Reactive oxygen species trigger inflammasome activation after intracellular microbial interaction.

The intracellular production of reactive oxygen species (ROS), composed of oxygen-reduced molecules, is important not only because of their lethal effects on microorganisms but also due to their potential inflammatory and metabolic regulation properties. The ROS pro-inflammatory properties are associated with the second signal to inflammasome activation, leading to cleaving pro-IL-1ß and pro-IL18 before their secretion, as well as gasdermin-D, leading to pyroptosis. Some microorganisms can modulate NLRP3 and AIM-2 inflammasomes through ROS production: whilst Mycobacterium bovis, Mycobacterium kansasii, Francisella novicida, Brucella abortus, Listeria monocytogenes, Influenza virus, Syncytial respiratory virus, Porcine reproductive and respiratory syndrome virus, SARS-CoV, Mayaro virus, Leishmania amazonensis and Plasmodium sp. enhance inflammasome assembly, Hepatitis B virus, Mycobacterium marinum, Mycobacterium tuberculosis, Francisella tularensis and Leishmania sp. disrupt it. This process represents a recent cornerstone in our knowledge of the immunology of intracellular pathogens, which is reviewed in this mini-review.

Ivermectin-induced bacterial gut dysbiosis does not increase susceptibility to Pseudomonas aeruginosa lung infection but exacerbates liver damage.

Excessive use of medications, including the antiparasitic drug ivermectin, can lead to bacterial gut dysbiosis, an imbalance in the intestinal microbiome, which in turn may increase or decrease susceptibility to infectious processes. To better understand the effects of continuous ivermectin usage on the gut bacterial community, C57BL/6 isogenic mice were treated by gavage with ivermectin or saline. Ivermectin-induced bacterial gut dysbiosis is characterized by a decrease in Bacteroidetes, Firmicutes, Proteobacteria and Tenericutes and an increase in species of the phylum Verrucomicrobia. A pro-inflammatory immunostimulatory caecal content, as well as disruption of caecal tissue organization and liver tissue damage, was observed in mice with gut dysbiosis. However, ivermectin-induced gut dysbiosis did not lead to acute susceptibility to Pseudomonas aeruginosa lung infection: infected mice with and without gut dysbiosis showed similar rates of recovery of viable bacteria in organs, histopathology and differential cytokine expression in the lung. Therefore, an extension of liver damage was observed in ivermectin-treated and P. aeruginosa-infected mice, which was exacerbated by infection.

O "ser homem" nos serviços oferecidos pela Estratégia Saúde da Família: olhar do usuário / "Being a man" in the services offered by the family health strategy: the user's perspective

O trabalho buscou identificar o conhecimento do usuário e suas propostas acerca da oferta de serviços específicos à saúde do homem na Atenção Básica, tema de poucos estudos publicados. Foram entrevistados 101 homens nas 14 equipes da Estratégia Saúde da Família da zona urbana de um município do Estado de Minas Gerais. Utilizou-se a técnica de Análise Temática. Identificou-se insatisfação com o tempo de espera para o atendimento, marcação de consultas; falta de empatia dos profissionais de saúde; criticou-se a ausência de ações de promoção à saúde, divulgação de campanhas, falhas na administração pública e busca ativa para serviços em saúde do homem; a questão de gênero refletiu o contexto social do "ser homem", sendo o serviço de saúde tradicionalmente organizado na perspectiva materno-infantil, o que marginaliza o público-alvo e não contempla as dimensões da masculinidade.

This study aims to identify the user's knowledge and proposals about providing specific services towards men's health in Primary Care, the subject of few published studies. One hundred one men were interviewed in the 14 Family Health Strategy teams in an urban area of a municipality located in the state of Minas Gerais. The Thematic Analysis technique has been employed. Dissatisfaction concerning extended waiting periods for assistance, scheduling appointments, lack of empathy of health professionals, criticism about the absence of actions to promote health, dissemination campaigns, flaws in public administration, and active search for men's health services were identified; the gender issue reflected the social context of "being a man", with the health service traditionally organized from a maternal and child perspective, marginalizing the target audience and not including the masculinity dimensions.

Amoxicillin-induced gut dysbiosis influences estrous cycle in mice and cytokine expression in the ovary and the caecum.

PROBLEM: Gut dysbiosis is caused by several factors, including the use of antibiotics. Since intestinal dysbiosis is associated with a wide range of immunopathological and reproductive conditions, the main goal of this study was to evaluate amoxicillin-induced gut dysbiosis and its influence on the oestrous cycle in mice. METHOD OF STUDY: Mice were treated with amoxicillin or PBS, and faecal microbiota was evaluated by 16S rDNA metagenomic sequencing. The oestrous cycle was evaluated by vaginal cytology, vaginal opening and flow cytometry. After the induction of gut dysbiosis, the ovaries and the caecum were analysed to differential expression of IL-1ß and IL-10 genes and histological analysis. RESULTS: Amoxicillin-treated mice presented differing bacterial groups in the faecal microbiota when compared to the PBS-treated group indicating that amoxicillin treatment-induced gut dysbiosis and they gained weight. The vaginal cytology analysis showed that amoxicillin-induced gut dysbiosis decreased the number of cells but increased the relative number of leucocytes and altered the oestrous cycle. IL-1ß was shown to be upregulated in the caecum and in the ovary of the dysbiotic mice. On the other hand, IL-10 expression was shown to be diminished in both organs of the dysbiotic mice. The oocyte area from dysbiotic group presented lower than non-dysbiotic mice with increasing thickness of the pellucid zone. The follicular teak from dysbiotic mice showed lower thickness than non-dysbiotic mice. CONCLUSION: The results indicate that amoxicillin induces gut dysbiosis and influences the oestrous cycle and the inflammatory status of the ovary and the caecum.

Vancomycin-induced gut dysbiosis during Pseudomonas aeruginosa pulmonary infection in a mice model.

Pseudomonas aeruginosa is one of the most common opportunistic pathogens causing respiratory infections in hospitals. Vancomycin, the antimicrobial agent usually used to treat bacterial nosocomial infections, is associated with gut dysbiosis. As a lung-gut immunologic axis has been described, this study aimed to evaluate both the immunologic and histopathologic effects on the lungs and the large intestine resulting from vancomycin-induced gut dysbiosis in the P. aeruginosa pneumonia murine model. Metagenomic analysis demonstrated that vancomycin-induced gut dysbiosis resulted in higher Proteobacteria and lower Bacteroidetes populations in feces. Given that gut dysbiosis could augment the proinflammatory status of the intestines leading to a variety of acute inflammatory diseases, bone marrow-derived macrophages were stimulated with cecal content from dysbiotic mice showing a higher expression of proinflammatory cytokines and lower expression of IL-10. Dysbiotic mice showed higher levels of viable bacteria in the lungs and spleen when acutely infected with P. aeruginosa, with more lung and cecal damage and increased IL-10 expression in bronchoalveolar lavage. The susceptible and tissue damage phenotype was reversed when dysbiotic mice received fecal microbiota transplantation. In spite of higher recruitment of CD11b+ cells in the lungs, there was no higher CD80+ expression, DC+ cell amounts or proinflammatory cytokine expression. Taken together, our results indicate that the bacterial community found in vancomycin-induced dysbiosis dysregulates the gut inflammatory status, influencing the lung-gut immunologic axis to favor increased opportunistic infections, for example, by P. aeruginosa.

Satisfação do usuário com os serviços de saúde de atenção básica: percepção masculina / Satisfacción del usuario con los servicios de salud en la atención primaria: percepción masculina / User satisfaction with primary health care services: men's perception

RESUMO Objetivo: avaliar a satisfação do usuário do sexo masculino com os serviços oferecidos na atenção primária à saúde. Método: estudo descritivo, transversal, realizado em unidades da Estratégia de Saúde da Família por meio de entrevista com 104 homens, utilizando questionário social e instrumento validado. Na análise, utilizou-se o teste Exato de Fisher, considerando a significância de 5%. Resultado: o perfil predominante foi de homens brancos, heterossexuais, casados, com idade entre 50 e 59 anos, com emprego fixo, renda mensal entre um e dois salários mínimos e que não concluíram o ensino fundamental. Os maiores percentuais de satisfação foram com a cordialidade, o exame clínico e a atenção dada às queixas pelo médico/enfermeiro. O tempo em sala de espera, o acesso e o agendamento da consulta apresentaram os menores percentuais de satisfação. Usuários com ensino médio incompleto apresentaram avaliação mais positiva em relação à consulta, cordialidade do profissional e o tempo na sala de espera (p<0,05). Por sua vez, as explicações recebidas em consulta geraram mais insatisfação entre sujeitos que utilizam o serviço anualmente. Conclusão: os homens participantes do estudo estão mais insatisfeitos com a organização dos serviços de saúde do que com o atendimento dos profissionais

RESUMEN Objetivo: evaluar la satisfacción del usuario del género masculino con los servicios ofertados en la atención primaria de salud. Método: estudio descriptivo, transversal, conducido en unidades de la Estrategia de Salud de la Familia, mediante entrevistas con 104 hombres, utilizando cuestionario social e instrumento validado. En el análisis, se utilizó la prueba Exacta de Fisher, considerando la significación del 5%. Resultado: el perfil predominante consistió en hombres blancos, heterosexuales, casados, con edades entre 50 y 59 años, con empleo fijo, ingreso mensual entre uno y dos salarios mínimos y que no terminaron la escuela primaria. Los porcentajes más altos de satisfacción fueron con la cordialidad, el examen clínico y la atención prestada a las quejas por parte del médico/enfermero. El tiempo en la sala de espera, el acceso y la programación de consultas tuvieron los porcentajes más bajos de satisfacción. Los usuarios con escuela secundaria incompleta presentaron una evaluación más positiva con respecto a la consulta, la cordialidad del profesional y el tiempo en la sala de espera (p<0,05). A su vez, las explicaciones recibidas en las consultas generaron más insatisfacción entre los sujetos que usan el servicio anualmente. Conclusión: los hombres que participan en el estudio están más insatisfechos con la organización de los servicios de salud que con la atención brindada por los profesionales.

ABSTRACT Objective: To evaluate the satisfaction of male users with the services offered in primary health care. Method: descriptive cross-sectional study conducted in Family Health Strategy units through interviews with 104 men, using a social questionnaire and a validated instrument. The Fisher's exact test was used to analyze the data, considering the significance level of 5%. Result: the predominant profile was white, heterosexual, married men aged between 50 and 59 years, with fixed employment, monthly income between one and two minimum wages, and who had not completed elementary school. The highest percentages of satisfaction were found in the aspects of friendliness, clinical examination, and attention given by the doctor/nurse to the complaints presented. Length of time spent in the waiting room, access to consultations, and scheduling of consultations had the lowest percentages of satisfaction. Users with incomplete high school made a more positive assessment of the aspects consultation, friendliness of the professional, and time spent in the waiting room (p < 0.05). In turn, the explanations received in consultations generated more dissatisfaction among subjects who use the service in an annual basis. Conclusion: the men participating in the study were more dissatisfied with the organization of health services than with the care provided by professionals.

Satisfação do usuário com os serviços de saúde de atenção básica: percepção masculina / User satisfaction with primary health care services: men's perception

Objective: To evaluate the satisfaction of male users with the services offered in primary health care. Method:descriptive cross-sectional study conducted in Family Health Strategy units through interviews with 104 men, using a social questionnaire and a validated instrument. The Fisher's exact test was used to analyze the data, considering the significance level of 5%. Result:the predominant profile was white, heterosexual, married men aged between 50 and 59 years, with fixed employment, monthly income between one and two minimum wages, and who had not completed elementary school. The highest percentages of satisfaction were found in the aspects of friendliness, clinical examination, and attention given by the doctor/nurse to the complaints presented. Length of time spent in the waiting room, access to consultations, and scheduling of consultations had the lowest percentages of satisfaction. Users with incomplete high school made a more positive assessment of the aspects consultation, friendliness of the professional, andtime spent in the waiting room (p < 0.05). In turn, the explanations received in consultations generated more dissatisfaction among subjects who use the service in an annual basis. Conclusion:the men participating in the study were more dissatisfied withthe organization of health services than with the care provided by professionals.

Objetivo: avaliar a satisfação do usuário do sexo masculino com os serviços oferecidos na atenção primária à saúde. Método: estudo descritivo, transversal, realizado em unidades da Estratégia de Saúde da Família por meio de entrevista com 104 homens, utilizando questionário social e instrumento validado. Na análise, utilizou-se o teste Exato de Fisher, considerando a significância de 5%. Resultado: o perfil predominante foi de homens brancos, heterossexuais, casados, com idade entre 50 e 59 anos, com emprego fixo, renda mensal entre um e dois salários mínimos e que não concluíram o ensino fundamental. Os maiores percentuais de satisfação foram com a cordialidade, o exame clínico e a atenção dada às queixas pelo médico/enfermeiro. O tempo em sala de espera, o acesso e o agendamento da consulta apresentaram os menores percentuais de satisfação. Usuários com ensino médio incompleto apresentaram avaliação mais positiva em relação à consulta, cordialidade do profissional e o tempo na sala de espera (p<0,05). Por sua vez, as explicações recebidas em consulta geraram mais insatisfação entre sujeitos que utilizam o serviço anualmente. Conclusão: os homens participantes do estudo estão mais insatisfeitos com a organização dos serviços de saúde do que com o atendimento dos profissionais.

Antibiotic-induced dysbiosis effects on the murine gastrointestinal tract and their systemic repercussions.

The gastrointestinal tract has become a focus of study recently. The crosstalk between microbiota, especially bacteria, and the intestinal mucosa has to be accurately balanced in order to maintain physiological homeostasis in the human body. This dynamic interaction results in different levels of short-chain fatty acids (SCFAs), IgA, and T cell lymphocyte subsets, which could lead the human body towards health or disease. The disruption of this microbiome characterises gut dysbiosis. Antibiotics are usually prescribed to fight against bacterial infection. They can also modulate the human microbiome, since it acts directly over organisational taxonomic units (OTUs) when taken orally. As a result, these pharmaceuticals enable gut dysbiosis and its systemic effects due to microbiome disturbance. Here, current data have been gathered from mice model experiments and epidemiological studies in an antibiotic-centred perspective. The presented data suggest the importance of translational studies in a murine model focusing on GIT homeostasis with bacterial groups since any changes to the GIT-microbiota have systemic repercussions in human health and disease.