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Introdução:A inserção das equipes de saúde bucal na Estratégia Saúde da Família, embora tardia, representa um avanço significativo para a ampliação da cobertura e da qualidade dos serviços odontológicos no Brasil. No entanto, aindaexistem muitosdesafiosnas práticas do cirurgião-dentista na Estratégia Saúde da Família. A atuação majoritariamente clínica prejudica a realização deum trabalho humanístico, resolutivo, interdisciplinar e multiprofissional. Objetivo:Relatar a experiência de atuação de uma cirurgiã-dentista residente na Atenção Primária em Saúde no município de Santo Estêvão, Bahia, Brasil, durante o Programa de Residência Multiprofissional em Saúde da Família da Universidade Estadual de Feira de Santana. Metodologia:Trata-se de um estudo qualitativo, do tipo relato de experiência, que visa descrever as atividades desenvolvidas durante o Programa de Residência Multiprofissional em Saúde da Família, da Universidade Estadual de Feira de Santana, no município de Santo Estêvão, Bahia, Brasil, no período de março de 2022 a novembro de 2023. Resultados:As atividades descritas abrangem as diferentes possibilidades de trabalho do cirurgião-dentista na Atenção Primária, envolvendo ações assistenciais através das consultas individuais e levantamento epidemiológico, educação permanente e em saúde com atuação nos grupos operativos e capacitações com os profissionais da rede e as ações de planejamento e gestão, através do desenvolvimento de estratégias para fortalecer a rede de atenção à saúde. Conclusões:É preciso motivar os profissionais de saúde bucal a repensarem suas práticas, tendo como ponto de partida o investimento e o estímulo à educação permanente e continuada. A especialização em saúde da família permite que cirurgiões-dentistas que atuam ou têminteresse em trabalhar no serviço público desenvolvam habilidades e práticas voltadas para uma assistência integral e multiprofissional da saúde, contribuindo para a consolidação do Sistema Único de Saúde (AU).

Introduction:The oral health team inclusion in the Family Health Strategy represents a significant advance in expanding the coverage and quality of dental services in Brazil. However, there arestill many challenges in the dental surgeons practices in the Family Health Strategy. The ppredominantly clinical approach hinders the achievement of ahumanistic, problem-solving, and interdisciplinary and multidisciplinary. Objective:To report the experience of a dental surgeon resident in Primary Health Care in the city of Santo Estêvão, Bahia, Brazil, during the Multidisciplinary Residency Program in Family Health at the Universidade Estadual de Feira de Santana. Methodology:This is a qualitative study, experience report type, which aims to describe the activities developed during the Multidisciplinary Residency Program in Family Health at the Universidade Estadual de Feira de Santana, in the city of Santo Estêvão, Bahia, Brazil, from March 2022 to November 2023. Results:The activities described cover the different work possibilities of dental surgeons in Primary Care, involving assistance actions through individual consultations and epidemiological surveys, ongoing health education with work in operative groups and training with network professionals, and planning and management actions through the development of strategies to strengthen the health care network. Conclusion:It is necessary to motivate oral health professionals to rethink their practices, with investment and encouragement for permanent and continuing education as a starting point. Specialization in family health allows dental surgeons who work or are interested in working in the public service to develop skills and practices aimed at comprehensive and multidisciplinary health care, contributing to the consolidation of the Unified Health System (AU).

Introducción: La inclusión de los equipos de salud dental en la Estrategia de Salud Familiar, aunque tardía, representa un avance significativo en la ampliación de la cobertura y la calidad de los servicios dentales en Brasil. Sin embargo, los cirujanos dentistas siguen enfrentándose a muchos retos em la Estrategia de Salud Familiar. El enfoque mayoritariamente clínico obstacualiza la realización de um enfoque humanista, resolutivo, interdisciplinario y multiprofesional.Objetivo:Reportar la experiencia de un cirujano dentista residente en Atención Primaria de Salud en el ayuntamiento de Santo Estêvão, Bahía, Brasil, durante el Programa de Residencia Multiprofesional en Salud Familiar de la Universidad Estadual de Feira de Santana.Metodología:Se trata de un estudio cualitativo, del tipoinforme de experiencia, que tiene como objetivo describir las actividades desarrolladas durante el Programa de Residencia Multiprofesional en Salud Familiar de la Universidad Estadual de Feira de Santana, en el ayuntamiento de Santo Estêvão, Bahía, Brasil, de marzo de 2022 a noviembre de 2023. Resultados:Las actividades descritas abarcan las diferentes posibilidades de trabajo del cirujano dentista en la Atención Primaria, implicando actividades asistenciales mediante consultas individuales y encuestas epidemiológicas, educación sanitaria continuada con actuación en los grupos operativos y capacitaciones con los profesionales de la red y actividades de planificación y gestión mediante el desarrollo de estrategias de fortalecimiento de la red de atención sanitaria.Conclusiones:Es necesario motivar a los profesionales de la salud dental a replantear sus prácticas, con la inversión y el fomento de la formación permanente y continua como punto de partida. La especialización en salud familiar permite a los cirujanos dentistas que trabajan o están interesados en trabajar en el servicio público desarrollar competencias y prácticas dirigidas a la atención sanitaria integral y multiprofesional, contribuyendo a la consolidación del Sistema Único de Salud (AU).

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Chrysophyllum rufum leaves collected under different light conditions provide information on how this fact can influence the morphology of the species. The anatomy techniques applied to the samples showed that there were discreet differences in the characters considered diagnostic. This indicates that the plant is capable of adapting, despite its prevalence in both dry and humid environments. The pollen grains were acetolyzed, measured, described qualitatively, analyzed quantitatively, and illustrated using light microscopy (LM).

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Chagas disease (CD) is a worldwide public health problem. Benznidazole (BZ) is the drug used to treat it. However, in its commercial formulation, it has significant side effects and is less effective in the chronic phase of the infection. The development of particulate systems containing BZ is therefore being promoted. The objective of this investigation was to develop polymeric nanoparticles loaded with BZ and examine their trypanocidal impact in vitro. Two formulas (BNP1 and BNP2) were produced through double emulsification and freeze drying. Subsequent to physicochemical and morphological assessment, both formulations exhibited adequate yield, average particle diameter, and zeta potential for oral administration. Cell viability was assessed in H9C2 and RAW 264.7 cells in vitro, revealing no cytotoxicity in cardiomyocytes or detrimental effects in macrophages at specific concentrations. BNP1 and BNP2 enhanced the effect of BZ within 48 h using a treatment of 3.90 µg/mL. The formulations notably improved NO reduction, particularly BNP2. The findings imply that the compositions are suitable for preclinical research, underscoring their potential as substitutes for treating CD. This study aids the quest for new BZ formulations, which are essential in light of the disregard for the treatment of CD and the unfavorable effects associated with its commercial product.

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Optical microscopy videos enable experts to analyze the motion of several biological elements. Particularly in blood samples infected with Trypanosoma cruzi (T. cruzi), microscopy videos reveal a dynamic scenario where the parasites' motions are conspicuous. While parasites have self-motion, cells are inert and may assume some displacement under dynamic events, such as fluids and microscope focus adjustments. This paper analyzes the trajectory of T. cruzi and blood cells to discriminate between these elements by identifying the following motion patterns: collateral, fluctuating, and pan-tilt-zoom (PTZ). We consider two approaches: i) classification experiments for discrimination between parasites and cells; and ii) clustering experiments to identify the cell motion. We propose the trajectory step dispersion (TSD) descriptor based on standard deviation to characterize these elements, outperforming state-of-the-art descriptors. Our results confirm motion is valuable in discriminating T. cruzi of the cells. Since the parasites perform the collateral motion, their trajectory steps tend to randomness. The cells may assume fluctuating motion following a homogeneous and directional path or PTZ motion with trajectory steps in a restricted area. Thus, our findings may contribute to developing new computational tools focused on trajectory analysis, which can advance the study and medical diagnosis of Chagas disease.

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The adequate management of parasite co-infections represents a challenge that has not yet been overcome, especially considering that the pathological outcomes and responses to treatment are poorly understood. Thus, this study aimed to evaluate the impact of Schistosoma mansoni infection on the efficacy of benznidazole (BZN)-based chemotherapy in Trypanosoma cruzi co-infected mice. BALB/c mice were maintained uninfected or co-infected with S. mansoni and T. cruzi, and were untreated or treated with BZN. Body weight, mortality, parasitemia, cardiac parasitism, circulating cytokines (Th1/Th2/Th17); as well as heart, liver and intestine microstructure were analyzed. The parasitemia peak was five times higher and myocarditis was more severe in co-infected than T. cruzi-infected mice. After reaching peak, parasitemia was effectively controlled in co-infected animals. BZN successfully controlled parasitemia in both co-infected and T. cruzi-infected mice and improved body mass, cardiac parasitism, myocarditis and survival in co-infected mice. Co-infection dampened the typical cytokine response to either parasite, and BZN reduced anti-inflammatory cytokines in co-infected mice. Despite BZN normalizing splenomegaly and liver cellular infiltration, it exacerbated hepatomegaly in co-infected mice. Co-infection or BZN exerted no effect on hepatic granulomas, but increased pulmonary and intestinal granulomas. Marked granulomatous inflammation was identified in the small intestine of all schistosomiasis groups. Taken together, our findings indicate that BZN retains its therapeutic efficacy against T. cruzi infection even in the presence of S. mansoni co-infection, but with organ-specific repercussions, especially in the liver.

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Background: The interplay between bacterial virulence factors and the host innate immune response in pneumococcal meningitis (PM) can result in uncontrolled neuroinflammation, which is known to induce apoptotic death of progenitor cells and post-mitotic neurons in the hippocampal dentate gyrus, resulting in cognitive impairment. Vitamin B12 attenuates hippocampal damage and reduces the expression of some key inflammatory genes in PM, by acting as an epidrug that promotes DNA methylation, with increased production of S-adenosyl-methionine, the universal donor of methyl. Material and methods: Eleven-day-old rats were infected with S. pneumoniae via intracisternal injection and then administered either vitamin B12 or a placebo. After 24 hours of infection, the animals were euthanized, and apoptosis in the hippocampal dentate gyrus, microglia activation, and the inflammatory infiltrate were quantified in one brain hemisphere. The other hemisphere was used for RNA-Seq and RT-qPCR analysis. Results: In this study, adjuvant therapy with B12 was found to modulate the hippocampal transcriptional signature induced by PM in infant rats, mitigating the effects of the disease in canonical pathways related to the recognition of pathogens by immune cells, signaling via NF-kB, production of pro-inflammatory cytokines, migration of peripheral leukocytes into the central nervous system, and production of reactive species. Phenotypic analysis revealed that B12 effectively inhibited microglia activation in the hippocampus and reduced the inflammatory infiltrate in the central nervous system of the infected animals. These pleiotropic transcriptional effects of B12 that lead to neuroprotection are partly regulated by alterations in histone methylation markings. No adverse effects of B12 were predicted or observed, reinforcing the well-established safety profile of this epidrug. Conclusion: B12 effectively mitigates the impact of PM on pivotal neuroinflammatory pathways. This leads to reduced microglia activation and inflammatory infiltrate within the central nervous system, resulting in the attenuation of hippocampal damage. The anti-inflammatory and neuroprotective effects of B12 involve the modulation of histone markings in hippocampal neural cells.

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Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production.

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Oropouche virus (OROV) is the aetiological agent of Oropouche fever, the symptoms of which are common to most arboviruses, such as fever, headache, malaise, nausea and vomiting. More than half a million people have been infected with OROV since its isolation in 1955. Although Oropouche fever is classified as a neglected and emerging disease, to date, there are no antiviral drugs or vaccines available against the infection and little is known about its pathogenicity. Therefore, it is essential to elucidate the possible mechanisms involved in its pathogenesis. Since oxidative stress plays a pivotal role in the progression of various viral diseases, in this study, redox homeostasis in the target organs of OROV infection was evaluated using an animal model. Infected BALB/c mice exhibited reduced weight gain, splenomegaly, leukopenia, thrombocytopenia, anaemia, development of anti-OROV neutralizing antibodies, increased liver transaminases, and serum levels of pro-inflammatory cytokines tumour necrosis factor (TNF-α) and interferon-γ (IFN-γ). The OROV genome and infectious particles were detected in the liver and spleen of infected animals, with liver inflammation and an increase in the number and total area of lymphoid nodules in the spleen. In relation to redox homeostasis in the liver and spleen, infection led to an increase in reactive oxygen species (ROS) levels, increased oxidative stress biomarkers malondialdehyde (MDA) and carbonyl protein, and decreased activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Taken together, these results help elucidate some important aspects of OROV infection that may contribute to the pathogenesis of Oropouche.

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The present observational study was designed to characterize the integrative profile of serum soluble mediators to describe the immunological networks associated with clinical findings and identify putative biomarkers for diagnosis and prognosis of active tuberculosis. The study population comprises 163 volunteers, including 84 patients with active pulmonary tuberculosis/(TB), and 79 controls/(C). Soluble mediators were measured by multiplexed assay. Data analysis demonstrated that the levels of CCL3, CCL5, CXCL10, IL-1ß, IL-6, IFN-γ, IL-1Ra, IL-4, IL-10, PDGF, VEGF, G-CSF, IL-7 were increased in TB as compared to C. Patients with bilateral pulmonary involvement/(TB-BI) exhibited higher levels of CXCL8, IL-6 and TNF with distinct biomarker signatures (CCL11, CCL2, TNF and IL-10) as compared to patients with unilateral infiltrates/(TB-UNI). Analysis of biomarker networks based in correlation power graph demonstrated small number of strong connections in TB and TB-BI. The search for biomarkers with relevant implications to understand the pathogenetic mechanisms and useful as complementary diagnosis tool of active TB pointed out the excellent performance of single analysis of IL-6 or CXCL10 and the stepwise combination of IL-6 â†’ CXCL10 (Accuracy = 84 %; 80 % and 88 %, respectively). Together, our finding demonstrated that immunological networks of serum soluble biomarkers in TB patients differ according to the unilateral or bilateral pulmonary involvement and may have relevant implications to understand the pathogenetic mechanisms involved in the clinical outcome of Mtb infection.

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The use of mathematical modeling to represent, analyze, make predictions or providing information on data obtained in drug research and development has made pharmacometrics an area of great prominence and importance. The main purpose of pharmacometrics is to provide information relevant to the search for efficacy and safety improvements in pharmacotherapy. Regulatory agencies have adopted pharmacometrics analysis to justify their regulatory decisions, making those decisions more efficient. Demand for specialists trained in the field is therefore growing. In this review, we describe the meaning, history, and development of pharmacometrics, analyzing the challenges faced in the training of professionals. Examples of applications in current use, perspectives for the future, and the importance of pharmacometrics for the development and growth of precision pharmacology are also presented.

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Our aims were to create a catalog of cytological pictures and to evaluate the valence (level of pleasantness/unpleasantness) and arousal (level of calm/excitement) of these pictures in individuals with different occupations. The sample consisted of medical and law college students and cytopathologists. Valence and arousal score for general pictures were not modulated by expertise in cytology. However, students judged the cytological pictures to be lower in valence and in arousal than the cytopathologists. The cytopathologists classified cytological pictures with lesions as lower in valence and higher in arousal than cytological pictures without lesions.

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Objetivo: relatar a experiência do Grupo Tutorial III, no âmbito da gestão dos serviços, no que tange a interprofissionalidade e de como essa vivência pode contribuir para a tríade ensino-serviço-comunidade. Método: Trata-se de um relato de experiência, desenvolvido na Policlínica do George Américo e no Centro de Especialidades Odontológicas (CEO) Célia Pamponet, ao longo de doze meses, por bolsistas, preceptores e tutores, integrantes de um projeto de extensão desenvolvido pela Universidade Estadual de Feira de Santana. Resultados: Foi realizado um diagnóstico situacional das unidades que possibilitou intervenções como: oficinas para discussão de processos de trabalho, atuação com os diversos profissionais que compõem o quadro de servidores da Policlínica e CEO e montagem de melhorias operacionais em ambas unidades. Conclusão: Através das atividades desenvolvidas, o PET-Saúde contribuiu com a formação interprofissional de estudantes de saúde da Universidade Estadual de Feira de Santana, capacitando-os para enfrentar os desafios do SUS e fornecer uma assistência de qualidade

Objective: Reporting the experience of Tutorial Group III, in the scope of service management, regarding interprofessionalism and how this experience can contribute to the teaching-service-community triad. Method: This is an experience report, developed at Polyclínica do George Américo and at Centro de Especialidades Odontológicas (CEO) Célia Pamponet, over twelve months, by scholarship holders, preceptors and tutors, members of an extension project developed by State University of Feira de Santana. Results: a situational diagnosis of the units was carried out, which enabled interventions such as: workshops for the discussion of work processes, collaboration with the various professionals who make up the staff of the Polyclinic and CEO, and implementation of operational improvements in both units. Conclusion: Through the activities carried out, PET-Saúde contributed to the interprofessional training of health students at the State University of Feira de Santana, enabling them to face the challenges of the SUS and provide quality care.

Objetivo: Informar la experiencia del Grupo Tutorial III, en el ámbito de la gestión de servicios, en lo que respecta a la interprofesionalidad y cómo esta vivencia puede contribuir a la tríada enseñanza-servicio-comunidad. Método: Se trata de un relato de experiencia, desarrollado en la Policlínica do George Américo y en el Centro de Especialidades Odontológicas (CEO) Célia Pamponet, en un período de doce meses, por becarios, preceptores y tutores, integrantes de un proyecto de extensión desarrollado por la Universidad del Estado de Feria de Santana. Resultados: Se realizó un diagnóstico situacional de las unidades que permitió intervenciones como: talleres para discutir los procesos de trabajo, colaboración con los diversos profesionales que conforman el equipo de la Policlínica y el CEO, y implementación de mejoras operativas en ambas unidades. Conclusión: A través de las actividades realizadas, el PET-Saúde contribuyó para la formación interprofesional de los estudiantes de salud de la Universidad Estadual de Feira de Santana, capacitándonos para enfrentar los desafíos del SUS y brindar una atención de calidad.

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CONTEXT: The role of silymarin in hepatic lipid dysfunction and its possible mechanisms of action were investigated. OBJECTIVE: To evaluate the effects of silymarin on hepatic and metabolic profiles in mice fed with 30% fructose for 8 weeks. METHODS: We evaluated the antioxidant profile of silymarin; mice consumed 30% fructose and were treated with silymarin (120 mg/kg/day or 240 mg/kg/day). We performed biochemical, redox status, and histopathological assays. RT-qPCR was performed to detect ACC-1, ACC-2, FAS, and CS expression, and western blotting to detect PGC-1α levels. RESULTS: Silymarin contains high levels of phenolic compounds and flavonoids and exhibited significant antioxidant capacity in vitro. In vivo, the fructose-fed groups showed increased levels of AST, ALT, SOD/CAT, TBARS, hepatic TG, and cholesterol, as well as hypertriglyceridaemia, hypercholesterolaemia, and increased ACC-1 and FAS. Silymarin treatment reduced these parameters and increased mRNA levels and activity of hepatic citrate synthase. CONCLUSIONS: These results suggest that silymarin reduces worsening of NAFLD.

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Dogs are the most common domestic reservoir of Leishmania infantum, making canine visceral leishmaniasis (CVL) a serious public health issue. Identifying new methodologies that can mimic lymphoid and myeloid competence in naturally infected dogs could lower costs and save time in preliminary screenings of potential immunotherapeutic agents and vaccines against CVL. For that, we established a cell-to-cell communication approach between lymphocytes and myeloid cells from healthy, asymptomatic (infected, without apparent clinical signs) and symptomatic (infected with apparent clinical signs) dogs. Peripheral blood mononuclear cells (PBMC) from these dogs were used as source of CD4+, CD8+ T lymphocytes and macrophages, that were posteriorly infected with L. infantum GFP+ promastigotes (green fluorescent protein). Macrophages co-cultured with purified lymphocytes were tested for the ability to control cellular parasitism, and their microbicidal function by producing nitric oxide (NO) and reactive oxygen species (ROS). The kind of T cell response within the co-culture was also evaluated, by assessing their ability to produce interferon-gamma (IFN-γ) and interleukin 4 (IL-4). The data suggests that T lymphocytes from symptomatic dogs are more prone to produce IL-4 than the ones from asymptomatic dogs. Macrophages from asymptomatic dogs also demonstrated a higher microbicidal potential, with increased levels of NO and ROS production, compared to symptomatic dogs, mainly in highly parasitized cells. Together, our results identify the ratio of IL-4/IFN-γ produced by CD4+ and CD8+ T cells, as well as, the ratio between parasite GFP signal/NO and ROS signal in macrophages as potential immunological biomarkers of failure and success of the screened agents. Our findings also propose a reliable methodology that can be used to follow the immune response in trials of potential drugs or vaccines targeting CVL.

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This work presents the effects of the high-fat diet (H) consumed by the progenitor (G0) on cardiometabolic disorders and intestinal microbiota in the second-generation offspring (F2). The rats submitted to H (G0H) or control (C) (G0C) diets, during mating, gestation and lactation, generated F2 offspring (F2-G0H and F2-G0C, respectively), which received only the C diet. Both, G0H and F2-G0H, showed changes in the intestinal microbiota, increased MAP, plasma TAG levels, adiposity index and the inflammatory process in retroperitoneal fat and in the colon shown by increased TNF-α, MCP-1, MyD88 and CAV-1 gene expression. In addition, F2-G0H showed increased food intake, leptin resistance, total cholesterol and plasma levels of MCP-1 and reduced adiponectin. Regarding microbial communities, a greater diversity was observed in 5 unique families of bacteria that was correlated with cardiometabolic disorders. Overall, progenitors with cardiometabolic disorders induce an increase in food intake, systemic inflammation and microbiota alterations in the F2-G0H offspring.

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DNA methylation is an important epigenetic mechanism of gene expression control. The present study aimed to evaluate the temporal effect of isocaloric high-sugar diet (HSD) intake on the development of nonalcoholic fatty liver disease (NAFLD) and the role of DNA methylation in this event. Newly weaned Wistar rats were divided into eight groups and fed a standard chow diet or an HSD ad libitum for 4 weeks, 8 weeks, 15 weeks, and 18 weeks. After the experimental periods, the animals were euthanized and their livers were removed for histological analysis, gene expression of maintenance methylase (Dnmt1), de novo methylases (Dnmt3a and Dnmt3b), demethylases (Tet2 and Tet3) of DNA, and global DNA methylation. HSD intake led to the gradual development of NAFLD. HSD intake for 18 weeks was associated with downregulation of Dnmt1 expression and global DNA hypomethylation; these results were negatively correlated with more severe steatosis scores observed in these animals. The HSD consumption for 18 weeks was also associated with a decrease in Dnmt3a and Tet2 expression. Interestingly, the expression of de novo methyltransferase Dnmt3b was reduced by HSD during all experimental periods. Together, these results indicate that the downregulation of de novo DNA methylation, Dnmt3b, induced by HSD is the primary factor in the development of NAFLD. On the other hand, disease progression is associated with downregulation of maintenance DNA methylation and global DNA hypomethylation. These results suggest a link between the dynamic changes in hepatic DNA methylation and the development of NAFLD induced by an HSD intake.

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The control of human visceral leishmaniasis (VL) is hard since there are no vaccines available as well as the treatment is hampered by toxicity and resistant parasites. Furthermore, as human, and canine VL causes immunosuppression, the combination of drugs with immunostimulatory agents is interesting to upregulate the immunity, reducing side-effects, improving treatment approaches against disease. Herein, we assessed the immunochemotherapy using miltefosine along with a vaccine formulated by Leishmania braziliensis antigens + saponin + monophosphoryl lipid-A (LBSapMPL) in L. infantum-infected hamsters. Two months after infection, the animals received treatments, and after 15 days they were evaluated for the treatment effect. The potential anti-Leishmania effect of miltefosine + LBSapMPL-vaccine was revealed by a specific immune response activation reflecting in control of spleen parasitism using half the miltefosine treatment time. The treated animals also showed an increase of total and T-CD4 splenocytes producing IFN-γ and TNF-α and a decrease of interleukin-10 and anti-Leishmania circulating IgG. In addition, it was demonstrated that the control of spleen parasitism is related to the generation of a protective Th1 immune response. Hence, due to the combinatorial action of miltefosine with LBSapMPL-vaccine in immunostimulating and controlling parasitism, this immunochemotherapy protocol can be an important alternative option against canine and human VL.

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The incidence of cardiovascular diseases and metabolic disorders has increased worldwide. Clinical and experimental research has shown that the consumption of ω-3 FAs can be beneficial to metabolism in several ways, as they can act on metabolic pathways. Our objective was to evaluate the effect of treatment with linseed oil, a vegetable oil rich in alpha-linolenic acid, and EPA and DHA in different proportions (3:1 EPA:DHA, and 1:3 EPA:DHA), on the metabolic disorders induced by a high-fat diet (20 % lipids) in rats for 2 weeks, after 18 weeks of consumption of a high-fat diet. In 18 weeks, the high-fat diet increased blood glucose, systolic blood pressure, triglyceride concentration in the liver and adipose tissue, and impaired insulin sensibility without interfering in the weight of the animals. All treatments were effective in reducing the deposition of hepatic type III collagen, the proportion of ω-6/ω-3 in the liver and WAT (white adipose tissue), the proportion of area/number of adipocytes, and the gene expression of the ACC, FAS, and CPT1 enzymes. In addition, treatment with EPA and DHA reduced blood glucose, serum TNF-α concentration, amount of liver fat, degree of microsteatosis and type I collagen deposition in the liver, deposition of type I and III collagen in TA, gene expression of the transcription factor SREBP-1c, and increased hepatic binucleation. EPA in major proportion was more effective in reducing the area of adipocytes, hepatic triglyceride concentration, PPAR-α expression, and WAT fat weight. DHA in a major proportion reduced the concentration of MCP1 in WAT. LO treatment did not have any isolated effects. We concluded that EPA and DHA were more effective in treating metabolic damage than treatment with LO, leading to a more favorable metabolic profile.

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To analyze the association of cervical cytological abnormalities with genetic polymorphisms of enzymes involved in folate metabolism, and the effect of micronutrients on association of polymorphisms with cervical carcinogenesis. Our samples were divided in Control (120 women with normal cytology), and Cases: 37 women with Atypical Squamous Cells of Undetermined Significance(ASC-US), 33 participants presenting Low-Grade Squamous Intraepithelial Lesion(LSIL), and 24 women presenting High-Grade cervical lesions(HSIL/ASC-H). We obtained cervical samples for cytological analysis, HPV detection, and analysis of polymorphisms and cervical cell folate. Blood samples were obtained for serum folate and vitamin B12 evaluation. To analyze all polymorphisms simultaneously, we calculated Genetic Risk Score(GRS). Median concentrations were used as cutoff for determination of micronutrient levels. We observed no differences of genotype or allelic frequencies of polymorphisms according to cervical lesions. However, high levels of cervical cell folate and high number of genetic alterations increased risk of High-Grade lesions [OR(IC95%):1.85(0.42-8.11)]. Instead, women with vitamin B12 ≤ 274 pg/ml and GRS ≥ 3 presented even greater risk of HSIL/ASC-H [OR(IC95%):2.91(0.46-18.62)]. High frequency of genetic polymorphisms involved in one-carbon metabolism associated with high levels of cell folate or low levels of serum vitamin B12, increased the risk of High-Grade lesion in uterine cervix.

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