Frankincense (Boswellia serrata) Extract Effects on Growth and Biofilm Formation of Porphyromonas gingivalis, and Its Intracellular Infection in Human Gingival Epithelial Cells.

Frankincense is produced by Boswellia trees, which can be found throughout the Middle East and parts of Africa and Asia. Boswellia serrata extract has been shown to have anti-cancer, anti-inflammatory, and antimicrobial effects. Periodontitis is an oral chronic inflammatory disease that affects nearly half of the US population. We investigated the antimicrobial effects of B. serrata extract on two oral pathogens associated with periodontitis. Using the minimum inhibitory concentration and crystal violet staining methods, we demonstrated that Porphyromonas gingivalis growth and biofilm formation were impaired by treatment with B. serrata extracts. However, the effects on Fusobacterium nucleatum growth and biofilm formation were not significant. Using quantification of colony-forming units and microscopy techniques, we also showed that concentrations of B. serrata that were not toxic for host cells decreased intracellular P. gingivalis infection in human gingival epithelial cells. Our results show antimicrobial activity of a natural product extracted from Boswellia trees (B. serrata) against periodontopathogens. Thus, B. serrata has the potential for preventing and/or treating periodontal diseases. Future studies will identify the molecular components of B. serrata extracts responsible for the beneficial effects.

P2X7 Receptor Modulation of the Gut Microbiota and the Inflammasome Determines the Severity of Toxoplasma gondii-Induced Ileitis.

In mice, oral Toxoplasma gondii infection induces severe ileitis. The aim of the present study was to investigate the impact of the P2X7 receptor (P2X7) on the inflammatory response to T. gondii-induced ileitis. Cysts of the ME49 strain of T. gondii were used to induce ileitis. The infected mice were euthanized on day 8 and ileal tissue and peripheral blood were collected for histopathological and immunohistochemical analyses. Ileal contractility, inflammatory mediators, inflammasome activation, quantitative PCR analysis of gene expression, and fecal microbiota were assessed using appropriate techniques, respectively. The infected P2X7-/- mice had greater disease severity, parasitic burden, liver damage, and intestinal contractility than the infected wild-type (WT) mice. Infection increased serum IL-6 and IFN-γ and tissue caspase-1 but not NLRP3 in P2X7-/- mice compared to WT mice. Bacteroidaceae, Rikenellaceae, and Rhodospirillales increased while Muribaculaceae and Lactobacillaceae decreased in the infected WT and P2X7-/- mice. Bacteroidia and Tannerellaceae increased in the P2X7-/- mice with ileitis. By contrast, Clostridiales and Mollicutes were absent in the P2X7-/- mice but increased in the WT mice. P2X7 protects mice against T. gondii infection by activating the inflammasome and regulating the local and systemic immune responses. Specific gut bacterial populations modulated by P2X7 determine disease severity.

Toxoplasma gondii virulence factor ROP1 reduces parasite susceptibility to murine and human innate immune restriction.

Toxoplasma gondii is an intracellular parasite that can infect many host species and is a cause of significant human morbidity worldwide. T. gondii secretes a diverse array of effector proteins into the host cell which are critical for infection. The vast majority of these secreted proteins have no predicted functional domains and remain uncharacterised. Here, we carried out a pooled CRISPR knockout screen in the T. gondii Prugniaud strain in vivo to identify secreted proteins that contribute to parasite immune evasion in the host. We demonstrate that ROP1, the first-identified rhoptry protein of T. gondii, is essential for virulence and has a previously unrecognised role in parasite resistance to interferon gamma-mediated innate immune restriction. This function is conserved in the highly virulent RH strain of T. gondii and contributes to parasite growth in both murine and human macrophages. While ROP1 affects the morphology of rhoptries, from where the protein is secreted, it does not affect rhoptry secretion. Finally, we show that ROP1 co-immunoprecipitates with the host cell protein C1QBP, an emerging regulator of innate immune signaling. In summary, we identify putative in vivo virulence factors in the T. gondii Prugniaud strain and show that ROP1 is an important and previously overlooked effector protein that counteracts both murine and human innate immunity.

Posicionamento cirúrgico: uma atualização das evidências científicas para intervenções de enfermagem / Surgical positioning: an update scientific evidence for interventions of nurs / Posicionamiento quirúrgico: una actualización de la evidencia científica para intervenciones de enfermería

Objetivo: Realizar uma revisão integrativa sobre as evidências relacionadas às intervenções de Enfermagem durante o posicionamento cirúrgico do paciente. Método: Revisão integrativa da literatura realizada em fevereiro de 2021 por meio de consulta às bases de dados MEDLINE, PubMed, Web of Science, BDEnf e LILACS para responder ao questionamento: "Quais as evidências disponíveis sobre as intervenções de enfermagem durante o posicionamento cirúrgico do paciente adulto?" Resultados: Após busca e análise, nove artigos contemplaram o objetivo da pesquisa e compuseram a amostra final. Foi possível constatar uma variedade de intervenções, com predomínio de avaliação de fatores preexistentes e externos, uso de escalas de avaliação de risco, superfícies de suporte e uso de curativos profiláticos. Conclusão: Foi possível atualizar as evidências científicas quanto à aplicação das intervenções direcionadas ao posicionamento cirúrgico. O uso de ELPO, SAEP e Scott-Triggers é o mais eficaz, bem como a avaliação do paciente previamente associada à utilização de escalas/instrumentos, permitindo resultados positivos e diminuição das complicações associadas à posição cirúrgica. Faz-se necessário realizar novas pesquisas com maiores níveis de evidência científica, visando qualificar a assistência de Enfermagem.

Objective: To carry out an integrative review on the evidence related to Nursing interventions during the surgical positioning of the patient. Method: Integrative literature review carried out in February 2021 by consulting the MEDLINE, PubMed, Web of Science, BDEnf, and LILACS databases to answer the question: "What evidence is available on nursing interventions during surgical positioning of the adult patient?" Results: After search and analysis, nine articles contemplated the research objective and composed the final sample. It was possible to verify a variety of interventions, with a predominance of evaluation of preexisting and external factors, use of risk assessment scales, support surfaces, and use of prophylactic dressings. Conclusions: It was possible to update the scientific evidence regarding the application of interventions aimed at surgical positioning. The use of ELPO, SAEP, and Scott-Triggers is the most effective, as the patient's assessment previously associated with the use of scales/instruments, allowing positive results and reduction of complications associated with the surgical position. It is necessary to carry out new research with higher levels of scientific evidence, aiming to qualify nursing care.

Objetivo: Realizar una revisión integradora sobre la evidencia relacionada con las intervenciones de enfermería durante el posicionamiento quirúrgico del paciente. Método: Revisión integrativa de la literatura realizada en febrero de 2021 en las bases de datos MEDLINE, PubMed, Web of Science, BDEnf y LILACS para responder a la pregunta: "¿Qué evidencia está disponible sobre las intervenciones de enfermería durante el posicionamiento quirúrgico de pacientes adultos?" Resultados: Luego de la búsqueda y análisis, 9 artículos cubrieron el objetivo de la investigación y conformaron la muestra final. Fue posible verificar una variedad de intervenciones con predominio de la evaluación de factores preexistentes y externos, uso de escalas de evaluación de riesgo, superficies de apoyo y el uso de apósitos profilácticos. Conclusión: Fue posible actualizar la evidencia científica en cuanto a la aplicación de intervenciones dirigidas al posicionamiento quirúrgico. El uso de ELPO, SAEP y Scott-Triggers son los más efectivos, así como la evaluación del paciente previamente asociado al uso de escalas/instrumentos, permitiendo resultados positivos y reducción de complicaciones asociadas a la posición quirúrgica. Es necesario realizar nuevas investigaciones con mayores niveles de evidencia científica, con el objetivo de calificar el cuidado de enfermería.

The Complexity of Purinergic Signaling During Toxoplasma Infection.

Toxoplasmosis is a neglected disease caused by infection by the protozoan Toxoplasma gondii. One-third of the global population is expected to be by infected T. gondii. In Europe and North America, most infections do not induce disease, except in the context of immunosuppression. However, in endemic regions such Central and South America, infections induce severe ocular and potentially lethal disease, even in immunocompetent individuals. The immune response against T. gondii infection involves components of innate immunity even in the chronic phase of the disease, including dangerous signal molecules such as extracellular nucleotides. Purinergic signaling pathways include ionotropic and metabotropic receptors activated by extracellular nucleotides that are divided into P2X, P2Y, and A1 receptor families. The activation of purinergic signaling impacts biological systems by modulating immune responses to intracellular pathogens such as T. gondii. Ten years ago, purinergic signaling in the T. gondii infection was reported for the first time. In this review, we update and summarize the main findings regarding the role of purinergic signaling in T. gondii infection; these include in vitro findings: the microbicidal effect of P2Y and P2X7 activation phagocytic cells and parasite control by P2X7 activation in non-phagocytic cells; and in vivo findings: the promotion of early pro-inflammatory events that protect the host in acute and chronic models.

Non-canonical NLRP3 inflammasome activation and IL-1ß signaling are necessary to L. amazonensis control mediated by P2X7 receptor and leukotriene B4.

Leishmaniasis is a neglected tropical disease affecting millions of individuals worldwide. P2X7 receptor has been linked to the elimination of Leishmania amazonensis. Biological responses evoked by P2X7 receptor activation have been well-documented, including apoptosis, phagocytosis, cytokine release, such as IL-1ß. It was demonstrated that NLRP3 inflammasome activation and IL-1ß signaling participated in resistance against L. amazonensis. Furthermore, our group has shown that L. amazonensis elimination through P2X7 receptor activation depended on leukotriene B4 (LTB4) production and release. Therefore, we investigated whether L. amazonensis elimination by P2X7 receptor and LTB4 involved NLRP3 inflammasome activation and IL-1ß signaling. We showed that macrophages from NLRP3-/-, ASC-/-, Casp-1/11-/-, gp91phox-/- , and IL-1R-/- mice treated with ATP or LTB4 did not decrease parasitic load as was observed in WT mice. When ASC-/- macrophages were treated with exogenous IL-1ß, parasite killing was noted, however, we did not see parasitic load reduction in IL-1R-/- macrophages. Similarly, macrophages from P2X7 receptor-deficient mice treated with IL-1ß also showed decreased parasitic load. In addition, when we infected Casp-11-/- macrophages, neither ATP nor LTB4 were able to reduce parasitic load, and Casp-11-/- mice were more susceptible to L. amazonensis infection than were WT mice. Furthermore, P2X7-/- L. amazonensis-infected mice locally treated with exogenous LTB4 showed resistance to infection, characterized by lower parasite load and smaller lesions compared to untreated P2X7-/- mice. A similar observation was noted when infected P2X7-/- mice were treated with IL-1ß, i.e., lower parasite load and smaller lesions compared to P2X7-/- mice. These data suggested that L. amazonensis elimination mediated by P2X7 receptor and LTB4 was dependent on non-canonical NLRP3 inflammasome activation, ROS production, and IL-1ß signaling.

Disruption of Purinergic Receptor P2X7 Signaling Increases Susceptibility to Cerebral Toxoplasmosis.

Toxoplasmosis is a neglected disease that affects millions of individuals worldwide. Toxoplasma gondii infection is an asymptomatic disease, with lethal cases occurring mostly in HIV patients and organ transplant recipients. Nevertheless, atypical strains of T. gondii in endemic locations cause severe pathology in healthy individuals. Toxoplasmosis has no cure but it can be controlled by the proinflammatory immune response. The purinergic receptor P2X7 (P2X7) is involved in many inflammatory events and has been associated with genes that confer resistance against toxoplasmosis in humans. In vitro studies have reported parasite death after P2X7-receptor activation in various cell types. To understand the contribution of P2X7 during cerebral toxoplasmosis, wild-type and P2rx7 knockout mice were infected orally with T. gondii and their pathologic profiles were analyzed. We found that all P2rx7-/- mice died 8 weeks after infection with an increased number of cysts and fewer inflammatory infiltrates in their brains. The cytokines interleukin-1ß, interleukin-12, tumor necrosis factor-α, and reactive oxygen species were absent or reduced in P2rx7-/- mice. Taken together, these data suggest that the P2X7 receptor promotes inflammatory infiltrates, proinflammatory cytokines, and reactive oxygen species production in the brain, and that P2X7 signaling mediates major events that confer resistance to cerebral toxoplasmosis.

The P2X7 Receptor Mediates Toxoplasma gondii Control in Macrophages through Canonical NLRP3 Inflammasome Activation and Reactive Oxygen Species Production.

Toxoplasma gondii (T. gondii) is the protozoan parasite that causes toxoplasmosis, a potentially fatal disease to immunocompromised patients, and which affects approximately 30% of the world's population. Previously, we showed that purinergic signaling via the P2X7 receptor contributes to T. gondii elimination in macrophages, through reactive oxygen species (ROS) production and lysosome fusion with the parasitophorous vacuole. Moreover, we demonstrated that P2X7 receptor activation promotes the production of anti-parasitic pro-inflammatory cytokines during early T. gondii infection in vivo. However, the cascade of signaling events that leads to parasite elimination via P2X7 receptor activation remained to be elucidated. Here, we investigated the cellular pathways involved in T. gondii elimination triggered by P2X7 receptor signaling, during early infection in macrophages. We focused on the potential role of the inflammasome, a protein complex that can be co-activated by the P2X7 receptor, and which is involved in the host immune defense against T. gondii infection. Using peritoneal and bone marrow-derived macrophages from knockout mice deficient for inflammasome components (NLRP3-/-, Caspase-1/11-/-, Caspase-11-/-), we show that the control of T. gondii infection via P2X7 receptor activation by extracellular ATP (eATP) depends on the canonical inflammasome effector caspase-1, but not on caspase-11 (a non-canonical inflammasome effector). Parasite elimination via P2X7 receptor and inflammasome activation was also dependent on ROS generation and pannexin-1 channel. Treatment with eATP increased IL-1ß secretion from infected macrophages, and this effect was dependent on the canonical NLRP3 inflammasome. Finally, treatment with recombinant IL-1ß promoted parasite elimination via mitochondrial ROS generation (as assessed using Mito-TEMPO). Together, our results support a model where P2X7 receptor activation by eATP inhibits T. gondii growth in macrophages by triggering NADPH-oxidase-dependent ROS production, and also by activating a canonical NLRP3 inflammasome, which increases IL-1ß production (via caspase-1 activity), leading to mitochondrial ROS generation.

Atuação do fisioterapeuta nos Centros de Referência em Saúde do Trabalhador: indicadores das notificações dos Dort / Actuación del fisioterapeuta en Centros de Referência em Saúde do Trabalho do Brasil: indicadores de las notificaciones de Dort / Physical therapist's performance in Cerests: indicators of notification of work-related musculoskeletal disorders

RESUMO Neste trabalho, descreveu-se a atuação de fisioterapeutas nos Centros de Referência em Saúde do Trabalhador (Cerest) do Brasil e foi estimado o volume de notificações de distúrbios osteomusculares relacionados ao trabalho (Dort) no país. Este estudo foi conduzido com dados primários obtidos por questionário eletrônico para levantamento de inserção e de ações realizadas por fisioterapeutas nos Cerest do país e dados secundários relativos à casuística das notificações de Dort no Sistema de Informação de Agravos de Notificação (Sinan), entre 2009 a 2013. Foi constatado que 71,1% dos Cerest tinham pelo menos um fisioterapeuta na equipe em 2015. A maior parte desses profissionais estava alocada nas regiões Sudeste (37,6%) e Nordeste (31,6%), que também caracterizam-se como a origem geográfica da maioria das notificações de Dort (62,3% e 26,7 %, respectivamente). A média nacional de inserção de profissionais nos Cerest foi de 1,02 fisioterapeutas por unidade. Os profissionais de fisioterapia estão presentes na maioria dos Cerest, e sua concentração geográfica corresponde às regiões com maior proporção de casos de Dort. Apesar da preponderância das ações de vigilância em saúde do trabalhador, ainda coexistem ações reabilitadoras exercidas por fisioterapeutas.

RESUMEN En este trabajo, se describió la actuación de fisioterapeutas en Centros de Referência em Saúde do Trabalhador (Cerest) de Brasil y fue estimado el volumen de notificaciones de disturbios osteomusculares relacionados al trabajo (Dort) en el país. Este estudio fue conducido con datos primarios obtenidos por cuestionario electrónico para levantamiento de inserción y de acciones realizadas por fisioterapeutas en Cerest del país y datos secundarios relativos a la casuística de las notificaciones de Dort en Sistema de Informação de Agravos de Notificação (Sinan) entre 2009 a 2013. Fue constatado que 71,1% de los Cerest tenían por lo menos un fisioterapeuta en el equipo en 2015. La mayor parte de eses profisionales estuvo alocada en las regiones Sudeste (37,6%) y Nordeste (31,6%), que también se caracterizan como el orígen geográfico de la mayoria de las notificaciones de Dort (62,3% e 26,7 %, respectivamente). La media nacional de inserción de profisionales en Cerest fue de 1,02 fisioterapeutas por unidad. Los profisionales de fisioterapia están presentes en la mayoría de los Cerest y su concentración geográfica corresponde a las regiones con mayor proporción de casos de Dort. Además la preponderancia de las acciones de vigilancia en salud del trabajador, aun coexisten acciones rehabilitadoras ejercidas por fisioterapeutas.

ABSTRACT This study described the role of physical therapists in Cerests (Occupational Health Reference Centers in Brazil) and estimated the number of notifications of work-related musculoskeletal disorders in the country. This study was conducted with primary dada obtained from an electronic questionnaire to verify the insertion and actions performed by physical therapists in Cerests in Brazil, and with secondary data related to the notifications to SINAN between 2009 and 2013. Results: in Cerests, 71.1% had at least one physical therapist in the health team in 2015. Most physical therapists were allocated in the Southeast (37.6%) and Northeast (31.6%) regions, which were also the geographical origins of most notifications (62.3% and 26.7%, respectively). The national average insertion of these professionals in Cerests was 1.02 physical therapists per health unit. Physical therapists are present in most Cerests, and their geographical concentration corresponds to the regions with the highest proportion of cases of work-related musculoskeletal disorders. Despite the preponderance of surveillance actions in occupational health, rehabilitative actions conducted by physical therapists still coexist.

Potential role of P2X7R in esophageal squamous cell carcinoma proliferation.

Esophageal cancer is an aggressive tumor and is the sixth leading cause of cancer death worldwide. ATP is well known to regulate cancer progression in a variety of models by different mechanisms, including P2X7R activation. This study aimed to evaluate the role of P2X7R in esophageal squamous cell carcinoma (ESCC) proliferation. Our results show that treatment with high ATP concentrations induced a decrease in cell number, cell viability, number of polyclonal colonies, and reduced migration of ESCC. The treatment with the selective P2X7R antagonist A740003 or siRNA for P2X7 reverted this effect in the KYSE450 cell line. In addition, results showed that P2X7R is highly expressed, at mRNA and protein levels, in KYSE450 lineage. Additionally, KYSE450, KYSE30, and OE21 cells express P2X3R, P2X4R, P2X5R, P2X6R, and P2X7R genes. P2X1R is expressed by KYSE30 and KYSE450, and only KYSE450 expresses the P2X2R gene. Furthermore, esophageal cancer cell line KYSE450 presented higher expression of E-NTPDases 1 and 2 and of Ecto-5'-NT/CD73 when compared to normal cells. This cell line also exhibits ATPase, ADPase, and AMPase activity, although in different levels, and the co-treatment of apyrase was able to revert the antiproliferative effects of ATP. Moreover, results showed high immunostaining for P2X7R in biopsies of patients with esophageal carcinoma, indicating the involvement of this receptor in the growth of this type of cancer. The results suggest that P2X7R may be a potential pharmacological target to treat ESCC and can lead us to further investigate the effect of this receptor in cancer cell progression.

Inflammatory early events associated to the role of P2X7 receptor in acute murine toxoplasmosis.

Activation of the purinergic P2X7 receptor by extracellular ATP (eATP) potentiates proinflammatory responses during infections by intracellular pathogens. Extracellular ATP triggers an antimicrobial response in macrophages infected with Toxoplasma gondii in vitro, suggesting that purinergic signaling may stimulate host defense mechanisms against toxoplasmosis. Here, we provide in vivo evidence in support of this hypothesis, by showing that P2X7-/- mice are more susceptible than P2X7+/+ mice to acute infection by the RH strain of T. gondii, and that this phenomenon is associated with a deficient proinflammatory response. Four days post-infection, peritoneal washes from infected P2X7-/- mice had no or little increase in the levels of the proinflammatory cytokines IL-12, IL-1ß, IFN-γ, and TNF-α, whose levels increased markedly in samples from infected P2X7+/+ mice. Infected P2X7-/- mice displayed an increase in organ weight and histological alterations in some of the 'shock organs' in toxoplasmosis - the liver, spleen and mesenteric lymph nodes. The liver of infected P2X7-/- mice had smaller granulomas, but increased parasite load/granuloma. Our results confirm that the P2X7 receptor is involved in containing T. gondii spread in vivo, by stimulating inflammation.

P2X7 Receptor Signaling Contributes to Sepsis-Associated Brain Dysfunction.

Sepsis results in unfettered inflammation, tissue damage, and multiple organ failure. Diffuse brain dysfunction and neurological manifestations secondary to sepsis are termed sepsis-associated encephalopathy (SAE). Extracellular nucleotides, proinflammatory cytokines, and oxidative stress reactions are associated with delirium and brain injury, and might be linked to the pathophysiology of SAE. P2X7 receptor activation by extracellular ATP leads to maturation and release of IL-1ß by immune cells, which stimulates the production of oxygen reactive species. Hence, we sought to investigate the role of purinergic signaling by P2X7 in a model of sepsis. We also determined how this process is regulated by the ectonucleotidase CD39, a scavenger of extracellular nucleotides. Wild type (WT), P2X7 receptor (P2X7-/-), or CD39 (CD39-/-) deficient mice underwent sham laparotomy or CLP induced by ligation and puncture of the cecum. We noted that genetic deletion of P2X7 receptor decreased markers of oxidative stress in murine brains 24 h after sepsis induction. The pharmacological inhibition or genetic ablation of the P2X7 receptor attenuated the IL-1ß and IL-6 production in the brain from septic mice. Furthermore, our results suggest a crucial role for the enzyme CD39 in limiting P2X7 receptor proinflammatory responses since CD39-/- septic mice exhibited higher levels of IL-1ß in the brain. We have also demonstrated that P2X7 receptor blockade diminished STAT3 activation in cerebral cortex and hippocampus from septic mice, indicating association of ATP-P2X7-STAT3 signaling axis in SAE during sepsis. Our findings suggest that P2X7 receptor might serve as a suitable therapeutic target to ameliorate brain damage in sepsis.

Prevalence and risk factors of embolic cerebrovascular events associated with Chagas heart disease.

BACKGROUND: Patients with Chagas disease are at increased risk for stroke that may result in major clinical disability and death. Identification of risk factors involved in the genesis of thromboembolic events related to this disease may lead to improved therapeutic decision making and outcomes. OBJECTIVES: This study sought to assess the prevalence of ischemic cerebrovascular events (ICE) among patients with Chagas heart disease and to identify the risk factors associated with cardioembolism in this population. METHODS: This study involved 330 patients, 193 were men (58%), with a mean age of 49 ± 12 years with Chagas disease classified in the chronic cardiac form of the disease. Comprehensive echocardiography was performed to search a substrate for cardioembolic events, especially apical aneurysm and intracavitary thrombus. RESULTS: Most of the patients were classified as New York Heart Association classes I or II (75%) with mean left ventricular (LV) ejection fraction of 39 ± 14%. Sixty-seven patients had a previous ICE with the overall prevalence of 20%. Apical aneurysms were detected in 128 patients (39%), whereas LV mural thrombi were found in 48 patients (15%). In multivariate analysis including the potential predictors of ICE, apical aneurysm (adjusted odds ratio [OR]: 2.19, 95% confidence interval [CI]: 1.11 to 4.34; p = 0.024) and LV thrombus (adjusted OR: 2.43, 95% CI: 1.09 to 5.42; p = 0.030) emerged as important determinants of ICE, after adjusting for anticoagulation therapy. CONCLUSIONS: In a selected population referred to a tertiary center for Chagas disease that included patients with different severities of cardiac involvement, the prevalence of ICE was 20%. The presence of apical aneurysm and intracavitary thrombus were independently associated with ICE, after adjustment for other risk factors for stroke.

Pyrimidinergic Receptor Activation Controls Toxoplasma gondii Infection in Macrophages.

Infection by the protozoan parasite Toxoplasma gondii is highly prevalent worldwide and may have serious clinical manifestations in immunocompromised patients. T. gondii is an obligate intracellular parasite that infects almost any cell type in mammalian hosts, including immune cells. The immune cells express purinergic P2 receptors in their membrane--subdivided into P2Y and P2X subfamilies--whose activation is important for infection control. Here, we examined the effect of treatment with UTP and UDP in mouse peritoneal macrophages infected with T. gondii tachyzoites. Treatment with these nucleotides reduced parasitic load by 90%, but did not increase the levels of the inflammatory mediators NO and ROS, nor did it modulate host cell death by apoptosis or necrosis. On the other hand, UTP and UDP treatments induced early egress of tachyzoites from infected macrophages, in a Ca2+-dependent manner, as shown by scanning electron microscopy analysis, and videomicroscopy. In subsequent infections, prematurely egressed parasites had reduced infectivity, and could neither replicate nor inhibit the fusion of lysosomes to the parasitophorous vacuole. The use of selective agonists and antagonists of the receptor subtypes P2Y2 and P2Y4 and P2Y6 showed that premature parasite egress may be mediated by the activation of these receptor subtypes. Our results suggest that the activity of P2Y host cell receptors controls T. gondii infection in macrophages, highlighting the importance of pyrimidinergic signaling for innate immune system response against infection. Finally the P2Y receptors should be considered as new target for the development of drugs against T. gondii infection.

Comparative study of the imitation ability in Specific Language Impairment and Autism Spectrum Impairment.

PURPOSE: To compare abilities of imitating generic and sequential motion gesture schemes in family routines among children with Autism Spectrum Disorder (ASD) and Specific Language Impairment (SLI) and to analyze the relation between imitation index and verbal production in the ASD group. METHODS: The sample was constituted by 2:1 pairing of 36 children, according to gender and age. All of them were diagnosed by a multidisciplinary team as belonging to the ASD group (n=24) or SLI group (n=12) and were under direct and indirect intervention in a school clinic. We have used the stage of imitation of the Assessment of Symbolic Maturity, which entails the imitation of nine generic and three sequential motion gesture schemes. RESULTS: There was a tendency to a better performance of the SLI group at imitating both generic and sequential gesture schemes. As we have related the ability of imitation to the verbal production in the ASD group, a direct relation between the production of phrases and the imitation of sequential schemes was detected. CONCLUSION: The ability to imitate gesture and sequential schemes could be compared, and a more prominent impairment was identified in children with autism. Among them, a direct significant relationship between the ability of imitating sequential gesture schemes in family routine and verbal production of words and sentences was verified.

Relação entre vocabulário receptivo e expressivo em crianças com transtorno específico do desenvolvimento da fala e da linguagem / Relationship between receptive and expressive vocabulary in chidren with specific language impairment

OBJETIVO: comparar os índices de vocabulário receptivo e expressivo de crianças com Transtorno Específico do Desenvolvimento da Fala e da Linguagem. MÉTODOS: trata-se de estudo transversal, com amostra constituída por 21 crianças com Transtorno Específico do Desenvolvimento da Fala e da Linguagem, avaliadas em clínica-escola de Fonoaudiologia, sendo 9 crianças do gênero feminino e 12 crianças do gênero masculino, com idades entre 3 e 11 anos. Para este estudo foi utilizada a Prova de Vocabulário do Teste ABFW e o Teste de Vocabulário por Imagem Peabody - TVIP. RESULTADOS: 80,95% das crianças apresentaram desempenho adequado na avaliação do vocabulário expressivo, enquanto 52,4% apresentaram desempenho compatível com a faixa etária na avaliação do vocabulário receptivo. Não houve significância estatística. CONCLUSÃO: as crianças apresentaram melhor desempenho em avaliação do vocabulário expressivo em relação ao vocabulário receptivo. Esses dados comprovam a necessidade de um olhar atento e investigativo do fonoaudiólogo para os aspectos tanto de produção quanto de compreensão da linguagem. .

PURPOSE: to compare receptive and expressive vocabulary indexes in children with Specific Language Impairment. METHODS: cross-sectional study, with sample constituted of 21 children with Specific Developmental Disorder of Speech and Language, assessed in a Speech Therapy school clinic, being 09 girls and 12 boys, with an age range between 3 and 11 years old. For this study,Proof of Vocabulary of Teste ABFW and the Teste of Vocabulary Picture Peabody-TVIP was used. RESULTS: 80,95% of the children presented adequate development compatible with the evaluation of expressive vocabulary, while 52,4% presented development compatible with the age range in evaluation of receptive vocabulary. There was no statistical significance. CONCLUSION: children in the present study presented better performance in the evaluation of expressive vocabulary in relation to receptive vocabulary. This data prove the need of a careful and investigative view by the speech therapist for both the aspects of production and understanding of language. .

Health-related quality of life in patients with Chagas disease: a review of the evidence.

Chagas disease (ChD), a neglected tropical disease caused by infection with the parasite Trypanosoma cruzi (T. cruzi), remains a serious public health issue in Latin America and is an emerging disease in several non-endemic countries, where knowledge of the condition and experience with its clinical management are limited. Regionally, the disease is the major cause of disability secondary to tropical diseases in young adults. Health-related quality of life (HRQoL) impairment is common in patients with ChD, especially in those with Chagas dilated cardiomyopathy, the most severe manifestation of the disease, which frequently leads to heart failure. The aim of this review was to conduct a literature search for studies that have evaluated the determining factors of HRQoL in ChD patients. We included cross-sectional, case-control, cohort, and experimental studies, as well as clinical trials that evaluated the HRQoL in ChD patients aged 18 to 60 years and are presenting an explicit description of statistical analysis. Using a combination of keywords based on Descriptors in Health Sciences (DeCS) and Medical Subject Headings (MeSH) for searches in PubMed and the Scientific Electronic Library Online (SciELO), 148 studies were found. After exclusions, 12 studies were selected for analysis. Three main findings were extracted from these studies: 1) cardiac involvement is associated with a worse HRQoL in ChD patients; 2) HRQoL is associated with the patients' functional capacity; and 3) simple and inexpensive therapeutic measures are effective for improving HRQoL in ChD patients. Hence, ChD patients' functional capacity, the effectiveness of non-surgical conservative treatment, and cardiac involvement are important determining factors for the HRQoL in ChD patients.

Exercise-induced ventricular arrhythmias and vagal dysfunction in Chagas disease patients with no apparent cardiac involvement.

INTRODUCTION: Exercise-induced ventricular arrhythmia (EIVA) and autonomic imbalance are considered as early markers of heart disease in Chagas disease (ChD) patients. The objective of the present study was to verify the differences in the occurrence of EIVA and autonomic maneuver indexes between healthy individuals and ChD patients with no apparent cardiac involvement. METHODS: A total of 75 ChD patients with no apparent cardiac involvement, aged 44.7 (8.5) years, and 38 healthy individuals, aged 44.0 (9.2) years, were evaluated using echocardiography, symptom-limited treadmill exercise testing and autonomic function tests. RESULTS: The occurrence of EIVA was higher in the chagasic group (48%) than in the control group (23.7%) during both the effort and the recovery phases. Frequent ventricular contractions occurred only in the patient group. Additionally, the respiratory sinus arrhythmia index was significantly lower in the chagasic individuals compared with the control group. CONCLUSIONS: ChD patients with no apparent cardiac involvement had a higher frequency of EIVA as well as more vagal dysfunction by respiratory sinus arrhythmia. These results suggest that even when asymptomatic, ChD patients possess important arrhythmogenic substrates and subclinical disease.

Exercise-induced ventricular arrhythmias and vagal dysfunction in Chagas disease patients with no apparent cardiac involvement

INTRODUCTION : Exercise-induced ventricular arrhythmia (EIVA) and autonomic imbalance are considered as early markers of heart disease in Chagas disease (ChD) patients. The objective of the present study was to verify the differences in the occurrence of EIVA and autonomic maneuver indexes between healthy individuals and ChD patients with no apparent cardiac involvement. METHODS : A total of 75 ChD patients with no apparent cardiac involvement, aged 44.7 (8.5) years, and 38 healthy individuals, aged 44.0 (9.2) years, were evaluated using echocardiography, symptom-limited treadmill exercise testing and autonomic function tests. RESULTS : The occurrence of EIVA was higher in the chagasic group (48%) than in the control group (23.7%) during both the effort and the recovery phases. Frequent ventricular contractions occurred only in the patient group. Additionally, the respiratory sinus arrhythmia index was significantly lower in the chagasic individuals compared with the control group. CONCLUSIONS : ChD patients with no apparent cardiac involvement had a higher frequency of EIVA as well as more vagal dysfunction by respiratory sinus arrhythmia. These results suggest that even when asymptomatic, ChD patients possess important arrhythmogenic substrates and subclinical disease. .