Role of the cGAS/STING pathway in the control of Brucella abortus infection acquired through the respiratory route.

Despite the importance of the respiratory route for Brucella transmission, the lung immune response to this pathogen is scarcely characterized. We investigated the role of the cGAS/STING pathway of microbial DNA recognition in the control of respiratory Brucella infection. After in vitro B. abortus infection, CFU numbers were significantly higher in alveolar macrophages (AM) and lung explants from STING KO mice than in samples from wild type (WT) mice, but no difference was observed for cGAS KO samples. CFU were also increased in WT AM and lung epithelial cells preincubated with the STING inhibitor H151. Several proinflammatory cytokines (TNF-α, IL-1ß, IL-6, IP-10/CXCL10) were diminished in Brucella-infected lung explants and/or AM from STING KO mice and cGAS KO mice. These cytokines were also reduced in infected AM and lung epithelial cells pretreated with H151. After intratracheal infection with B. abortus, STING KO mice exhibited increased CFU in lungs, spleen and liver, a reduced expression of IFN-ß mRNA in lungs and spleen, and reduced levels of proinflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and lung homogenates. Increased lung CFU and reduced BALF cytokines were also observed in cGAS KO mice. In summary, the cGAS/STING pathway induces the production of proinflammatory cytokines after respiratory Brucella infection, which may contribute to the STING-dependent control of airborne brucellosis.

Credibility, accuracy and readability of patient-oriented information about low back pain on Brazilian websites: a mixed-method review / Credibilidade, acurácia e legibilidade das informações orientadas ao paciente sobre dor lombar em sites brasileiros: uma revisão de método misto

ABSTRACT BACKGROUND AND OBJECTIVES: Low-quality online health-related content may lead to inefective or harmful decision-making from patients related to their healthcare. The aim of this study was to evaluate the credibility, accuracy and readability of web-based content on Brazilian websites. METHODS: This is a mixed-method review with exploratory sequential design. Google was selected as the search engine for retrieving web-information about low back pain (LBP) in Brazilian websites. We assessed the URL on three domains: credibility, accuracy, and readability. Qualitative analysis of each URL was performed in three steps: (1) organization into thematic units; (2) data exploration; and (3) interpretation of the data and summarization. RESULTS: Credibility was assessed in 135 URLs, 72 (53%) URLs had no authorship, 119 (88%) did not mention the sources of their information, none presented a declaration of conflict of interest or the declared source of funding, 76 (56%) URLs present the date of creation. Accuracy was assessed in 121 URLs and none fully adhered to the guidelines. Readability was assessed in 128 and texts were classified as "very easy" or "easy" to read. Five main themes emerged in the qualitative analysis: (1) Explanations and causes for low back pain, (2) diagnosis, (3) recommendation about treatment, (4) recommendation for coping and self-management, and (5) lifestyle factors. CONCLUSION: Content analysis of web-based searches on the Brazilian Portuguese language demonstrated low credibility standards, mostly inaccurate information, and moderate-high readability levels about low back pain.

RESUMO JUSTIFICATIVA E OBJETIVOS: O conteúdo on-line relacionado à saúde quando apresenta baixa qualidade pode levar a tomadas de decisão ineficazes ou prejudiciais por parte dos pacientes. O objetivo deste estudo foi avaliar a credibilidade, acurácia e legibilidade do conteúdo em portais brasileiros. MÉTODOS: Esta é uma revisão de método misto com design sequencial exploratório. O Google foi selecionado como o mecanismo de busca para recuperar informações da web sobre dor lombar em sites brasileiros. Avaliamos os URL em três domínios: credibilidade, acurácia e legibilidade. A análise qualitativa de cada URL foi realizada em três etapas: (1) organização em unidades temáticas; (2) exploração de dados; e (3) interpretação dos dados e resumo. RESULTADOS: A credibilidade foi avaliada em 135 URLs, 72 (53%) URLs não tinham autoria, 119 (88%) não mencionavam as fontes de suas informações, nenhuma apresentava declaração de confito de interesse ou fonte de fnanciamento declarada, 76 (56%) URLs apresentam a data de criação. A acurácia foi avaliada em 121 URLs e nenhuma aderiu totalmente às diretrizes. A legibilidade foi avaliada em 128 e os textos foram classificados como "muito fáceis" ou "fáceis" de ler. Cinco temas principais emergiram na análise qualitativa: (1) Explicações e causas da dor lombar, (2) diagnóstico, (3) recomendação sobre tratamento, (4) recomendação para enfrentamento e autogerenciamento e (5) fatores de estilo de vida. CONCLUSÃO: A análise de conteúdo de pesquisas baseadas na web, no idioma português do Brasil, demonstrou baixos padrões de credibilidade, acurácia e níveis moderados a altos de legibilidade sobre a dor lombar.

Caspase-8 but not caspase-7 influences inflammasome activation to act in control of Brucella abortus infection.

Programmed cell death (PCD) is an important mechanism of innate immunity against bacterial pathogens. The innate immune PCD pathway involves the molecules caspase-7 and caspase-8, among others. Brucella abortus is a gram-negative bacterium that causes a zoonotic disease termed brucellosis. The innate immune response against this pathogen involves activation of inflammasome components and induction of pyroptosis. However, no studies so far have revealed the role of caspase-7 or caspase-8 during this bacterial infection. Herein, we demonstrate that caspase-7 is dispensable for caspase-1 processing, IL-1ß secretion and cell death in macrophages. Additionally, caspase-7 deficient animals control B. abortus infection as well as the wild type mice. Furthermore, we addressed the role of caspase-8 in inflammasome activation and pyroptosis during this bacterial infection. Macrophages deficient in caspase-8 secreted reduced amounts of IL-1ß that parallels with diminished caspase-1 activity when compared to wild type cells. Additionally, caspase-8 KO macrophages showed reduced LDH release when compared to wild type, suggesting that caspase-8 may play an important role in pyroptosis in response to B. abortus. Finally, caspase-8 KO animals were more susceptible to Brucella infection when compared to wild type mice. Overall, this study contributes to a better understanding of the involvement of caspase-7 and caspase-8 in innate immunity against B. abortus infection.

Patients should not rely on low back pain information from Brazilian official websites: A mixed-methods review.

BACKGROUND: Websites from official organizations (e.g., Ministry of Health and Professional Councils) are assumed to be trustworthy sources of information. OBJECTIVE: To investigate the credibility, accuracy, and readability of low back pain (LBP) web-based content in Brazilian official websites. METHODS: Mixed-methods review. Google search was used for retrieving web-information about Brazilian trustworthy organizations. We assessed the URLs on three domains: credibility, accuracy, and readability of LBP contents. Qualitative analysis was performed using an open source platform in three stages: (1) organization into thematic units; (2) data exploration; and (3) interpretation of the data and summarization. RESULTS: We included 84 URLs. Accuracy was assessed for 58 URLs and none fully adhered to the guidelines. Credibility analysis was performed for 67 URLs. Disclosure of authorship was not mentioned in 58 (87%) of the URLs, 63 (94%) did not mention the sources of their information, none presented a declaration of conflict of interest, and 16 (24%) did not provide the date of creation. Readability was assessed for 72 URLs and was classified as "easy" to read in 65%. Six main themes emerged in the qualitative analysis: (1) Explanations and causes for LBP, (2) diagnosis, (3) recommendations about medication, (4) recommendations for coping and self-management, (5) performing exercises, and (6) recommendations for children and adolescents. CONCLUSIONS: The reading level is appropriate for patient-oriented information. However, Brazilian official websites demonstrated low credibility standards and while some of the content is partially supported by the current literature, there is also much inaccurate information about LBP.

Desfechos em fetos e recém-nascidos expostos a infecções na gravidez.

OBJECTIVE: To analyze outcomes in fetuses and newborns exposed to infections during pregnancy. METHODS: Cross-sectional, quantitative study, carried out in a public maternity hospital in Maceió, Alagoas, Brazil. The sample consisted of 145 medical records of pregnant women admitted between 2015 and 2018 with possible vertically transmitted infections. Incomplete medical records or those that did not make it possible to describe fetal/neonatal exposure were excluded. The chi-squared test was used to verify the association between variables. RESULTS: A greater occurrence of congenital syphilis was observed (28.8%). There was more than one outcome in the same individual, such as low birth weight (39%), respiratory distress (20.5%), oligohydramnios (20%), congenital malformation and small size for gestational age (10.8%). Maternal infections and the number of prenatal visits revealed an association with fetal/neonatal outcome (p ≤ 0.05). CONCLUSION: The data obtained indicate the occurrence of unfavorable fetal/neonatal outcomes when related to neonatal infections and indicate the need for strategies that strengthen the coping with vertical transmissions.

NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus.

Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection-Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.

Desfechos em fetos e recém-nascidos expostos a infecções na gravidez / Resultados en fetos y neonatos expuestos a infecciones en el embarazo / Desfechos em fetos e recém-nascidos expostos a infecções na gravidez

ABSTRACT Objective: To analyze outcomes in fetuses and newborns exposed to infections during pregnancy. Methods: Cross-sectional, quantitative study, carried out in a public maternity hospital in Maceió, Alagoas, Brazil. The sample consisted of 145 medical records of pregnant women admitted between 2015 and 2018 with possible vertically transmitted infections. Incomplete medical records or those that did not make it possible to describe fetal/neonatal exposure were excluded. The chi-squared test was used to verify the association between variables. Results: A greater occurrence of congenital syphilis was observed (28.8%). There was more than one outcome in the same individual, such as low birth weight (39%), respiratory distress (20.5%), oligohydramnios (20%), congenital malformation and small size for gestational age (10.8%). Maternal infections and the number of prenatal visits revealed an association with fetal/neonatal outcome (p ≤ 0.05). Conclusion: The data obtained indicate the occurrence of unfavorable fetal/neonatal outcomes when related to neonatal infections and indicate the need for strategies that strengthen the coping with vertical transmissions.

RESUMEN Objetivo: Analizar resultados en fetos y neonatos expuestos a infecciones en el embarazo. Métodos: Estudio transversal, cuantitativo, realizado en maternidad pública, en Maceió, Alagoas, Brasil. Muestra compuesta por 145 prontuarios de embarazadas admitidas entre 2015 y 2018 con posibles infecciones de trasmisión vertical. Excluidos prontuarios incompletos lo que no posibilitaron describir la exposición fetal/neonatal. Utilizó prueba chi-cuadrado para verificar la relación entre las variables. Resultados: Observó mayor ocurrencia de la sífilis congénita (28,8%). Hubo más de un resultado en el mismo individuo, como bajo peso al nacimiento (39%), dificultad respiratoria (20,5%), oligohidramnios (20%), malformación congénita y tamaño pequeño para edad gestacional (10,8%). Las infecciones maternas y el número de consultas prenatal mostraron relación con el resultado fetal/neonatal (p ≤ 0,05). Conclusión: Los datos obtenidos apuntan ocurrencia de resultados fetales/neonatales desfavorables cuando relacionados a las infecciones neonatales e indican la necesidad de estrategias que fortalezcan el enfrentamiento a las transmisiones verticales.

RESUMO Objetivo: Analisar desfechos em fetos e recém-nascidos expostos a infecções na gravidez. Métodos: Estudo transversal, quantitativo, realizado em uma maternidade pública, em Maceió, Alagoas, Brasil. A amostra foi composta por 145 prontuários de gestantes admitidas entre 2015 e 2018 com possíveis infecções de transmissão vertical. Foram excluídos prontuários incompletos ou que não possibilitaram descrever a exposição fetal/neonatal. Utilizou-se teste qui-quadrado para verificar a associação entre as variáveis. Resultados: Observou-se maior ocorrência da sífilis congênita (28,8%). Houve mais de um desfecho no mesmo indivíduo, como baixo peso ao nascimento (39%), desconforto respiratório (20,5%), oligodramnia (20%), malformação congênita e tamanho pequeno para idade gestacional (10,8%). As infecções maternas e o número de consultas pré-natal mostraram associação com o desfecho fetal/neonatal (p ≤ 0,05). Conclusão: Os dados obtidos apontam a ocorrência de desfechos fetais/neonatais desfavoráveis quando relacionados a infecções neonatais e indicam a necessidade de estratégias que fortaleçam o enfrentamento das transmissões verticais.

Desfechos em fetos e recém-nascidos expostos a infecções na gravidez / Resultados en fetos y neonatos expuestos a infecciones en el embarazo / Desfechos em fetos e recém-nascidos expostos a infecções na gravidez

ABSTRACT Objective: To analyze outcomes in fetuses and newborns exposed to infections during pregnancy. Methods: Cross-sectional, quantitative study, carried out in a public maternity hospital in Maceió, Alagoas, Brazil. The sample consisted of 145 medical records of pregnant women admitted between 2015 and 2018 with possible vertically transmitted infections. Incomplete medical records or those that did not make it possible to describe fetal/neonatal exposure were excluded. The chi-squared test was used to verify the association between variables. Results: A greater occurrence of congenital syphilis was observed (28.8%). There was more than one outcome in the same individual, such as low birth weight (39%), respiratory distress (20.5%), oligohydramnios (20%), congenital malformation and small size for gestational age (10.8%). Maternal infections and the number of prenatal visits revealed an association with fetal/neonatal outcome (p ≤ 0.05). Conclusion: The data obtained indicate the occurrence of unfavorable fetal/neonatal outcomes when related to neonatal infections and indicate the need for strategies that strengthen the coping with vertical transmissions.

RESUMEN Objetivo: Analizar resultados en fetos y neonatos expuestos a infecciones en el embarazo. Métodos: Estudio transversal, cuantitativo, realizado en maternidad pública, en Maceió, Alagoas, Brasil. Muestra compuesta por 145 prontuarios de embarazadas admitidas entre 2015 y 2018 con posibles infecciones de trasmisión vertical. Excluidos prontuarios incompletos lo que no posibilitaron describir la exposición fetal/neonatal. Utilizó prueba chi-cuadrado para verificar la relación entre las variables. Resultados: Observó mayor ocurrencia de la sífilis congénita (28,8%). Hubo más de un resultado en el mismo individuo, como bajo peso al nacimiento (39%), dificultad respiratoria (20,5%), oligohidramnios (20%), malformación congénita y tamaño pequeño para edad gestacional (10,8%). Las infecciones maternas y el número de consultas prenatal mostraron relación con el resultado fetal/neonatal (p ≤ 0,05). Conclusión: Los datos obtenidos apuntan ocurrencia de resultados fetales/neonatales desfavorables cuando relacionados a las infecciones neonatales e indican la necesidad de estrategias que fortalezcan el enfrentamiento a las transmisiones verticales.

RESUMO Objetivo: Analisar desfechos em fetos e recém-nascidos expostos a infecções na gravidez. Métodos: Estudo transversal, quantitativo, realizado em uma maternidade pública, em Maceió, Alagoas, Brasil. A amostra foi composta por 145 prontuários de gestantes admitidas entre 2015 e 2018 com possíveis infecções de transmissão vertical. Foram excluídos prontuários incompletos ou que não possibilitaram descrever a exposição fetal/neonatal. Utilizou-se teste qui-quadrado para verificar a associação entre as variáveis. Resultados: Observou-se maior ocorrência da sífilis congênita (28,8%). Houve mais de um desfecho no mesmo indivíduo, como baixo peso ao nascimento (39%), desconforto respiratório (20,5%), oligodramnia (20%), malformação congênita e tamanho pequeno para idade gestacional (10,8%). As infecções maternas e o número de consultas pré-natal mostraram associação com o desfecho fetal/neonatal (p ≤ 0,05). Conclusão: Os dados obtidos apontam a ocorrência de desfechos fetais/neonatais desfavoráveis quando relacionados a infecções neonatais e indicam a necessidade de estratégias que fortaleçam o enfrentamento das transmissões verticais.

The Role of ST2 Receptor in the Regulation of Brucella abortus Oral Infection.

The ST2 receptor plays an important role in the gut such as permeability regulation, epithelium regeneration, and promoting intestinal immune modulation. Here, we studied the role of ST2 receptor in a murine model of oral infection with Brucella abortus, its influence on gut homeostasis and control of bacterial replication. Balb/c (wild-type, WT) and ST2 deficient mice (ST2-/-) were infected by oral gavage and the results were obtained at 3 and 14 days post infection (dpi). Our results suggest that ST2-/- are more resistant to B. abortus infection, as a lower bacterial colony-forming unit (CFU) was detected in the livers and spleens of knockout mice, when compared to WT. Additionally, we observed an increase in intestinal permeability in WT-infected mice, compared to ST2-/- animals. Breakage of the intestinal epithelial barrier and bacterial dissemination might be associated with the presence of the ST2 receptor; since, in the knockout mice no change in intestinal permeability was observed after infection. Together with enhanced resistance to infection, ST2-/- produced greater levels of IFN-γ and TNF-α in the small intestine, compared to WT mice. Nevertheless, in the systemic model of infection ST2 plays no role in controlling Brucella replication in vivo. Our results suggest that the ST2 receptor is involved in the invasion process of B. abortus by the mucosa in the oral infection model.

Effectiveness of Kinesio Taping in Patients With Chronic Nonspecific Low Back Pain: A Systematic Review With Meta-analysis.

STUDY DESIGN: Systematic review. OBJECTIVE: To investigate the effects of Kinesio Taping (KT) in patients with nonspecific low back pain. SUMMARY OF BACKGROUND DATA: KT is widely used in patients with low back pain. METHODS: We conducted searches on PubMed, EMBASE, PEDro, SciELO, and LILACS up to February 26, 2018. We included only randomized controlled trials (RCTs) in adults with chronic nonspecific low back pain that compared KT to no intervention or placebo as well as RCTs that compared KT combined with exercise against exercise alone. The methodological quality and statistical reporting of the eligible trials were measured by the 11-item PEDro scale. The quality of the evidence was assessed using the GRADE classification. We considered pain intensity and disability as the primary outcomes. Whenever possible, the data were pooled through meta-analysis. RESULTS: We identified 11 RCTs for this systematic review (pooled n = 743). Two clinical trials (pooled n = 100) compared KT to no intervention at the short-term follow-up. Four studies compared KT to placebo (pooled n = 287) at short-term follow-up and two trials (pooled n = 100) compared KT to placebo at intermediate-term follow-up. Five trials (pooled n = 296) compared KT combined with exercises or electrotherapy to exercises or spinal manipulation alone. No statistically significant difference was found for most comparisons. CONCLUSION: Very low to moderate quality evidence shows that KT was no better than any other intervention for most the outcomes assessed in patients with chronic nonspecific low back pain. We found no evidence to support the use of KT in clinical practice for patients with chronic nonspecific low back pain. LEVEL OF EVIDENCE: 1.

Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity.

In seeking substitutions for the current Chagas disease treatment, which has several relevant side effects, new therapeutic candidates have been extensively investigated. In this context, a balanced interaction between mediators of the host immune response seems to be a key element for therapeutic success, as a proinflammatory microenvironment modulated by interleukin-10 (IL-10) is shown to be relevant to potentiate anti-Trypanosoma cruzi drug activity. This study aimed to identify the potential immunomodulatory activities of the anti-T. cruzi K777, pyronaridine (PYR), and furazolidone (FUR) compounds in peripheral blood mononuclear cells (PBMC) from noninfected (NI) subjects and chronic Chagas disease (CD) patients. Our results showed low cytotoxicity to PBMC populations, with 50% cytotoxic concentrations (CC50) of 71.0 µM (K777), 9.0 µM (PYR), and greater than 20 µM (FUR). In addition, K777 showed no impact on the exposure index (EI) of phytohemagglutinin-stimulated leukocytes (PHA), while PYR and FUR treatments induced increased EI of monocytes and T lymphocytes at late stages of apoptosis in NI subjects. Moreover, K777 induced a more prominent proinflammatory response (tumor necrosis factor alpha-positive [TNF-α+] CD8+/CD4+, gamma interferon-positive [IFN-γ+] CD4+/CD8+ modulated by interleukin-10-positive [IL-10+] CD4+ T/CD8+ T) than did PYR (TNF-α+ CD8+, IL-10+ CD8+) and FUR (TNF-α+ CD8+, IL-10+ CD8+). Signature analysis of intracytoplasmic cytokines corroborated the proinflammatory/modulated (K777) and proinflammatory (PYR and FUR) profiles previously found. In conclusion, the lead compound K777 may induce beneficial changes in the immunological profile of patients presenting the chronic phase of Chagas disease and may contribute to a more effective therapy against the disease.

Booster dose after 10 years is recommended following 17DD-YF primary vaccination.

A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT≥2.9Log10mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to naïve baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-α(+) and IFN-γ(+) produced by CD4(+) and CD8(+) T-cells along with increasing levels of IL-10(+)CD4(+)T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the naïve baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8(+) memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination.