in vitro ACE-2 binding assay. Immunogenicity studies of RBD219-N1C1 and RBD219-WT proteins formulated with Alhydrogel® were conducted in mice, and, after two doses, both the RBD219-WT and RBD219-N1C1 vaccines induced high levels of binding IgG antibodies. Using a SARS-CoV-2 pseudovirus, we further showed that sera obtained after a two-dose immunization schedule of the vaccines were sufficient to elicit strong neutralizing antibody titers in the 1:1,000 to 1:10,000 range, for both antigens tested. The vaccines induced IFN-γ IL-6, and IL-10 secretion, among other cytokines. Overall, these data suggest that the RBD219-N1C1 recombinant protein, produced in yeast, is suitable for further evaluation as a human COVID-19 vaccine, in particular, in an Alhydrogel® containing formulation and possibly in combination with other immunostimulants.

SARS-CoV-2 RBD219-N1C1: A Yeast-Expressed SARS-CoV-2 Recombinant Receptor-Binding Domain Candidate Vaccine Stimulates Virus Neutralizing Antibodies and T-cell Immunity in Mice.

There is an urgent need for an accessible and low-cost COVID-19 vaccine suitable for low- and middle-income countries. Here we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed at high levels in yeast ( Pichia pastoris ), as a suitable vaccine candidate against COVID-19. After introducing two modifications into the wild-type RBD gene to reduce yeast-derived hyperglycosylation and improve stability during protein expression, we show that the recombinant protein, RBD219-N1C1, is equivalent to the wild-type RBD recombinant protein (RBD219-WT) in an in vitro ACE-2 binding assay. Immunogenicity studies of RBD219-N1C1 and RBD219-WT proteins formulated with Alhydrogel ® were conducted in mice, and, after two doses, both the RBD219-WT and RBD219-N1C1 vaccines induced high levels of binding IgG antibodies. Using a SARS-CoV-2 pseudovirus, we further showed that sera obtained after a two-dose immunization schedule of the vaccines were sufficient to elicit strong neutralizing antibody titers in the 1:1,000 to 1:10,000 range, for both antigens tested. The vaccines induced IFN-γ, IL-6, and IL-10 secretion, among other cytokines. Overall, these data suggest that the RBD219-N1C1 recombinant protein, produced in yeast, is suitable for further evaluation as a human COVID-19 vaccine, in particular, in an Alhydrogel ® containing formulation and possibly in combination with other immunostimulants.

Linear B-cell epitope mapping of MAPK3 and MAPK4 from Leishmania braziliensis: implications for the serodiagnosis of human and canine leishmaniasis.

The correct and early identification of humans and dogs infected with Leishmania are key steps in the control of leishmaniasis. Additionally, a method with high sensitivity and specificity at low cost that allows the screening of a large number of samples would be extremely valuable. In this study, we analyzed the potential of mitogen-activated protein kinase 3 (MAPK3) and mitogen-activated protein kinase 4 (MAPK4) proteins from Leishmania braziliensis to serve as antigen candidates for the serodiagnosis of human visceral and tegumentary leishmaniasis, as well as canine visceral disease. Moreover, we mapped linear B-cell epitopes in these proteins and selected those epitopes with sequences that were divergent in the corresponding orthologs in Homo sapiens, in Canis familiaris, and in Trypanosoma cruzi. We compared the performance of these peptides with the recombinant protein using ELISA. Both MAPK3 and MAPK4 recombinant proteins showed better specificity in the immunodiagnosis of human and canine leishmaniasis than soluble parasite antigens and the EIE-leishmaniose-visceral-canina-bio-manguinhos (EIE-LVC) kit. Furthermore, the performance of this serodiagnosis assay was improved using synthetic peptides corresponding to B-cell epitopes derived from both proteins.

Ansiedade pré-competitiva em jovens atletas de nado sincronizado: uma análise à luz dos aspectos emocionais / Pre-competitive anxiety in young athletes of synchronized swimming: an analysis in the light of emotional aspects

A ansiedade dos atletas nos momentos pré-competitivos coloca em cena as emoções, capazes de provocar comportamentos positivos e/ou negativos que influenciarão no desempenho dos mesmos. O estudo objetivou identificar as emoções negativas e positivas em jovens atletas de nado sincronizado e, assim, compreender os sentimentos vivenciados nos momentos que antecedem uma competição. A amostra foi composta por 19 atletas (sexo feminino) de nado sincronizado com idades entre 12 e 19 anos. Os instrumentos foram: Ficha de Identificação Sociodemográfica e Inventário de Ansiedade Traço e Estado (IDATE). Os dados foram analisados por meio do SPSS versão 10.0. Em seguida, os resultados foram expostos de forma descritiva, utilizando a técnica de Análise de Conteúdo. Para construção dos diagramas, foi utilizado o software GoDiagram Express v.2.6.2. Os resultados apontaram que as atletas estão vulneráveis a fatores emocionais positivos (Realização Pessoal, Tranquilidade Ambiental e Equilíbrio Emocional) e/ou negativos (Preocupação, Ansiedade, Obstáculos e Desânimo/Cansaço).

The anxiety of athletes in the pre-competitive stage puts in evidence the emotions and behaviors that can cause positive and/or negative influence on their performance. The study aimed to identify negative and positive emotions in young synchronized swimmers and thus understand the feelings experienced in moments before a competition. The sample consisted of 19 synchronized swimmers aged between 12 and 19 years. The instruments were: Sociodemographic Identification Form and State-Trait Anxiety Inventory (STAI). Data were analyzed using SPSS 10.0. The results were presented in a descriptive way, using the content analysis technique. For constructing the diagrams it was used the software GoDiagram Express 2.6.2. The results showed that athletes are vulnerable to emotional factors whether positive (Personal Achievement, Environmental Tranquility and Emotional Balance) and/or negative (Worry, Anxiety, Obstacles and Discouragement/fatigue).

Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi.

A novel large multigene family was recently identified in the human pathogen Trypanosoma cruzi, causative agent of Chagas disease, and corresponds to approximately 6% of the parasite diploid genome. The predicted gene products, mucin-associated surface proteins (MASPs), are characterized by highly conserved N- and C-terminal domains and a strikingly variable and repetitive central region. We report here an analysis of the genomic organization and expression profile of masp genes. Masps are not randomly distributed throughout the genome but instead are clustered with genes encoding mucin and other surface protein families. Masp transcripts vary in size, are preferentially expressed during the trypomastigote stage and contain highly conserved 5' and 3' untranslated regions. A sequence analysis of a trypomastigote cDNA library reveals the expression of multiple masp variants with a bias towards a particular masp subgroup. Immunofluorescence assays using antibodies generated against a MASP peptide reveals that the expression of particular MASPs at the cell membrane is limited to subsets of the parasite population. Western blots of phosphatidylinositol-specific phospholipase C (PI-PLC)-treated parasites suggest that MASP may be GPI-anchored and shed into the medium culture, thus contributing to the large repertoire of parasite polypeptides that are exposed to the host immune system.

Aspectos psicossociais que interferem no rendimento de modalidades desportivas coletivas / Psychosocial aspects that influence performance in team sports

Esta investigação objetiva discutir os aspectos psicossociais que inibem ou favorecem o desempenho, apresentando sugestões de treinamento com interferências favoráveis à performance; e ainda, discutir o rendimento desportivo sob o prisma qualidade de vida. Participaram do estudo descritivo 103 atletas de rendimento de modalidades coletivas, de cinco instituições da cidade do Recife-Pernambuco. Os questionários foram o WHOQOL, o FISSB e FISS-J. Os resultados encontrados foram: o espírito de equipe é muito importante para vencer (98,0%); satisfação em trabalhar em equipe (95,0%). No tocante às situações inibidorasde desempenho, os índices mais representativos foram: arbitragem prejudicial (81,4%); perder jogo praticamente ganho (75,7%). No âmbito da qualidade de vida, os indicadores relevantes foram: minha vida tem sentido (92,2%); avaliação de uma boa qualidade de vida (89,2%). Essas categorias apontaram a necessidade do treinamento desportivo sob a ótica humanista, interagindo a tecnologia do treinamento e as necessidades sociopsicológicas, potencializando as qualidades físicas, técnicas e táticas dos atletas.

The objective of the present investigation was to discuss the psychosocial factors that inhibit or stimulate performance, presenting training suggestions that include interventions to enhance performance. In addition, sports performance was discussed from the perspective of quality of life. A descriptive quantitative-cum-qualitative field method was employed. A total of 103 athletes engaged in team sports from five institutions in the city of Recife, Pernambuco, participated in the study. The WHOQOL, FISSB and FISS-J questionnaires were used. The following results were obtained: “team spirit is extremely important for winning” (98.0%) and “satisfaction in working as a team” (95.0%). With respect to situations that inhibit performance, the most representative findings were “poor refereeing” (81.4%) and “losing a game practically already won” (75.7%). From the quality of life perspective, the main indicators were “my life is meaningful” (92.2%) and “a good quality of life rating” (89.2%). These analytical categories indicate the need for sports training to be carried out from a humanistic standpoint in which the training technology interacts with sociopsychological needs, thus potentiating the physical, technical and tactical qualities of the athletes.

Aspectos motivacionais que influenciam a adesão e manutenção de idosos a programas de exercícios físicos / Motivacional aspects that influence the elderly to enroll on and continue participating in physical exercise prorams

O objetivo desse estudo foi investigar as relações do exercício físico com o dano muscular e dor muscular de iníciotardio (DMIT). Para tanto, foi realizada uma revisão de literatura de periódicos nacionais e internacionais. O dano muscular pode ocorrer em estruturas musculares (membranas, linha Z, sarcolema, túbulos T e miofi brilas) em função da sobrecarga mecânicaimposta, destacam-se os exercícios de força, principalmente com ação muscular excêntrica. Danos a musculatura esqueléticapodem ser analisados através de métodos diretos (amostras do músculo ou por ressonância magnética) ou por métodos indiretos (ação voluntária máxima, escalas subjetivas da percepção de dor, análise das concentrações de enzimas e proteínas no sangue). A creatina quinase (CK), lactato desidrogenase (LDH), fragmentos da cadeia pesada de miosina, troponina-I e mioglobina podemser utilizadas como marcadores indiretos de dano muscular. A DMIT e o dano muscular podem ser infl uenciados pelo tipo de ação, com ênfase nas ações musculares excêntricas, tipo de exercício, velocidade de movimento, tempo de intervalo entre as séries,nível de treinamento individual, acometendo principalmente iniciantes. Frente a uma microlesão, os leucócitos migram para o local iniciando a reparação do dano muscular, ao passo que, histaminas, prostaglandinas, cininas e K+ produzidos por neutrófi lose macrófagos estimulam as terminações nervosas livres do músculo, instalando a DMIT. Apesar da aparente relação entre dano muscular e DMIT, não é possível estabelecer uma relação linear entre essas duas variáveis, uma vez que, existe divergência entre os estudos publicados.

The objective of the present study was to investigate the relationship between physical exercise involving muscledamage and delayed-onset muscle soreness (DOMS). A literature review of national and international periodicals was carried out. Muscle structures (membranes, Z-line, sarcomeres, T tubules and myofi brils) can become damaged as a result of an imposedmechanical overload. Of greatest note are exercises requiring strength, particularly when muscular action is eccentric. Damage to skeletal musculature can be analyzed by direct methods (muscle biopsy or magnetic resonance) or by indirect methods (maximum voluntary movement, subjective pain perception scales, analysis of enzyme and protein concentrations in blood). Creatine kinase(CK), lactate dehydrogenase (LDH), myosin heavy chain fragments, troponin-I and myoglobin can be used as indirect markers of muscle damage. Both DOMS and muscle damage can be infl uenced by the type of activity, with emphasis on eccentric muscle movements, type of exercise, velocity of the movement, interval period between series, the level of individual fi tness, this lastprimarily affecting beginners. When myotrauma occurs, muscle damage repair is initiated by leukocytes migrating to the injured area,although, the histamines, prostaglandins, kinins and K+ produced by neutrophils and macrophages stimulate free nerve endingsin the muscle, causing the DOMS. Despite this apparent relationship between muscle damage and DOMS, it is not possible to establish a linear relationship between these two variables, since published data are divergent

Tempo livre e lazer na juventude noronhense: influência na qualidade de vida e implicações sociais / Free time and leisure in youth noronhense: social influences in the quality of life and implications

Essa investigação surgiu do propósito de elucidar questões sobre o tempo livre e lazer que fazem parte do cotidiano de jovens do Distrito Estadual de Fernando de Noronha em Pernambuco. A metodologia adotada foi a descritiva quanti/qualitativa de campo, com aplicação de dois instrumentos um questionário da OMS-WHOQOL, para avaliar a percepção de qualidade de vida dos indivíduos; e uma ficha observacional, para descrição de atividadescoletivas e individuais de lazer. Os sujeitos foram jovens, entre 15 e 24 anos, de ambos os sexos. O universo compreendeu 403 sujeitos, e a amostra aleatória não probabilística acidentalde no mínimo 97 sujeitos, garantiu os princípios para validação e fidedignidade. Os resultados foram interpretados à luz da Análise de Conteúdo e apresentados estatisticamente através doPrograma SPSS for Windows, 11.0. Nesse cenário e tendo em vista a baixa densidade demográfica, foi constatada que a rotina faz-se presente mais do que em outro espaço que disponha detanta beleza natural e especulação turística, caracterizando o arquipélago como opção de lazer de uma minoria que pode ter acesso, devido ao alto custo e controle pelas autoridades. Assim, considerando o lazer como direito social, diretamente associado à qualidade de vida, e de acentuada importância na formação e realização do ser humano, foi prioritário esse estudo que evidenciou sinais de carência na qualidade e possibilidade de crescimento que essa esfera doconvívio social pode oferecer, uma vez que são praticamente inexistentes as políticas públicas de esporte e lazer voltadas para este público.

This inquiry appeared of the intention to elucidate questions on the free time and leisure that are part of the daily one of young of the State District of Fernando de Noronha in Pernambuco. The adopted methodology quanti/qualitative descriptive, with application of two instruments a questionnaire of the OMS-WHO QOL, to evaluate the perception of quality of life of the individuals; the comment fiche, for description of collective and individual activities of leisure. The citizens had been young, between 15 and 24 years, of both the sorts. The universe understood 403 citizens, and accidental not probabilistic the random sample of at least 97 citizens, guaranteed the principles for validation and trustworthy. The results had been interpreted to the light of the Analysis of Content and presented statistical through Program SPSS it will be Windows, 11.0. In this scene and in view of low the demographic density, it was evidenced that the routine becomes more than present what in another space that makes use of as much natural beauty and tourist speculation, characterizing the archipelago as option of leisure of a minority that can have access, due to the high cost and control for the authorities. Thus, considering the social leisure as right, directly associate to the quality of life, and of accented importance in the formation and accomplishment of the human being, was with priority this study that evidenced signals of lack in the quality and possibility of growth that this sphere of the social conviviality can offer, a time that is practically inexistent the public politics of sport and leisure directed toward this public.