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Justificativas e Objetivos: A sífilis é a infecção bacteriana mais disseminada na população humana, sendo a principal forma de transmissão por contato sexual. Analisar os dados epidemiológico da população do município de Rio Branco ­ Acre ­ Brasil com diagnóstico positivo da Sífilis entre os anos de 2013 e 2017. Métodos: Trata-se de um estudo descritivo, do tipo transversal e abordagem quantitativa aplicado aos dados do Laboratório Central de Saúde Pública do Acre da população infectada com T. pallidum. Resultados: De um total de 5.239 pessoas infectadas com sífilis, 56,8% são do sexo feminino entre idade de 20 a 30 anos e autodeclaradas de cor parda. Além disso, 1006 gestantes, 43% das quais estavam na faixa de 11 a 20 anos e 37,5% estavam no segundo trimestre da gestação. Para os nascidos vivos, 107 crianças com sífilis congênita precoce foram diagnosticadas. Conclusão: As informações para a prevenção da infecção devem ser intensificadas principalmente as pessoas que estão desinformadas sobre a IST na cidade como os: adolescentes, idosos e populações indígenas afim de evitar a transmissão da sífilis.(AU)

Justifications and Objectives: Syphilis is the most widespread bacterial infection in the human population, being the main form of transmission through sexual contact. Analyze the epidemiological data of the population of the municipality of Rio Branco - Acre - Brazil with a positive diagnosis of Syphilis between the years 2013 and 2017. Methods: This is a descriptive, cross-sectional study with a quantitative approach applied to data from the Central Laboratory of Public Health in Acre of the population infected with T. pallidum. Results: Of a total of 5,239 people infected with syphilis, 56.8% are female between the ages of 20 and 30 years old and self-declared to be brown. In addition, 1006 pregnant women, 43% of whom were between 11 and 20 years old and 37.5% were in the second trimester of pregnancy. For live births, 107 children with early congenital syphilis were diagnosed. Conclusion: Information for the prevention of infection should be intensified, especially for people who are uninformed about STIs in the city, such as: adolescents, the elderly and indigenous populations in order to avoid syphilis transmission.(AU)

Justificación y objetivos: La sífilis es la infección bacteriana más extendida en la población humana, siendo la principal forma de transmisión a través del contacto sexual. Analice los datos epidemiológicos de la población del municipio de Rio Branco - Acre - Brasil con un diagnóstico positivo de sífilis entre los años 2013 y 2017. Métodos: Este es un estudio descriptivo, transversal con un enfoque cuantitativo aplicado a los datos del Laboratorio Central de Salud Pública en Acre de la población infectada con T. pallidum. Resultados: De un total de 5,239 personas infectadas con sífilis, el 56.8% son mujeres entre las edades de 20 y 30 años y se declaran marrones. Además, 1006 mujeres embarazadas, el 43% de las cuales tenían entre 11 y 20 años y el 37.5% estaban en el segundo trimestre del embarazo. Para los nacimientos vivos, se diagnosticaron 107 niños con sífilis congénita temprana. Conclusión: La información para la prevención de la infección debe intensificarse, especialmente para las personas que no están informadas sobre las ITS en la ciudad, como: adolescentes, ancianos y poblaciones indígenas para evitar la transmisión de la sífilis.(AU)

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The inflammatory and autoimmune events preceding clinical symptoms in rheumatoid arthritis (RA) and other autoimmune diseases are difficult to study in human patients. Therefore, animal models that share immunologic and clinical features with human RA, such as pristane-induced arthritis (PIA), are valuable tools for assessing the primordial events related to arthritis susceptibility. PIA-resistant HIII and susceptible LIII mice were injected i.p. with pristane, and peritoneal lavage fluid was harvested in the early (7 days) and late (35 days) preclinical phases of PIA. Chemokine and cytokine levels were measured in lavage supernatant with ELISA, peritoneal inflammatory leukocytes were immunophenotyped by flow cytometry, and gene expression was determined by qRT-PCR. Leukocyte recruitment was quantitatively and qualitatively divergent in the peritoneum of HIII and LIII mice, with an early increase of CC chemokines (CCL2/CCL3/CCL5/CCL12/CCL22) in the susceptible LIII strain. Also, cytokines such as IL-12p40, IL-23, and IL-18 were elevated in LIII mice while IL-6 was increased in HIII animals. The results show that an early peritoneal CC chemokine response is an important feature of arthritis susceptibility and defines potential biomarkers in this model.

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In malignant transformation, cellular stress-response pathways are dynami-cally mobilized to counterbalance oncogenic activity, keeping cancer cellsviable. Therapeutic disruption of this vulnerable homeostasis might changethe outcome of many human cancers, particularly those for which no effec-tive therapy is available. Here, we report the use of fibroblast growth factor2 (FGF2) to demonstrate that further mitogenic activation disrupts cellularhomeostasis and strongly sensitizes cancer cells to stress-targeted therapeu-tic inhibitors. We show that FGF2 enhanced replication and proteotoxicstresses in a K-Ras-driven murine cancer cell model, and combinations ofFGF2 and proteasome or DNA damage response-checkpoint inhibitorstriggered cell death. CRISPR/Cas9-mediated K-Ras depletion suppressedthe malignant phenotype and prevented these synergic toxicities in thesemurine cells. Moreover, in a panel of human Ewing’s sarcoma family tumorcells, sublethal concentrations of bortezomib (proteasome inhibitor) or VE-821 (ATR inhibitor) induced cell death when combined with FGF2. Sus-tained MAPK-ERK1/2 overactivation induced by FGF2 appears to under-lie these synthetic lethalities, as late pharmacological inhibition of thispathway restored cell homeostasis and prevented these described synergies.Our results highlight how mitotic signaling pathways which are frequentlyoverridden in malignant transformation might be exploited to disrupt therobustness of cancer cells, ultimately sensitizing them to stress-targeted ther-apies. This approach provides a new therapeutic rationale for human can-cers, with important implications for tumors still lacking effectivetreatment, and for those that frequently relapse after treatment with avail-able therapies.

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The inflammatory and autoimmune events preceding clinical symptoms in rheumatoid arthritis (RA) and other autoimmune diseases are difficult to study in human patients. Therefore, animal models that share immunologic and clinical features with human RA, such as pristane-induced arthritis (PIA), are valuable tools for assessing the primordial events related to arthritis susceptibility. PIA-resistant HIII and susceptible LIII mice were injected i.p. with pristane, and peritoneal lavage fluid was harvested in the early (7 days) and late (35 days) preclinical phases of PIA. Chemokine and cytokine levels were measured in lavage supernatant with ELISA, peritoneal inflammatory leukocytes were immunophenotyped by flow cytometry, and gene expression was determined by qRT-PCR. Leukocyte recruitment was quantitatively and qualitatively divergent in the peritoneum of HIII and LIII mice, with an early increase of CC chemokines (CCL2/CCL3/CCL5/CCL12/CCL22) in the susceptible LIII strain. Also, cytokines such as IL-12p40, IL-23, and IL-18 were elevated in LIII mice while IL-6 was increased in HIII animals. The results show that an early peritoneal CC chemokine response is an important feature of arthritis susceptibility and defines potential biomarkers in this model.

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In malignant transformation, cellular stress-response pathways are dynami-cally mobilized to counterbalance oncogenic activity, keeping cancer cellsviable. Therapeutic disruption of this vulnerable homeostasis might changethe outcome of many human cancers, particularly those for which no effec-tive therapy is available. Here, we report the use of fibroblast growth factor2 (FGF2) to demonstrate that further mitogenic activation disrupts cellularhomeostasis and strongly sensitizes cancer cells to stress-targeted therapeu-tic inhibitors. We show that FGF2 enhanced replication and proteotoxicstresses in a K-Ras-driven murine cancer cell model, and combinations ofFGF2 and proteasome or DNA damage response-checkpoint inhibitorstriggered cell death. CRISPR/Cas9-mediated K-Ras depletion suppressedthe malignant phenotype and prevented these synergic toxicities in thesemurine cells. Moreover, in a panel of human Ewing’s sarcoma family tumorcells, sublethal concentrations of bortezomib (proteasome inhibitor) or VE-821 (ATR inhibitor) induced cell death when combined with FGF2. Sus-tained MAPK-ERK1/2 overactivation induced by FGF2 appears to under-lie these synthetic lethalities, as late pharmacological inhibition of thispathway restored cell homeostasis and prevented these described synergies.Our results highlight how mitotic signaling pathways which are frequentlyoverridden in malignant transformation might be exploited to disrupt therobustness of cancer cells, ultimately sensitizing them to stress-targeted ther-apies. This approach provides a new therapeutic rationale for human can-cers, with important implications for tumors still lacking effectivetreatment, and for those that frequently relapse after treatment with avail-able therapies.

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