Treatment with lipoxin A 4 improves influenza A infection outcome through macrophage reprogramming, anti-inflammatory and pro-resolutive responses.

OBJECTIVE AND DESIGN: Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model. TREATMENT: Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 mg/kg/day, i.p.) at day 3 post-infection. Methods Mortality rate was assessed up to day 21 and inflammatory parameters were assessed at days 5 and 7. Results AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in FPR2/3 -/- animals. In mice treated with LXA 4 (50mg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of anti-inflammatory T cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice. Conclusions Therefore, treatment with a lipoxin A 4 analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.

Post-mortem detection of hemoplasmas (hemotropic Mycoplasma spp.) in South American fur seal (Arctocephalus australis) sampled in Rio Grande do Sul State, southern Brazil.

Hemotropic mycoplasmas are bacteria that attaches to erythrocytes surface, which some species presents zoonotic concerns. In the suborder Pinnipedia, genera Otaria and Arctocephalus are prominent in Brazil. This study investigated the occurrence of hemoplasmas in Arctocephalus sp. and Otaria flavescens found dead along the coast of a Southern Brazilian State. DNA from 135 spleen samples were extracted and subjected to conventional PCR protocols, targeting the 16 S rRNA and 23 S rRNA gene. Three (2.22 %) Arctocephalus australis were positive in the 16 S rRNA gene, and no samples amplified in the 23 S rRNA gene. Samples from this study clustered with Zalophus californianus and Arctocephalus tropicalis mycoplasmas on a Bayesian phylogenetic analysis. Genetic diversity analysis suggested distinct genotypes, indicating A. australis as a new host for hemoplasma, and also a potential putative novel hemoplasma genotype. These findings raises future awareness for pinnipeds conservation, and adds Mycoplasma spp. to be taken into consideration when clinically evaluating rescued animals.

The Toxoplasma gondii effector GRA83 modulates the host's innate immune response to regulate parasite infection.

Toxoplasma gondii's propensity to infect its host and cause disease is highly dependent on its ability to modulate host cell functions. One of the strategies the parasite uses to accomplish this is via the export of effector proteins from the secretory dense granules. Dense granule (GRA) proteins are known to play roles in nutrient acquisition, host cell cycle manipulation, and immune regulation. Here, we characterize a novel dense granule protein named GRA83, which localizes to the parasitophorous vacuole (PV) in tachyzoites and bradyzoites. Disruption of GRA83 results in increased virulence, weight loss, and parasitemia during the acute infection, as well as a marked increase in the cyst burden during the chronic infection. This increased parasitemia was associated with an accumulation of inflammatory infiltrates in tissues in both acute and chronic infections. Murine macrophages infected with ∆gra83 tachyzoites produced less interleukin-12 (IL-12) in vitro, which was confirmed with reduced IL-12 and interferon-gamma in vivo. This dysregulation of cytokines correlates with reduced nuclear translocation of the p65 subunit of the nuclear factor-κB (NF-κB) complex. While GRA15 similarly regulates NF-κB, infection with ∆gra83/∆gra15 parasites did not further reduce p65 translocation to the host cell nucleus, suggesting these GRAs function in converging pathways. We also used proximity labeling experiments to reveal candidate GRA83 interacting T. gondii-derived partners. Taken together, this work reveals a novel effector that stimulates the innate immune response, enabling the host to limit the parasite burden. Importance Toxoplasma gondii poses a significant public health concern as it is recognized as one of the leading foodborne pathogens in the United States. Infection with the parasite can cause congenital defects in neonates, life-threatening complications in immunosuppressed patients, and ocular disease. Specialized secretory organelles, including the dense granules, play an important role in the parasite's ability to efficiently invade and regulate components of the host's infection response machinery to limit parasite clearance and establish an acute infection. Toxoplasma's ability to avoid early clearance, while also successfully infecting the host long enough to establish a persistent chronic infection, is crucial in allowing for its transmission to a new host. While multiple GRAs directly modulate host signaling pathways, they do so in various ways highlighting the parasite's diverse arsenal of effectors that govern infection. Understanding how parasite-derived effectors harness host functions to evade defenses yet ensure a robust infection is important for understanding the complexity of the pathogen's tightly regulated infection. In this study, we characterize a novel secreted protein named GRA83 that stimulates the host cell's response to limit infection.

The Toxoplasma gondii effector GRA83 modulates the host's innate immune response to regulate parasite infection.

Toxoplasma gondii 's propensity to infect its host and cause disease is highly dependent on its ability to modulate host cell functions. One of the strategies the parasite uses to accomplish this is via the export of effector proteins from the secretory dense granules. Dense granule (GRA) proteins are known to play roles in nutrient acquisition, host cell cycle manipulation, and immune regulation. Here, we characterize a novel dense granule protein named GRA83, which localizes to the parasitophorous vacuole in tachyzoites and bradyzoites. Disruption of GRA83 results in increased virulence, weight loss, and parasitemia during the acute infection, as well as a marked increase in the cyst burden during the chronic infection. This increased parasitemia was associated with an accumulation of inflammatory infiltrates in tissues in both the acute and chronic infection. Murine macrophages infected with Δ gra83 tachyzoites produced less interleukin-12 (IL-12) in vitro , which was confirmed with reduced IL-12 and interferon gamma (IFN-γ) in vivo . This dysregulation of cytokines correlates with reduced nuclear translocation of the p65 subunit of the NF-κB complex. While GRA15 similarly regulates NF-κB, infection with Δ gra83/ Δ gra15 parasites did not further reduce p65 translocation to the host cell nucleus, suggesting these GRAs function in converging pathways. We also used proximity labelling experiments to reveal candidate GRA83 interacting T. gondii derived partners. Taken together, this work reveals a novel effector that stimulates the innate immune response, enabling the host to limit parasite burden. Importance: Toxoplasma gondii poses a significant public health concern as it is recognized as one of the leading foodborne pathogens in the United States. Infection with the parasite can cause congenital defects in neonates, life-threatening complications in immunosuppressed patients, and ocular disease. Specialized secretory organelles, including the dense granules, play an important role in the parasite's ability to efficiently invade and regulate components of the host's infection response machinery to limit parasite clearance and establish an acute infection. Toxoplasma' s ability to avoid early clearance, while also successfully infecting the host long enough to establish a persistent chronic infection, is crucial in allowing for its transmission to a new host. While multiple GRAs directly modulate host signaling pathways, they do so in various ways highlighting the parasite's diverse arsenal of effectors that govern infection. Understanding how parasite-derived effectors harness host functions to evade defenses yet ensure a robust infection are important for understanding the complexity of the pathogen's tightly regulated infection. In this study, we characterize a novel secreted protein named GRA83 that stimulates the host cell's response to limit infection.

Long-term care facilities for older people and the COVID-19 pandemic: epidemiological data and preventive measures / Instituições de longa permanência para idosos e a pandemia de COVID-19: dados epidemiológicos e medidas preventiva

Objectives: The COVID-19 pandemic has challenged society, especially residents of long-term care facilities (LTCF). This study investigated rates of infection, hospitalization, and death due to COVID-19 among LTCF residents and staff in Minas Gerais, Brazil and identified strategies to control the spread of the disease.Methods: This cross-sectional study collected data from 164 LTCF (6017 older adults). The owners or managers were invited to answer an electronic questionnaire. The questionnaire included 55 items, divided into 3 sections.Results: Of the participating LTCF, 48.7%, 39.6%, and 32.3% reported COVID-19 infections, hospitalizations, and deaths, respectively, among residents, while 68.9%, 7.3%, and 1.2% reported COVID-19 infections, hospitalizations, and deaths, respectively, among staff. Preventive measures were identified and classified as organizational, infrastructural, hygiene items/personal protective equipment, and staff training.Conclusion: The strategies used in the daily routines of LTCF during the pandemic were classified. The challenges experienced in Brazilian facilities were similar to those observed worldwide. The results highlight the importance of continuity and the need to improve protective measures for LTCF residents, especially in low- and middle-income countries

Objetivos: A pandemia da COVID-19 tem sido desafiadora para a sociedade, principalmente para aqueles que residem em Instituições de Longa Permanência (ILPI). Este estudo teve como objetivo descrever as taxas de infecção, hospitalização e óbito por COVID-19 entre idosos e funcionários de ILPI de Minas Gerais/Brasil e identificar estratégias de prevenção e controle da disseminação da doença.Metodologia: Este estudo transversal foi realizado com 164 ILPI (6.017 idosos). Os gestores ou proprietários foram convidados a responder ao questionário eletrônico. O questionário incluiu 55 itens, divididos em três seções.Resultados: Entre as ILPI estudadas, 48,7% confirmaram a infecção por COVID-19 em idosos, resultando em 39,6% de internação e 32,3% de óbito entre os infectados. Além disso, 68,9% das ILPI confirmaram infecção por COVID-19 na equipe, com 7,3% de internação e 1,2% de óbito. As medidas preventivas foram identificadas e classificadas como organizacionais, infraestrutura, itens de higiene e equipamentos de proteção individual e treinamento de pessoal contra a COVID-19.Conclusão: Essas medidas revelaram estratégias e barreiras vivenciadas no cotidiano das ILPI durante a pandemia. As ILPI no Brasil passaram por desafios semelhantes aos observados mundialmente. Os resultados destacaram a importância da continuidade e melhoria das medidas de proteção para idosos em ILPI, especialmente em países de baixa e média renda

PI3K, mTOR and GSK3 modulate cytokines' production in peripheral leukocyte in temporal lobe epilepsy.

INTRODUCTION: Epilepsy is a common pathological condition that predisposes individuals to seizures, as well as cognitive and emotional dysfunctions. Different studies have demonstrated that inflammation contributes to the pathophysiology of epilepsy. Indeed, seizures change the peripheral inflammatory pattern, which, in turn, could contribute to seizures. However, the cause of the altered production of peripheral inflammatory mediators is not known. The PI3K/mTOR/GSK3ß pathway is important for different physiological and pharmacological phenomena. Therefore, in the present study, we tested the hypothesis that the PI3K/mTOR/GSK3ß pathway is deregulated in immune cells from patients with epilepsy and contributes to the abnormal production of inflammatory mediators. METHODS: Patients with temporal lobe epilepsy presenting hippocampal sclerosis and controls aged between 18 and 65 years-old were selected for this study. Peripheral blood was collected for the isolation of peripheral mononuclear blood cells (PBMC). Cells were pre-incubated with different PI3K, mTOR and GSK-3 inhibitors for 30 min and further stimulated with phytohaemaglutinin (PHA) or vehicle for 24 h. The supernatant was used to evaluate the production of IL-1ß, IL-6, IL-10, TNF e IL-12p70. RESULTS: Non-selective inhibition of PI3K, as well as inhibition of PI3Kγ and GSK-3, reduced the levels of TNF and IL-10 in PHA-stimulated cells from TLE individuals. This stimulus increased the production of IL-12p70 only in cells from TLE individuals, while the inhibition of PI3K and mTOR enhanced the production of this cytokine. On the other hand, inhibition of GSK3 reduced the PHA-induced production of IL-12p70. CONCLUSIONS: Herein we demonstrated that the production of cytokines by immune cells from patients with TLE differs from non-epileptic patients. This differential regulation may be associated with the altered activity and responsiveness of intracellular molecules, such as PI3K, mTOR and GSK-3, which, in turn, might contribute to the inflammatory state that exists in epilepsy and its pathogenesis.

Serotonin and dopamine receptors profile on peripheral immune cells from patients with temporal lobe epilepsy.

The role of inflammation and immune cells has been demonstrated in neurological diseases, including epilepsy. Leukocytes, as well as inflammatory mediators, contribute to abnormal processes that lead to a reduction in seizure threshold and synaptic reorganization. In this sense, identifying different phenotypes of circulating immune cells is essential to understanding the role of these cells in epilepsy. Immune cells can express a variety of surface markers, including neurotransmitter receptors, such as serotonin and dopamine. Alteration in these receptors expression patterns may affect the level of inflammatory mediators and the pathophysiology of epilepsy. Therefore, in the current study, we evaluated the expression of dopamine and serotonin receptors on white blood cells from patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Blood samples from 17 patients with TLE-HS and 21 controls were collected. PBMC were isolated and stained ex vivo for flow cytometry. We evaluated the expression of serotonin (5-HT1A, 5-HT1B, 5-HT2, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4), and dopamine receptors (D1, D2, D3, D4, and D5) on the cell surface of lymphocytes and innate immune cells (monocytes and granulocytes). Our results demonstrated that innate cells and lymphocytes from patients with TLE-HS showed high mean fluorescent intensity (MFI) for 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 compared to controls. No difference was observed for 5-HT2B. For dopamine receptors, the expression of D1, D2, D4, and D5 receptors was higher on innate cells from patients with TLE-HS when compared to controls for the MFI. Regarding lymphocytes population, D2 expression was increased in patients with TLE-HS. In conclusion, there are alterations in the expression of serotonin and dopamine receptors on immune blood cells of patients with TLE-HS. Although the biological significance of these findings still needs to be further investigated, these changes may contribute to the understanding of TLE-HS pathophysiology.

Slaughter condemnation in bovine due to parasitic lesions and their economic impact in Federal Inspection System establishments in Brazil and in State inspection System in Rio Grande do Sul State.

Slaughter condemnations are important sources of information on cattle health. The incidence of bovine parasitic diseases is still very high in Brazil. These diseases, in addition to causing harm to the animals health, are neglected zoonotic diseases in several parts of world. The study analysed not only the Carcass losses, but also the economic damage resulting from slaughter condemnations due to parasitic causes. Cattle slaughter data from the Brazilian Ministry of Agriculture, Livestock and Supply (MAPA), over the period of 2012 to 2015 and data from the Secretary of Livestock and Irrigation of the state of Rio Grande do Sul (SEAPI-RS) were analyzed between 2014 and 2018.The number of organs and carcasses condemned was multiplied by the respective values (in Brazilian Real) obtained from slaughterhouses and subsequently converted into dollars. Brazilian analysis in SIF (Federal Inspection System) establishments showed that more than 1.2 million organs (3,884,505 kg) and 20,000 carcasses (4,547,718 kg) were condemned only due to parasitic causes during post-mortem inspection. In Rio Grande do Sul, in state inspection establishments, more than 1.7 million organs (8,210,559 kg) and 5,000 carcasses (1,243,200 kg) were condemned. These data are alarming and support the need for public policies to control these parasitic diseases.

Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection.

Resolution failure of exacerbated inflammation triggered by Influenza A virus (IAV) prevents return of pulmonary homeostasis and survival, especially when associated with secondary pneumococcal infection. Therapeutic strategies based on pro-resolving molecules have great potential against acute inflammatory diseases. Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator that acts on its Mas receptor (MasR) to promote resolution of inflammation. We investigated the effects of Ang-(1-7) and the role of MasR in the context of primary IAV infection and secondary pneumococcal infection and evaluated pulmonary inflammation, virus titers and bacteria counts, and pulmonary damage. Therapeutic treatment with Ang-(1-7) decreased neutrophil recruitment, lung injury, viral load and morbidity after a primary IAV infection. Ang-(1-7) induced apoptosis of neutrophils and efferocytosis of these cells by alveolar macrophages, but had no direct effect on IAV replication in vitro. MasR-deficient (MasR-/-) mice were highly susceptible to IAV infection, displaying uncontrolled inflammation, increased viral load and greater lethality rate, as compared to WT animals. Ang-(1-7) was not protective in MasR-/- mice. Interestingly, Ang-(1-7) given during a sublethal dose of IAV infection greatly reduced morbidity associated with a subsequent S. pneumoniae infection, as seen by decrease in the magnitude of neutrophil influx, number of bacteria in the blood leading to a lower lethality. Altogether, these results show that Ang-(1-7) is highly protective against severe primary IAV infection and protects against secondary bacterial infection of the lung. These effects are MasR-dependent. Mediators of resolution of inflammation, such as Ang-(1-7), should be considered for the treatment of pulmonary viral infections.

Slaughter condemnation in bovine due to parasitic lesions and their economic impact in Federal Inspection System establishments in Brazil and in State inspection System in Rio Grande do Sul State / Condenação ao abate em bovinos devido a lesões parasitárias e seu impacto econômico em estabelecimentos do Sistema Federal de Inspeção no Brasil e no Sistema Estadual de Inspeção no Rio Grande do Sul

Abstract Slaughter condemnations are important sources of information on cattle health. The incidence of bovine parasitic diseases is still very high in Brazil. These diseases, in addition to causing harm to the animals health, are neglected zoonotic diseases in several parts of world. The study analysed not only the Carcass losses, but also the economic damage resulting from slaughter condemnations due to parasitic causes. Cattle slaughter data from the Brazilian Ministry of Agriculture, Livestock and Supply (MAPA), over the period of 2012 to 2015 and data from the Secretary of Livestock and Irrigation of the state of Rio Grande do Sul (SEAPI-RS) were analyzed between 2014 and 2018.The number of organs and carcasses condemned was multiplied by the respective values (in Brazilian Real) obtained from slaughterhouses and subsequently converted into dollars. Brazilian analysis in SIF (Federal Inspection System) establishments showed that more than 1.2 million organs (3,884,505 kg) and 20,000 carcasses (4,547,718 kg) were condemned only due to parasitic causes during post-mortem inspection. In Rio Grande do Sul, in state inspection establishments, more than 1.7 million organs (8,210,559 kg) and 5,000 carcasses (1,243,200 kg) were condemned. These data are alarming and support the need for public policies to control these parasitic diseases.

Resumo Condenações durante o abate são importantes fontes de informação sobre a sanidade dos rebanhos. Ainda são altas as incidências de doenças parasitárias, as quais trazem consequências à saúde dos animais, são zoonoses e têm sua importância negligenciada em diversos países. O estudo objetivou quantificar não apenas as perdas encontradas, mas o prejuízo econômico resultante das condenações ao abate por causas parasitárias. Para isso foram analisados dados de abate de bovinos do Ministério da Agricultura Pecuária e Abastecimento, no período de 2012 a 2015, e dados da Secretaria da Agricultura Pecuária e Irrigação, do estado do Rio Grande do Sul, no período de 2014 a 2018. A quantidade de órgãos e carcaças condenados foi multiplicada pelos respectivos valores (em Reais), obtidos da indústria frigorífica e, posteriormente, convertidos para dólar. A análise brasileira de estabelecimentos com SIF (Serviço de Inspeção Federal) mostrou que mais de 1,2 milhão de órgãos (3.884.505 kg) e 20 mil carcaças (4.547.718 kg) foram condenados devido a causas parasitárias durante a inspeção. No estado do Rio Grande do Sul, nos estabelecimentos de inspeção estadual, foram condenados mais de 1,7 milhão de órgãos (8.210.559 kg) e 5 mil carcaças (1.243.200 kg). Os dados são alarmantes e ressaltam a necessidade de políticas públicas para controlar estas parasitoses.

Protocol for a randomized clinical trial: telephone-based psychoeducation and support for female informal caregivers of patients with dementia / Protocolo para ensaio clínico randomizado: psicoeducação por telefone e apoio para cuidadoras informais femininas de pacientes com demência

OBJECTIVE: The burden felt by informal caregivers of patients with dementia is a source of physical, emotional, and financial problems. Face-to-face interventions for caregivers have accessibility limitations that may prevent them from receiving adequate care. Telehealth tools can be a solution to this problem. We will compare a telephone psychoeducational and support intervention protocol to usual care for informal female caregivers of patients with dementia treated at Brazilian specialized outpatient clinics. METHODS: In this single-blind randomized clinical trial, the intervention group will receive one weekly call for 8 weeks that addresses issues such as disease education, communication with the patient, and problematic behaviors. The control group will receive printed material on problematic behaviors in dementia. The primary outcome will be the difference in caregiver burden between baseline and 8 weeks, which will be assessed by blinded investigators through the Zarit Burden Interview scale. Caregiver burden at 16 weeks after baseline, depression, anxiety, and quality of life at 8 and 16 weeks are secondary outcomes. CONCLUSIONS: We expect the intervention to reduce caregiver burden. These results could lead to public health programs for improving dementia care in lower-middle-income countries. Ethics and dissemination: This trial was approved by an independent ethics committee. The results will be published in an international peer-reviewed medical journal. Trial registration number: NCT03260608

OBJETIVO: A sobrecarga sentida por cuidadores informais de pacientes com demência é uma fonte de problemas físicos, emocionais e financeiros. As intervenções face a face para cuidadores apresentam limitações de acessibilidade que podem impedilos de receber cuidados adequados. As ferramentas de telessaúde podem ser uma solução para esse problema. Comparamos um protocolo de intervenção psicoeducacional e de apoio por telefone ao tratamento usual para cuidadoras informais de pacientes com demência tratados em ambulatórios especializados. METODOLOGIA: Será realizado um ensaio clínico randomizado simples-cego. Durante 8 semanas, o grupo de intervenção receberá uma ligação semanal abordando questões como educação sobre a doença, comunicação com o paciente e comportamentos problemáticos. O grupo controle receberá material impresso sobre comportamentos problemáticos na demência. O resultado primário será a diferença na sobrecarga da cuidadora entre o ponto de partida e oito semanas, que será avaliada por pesquisadores cegos com a escala Zarit Burden Interview. Sobrecarga da cuidadora em dezesseis semanas após o início do estudo, depressão, ansiedade e qualidade de vida após oito e dezesseis semanas são resultados secundários. CONCLUSÕES: Esperamos que a intervenção reduza a sobrecarga da cuidadora. Esses resultados podem levar a programas de saúde pública para melhorar o tratamento da demência em países de renda médiabaixa. Ética e divulgação: Este estudo foi aprovado por um comitê de ética independente. Os resultados serão publicados em uma revista médica internacional revisada por pares. Número de registro do teste: NCT03260608.

Motivações do acesso de usuários em situações caracterizadas como não urgência em pronto atendimento / Motivations of user access in situations characterized as non-urgent ready / Motivaciones del acceso del usuario en situaciones caracterizadas como listo no urgente

Objetivo: identificar os motivos pelos quais os usuários em situações caracterizadas como não urgentes acessam o Pronto Atendimento em um município do estado do Rio Grande do Sul. Método: trata-se de um estudo descritivo e exploratório, desenvolvido a partir de uma abordagem qualitativa. Os dados foram coletados mediante entrevista semiestruturada com 21 usuários de um Pronto Atendimento em um município do estado do Rio Grande do Sul (RS), em novembro de 2016, e submetidos à análise de discurso. Resultados: apontam que a Atenção Primária não tem sido efetiva como porta de entrada para o sistema de saúde. As justificativas pela busca ao serviço de urgência foram: falta de profissional médico nas unidades de saúde; Unidade Básica de Saúde com pouca resolutividade; horário de funcionamento inadequado aos usuários; filas; demanda maior que a oferta em relação às consultas médicas; facilidade em realizar exames e receber medicação. Conclusão: o acesso dos usuários aos serviços de saúde deve permear os planejamentos em saúde, preferencialmente a nível local, de modo a permitir a definição de ações que sejam aplicáveis em conformidade com a realidade da comunidade

Objective: to identify the reasons why users in situations characterized as non-urgent access the Emergency Service in a municipality in the state of Rio Grande do Sul. Method: this is a descriptive and exploratory study, developed from a qualitative approach. Data were collected through semi-structured interviews with 21 users of an Emergency Department in a municipality in the state of Rio Grande do Sul (RS), in November 2016, and submitted to content analysis, thematic modality. Results: they point out that Primary Care has not been effective as a gateway to the health system. The justifications for seeking emergency services were: lack of medical professionals in health units; Basic Health Unit with little resolution; inadequate opening hours for users; queues; greater demand than supply in relation to medical consultations; ease in performing exams and receiving medication. Conclusion: users' access to health services must permeate health planning, preferably at the local level, in order to allow the definition of actions that are applicable in accordance with the reality of the community

Objetivo: identificar las razones por las cuales los usuarios en situaciones caracterizadas como no urgentes acceden al Servicio de Emergencia en un municipio del estado de Rio Grande do Sul. Método: se trata de un estudio descriptivo y exploratorio, desarrollado a partir de un enfoque cualitativo. Los datos fueron recolectados a través de entrevistas semiestructuradas con 21 usuarios de un Servicio de Emergencia en un municipio del estado de Rio Grande do Sul (RS), en noviembre de 2016, y sometidos a análisis de contenido, modalidad temática. Resultados: señalan que la Atención Primaria no ha sido eficaz como puerta de entrada al sistema de salud. Las justificaciones para buscar servicios de emergencia fueron: falta de profesionales médicos en las unidades de salud; Unidad Básica de Salud con poca resolución; horarios de apertura inadecuados para los usuarios; colas mayor demanda que oferta en relación a consultas médicas; facilidad para realizar exámenes y recibir medicamentos. Conclusión: el acceso de los usuarios a los servicios de salud debe permear la planificación de la salud, preferiblemente a nivel local, para permitir la definición de acciones que sean aplicables de acuerdo con la realidad de la comunidad

Peripheral levels of sST2 are increased in patients with temporal lobe epilepsy: Additional evidence of low-grade inflammation.

Inflammation plays a pivotal role in temporal lobe epilepsy (TLE) pathophysiology. IL-33 can act as a transcription factor or as a cytokine, the latter through the transmembrane ST2 receptor or its soluble isoform (sST2), presenting a dual role in neurological diseases. The aim of this study was to determine the plasma levels of IL-33 and sST2 in parallel with clinical features in patients with TLE. Peripheral blood from patients and controls was sampled for the measurement of plasma levels of IL-33 and sST2 by enzyme-linked immunoassay (ELISA). While there were similar levels of IL-33 between controls and patients, sST2 were increased in patients. IL33 and sST2 plasma levels were not associated with TLE-related clinical features. In a subgroup analysis, IL-33 levels correlated with memory performance. In conclusion, our results reinforce the concept of chronic low-grade inflammation in patients with TLE.

ACKR2 contributes to pulmonary dysfunction by shaping CCL5:CCR5-dependent recruitment of lymphocytes during influenza A infection in mice.

Inflammation triggered by influenza A virus (IAV) infection is important for viral clearance, induction of adaptive responses, and return to lung homeostasis. However, an exaggerated immune response, characterized by the overproduction of chemokines, can lead to intense lung injury, contributing to mortality. Chemokine scavenger receptors, such as ACKR2, control the levels of CC chemokines influencing the immune responses. Among the chemokine targets of ACKR2, CCL5 is important to recruit and activate lymphocytes. We investigated the role of ACKR2 during IAV infection in mice. Pulmonary ACKR2 expression was increased acutely after IAV infection preceding the virus-induced lung dysfunction. ACKR2-knockout (ACKR2-/-) mice were protected from IAV, presenting decreased viral burden and lung dysfunction. Mechanistically, the absence of ACKR2 resulted in augmented airway CCL5 levels, secreted by mononuclear and plasma cells in the lung parenchyma. The higher chemokine gradient led to an augmented recruitment of T and B lymphocytes, formation of inducible bronchus-associated lymphoid tissue and production of IgA in the airways of ACKR2-/- mice post-IAV. CCL5 neutralization in ACKR2-/- mice prevented lymphocyte recruitment and increased bronchoalveolar lavage fluid protein levels and pulmonary dysfunction. Finally, CCR5-/- mice presented increased disease severity during IAV infection, displaying increased neutrophils, pulmonary injury and dysfunction, and accentuated lethality. Collectively, our data showed that ACKR2 dampens CCL5 levels and the consequent recruitment of CCR5+ T helper 1 (Th1), T regulatory cells (Tregs), and B lymphocytes during IAV infection, decreasing pathogen control and promoting lung dysfunction in wild type mice. Therefore, ACKR2 is detrimental and CCR5 is protective during IAV infection coordinating innate and adaptive immune responses in mice.

Brazilian Articles in Top-Tier Dental Journals and Influence of International Collaboration on Citation Rates.

This study investigated the presence of co-authorship from Brazil in articles published in top-tier dental journals and analyzed the influence of international collaboration, article type (original research or review), and funding on citation rates. Articles published between 2015 and 2017 in 38 selected journals from 14 dental subareas were screened in Scopus. Bibliographic information, citation counts, and funding details were recorded for all articles (N=15619). Collaboration with other top-10 publishing countries in dentistry was registered. Annual citations averages (ACA) were calculated. A linear regression model assessed differences in ACA between subareas. Multilevel linear regression models evaluated the influence of article type, funding, and presence of international collaboration in ACA. Brazil was a frequent co-author of articles published in the period (top 3: USA=25.5%; Brazil=13.8%; Germany=9.2%) and the country with most publications in two subareas. The subjects with the biggest share of Brazil are Operative Dentistry/Cariology, Dental Materials, and Endodontics. Brazil was second in total citations, but fifth in citation averages per article. From the total of 2155 articles co-authored by Brazil, 74.8% had no co-authorship from other top-10 publishing countries. USA (17.8%), Italy (4.2%), and UK (3.2%) were the main co-author countries, but the main collaboration country varied between subjects. Implantology and Dental Materials were the subjects with most international co-authorship. Review articles and articles with international collaboration were associated with increased citation rates, whereas the presence of study funding did not influence the citations.

Brazilian articles in top-tier dental journals and influence of international collaboration on citation rates

Abstract This study investigated the presence of co-authorship from Brazil in articles published in top-tier dental journals and analyzed the influence of international collaboration, article type (original research or review), and funding on citation rates. Articles published between 2015 and 2017 in 38 selected journals from 14 dental subareas were screened in Scopus. Bibliographic information, citation counts, and funding details were recorded for all articles (N=15619). Collaboration with other top-10 publishing countries in dentistry was registered. Annual citations averages (ACA) were calculated. A linear regression model assessed differences in ACA between subareas. Multilevel linear regression models evaluated the influence of article type, funding, and presence of international collaboration in ACA. Brazil was a frequent co-author of articles published in the period (top 3: USA=25.5%; Brazil=13.8%; Germany=9.2%) and the country with most publications in two subareas. The subjects with the biggest share of Brazil are Operative Dentistry/Cariology, Dental Materials, and Endodontics. Brazil was second in total citations, but fifth in citation averages per article. From the total of 2155 articles co-authored by Brazil, 74.8% had no co-authorship from other top-10 publishing countries. USA (17.8%), Italy (4.2%), and UK (3.2%) were the main co-author countries, but the main collaboration country varied between subjects. Implantology and Dental Materials were the subjects with most international co-authorship. Review articles and articles with international collaboration were associated with increased citation rates, whereas the presence of study funding did not influence the citations.

Resumo Este estudo investigou a presença de coautoria do Brasil em artigos publicados nos principais periódicos odontológicos e analisou a influência da colaboração internacional, tipo de artigo (artigo original ou revisão) e financiamento nas taxas de citação. Artigos publicados entre 2015 e 2017 em 38 periódicos selecionados de 14 subáreas foram pesquisados no Scopus. Informações bibliográficas, número de citações e detalhes de financiamento foram registrados para todos os artigos (N=15619). Colaboração com outros países no top-10 de publicações em odontologia foi coletada. Médias anuais de citação (MAC) foram calculadas. Um modelo de regressão linear avaliou as diferenças de MAC entre as subáreas. Modelos multinível de regressão linear avaliaram a influência do tipo de artigo, financiamento e presença de colaboração internacional nas MAC. O Brasil foi coautor frequente de artigos publicados no período (top 3: EUA=25,5%; Brasil=13,8%; Alemanha=9,2%) e o país com mais publicações em duas subáreas. As subáreas com maior participação do Brasil foram Dentística/Cariologia, Materiais Dentários e Endodontia. O Brasil foi o segundo no total de citações, porém quinto em citações médias por artigo. Do total de 2155 artigos de coautoria do Brasil, 74,8% não tiveram coautoria de outros países do top-10 de publicação. EUA (17,8%), Itália (4,2%) e Reino Unido (3,2%) foram os principais países coautores, porém o principal país de colaboração variou entre as subáreas. Implantodontia e Materiais Dentários foram as subáreas com mais coautoria internacional. Artigos de revisão e artigos com colaboração internacional foram associados a maiores taxas de citação, enquanto a presença de financiamento do estudo não influenciou as citações.

Modificação e avaliação de gel de ácido fosfórico 35% com agente aromatizante / Modification and evaluation of 35% phosphoric acid gel with flavoring agent

Objetivos: O condicionamento da superfície dos tecidos dentários duros com ácido fosfórico 35% é normalmente utilizado para fornecer retenção micromecânica para adesivos odontológicos. Quando lavado da superfície, o ácido pode gerar gosto amargo e desagradável ao paladar do paciente. O objetivo deste estudo foi analisar o efeito da adição de um agente aromatizante à composição do gel de ácido fosfórico 35% e investigar se existe alteração de características fundamentais deste material, como sua capacidade de desmineralizar a superfície dentária. Métodos: Além de um grupo controle (sem flavorizante), foram testados grupos de ácido fosfórico 35% com a adição de 0,5% ou 3% do aromatizante (Aroma Abacaxi Pó; Bio Green Ingredients). Foram realizadas análises de viscosidade, estabilidade do pH e de desmineralização da superfície de esmalte condicionada por microscopia eletrônica de varredura, além de teste de resistência de união ao esmalte por microcisalhamento. Resultados: Apesar dos grupos apresentarem pequenas diferenças entre si, nenhuma das alterações se mostrou significativa, exceto o aumento da viscosidade do gel contendo 3% do aromatizante. Conclusões: A adição de agente aromatizante ao gel condicionador de ácido fosfórico 35% parece ser alternativa viável para reduzir os problemas relacionados ao contato com o sabor desagradável do material, uma vez que não promoveu alteração negativa significativa nas características e comportamento do ácido(AU)

Objectives: Etching of dental hard tissues surfaces with 35% phosphoric acid is usually used to provide micromechanical interlocking with dental adhesives. When washed from the surface, the acid can cause a bitter taste unpleasant to the patient. The aim of this study was to analyze the effect of the addition of a flavoring agent to 35% phosphoric acid gel and investigate whether there is change in the fundamental characteristics of this material, including its ability to demineralize dental surfaces. Methods: In addition to a control group (without flavoring agent), groups were tested with the addition of 0.5% or 3% of the flavoring compound (pineapple flavor powder, Bio Green Ingredients) to 35% phosphoric acid. Analyses of viscosity, pH stability and demineralization of enamel surfaces by scanning electron microscopy were carried out, as well microshear bond strength to enamel. Results: Although the groups had minor differences among themselves, none of the changes were significant, except the increased viscosity of the gel containing 3% of the flavoring agent. Conclusions: The addition of flavoring agent to 35% phosphoric acid gel conditioner seems to be a viable alternative to reduce the problems related to contact with the unpleasant taste of the material, since it promoted no negative changes in the characteristics and behavior of the acid(AU)

Age-related differences in conversational discourse abilities A comparative study.

Conversational discourse (CD) is among the most complex tasks in everyday life and relies on multiple cognitive domains (communicative and executive abilities). Alterations in discourse comprehension and production are often present in pathological aging. However, there is still a need to identify changes in healthy aging. OBJECTIVE: This study aimed to compare young and older adults for the frequency of impaired communicative behaviors on a CD task. Performance was scored according to the Complementary Procedure of Conversational Discourse Analysis (CPCDA), developed based on the CD task from the Montreal Communication Evaluation Battery. METHODS: A total of 95 participants (54 young-adults and 41 older adults) were evaluated. The frequency of communicative behaviors was compared between groups using MANCOVA and Chi-square tests. RESULTS: Young adults showed fewer impairments in expression, pragmatics, cohesion, coherence, comprehension and emotional prosody. Older adults showed higher levels of verbal initiative and had fewer word finding difficulties. Communicative behaviors associated with planning and self-monitoring (e.g. repetition of information and syllabic false starts) appear to be common in the speech of healthy individuals in general. CONCLUSION: Studies which evaluate both discursive and cognitive skills are required to identify age-related changes. This would allow for the development of screening tools for CD assessment and preventive programs.

O discurso conversacional (DC) está entre as tarefas diárias mais complexas e dependentes de múltiplos domínios cognitivos (habilidades comunicativas e executivas). Alterações na compreensão e produção do discurso são relatadas classicamente durante o envelhecimento patológico. No entanto, ainda é necessário esclarecer mudanças no envelhecimento saudável. OBJETIVO: Este estudo tem como objetivo comparar jovens adultos e idosos quanto à frequência de comportamento comunicativo desviante em uma tarefa de DC utilizando o Procedimento Complementar de Análise do Discurso Conversacional (PCADC), inspirado na tarefa de DC da Bateria Montreal de Avaliação da Comunicação. MÉTODOS: Um total de 95 indivíduos (54 adultos jovens e 41 idosos) foram avaliados. A frequência dos comportamentos comunicativos desviantes foi comparadas entre os grupos usando análise MANCOVA e Qui-quadrado. RESULTADOS: Adultos jovens apresentaram melhor desempenho nas habilidades comunicativas referentes à: expressão, pragmática, coesão, coerência, compreensão e linguística prosódica e emocional. O grupo de idosos obteve melhor desempenho nas variáveis: "falta de iniciativa verbal" e "procura ou troca palavra" do que os jovens. Itens associados ao planejamento da fala e auto-monitoramento (ex: "repete informações" e "realiza false start"), parecem estar associados a um comportamento comum na fala de indivíduos saudáveis em geral. CONCLUSÃO: Estudos que avaliem habilidades discursivas e cognitivas são necessários para identificar mudanças ​​influenciadas pela idade. Dessa forma, seria possível propor uma ferramenta de triagem para avaliação discursiva, bem como programas de intervenção preventiva.

Top-100 Most Cited Dental Articles with Authors from Brazil.

This study analyzes the characteristics of the top-100 most cited articles published in international dental journals with at least one coauthor affiliated to Brazil. A search in Scopus database for articles published between 1996 and 2017 was carried out in the 178 journals belonging to the category "Dentistry" identified in SCImago Journals & Country Rank. From the top-100 most cited articles, variables related to the journal, article, and authors were collected. Annual citation averages (ACA) and relative citation ratios (RCR) were calculated. Data were analyzed descriptively. There were 75 original reports and 25 reviews in the sample. The number of citations ranged between 124 and 657 (mean=202, median=168). The papers were published in 31 different journals (46% in only four journals), none based in Brazil. The most frequent subjects (61%) were Dental Materials, Endodontics, and Periodontology, which accounted for 63.6% of the total citations. The subject with the highest ACA was Oral and Maxillofacial Surgery and the subject with the highest RCR was Oral Radiology. Only 12 articles were cited more than 300 times. International collaboration was present in 61 articles and funding was reported in 49 articles. The first author was from Brazil in 70% and corresponding author in 55% of the papers. Southeast (83%) and South (20%) were the regions of Brazil with most presence of coauthors. This top-100 list is presented to provide an overview of the most cited articles and aid in supporting further analyses regarding publication and citation behaviors of Brazilian dentistry.