Neutrophil to lymphocyte ratio and principal component analysis offer prognostic advantage for dogs with mammary tumors.

Introduction: In veterinary medicine, cancer is the leading cause of death in companion animals, and mammary gland tumors represent the most common neoplasm in female dogs. Several epidemiological risk factors, such as age, breed, hormones, diet, and obesity have been reported to be relevant for canine mammary tumors. Nowadays, the gold standard for diagnosis of canine mammary tumors is the pathological examination of the suspected tissue. However, tumor grade can only be assessed after surgical removal or biopsy of the altered tissue. Therefore, in cases of tumors that could be surgically removed, it would be very helpful to be able to predict the biological behavior of the tumor, before performing any surgery. Since, inflammation constitutes part of the tumor microenvironment and it influences each step of tumorigenesis, cellular and biochemical blood markers of systemic inflammation, such as the neutrophil to lymphocyte ratio (NLR) and the albumin to globulin ratio (AGR) have been proposed as prognostic factors for human cancer development. The NLR and the AGR have not been explored enough as prognostic factors for cancer development in veterinary medicine. Methods: To determine the prognostic value of NLR in canine mammary tumors, clinical records including biochemistry and hematological studies of female dogs with mammary tumors and of control healthy dogs, were used to determine the pre-treatment NLR and AGR. Other clinical data included age, breed, tumor size, histological tumor grade, and survival time after surgery. Results and discussion: It was found that a higher pre-treatment NLR value (NLR > 5) associates with less survival rate. In contrast, the AGR did not show any predictive value on the malignancy of the tumor. However, by combining the NLR with AGR, age of the dog, and tumor size in a principal component analysis (PCA), the grade of the tumor and survival after surgery could be appropriately predicted. These data strongly suggest that pre-treatment NLR values have a prognostic value for the survival rate after surgery of dogs with mammary tumors.

Neutrophils Actively Contribute to Obesity-Associated Inflammation and Pathological Complications.

Obesity is characterized by an increase in body weight associated with an exaggerated enlargement of the adipose tissue. Obesity has serious negative effects because it is associated with multiple pathological complications such as type 2 diabetes mellitus, cardiovascular diseases, cancer, and COVID-19. Nowadays, 39% of the world population is obese or overweight, making obesity the 21st century epidemic. Obesity is also characterized by a mild, chronic, systemic inflammation. Accumulation of fat in adipose tissue causes stress and malfunction of adipocytes, which then initiate inflammation. Next, adipose tissue is infiltrated by cells of the innate immune system. Recently, it has become evident that neutrophils, the most abundant leukocytes in blood, are the first immune cells infiltrating the adipose tissue. Neutrophils then get activated and release inflammatory factors that recruit macrophages and other immune cells. These immune cells, in turn, perpetuate the inflammation state by producing cytokines and chemokines that can reach other parts of the body, creating a systemic inflammatory condition. In this review, we described the recent findings on the role of neutrophils during obesity and the initiation of inflammation. In addition, we discuss the involvement of neutrophils in the generation of obesity-related complications using diabetes as a prime example.

Organophosphorus Pesticides as Modulating Substances of Inflammation through the Cholinergic Pathway.

Organophosphorus pesticides (OPs) are widespread insecticides used for pest control in agricultural activities and the control of the vectors of human and animal diseases. However, OPs' neurotoxic mechanism involves cholinergic components, which, beyond being involved in the transmission of neuronal signals, also influence the activity of cytokines and other pro-inflammatory molecules; thus, acute and chronic exposure to OPs may be related to the development of chronic degenerative pathologies and other inflammatory diseases. The present article reviews and discusses the experimental evidence linking inflammatory process with OP-induced cholinergic dysregulation, emphasizing the molecular mechanisms related to the role of cytokines and cellular alterations in humans and other animal models, and possible therapeutic targets to inhibit inflammation.

Successful endovascular treatment of severe chronic mesenteric ischemia facilitated by intraoperative positioning system image guidance.

We report our initial experience using the intraoperative positioning system (IOPS), a novel endovascular navigation system that does not require contrast or radiation, in the treatment of chronic mesenteric ischemia (CMI). We used IOPS to help treat three of four consecutive patients with CMI. Technical problems prevented successful use in one patient. For the patients for whom IOPS was used effectively, catheterization of the mesenteric artery was accomplished more quickly than for the patient for whom IOPS was not effective. Our experience has shown that IOPS can be safely and effectively used for CMI and can reduce the contrast load and radiation dose.

The Multiple Roles of Trogocytosis in Immunity, the Nervous System, and Development.

Trogocytosis is a general biological process that involves one cell physically taking small parts of the membrane and other components from another cell. In trogocytosis, one cell seems to take little "bites" from another cell resulting in multiple outcomes from these cell-cell interactions. Trogocytosis was first described in protozoan parasites, which by taking pieces of host cells, kill them and cause tissue damage. Now, it is known that this process is also performed by cells of the immune system with important consequences such as cell communication and activation, elimination of microbial pathogens, and even control of cancer cells. More recently, trogocytosis has also been reported to occur in cells of the central nervous system and in various cells during development. Some of the molecules involved in phagocytosis also participate in trogocytosis. However, the molecular mechanisms that regulate trogocytosis are still a mystery. Elucidating these mechanisms is becoming a research area of much interest. For example, why neutrophils can engage trogocytosis to kill Trichomonas vaginalis parasites, but neutrophils use phagocytosis to eliminate already death parasites? Thus, trogocytosis is a significant process in normal physiology that multiple cells from different organisms use in various scenarios of health and disease. In this review, we present the basic principles known on the process of trogocytosis and discuss the importance in this process to host-pathogen interactions and to normal functions in the immune and nervous systems.

Modification of Proliferation and Apoptosis in Breast Cancer Cells by Exposure of Antioxidant Nanoparticles Due to Modulation of the Cellular Redox State Induced by Doxorubicin Exposure.

In this report, we investigated whether the use of chitosan-carrying-glutathione nanoparticles (CH-GSH NPs) can modify proliferation and apoptosis, and reduce cell damage induced by doxorubicin on breast cancer cells. Doxorubicin is a widely used antineoplasic agent for the treatment of various types of cancer. However, it is also a highly toxic drug because it induces oxidative stress. Thus, the use of antioxidant molecules has been considered to reduce the toxicity of doxorubicin. CH-GSH NPs were characterized in size, zeta potential, concentration, and shape. When breast cancer cells were treated with CH-GSH nanoparticles, they were localized in the cellular cytoplasm. Combined doxorubicin exposure with nanoparticles increased intracellular GSH levels. At the same time, decreasing levels of reactive oxygen species and malondialdehyde were observed and modified antioxidant enzyme activity. Levels of the Ki67 protein were evaluated as a marker of cell proliferation and the activity of the Casp-3 protein related to cell apoptosis was measured. Our data suggests that CH-GSH NPs can modify cell proliferation by decreasing Ki67 levels, induce apoptosis by increasing caspase-3 activity, and reduce the oxidative stress induced by doxorubicin in breast cancer cells by modulating molecules associated with the cellular redox state. CH-GSH NPs could be used to reduce the toxic effects of this antineoplastic. Considering these results, CH-GSH NPs represent a novel delivery system offering new opportunities in pharmacy, material science, and biomedicine.

Low-Density Neutrophils in Healthy Individuals Display a Mature Primed Phenotype.

Neutrophils are the most abundant leukocytes in human peripheral blood, comprising about 70% of all leukocytes. They are regarded as the first line of defense of the innate immune system, but neutrophils have also the ability of regulating the adaptive immune response. Recently, However, multiple phenotypes and functional states of neutrophils have been reported, particularly in inflammation, autoimmunity, and cancer. One possible subtype of neutrophils, the so-called low-density neutrophils (LDN) is found among mononuclear cells (MNC), monocytes and lymphocytes, after separating the leukocytes from blood by density gradient centrifugation. LDN increase in numbers during several pathological conditions. However, LDN present in healthy conditions have not been investigated further. Therefore, in order to confirm the presence of LDN in blood of healthy individuals and to explore some of their cellular functions, neutrophils and MNC were isolated by density gradient centrifugation. Purified neutrophils were further characterized by multicolor flow cytometry (FACS) and then, using the same FACS parameters cells in the MNC fraction were analyzed. Within the MNC, LDN were consistently found. These LDN had a normal mature neutrophil morphology and displayed a CD10+, CD11b+, CD14low, CD15high, CD16bhigh, CD62L+, CD66b+, and CXCR4+ phenotype. These LDN had an enhanced reactive oxygen species (ROS) production and increased phagocytic capacity and were able to produce neutrophil extracellular traps (NET) similarly to neutrophils. These data confirm the presence of a small number of LDN is blood of healthy individuals and suggest that these LDN represent mature cells with a primed phenotype.

Correlation of hematological parameters and cycle threshold in ambulatory patients with SARS-CoV-2 infection.

INTRODUCTION: Former studies have shown that hematologic parameters are affected by the SARS-CoV-2 infection which has caused a global health problem. Therefore, this research aims to identify the most frequent symptoms and comorbidities in SARS-CoV-2 infected outpatients; besides, to analyze hematological parameters and their correlation with cycle threshold (Ct) values. METHODS: We analyzed a total of sixty outpatients with SARS-CoV-2 infection. They were divided according to sex. Afterward, a questionnaire was carried out to find out their symptoms and comorbidities. Additionally, blood biometry data were correlated with the Ct value, respectively. RESULTS: Sixty patients were analyzed; the mean age was 43 years. All patients were from Nayarit, Mexico. The frequency index showed that the main symptoms were headache and anosmia, and the comorbidities were obesity and smoking. The analysis of blood biometry showed a clear increase in red blood cells (RBC) related parameters in women. In both sexes an increase in the number of white blood cells (WBC) was observed. Also, all the hematological alterations correlated with the grade of infection. CONCLUSION: Headache and anosmia are the most common symptoms according to the frequency index, the main comorbidities were obesity and smoking. Also, there is a Ct value correlation with hematological parameters (WBC, mean corpuscular volume, mean corpuscular hemoglobin, hemoglobin); they can be used as a prognostic marker of infection.

Megacolon tóxico en paciente con COVID-19 / Toxic megacolon in a patient with Covid-19

Introducción: La pandemia derivada de la enfermedad por el nuevo coronavirus 2019 (COVID-19) se ha convertido en una emergencia de salud pública mundial, debido a que puede desarrollar complicaciones que amenazan la vida. Si bien se sabe que el SARS-CoV-2 causa enfermedad pulmonar sustancial, se han observado muchas manifestaciones extrapulmonares, incluyendo el compromiso del sistema gastrointestinal. El megacolon tóxico es una complicación rara pero, potencialmente, mortal que se asocia más con la enfermedad inflamatoria intestinal. Sin embargo, cualquier afección que conduzca a la inflamación del colon puede conducir a una dilatación tóxica. Objetivo: Se presenta el caso de un paciente con un síndrome de dificultad respiratoria aguda secundario a una infección por SARS-COV-2. De manera concomitante presentó un cuadro de dilatación no obstructiva del colon, asociado con toxicidad sistémica. Caso clínico: El desarrollo de megacolon tóxico en un paciente con SARS-COV-2 puede estar justificado debido a que el virus infecta las células huésped a través del receptor de la enzima convertidora de angiotensina 2. Se cumplieron los criterios diagnósticos para megacolon tóxico. Conclusiones: Esta también se encuentra altamente expresada en las células epiteliales intestinales, por lo tanto, se debe considerar su diagnóstico oportuno para una intervención temprana, en aras de reducir la tasa de mortalidad tanto como sea posible(AU)

Introduction: The pandemic derived from the 2019 novel coronavirus disease (COVID-19) has become a global public health emergency, due to the fact that it can develop life-threatening complications. Although SARS-CoV-2 is known to cause substantial lung disease, many extra-pulmonary manifestations have been observed, including involvement of the gastrointestinal system. Toxic mega colon is a rare but life-threatening complication most associated with inflammatory bowel disease. However, any condition that leads to inflammation of the colon can lead to toxic dilation. Objective: To report the case of a patient with ARDS secondary to a SARS-COV-2 infection. Concomitantly, she had non-obstructive dilation of the colon, associated with systemic toxicity. Clinical case report: The development of toxic mega colon in a patient with SARS-COV-2 may be justified because the virus infects host cells through the angiotensin-converting enzyme 2 receptor. The diagnostic criteria for toxic megacolon were met. Conclusions: It is also highly expressed in intestinal epithelial cells, therefore, its timely diagnosis should be considered for early intervention, in order to reduce the mortality rate as much as possible(AU)

Neutrophils at the crossroads of innate and adaptive immunity.

Neutrophils are the most abundant leukocytes in blood. From the circulation, they are quickly mobilized to sites of inflammation and/or infection. At the affected tissues, neutrophils display an impressive array of antimicrobial functions, including degranulation, production of reactive oxygen species (ROS), phagocytosis, and formation of neutrophil extracellular traps (NET). Because neutrophils are the first type of leukocytes to arrive at affected tissues and display potent microbicidal functions, they have been classically viewed as the first line of defense. In this view, neutrophils only destroy invading pathogens and then quietly die at the site of infection. However, in the last decade it has become increasingly evident that neutrophils are much more complex cells having not only effector functions in the innate immune response, but also the capacity of modulating the adaptive immune response, via direct interaction with, or by producing cytokines that affect dendritic cells and lymphocytes. In addition, neutrophil heterogeneity with clear different functional phenotypes has been recently described particularly in cancer and inflammation. This review provides an overview on the life of a neutrophil describing its beginnings, lifespan, and their principal functions in innate and adaptive immunity. Also, neutrophil heterogeneity and our current understanding of neutrophil contributions to health and disease are discussed.

Contribuições do Programa Mais Médicos ao desempenho de equipes de Saúde da Família na atenção à hipertensão e ao diabetes no Brasil, 2012 a 2015 / Contributions of the More Doctors Program to the performance of Family Health teams concerning hypertension and diabetes care in Brazil, 2012 to 2015 / Contribuciones del Programa Mais Médicos al desempeño de los equipos de salud de la familia en el cuidado de la hipertensión y la diabetes en Brasil, 2012-2015

Objetivo. Comparar as tendências temporais de acesso e utilização de serviços para controle de hipertensão arterial sistêmica (HAS) e diabetes mellitus (DM) em equipes com e sem a participação de profissionais do Programa Mais Médicos (PMM). Métodos. Utilizou-se um delineamento analítico-descritivo, com comparação entre equipes participantes do PMM (intervenção) e não participantes, em uma abordagem quase-experimental em série temporal. Comparouse o desempenho de uma amostra de 30 000 equipes da Estratégia Saúde da Família em 2012 e 20 000 equipes em 2015. Os padrões nos dois grupos foram analisados pela técnica de diferença-em-diferença com estratificação por região geopolítica, porte populacional e perfil municipal. A média semestral de atendimentos foi estimada pela divisão do número total de consultas de DM e HAS realizadas por médicos e enfermeiros em determinada equipe de saúde pelo total de usuários com DM/HAS cadastrados no mesmo local e período. Uma média de consultas/usuário maior do que 14,2 para DM e 10,8 para HAS foi considerada como outlier, sendo as equipes com essas médias excluídas das análises. Resultados. A análise de diferença-em-diferença indicou melhor desempenho na oferta de consulta para DM (P < 0,001) e HAS (P < 0,001) entre as equipes com PMM em comparação àquelas sem o programa. O efeito foi mais pronunciado nas regiões Norte e Nordeste, em municípios com mais de 20% da população em extrema pobreza e em municípios de todos os portes populacionais. Conclusões. Os resultados mostram que o PMM amplia o acesso e a utilização dos serviços de saúde.(AU)

Objective. To compare temporal trends in access and utilization of systemic arterial hypertension (SAH) and diabetes mellitus (DM) services provided by teams with or without physicians from the More Doctors Program (PMM). Method. An analytical-descriptive design was used, with comparison of teams that joined the PMM (intervention) vs. non-participants, using a quasi-experimental time series approach. The study compared the performance of a sample of 30 000 Family Health Strategy teams in 2012 and 20 000 teams in 2015. The patterns in both groups were analyzed using the difference-in-difference technique with stratification according to geopolitical region, population size, and municipal profile. The mean number of consultations per semester was estimated by dividing the total number of DM and HAS consultations provided by physicians and nurses in a given health care team by the total number of users with DM/HAS registered in the same location and period. A mean number of consultations/user > 14.2 for DM and > 10.8 for HAS was considered as an outlier, and thus the teams with these means were excluded from the analyses. Results. The difference-in-difference analysis indicated better performance in the provision of DM (P < 0.001) and SAH (P < 0.001) services among PMM teams vs. non-PMM teams. The effect was more pronounced in the North and Northeast regions, in municipalities with more than 20% of the population living in extreme poverty, and in municipalities of all population sizes. Conclusions. The results show that the PMM increased access and utilization of health care services.(AU)

Objetivo. Comparar las tendencias temporales del acceso y de la utilización de los servicios para el control de la hipertensión arterial sistémica (HAS) y la diabetes mellitus (DM) realizado por los equipos de salud de la familia que trabajan solos y por los que cuentan con la participación de profesionales del Programa Mais Médicos (PMM). Métodos. Se utilizó un diseño analítico y descriptivo, con comparación entre los equipos con participantes del PMM (intervención) y sin ellos, con un método cuasiexperimental de series temporales. Se comparó el desempeño de una muestra de 30 000 equipos que trabajaron dentro del marco de la estrategia de salud de la familia en el 2012 y de 20 000 equipos en el 2015. Se analizaron los patrones observados en ambos grupos con la técnica de doble diferencia con estratificación por zona geopolítica, tamaño de la población y perfil municipal. Se estimó la media semestral de casos atendidos con la división del número total de consultas por DM y HAS a cargo de médicos y miembros del personal de enfermería de un determinado equipo de salud por el total de usuarios con DM y HAS registrados en el mismo lugar y período. Se consideró que una media de consultas por DM por usuario mayor de 14,2 y por HAS mayor de 10,8 era un valor atípico y, por lo tanto, los equipos con esas medias se excluyeron de los análisis. Resultados. El análisis de doble diferencia indicó un mejor desempeño en la atención de consultas por DM (P < 0,001) y por HAS (P < 0,001) a cargo de los equipos con participantes del PMM en comparación con los que trabajaron sin ese programa. El efecto fue más pronunciado en las regiones norte y nordeste, en los municipios con más de 20% de la población en condiciones de extrema pobreza y en municipios de todos los tamaños de población. Conclusiones. Los resultados muestran que el PMM amplía el acceso y la utilización de los servicios de salud.(AU)

Sistema Integrado de Informações Mais Médicos: uma ferramenta de suporte à gestão baseada em evidências / More Doctors Integrated Information System: a tool to support evidence-based management / Sistema integrado de información de Más Médicos: una herramienta de apoyo a la gestión basada en la evidencia

O presente trabalho busca detalhar uma experiência pioneira de desenvolvimento de um sistema de informação em saúde voltado para subsidiar a gestão com base em evidências junto à atenção primária à saúde (APS). O processo de estruturação de programas e políticas públicas muitas vezes se dá sem acesso às melhores evidências científicas. Nesse contexto, o Sistema Integrado de Informações Mais Médicos (SIMM), aqui descrito, materializou um esforço para suprir a lacuna de informações para a gestão em saúde. Criado com objetivo de integrar os dados das principais fontes de informação relativas ao Projeto de Cooperação entre governo brasileiro e Organização Pan-Americana da Saúde/Organização Mundial da Saúde (OPAS/ OMS) para provimento de médicos no Programa Mais Médicos (PMM), o SIMM buscou otimizar a geração e a consolidação de informações que possam subsidiar decisões, além de apoiar o controle administrativo e financeiro. A experiência ilustra o desenvolvimento de uma solução auxiliar que pode ser ampliada para monitorar parâmetros de recursos humanos em saúde não apenas no PMM, mas na APS como um todo. A expertise desenvolvida criou condições para que o sistema pudesse ser configurado como um bem público, para além do suporte à gestão de um projeto em específico. O sistema pode ser adaptado e replicado em outros países das Américas para melhorar a disponibilidade e a qualidade das informações utilizadas por tomadores de decisão.(AU)

The present work provides details about a novel experience involving the development of a health information system focused on supporting evidence-based management at the primary health care (PHC) level. The process of structuring public health programs and policies is often developed without access to the best available scientific evidence. In this context, the proposed system (Sistema Integrado de Informações Mais Médicos, SIMM) materializes the effort to bridge the information gap for health management. Created with the aim of integrating data from the main information sources associated with the Cooperation Project between the Brazilian federal government and the Pan American Health Organization/World Health Organization (PAHO/ WHO) for provision of physicians for the More Doctors Program, SIMM strove to optimize the generation and consolidation of information to support decision-making, in addition to providing support for administrative and financial control. The experience illustrates the development of an ancillary solution that can be expanded to monitor human resources for health parameters across the entire PHC setting, far beyond the More Doctors Program. The resulting expertise created conditions for the system to be configured as a public asset, rather than being restricted to providing managerial support for a specific project. SIMM may be adapted and replicated in other American countries to improve the availability and quality of the information used by decision makers.(AU)

En el presente trabajo se detalla una experiencia pionera de desarrollo de un sistema de información de salud centrado en apoyar la gestión basada en la evidencia en el nivel de la atención primaria de salud. Muchas veces, el proceso de estructuración de los programas y políticas públicas se realiza sin acceso a las mejor evidencia científica. En ese contexto, el sistema integrado de información de Mais Médicos (SIMM) que se describe aquí materializó un esfuerzo para suplir la carencia de información para la gestión en materia de salud. El SIMM, creado con el objetivo de integrar los datos de las principales fuentes de información relativas al proyecto de cooperación entre el Gobierno del Brasil y la Organización Panamericana de la Salud/Organización Mundial de la Salud (OPS/OMS) para la provisión de médicos destinados al programa Más Médicos, se utilizó para optimizar la generación y consolidación de información a fin de sustentar las decisiones, además de servir de apoyo para el control administrativo y financiero. La experiencia ilustra el desarrollo de una solución complementaria que puede ampliarse para observar los parámetros de recursos humanos en salud no solo en el programa Más Médicos, sino en todo el ámbito de la atención primaria de salud. La pericia adquirida creó condiciones propicias para poder configurar el sistema como un bien público, con miras a ampliar su alcance más allá del apoyo a la gestión de un proyecto específico. Es posible adaptar y reproducir el sistema en otros países de la Región de las Américas para mejorar la disponibilidad y la calidad de la información utilizada por los responsables de tomar decisiones.(AU)

Análisis de la producción de conocimiento de los egresados de la especialización en salud de la familia del Programa Mais Médicos / Analysis of knowledge production by graduates of the family health specialization in the Mais Médicos Program / Análise da produção de conhecimento por egressos da especialização em saúde da família no Programa Mais Médicos

Objetivo. Identificar las principales categorías de análisis en los trabajos de conclusión de curso de los médicos egresados de la especialización en Salud de la Familia del Programa Mais Médicos. Métodos. Estudio de carácter bibliométrico de los 3021 trabajos de conclusión del curso disponibles en la base de datos del Acervo de Recursos Educativos en Salud, Universidad Abierta del Sistema Único de Salud, entre los años de 2016 y 2019. Para analizar los principales temas abordados se realizó un análisis por grupos, en dos etapas, de los descriptores referentes a cada trabajo. Resultados. De los 3021 trabajos de conclusión de curso, se analizaron 2750 con datos completos. En cuanto al perfil de los autores, hay una predominancia del sexo femenino, origen cubano y grupo etario de 31 a 40 años. Los resultados también evidencian una concentración de los núcleos de formación de los profesionales, así como de algunos conceptos alineados a los preceptos trabajados con mayor frecuencia relacionados al objeto de la atención primaria de salud. Conclusiones. El análisis del perfil de los trabajos de conclusión de curso destacó que los conceptos trabajados a lo largo del proceso de formación de los profesionales del Programa Mais Médicos se orientaron sobre todo a fortalecer la comprensión de las directrices estructurantes de la atención primaria. También logra el objetivo de acercar la capacitación médica sobre los problemas más relevantes en cada región del país.(AU)

Objective. Identify the main categories of analysis in the end-of-course projects completed by physicians who graduated in the family health specialization in the Mais Médicos Program. Methods. Bibliometric study of the 3,021 end-of-course projects found in the database of the Health Education Resources Collection (Open University of the Unified Health System) for the years 2016 to 2019. In order to analyze the main topics addressed in the projects, a two-step cluster analysis was conducted of the descriptors for each project. Results. Of the 3,021 end-of-course projects, 2,750 with complete data were analyzed. The profile of the authors was predominantly female, Cuban, and in the 31-40 years age group. The results show that professional training was concentrated in specific topics, most of them closely related to the goals of primary health care. Conclusions. The analysis of the profile of the end-of-course projects showed that the topics studied throughout the process of training the professionals in the Mais Médicos Program were focused mainly on greater understanding of the structural directives of primary care. Furthermore, the objective of focusing medical training on the most relevant problems in each region of the country was achieved.(AU)

Objetivo. Identificar as principais categorias de análise nos trabalhos de conclusão de curso realizados por médicos formados na especialização em saúde da família do Programa Mais Médicos (PMM). Métodos. Realizou-se um estudo bibliométrico que incluiu 3 021 trabalhos de conclusão identificados na base de dados da Coleção de Recursos Educativos em Saúde da Universidade Aberta do Sistema Único de Saúde (UMA-SUS) para os anos de 2016 a 2019. Os principais tópicos abordados nos projetos foram estudados a partir da análise em duas etapas dos descritores. Resultados. Dos 3 021 trabalhos de conclusão, 2 750 com dados completos foram analisados. Os autores foram predominantemente do sexo feminino, cubanos e na faixa etária de 31 a 40 anos. Os resultados mostram uma concentração em temas específicos, a maioria intimamente relacionada com os objetivos da atenção primária à saúde. Conclusões. A análise do perfil dos trabalhos de conclusão mostrou que os temas estudados ao longo do processo de formação dos profissionais do PMM enfocaram principalmente a maior compreensão das diretrizes estruturais da atenção primária. Além disso, foi alcançado o objetivo de direcionar a formação médica aos problemas mais relevantes em cada região do país.(AU)

Saúde e empoderamento das mulheres: estudo de caso do Programa Mais Médicos em municípios com presença de médicos cubanos / Women's health and empowerment: a case study of the More Doctors Program in municipalities with Cuban physicians / Salud y empoderamiento de las mujeres: estudio de caso del programa Mais Médicos en municipios con presencia de médicos cubanos

Objetivo. Descrever as representações de ser mulher das usuárias do Programa Mais Médicos (PMM), com perspectiva de gênero e raça, e as mudanças que o PMM trouxe quanto ao empoderamento e cuidado da saúde. Métodos. Trata-se de um estudo de caso descritivo, de corte transversal. O trabalho de campo foi realizado mediante entrevistas semiestruturadas, aplicação de uma técnica evocativa de associação de palavras e grupos focais em municípios com médicos cubanos, com amostras de tipo nominal para escolha dos municípios e de tipo intencional para a escolha de participantes. O tamanho das amostras foi definido em campo com base na técnica da saturação teórica. Os dados foram analisados por meio de análise de conteúdo e análise prototípica. Resultados. A cobertura da atenção básica foi fortalecida com os aportes do programa, segundo os quatro gestores entrevistados. As mulheres (103 na técnica evocativa e 120 nos grupos focais) relataram mudanças no modelo de atendimento, que se tornou mais humanizado, com impacto sobre sua percepção sobre os serviços de saúde, sobre a consulta médica, sobre os médicos e sobre a imagem de si mesmas e, em menor medida, sobre as práticas de cuidado da saúde. Conclusões. O PMM trouxe ganhos no empoderamento individual das mulheres, com reflexos potencialmente positivos para os comportamentos em saúde.(AU)

Objective. To describe the representations of being a woman by users of the More Doctors Program (Programa Mais Médicos, PMM) in Brazil, exploring the perspectives of gender and race, and the changes produced by PMM in terms of empowerment and health care. Methods. This is a descriptive, cross-sectional study. The field work was performed using semi-structured interviews, with application of an evocative word technique and focal groups in municipalities with Cuban physicians, with nominal selection of municipalities and intentional selection of participants. The size of the sample was defined in the field based on saturation. The data were analyzed by content and prototypical analyses. Results. Primary health care coverage was strengthened by the PMM, according to the four municipal health secretaries interviewed. Participants (103 in the evocative technique and 120 from focal groups) reported changes in the model of care, which became more humanized, with impact on their perception of health care services, medical consultations, and physicians, on the image they had of themselves and, to a lesser extent, on their health care practices. Conclusions. PMM produced individual empowerment gains for study participants, with potentially positive impacts on health care behaviors.(AU)

Objetivo. Describir las representaciones de la condición de ser mujer hechas por las usuarias del programa Mais Médicos, con una perspectiva de género y raza, y los cambios producidos por este programa en materia de empoderamiento y cuidado de la salud. Métodos. Se trata de un estudio de caso descriptivo y transversal. El trabajo de campo se realizó mediante entrevistas semiestructuradas, con aplicación de una técnica evocadora de asociación de palabras y grupos focales en municipios con presencia de médicos cubanos, con muestras de tipo nominal para la selección de los municipios y de tipo intencional para la selección de las participantes. El tamaño de las muestras se definió sobre el terreno con base en la técnica de la saturación teórica. Los datos se sometieron a análisis prototípico y de contenido. Resultados. Los aportes del programa fortalecieron la cobertura de la atención básica, según lo expresado por los cuatro gestores entrevistados. Las mujeres (103 de las entrevistadas con la técnica evocadora y 120 de los grupos focales) relataron cambios en los modelos de atención que hicieron que la atención se torne más humanizada y que incidieron en su percepción de los servicios de salud, las consultas médicas, los médicos, la imagen de sí mismas y, en menor grado, las prácticas de cuidado de la salud. Conclusiones. El programa Mais Médicos implicó adelantos en materia de empoderamiento individual de las mujeres, con repercusiones potencialmente favorables en los patrones de comportamiento relacionados con la salud.(AU)

Efeito do Programa Mais Médicos sobre internações sensíveis à atenção primária / Effect of the More Doctors Program on primary care sensitive conditions in Brazil / Efecto del Programa Más Médicos en las tasas de hospitalización por enfermedades que podrían tratarse en la atención primaria

O presente artigo teve como objetivo avaliar o efeito do Programa Mais Médicos (PMM) nas taxas de internação por condições sensíveis à atenção primária (ICSAP) por faixa etária no Brasil. Realizou-se um estudo longitudinal com abordagem em painel dinâmico. A unidade de análise foi o município, considerando os 5 570 municípios brasileiros no período de 2008 a 2016. Para avaliar o efeito do PMM, considerou-se a exposição do município ao programa. Identificaram-se os municípios em que pelo menos 50% dos médicos da atenção primária eram do PMM. Testes de robustez com exposições alternativas ao programa (30%, 40%, 60% e 70%) foram realizados. Um conjunto de variáveis de vulnerabilidade foi incluído como controle: número de médicos da APS e de enfermeiros/técnicos de enfermagem/auxiliares de enfermagem da Estratégia Saúde da Família por 10 000 habitantes; número de leitos hospitalares por 10 000 habitantes; índice de desenvolvimento municipal de educação e de renda e emprego; percentual da população com plano de saúde; e percentual de domicílios com rede de esgoto. Detectou-se um efeito consistente do PMM na redução das ICSAP. Esse resultado foi encontrado para todas as faixas etárias, apresentando maior efeito entre crianças (0 a 4 anos), com redução correspondente a 3,7% nas taxas de ICSAP. Em adultos (20 a 64 anos), a redução foi de 3,1%. Além disso, verificou-se que quanto maior a exposição do município ao PMM, maior o efeito na redução das ICSAP. Os municípios mais expostos ao PMM foram os municípios em maior condição de vulnerabilidade. Em conclusão, o PMM contribuiu para a melhoria da saúde da população, principalmente em áreas de alta vulnerabilidade.(AU)

The present article aimed at evaluating the effect of the More Doctors Program (PMM) on primary care sensitive conditions (PCSC) by age group in Brazil. A longitudinal study was performed using a dynamic panel data approach. Municipalities were considered as the unit of analysis; the 5 570 Brazilian municipalities existing in Brazil from 2008 to 2016 were analyzed. The effect of the PMM was evaluated according to the exposure of municipalities to the program. For that, the municipalities in which at least 50% of primary care physicians were linked to the PMM were identified. Robustness tests with alternative exposures to the program (30%, 40%, 60% and 70%) were performed. A set of vulnerability variables was included for control: number or primary care physicians, number of Family Health Strategy nurses/nursing technicians or assistants per 10 000 population; number of hospital beds per 10 000 population; municipal education development and income/employment indices; percentage of population with health insurance plans; and percentage of households with sewer lines. A consistent effect of the PMM on PCSC reduction was detected. This result was observed for all age groups, with greater impact on the 0 to 4 year-old group, in which a 3.7% reduction in PCSC rates was recorded. In adults (20 to 64 years), a 3.1% reduction was recorded. The results show that the higher the exposure to the PMM, the stronger the effect on PCSC reduction. Also, the municipalities with higher exposure to the PMM were the most vulnerable. In conclusion, the PMM contributed to improve the health of the population, especially in high vulnerability areas.(AU)

El objetivo de este artículo fue evaluar el efecto del Programa Más Médicos (PMM) en las tasas de hospitalización por enfermedades que podrían tratarse en la atención primaria por grupo etario en Brasil. Se realizó un estudio longitudinal con un método basado en una cohorte dinámica. Con el municipio como unidad de análisis, el estudio se extendió a los 5 570 municipios brasileños en el período 2008-2016. Para evaluar el efecto del PMM, se consideró la exposición de cada municipio al programa. Se identificaron los municipios donde al menos 50% de los médicos de atención primaria pertenecían al PMM. Se realizaron pruebas de robustez con diferentes grados de exposición al programa (30%, 40%, 60% y 70%). Se empleó como testigo un conjunto de variables de vulnerabilidad, a saber, el número de médicos de atención primaria de salud y de miembros del personal profesional, técnico y auxiliar de enfermería de la estrategia de salud de la familia por 10 000 habitantes; el número de camas hospitalarias por 10 000 habitantes; el índice de desarrollo municipal en materia de educación, ingresos y empleo; el porcentaje de la población con planes de atención de salud y el porcentaje de domicilios con red de alcantarillado. Se observó un marcado efecto del PMM en la reducción de la tasa de hospitalización por enfermedades que podrían tratarse en la atención primaria. Ese resultado se obtuvo en todos los grupos etarios, con un mayor efecto en los niños (de 0 a 4 años) cuyas tasas de hospitalización disminuyeron 3,7%. En adultos (de 20 a 64 años), la reducción fue de 3,1%. Además, se verificó que cuanto mayor era la exposición del municipio al PMM, más intenso era el efecto del programa en la reducción de dichas tasas. Los municipios más expuestos al PMM fueron los más vulnerables. En conclusión, el PMM contribuyó a mejorar la salud de la población, principalmente en las zonas con un alto índice de vulnerabilidade.(AU)

Surveillance for Hepatocellular Carcinoma: Does the Place Where Ultrasound Is Performed Impact Its Effectiveness?

BACKGROUND: Biannual ultrasound (US) is recommended as the clinical screening tool for hepatocellular carcinoma (HCC). The effectiveness of surveillance according to the place where US is performed has not been previously reported. AIMS: To compare the effectiveness of US performed in the center responsible for follow-up as opposed to US proceeding from centers other than that of follow-up. METHODS: This is a multicenter cohort study from Argentina. The last US was categorized as done in the same center or done in a different center from the institution of the patient's follow-up. Surveillance failure was defined as HCC diagnosis not meeting Barcelona Clinic Liver Cancer (BCLC) stages 0-A or when no nodules were observed at HCC diagnosis. RESULTS: From 533 patients with HCC, 62.4% were under routine surveillance with a surveillance failure of 38.8%. After adjusting for a propensity score matching, BCLC stage and lead-time survival bias, surveillance was associated with a significant survival benefit [HR of 0.51 (CI 0.38; 0.69)]. Among patients under routine surveillance (n = 345), last US was performed in the same center in 51.6% and in a different center in 48.4%. Similar rates of surveillance failure were observed between US done in the same or in a different center (32% vs. 26.3%; P = 0.25). Survival was not significantly different between both surveillance modalities [HR 0.79 (CI 0.53; 1.20)]. CONCLUSIONS: Routine surveillance for HCC in the daily practice improved survival either when performed in the same center or in a different center from that of patient's follow-up.

Entamoeba histolytica Induce Signaling via Raf/MEK/ERK for Neutrophil Extracellular Trap (NET) Formation.

Amoebiasis, the disease caused by Entamoeba histolytica is the third leading cause of human deaths among parasite infections. E. histolytica was reported associated with around 100 million cases of amoebic dysentery, colitis and amoebic liver abscess that lead to almost 50,000 fatalities worldwide in 2010. E. histolytica infection is associated with the induction of inflammation characterized by a large number of infiltrating neutrophils. These neutrophils have been implicated in defense against this parasite, by mechanisms not completely described. The neutrophil antimicrobial mechanisms include phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). Recently, our group reported that NETs are also produced in response to E. histolytica trophozoites. But, the mechanism for NETs induction remains unknown. In this report we explored the possibility that E. histolytica leads to NETs formation via a signaling pathway similar to the pathways activated by PMA or the Fc receptor FcγRIIIb. Neutrophils were stimulated by E. histolytica trophozoites and the effect of various pharmacological inhibitors on amoeba-induced NETs formation was assessed. Selective inhibitors of Raf, MEK, and NF-κB prevented E. histolytica-induced NET formation. In contrast, inhibitors of PKC, TAK1, and NADPH-oxidase did not block E. histolytica-induced NETs formation. E. histolytica induced phosphorylation of ERK in a Raf and MEK dependent manner. These data show that E. histolytica activates a signaling pathway to induce NETs formation, that involves Raf/MEK/ERK, but it is independent of PKC, TAK1, and reactive oxygen species (ROS). Thus, amoebas activate neutrophils via a different pathway from the pathways activated by PMA or the IgG receptor FcγRIIIb.

Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?

Neutrophils are the most abundant leukocytes in the circulation, and have been regarded as first line of defense in the innate arm of the immune system. They capture and destroy invading microorganisms, through phagocytosis and intracellular degradation, release of granules, and formation of neutrophil extracellular traps after detecting pathogens. Neutrophils also participate as mediators of inflammation. The classical view for these leukocytes is that neutrophils constitute a homogenous population of terminally differentiated cells with a unique function. However, evidence accumulated in recent years, has revealed that neutrophils present a large phenotypic heterogeneity and functional versatility, which place neutrophils as important modulators of both inflammation and immune responses. Indeed, the roles played by neutrophils in homeostatic conditions as well as in pathological inflammation and immune processes are the focus of a renovated interest in neutrophil biology. In this review, I present the concept of neutrophil phenotypic and functional heterogeneity and describe several neutrophil subpopulations reported to date. I also discuss the role these subpopulations seem to play in homeostasis and disease.

Adherence to Barcelona Clinic Liver Cancer therapeutic algorithm for hepatocellular carcinoma in the daily practice: a multicenter cohort study from Argentina.

BACKGROUND AND AIM: Adherence to the Barcelona Clinic Liver Cancer (BCLC) staging algorithm for the treatment of hepatocellular carcinoma is challenging in the daily practice. We aimed to analyze adherence to BCLC along with its effect on patient survival. PATIENTS AND METHODS: A cohort study was conducted in 14 hospitals from Argentina including patients with newly diagnosed hepatocellular carcinoma (2009-2016). Adherence was considered when the first treatment was the one recommended by the BCLC. RESULTS: Overall, 708 patients were included. At diagnosis, BCLC stages were as follows: stage 0 4%, A 43%, B 22%, C 9% and D 22%. Overall, 53% of the patients were treated according to BCLC, 24% were undertreated, and 23% overtreated. Adherence to BCLC increased to 63% in subsequent treatments. Independent factors associated with adherence to BCLC were the presence of portal hypertension [odds ratio: 1.63; 95% confidence interval (CI): 1.11-2.39] and BCLC stage C (odds ratio: 0.32; 95% CI: 0.12-0.72). In a multivariable model adjusting for portal hypertension and BCLC stages, adherence to BCLC showed improved survival (hazard ratio: 0.67; 95% CI: 0.52-0.87). CONCLUSION: Adherence to BCLC represents a challenge in the daily practice, with almost half of the patients being treated accordingly, showing that the decision-making process should be tailored to each individual patient.

Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina.

AIM: To investigate any changing trends in the etiologies of hepatocellular carcinoma (HCC) in Argentina during the last years. METHODS: A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease (NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit. RESULTS: A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers (n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC (37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLD-HCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015 (4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3% (P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups (6.6 ng/mL vs 26 ng/mL; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality. CONCLUSION: The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.