Transcriptome Analysis Identifies the Crosstalk between Dendritic and Natural Killer Cells in Human Cutaneous Leishmaniasis.

Skin ulcers of cutaneous leishmaniasis (CL) are characterized by a localized inflammatory response mediated by innate and adaptive immune cells, including dendritic cells (DC) and natural killer (NK) cells. Bidirectional interactions between DCs and NK cells contribute to tailor leishmaniasis outcome. Despite advances in the Leishmania biology field in recent decades, the mechanisms involved in DC/NK-mediated control of Leishmania sp. pathogenesis as well as the cellular and molecular players involved in such interaction remain unclear. The present study sought to investigate canonical pathways associated with CL arising from Leishmania braziliensis infection. Initially, two publicly available microarray datasets of skin biopsies from active CL lesions were analyzed, and five pathways were identified using differentially expressed genes. The "Crosstalk between DCs and NK cells" pathway was notable due to a high number of modulated genes. The molecules significantly involved in this pathway were identified, and our findings were validated in newly obtained CL biopsies. We found increased expression of TLR4, TNFRSF1B, IL-15, IL-6, CD40, CCR7, TNF and IFNG, confirming the analysis of publicly available datasets. These findings reveal the "crosstalk between DCs and NK cells" as a potential pathway to be further explored in the pathogenesis of CL, especially the expression of CCR7, which is correlated with lesion development.

A residência em saúde da família e comunidade no fortalecimento do Sistema Único de Saúde / La residencia de salud familiar y comunitaria en el fortalecimiento del Sistema Único de Salud / The family and community health residency in the strengthening of the Unified Health System

Objetivo: compreender a maneira como a residência em saúde da família e comunidade atua como instrumento para o fortalecimento e a defesa do Sistema Único de Saúde sob a ótica da enfermagem. Método: estudo do tipo exploratório-descritivo com abordagem qualitativa, desenvolvido com 13 enfermeiros residentes. Neste estudo, os dados foram coletados de modo remoto por meio de entrevista semiestruturada, processados pelo software IRaMuTeQ e interpretados conforme análise de conteúdo de Bardin. Resultados: os resultados apontam que as residências na área da saúde se expressam com força política, conhecimento teórico e formação na prática, essenciais para fortalecer o controle social. Conclusão: faz-se necessário que a formação dos profissionais seja orientada a partir dos princípios/objetivos do SUS e que ocorra o combate aos ataques iminentes, exemplificados pelo baixo financiamento e má gestão.

Objective: to understand the way in which residency in family and community health acts as an instrument for strengthening and defending the Unified Health System from the perspective of nursing. Method: exploratory-descriptive study with a qualitative approach, developed with 13 resident nurses.In this study, data were collected remotely with semi-structured interviews, processed by the IRAMUTEQ software, and interpreted according to Bardin's content analysis. Results: the results indicate that residencies in the health area express themselves with political force, theoretical knowledge, and training in practice, essential to strengthen social control. Conclusion: the training of professionals must be guided from the principles/objectives of the SUS and the fight against imminent attacks, exemplified by low funding and poor management, must occur.

Objetivo: comprender el modo en que la residencia en salud familiar y comunitaria actúa como instrumento de fortalecimiento y defensa del Sistema Único de Salud (SUS) desde la perspectiva de la enfermería. Método: estudio exploratório descriptivo, con enfoque cualitativo, desarrollado con 13 enfermeras residentes. En este estudio, los datos se recolectaron de forma remota mediante entrevistas semiestructuradas, que, posteriormente, fueron procesadas por el software IRaMuTeQ e interpretadas de acuerdo con el análisis de contenido de Bardin. Resultados: las residencias en el área de la salud se desarrollan con fuerza política, conocimiento teórico y formación práctica, lo que es esencial para fortalecer el control social. Conclusión: es necesario que la formación de los profesionales se base en los principios/objetivos del SUS y que ocurra la lucha contra los inminentes ataques, ejemplificados por una baja financiación y mala gestión.

The paradox of choice in the sexual and reproductive health and rights challenges of south-south migrant girls and women in Central America and Mexico: A scoping review of the literature.

The last decade has seen high levels of displacement in Central America and Mexico, with women and girls representing a growing share of this flow. Women and girls face a unique set of sexual and reproductive health risks, both as a direct result of the migration process, and as a consequence of violence, conflict and oppressive gender norms in the region. This scoping review adopts a five-stage process to search for, identify, and review selected literature to answer two questions: (1) what sexual and reproductive health and rights risks, challenges, and needs do women and girls face before and during displacement; and (2) how do issues of sexual and reproductive health and rights influence women and girls' coping mechanisms and decisions in displacement in the region? Extracted data from intersecting literature on migration, gender, and health in the corridors of migration in Central America and Mexico are mapped and analyzed against a framework adapted from the Guttmacher-Lancet Commission on components of sexual and reproductive health and rights. Many Central American and Mexican women and girls flee conditions of gang-related conflict, gender-based violence, poverty, and other situations of extreme disadvantage. Findings from this study demonstrate they face further deprivation and suffering from the denial of health and rights throughout the migratory cycle. This review finds that migrant women and girls encounter considerable barriers to accessing services of sexual and reproductive health, are vulnerable to sexually transmitted infections, and face many violations of sexual and reproductive rights. Young migrants and sex workers, who are often connected with irregular migration in border areas, appear to be particularly vulnerable. Findings also reveal that the literature tends to focus on sexual health and rights, with a relative paucity of evidence on wider reproductive health issues. Of critical importance is how women and girls must constantly balance risk and opportunity in situations of constrained choice, and how their coping strategies and decisions define and influence their migration trajectories and broader wellbeing. This review identifies a gap in the literature around comprehensive studies that define sexual and reproductive health and rights beyond the confines of disease and sexual behavior, as well as a need for greater focus on under-represented migrant groups such as adolescent girls.

Metabolic disorders and post-acute hospitalization in black/mixed-race patients with long COVID in Brazil: A cross-sectional analysis.

BACKGROUND: Although low-middle income countries have been disproportionately affected by the COVID-19 pandemic, there is scarce information about the impact of long COVID on their population. This study aimed to evaluate long COVID symptomatology, complications (hospital readmission and metabolic disorders), and main clinical features that impact Quality of Life (QoL). METHODS: This cross-sectional study provides a detailed clinical and laboratory picture of individuals who presented residual symptoms after mild to severe acute COVID-19. Between Aug-2020 to Sep-2021, long COVID patients were evaluated in a reference center for long COVID in Bahia State, Brazil. The EQ-5D-5L questionnaire accessed QoL. RESULTS: A total of 1164 (52 ±13.4 years, 57% female, 88% black/mixed-race) were evaluated 2.3 [IQR = 1.6-3.7] months after mild (n = 351, 30.2%), moderate (338, 29.0%) or severe (475, 40.8%) acute illness. Dyspnea (790, 67.9%), fatigue (738, 63.5%), and chest pain (525, 42.9%) were the most frequent residual symptoms regardless of acute severity, affecting the QoL of 88.9% of patients (n/N-826/925), mainly the domains of anxiety/depression and pain/discomfort. High levels of HbA1c were detected for 175 out of 664 patients (26.6%), 40% of them without a previous diagnosis of diabetes mellitus. Of note, hospital admission one-to-three months after the acute phase of disease was required for 51 (4.4%) patients. CONCLUSION: In this majority-black/mixed-race population, long COVID was associated with post-acute hospitalization, newly diagnosed diabetes mellitus, and decreased QoL, particularly in women and regardless of disease severity of acute infection, suggesting important implications for health care system.

Maternidade romatizada: expectativas do papel social feminino pós-concepção / Romatized motherhood: expectations of female social role post-conception / Maternidad romatizada: expectativas del rol social femenino post-concepción

O estudo objetivou compreender como a construção social em que a mulher está inserida, pode gerar implicaçõesparaamaternidade. Trata-sedeumestudodenaturezaexploratóriaedescritiva,comabordagemqualitativa,que utilizou a investigação em campo. Apopulação foi constituída por 13participantes as quais estivessem no períodopuerperal,usuárias da Atenção Básica da rede pública de saúde do município de Iguatu-CE. A coleta ocorreu no período de agosto a novembro de 2020. Ressalta-sequeasfalaexpostasnosresultados,retratamaexistênciade uma imposição social em torno da figura feminina para a maternidade, alémdisso,refere-seaalgunsdesafiosedificuldadesoriundosapósadescobertadagravidez.Quantoas consequências da romantização, denota-se a existência de uma sobrecarga, podendo geraruma gama de sentimentos, como angústia, tristeza, desamparo, frustração, entre outros.Verifica-se quematernidadeéummomentoímpar,devendoselevaremconsideraçãoahistóriadecadamulhere sua subjetividade. Logo, a mulher necessita de apoio esuporte das pessoas mais significantes da sua vida.

The study aimed to understand how the social construction in which women are inserted can generate implications for motherhood. This is an exploratory and descriptive study, with a qualitative approach, which used field research. The population consisted of 13 participants who were in the puerperal period, users of Primary Care of the public health network in the city of Iguatu-CE. The collection took place from August to November 2020. It is noteworthy that the speeches exposed in the results, portray the existence of a social imposition around the female figure for motherhood, in addition, it refers to some challenges and difficulties arising from after discovering the pregnancy. As for the consequences of romanticization, there is an overload, which can generate a range of feelings, such as anguish, sadness, helplessness, frustration, among others. It appears that motherhood is a unique moment, and the history of each woman and her subjectivity must be taken into account. Therefore, the woman needs supportand support from the most significant people in her life.

El estudio tuvo como objetivo comprender cómo la construcción social en la que se inserta la mujer puede generar implicaciones para la maternidad. Se trata de un estudio exploratorio y descriptivo, con abordaje cualitativo, que utilizó la investigación de campo. La población estuvo constituida por 13 participantes que se encontraban en el período puerperal, usuarias de la Atención Primaria de la red pública de salud en la ciudad de Iguatu-CE. La recolección se realizó de agosto a noviembre de 2020. Se destaca que los discursos expuestos en los resultados, retratan la existencia de una imposición socialen torno a la figura femenina para la maternidad, además, se refiere a algunos desafíos y dificultades surgidos a partir del descubrimiento de la el embarazo. En cuanto a las consecuencias de la romantización, existe una sobrecarga, que puede generar una gama de sentimientos, como angustia, tristeza, impotencia, frustración, entre otros. Parece que la maternidad es un momento único, y hay que tener en cuenta la historia de cada mujer y su subjetividad. Por lo tanto, la mujer necesita apoyo y apoyo de las personas más importantes de su vida.

SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study.

Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. Funding: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem.

Prediabetes Induces More Severe Acute COVID-19 Associated With IL-6 Production Without Worsening Long-Term Symptoms.

Aims: Pre-existing conditions, such as age, hypertension, obesity, and diabetes, constitute known risk factors for severe COVID-19. However, the impact of prediabetes mellitus (PDM) on COVID-19 severity is less clear. This study aimed to evaluate the influence of PDM in the acute and long-term phases of COVID-19. Materials and methods: We compared inflammatory mediators, laboratory and clinical parameters and symptoms in COVID-19 patients with prediabetes (PDM) and without diabetes (NDM) during the acute phase of infection and at three months post-hospitalization. Results: Patients with PDM had longer hospital stays and required intensive care unit admission more frequently than NDM. Upon hospitalization, PDM patients exhibited higher serum levels of interleukin 6 (IL-6), which is related to reduced partial pressure of oxygen (PaO2) in arterial blood, oxygen saturation (SpO2) and increased COVID-19 severity. However, at three months after discharge, those with PDM did not exhibit significant alterations in laboratory parameters or residual symptoms; however, PDM was observed to influence the profile of reported symptoms. Conclusions: PDM seems to be associated with increased risk of severe COVID-19, as well as higher serum levels of IL-6, which may constitute a potential biomarker of severe COVID-19 risk in affected patients. Furthermore, while PDM correlated with more severe acute-phase COVID-19, no long-term worsening of sequelae was observed.

In Vitro Differentiation of Human Dendritic Cells and their Markers in Leishmania Infection.

Leishmaniasis comprises a collection of clinical manifestations associated with the infection of obligate intracellular protozoans, Leishmania. The life cycle of Leishmania parasites consists of two alternating life stages (amastigotes and promastigotes), during which parasites reside within either arthropod vectors or vertebrate hosts, respectively. Notably, the complex interactions between Leishmania parasites and several cells of the immune system largely influence the outcome of infection. Importantly, although macrophages are known to be the main host niche for Leishmania replication, parasites are also phagocytosed by other innate immune cells, such as neutrophils and dendritic cells (DCs). DCs play a major role in bridging the innate and adaptive branches of immunity and thus orchestrate immune responses against a wide range of pathogens. The mechanisms by which Leishmania and DCs interact remain unclear and involve aspects of pathogen capture, the dynamics of DC maturation and activation, DC migration to draining lymph node (dLNs), and antigen presentation to T cells. Although a large body of studies support the notion that DCs play a dual role in modulating immune responses against Leishmania, the participation of these cells in susceptibility or resistance to Leishmania remains poorly understood. After infection, DCs undergo a maturation process associated with the upregulation of surface major histocompatibility complex (MHC) II, in addition to costimulatory molecules (namely, CD40, CD80, and CD86). Understanding the role of DCs in infection outcome is crucial to developing therapeutic and prophylactic strategies to modulate the immune response against Leishmania. This paper describes a method for the characterization of Leishmania-DC interaction. This detailed protocol provides guidance throughout the steps of DC differentiation, the characterization of cell surface molecules, and infection protocols, allowing scientists to investigate DC response to Leishmania infection and gain insight into the roles played by these cells in the course of infection.

DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination.

Background: Leishmaniasis is a neglected arthropod-borne disease that affects millions of people worldwide. Successful Leishmania infections require the mitigation of immune cell functions leading to parasite survival and proliferation. A large body of evidence highlights the involvement of neutrophils (PMNs) and dendritic cells (DCs) in the establishment of immunological responses against these parasites. However, few studies, contemplate to what extent these cells interact synergistically to constrain Leishmania infection. Objective: We sought to investigate how PMNs and infected DCs interact in an in vitro model of Leishmania amazonensis infection. Material and Methods: Briefly, human PMNs and DCs were purified from the peripheral blood of healthy donors. Next, PMNs were activated with fibronectin and subsequently co-cultured with L. amazonensis-infected DCs. Results: We observed that L. amazonensis-infected DC exhibited lower rates of infection when co-cultivated with either resting or activated PMNs. Surprisingly, we found that the release of neutrophil enzymes was not involved in Leishmania killing. Next, we showed that the interaction between PMNs and infected-DCs was intermediated by DC-SIGN, further suggesting that parasite elimination occurs in a contact-dependent manner. Furthermore, we also observed that TNFα and ROS production was dependent on DC-SIGN-mediated contact, as well as parasite elimination is dependent on TNFα production in the co-culture. Finally, we observed that direct contact between PMNs and DCs are required to restore the expression of DC maturation molecules during L. amazonensis infection. Conclusion: Our findings suggest that the engagement of direct contact between PMNs and L. amazonensis-infected DC via DC-SIGN is required for the production of inflammatory mediators with subsequent parasite elimination and DC maturation.

Investigating the Phagocytosis of Leishmania using Confocal Microscopy.

Phagocytosis is an orchestrated process that involves distinct steps: recognition, binding, and internalization. Professional phagocytes take up Leishmania parasites by phagocytosis, consisting of recognizing ligands on parasite surfaces by multiple host cell receptors. Binding of Leishmania to macrophage membranes occurs through complement receptor type 1 (CR1) and complement receptor type 3 (CR3) and Pattern Recognition Receptors. Lipophosphoglycan (LPG) and 63 kDa glycoprotein (gp63) are the main ligands involved in macrophage-Leishmania interactions. Following the initial recognition of parasite ligands by host cell receptors, parasites become internalized, survive, and multiply within parasitophorous vacuoles. The maturation process of Leishmania-induced vacuoles involves the acquisition of molecules from intracellular vesicles, including monomeric G protein Rab 5 and Rab 7, lysosomal associated membrane protein 1 (LAMP-1), lysosomal associated membrane protein 2 (LAMP-2), and microtubule-associated protein 1A/1B-light chain 3 (LC3). Here, we describe methods to evaluate the early events occurring during Leishmania interaction with the host cells using confocal microscopy, including (i) binding (ii) internalization, and (iii) phagosome maturation. By adding to the body of knowledge surrounding these determinants of infection outcome, we hope to improve the understanding of the pathogenesis of Leishmania infection and support the eventual search for novel chemotherapeutic targets.

Obtainment of Macrophages from Human Monocytes to Assess Leishmania braziliensis Infection Rate and Innate Host Immune Response.

Macrophages are multifunctional cells essential to the immune system function, and the primary host cell in Leishmania braziliensis (Lb) infection. These cells are specialized in microorganism recognition and phagocytosis, but also activate other immune cells and present antigens, as well as promote inflammation and tissue repair. Here, we describe a protocol to obtain mononuclear cells from peripheral blood (PBMC) of healthy donors to separate monocytes that then differentiate into macrophages. These cells can then be infected in vitro at different Lb concentrations to evaluate the ability to control infection, as well as evaluate host cell immune response, which can be measured by several methods. PBMCs were first isolated by centrifuging with Ficoll-Hypaque gradient and then plated to allow monocytes to adhere to culture plates; non-adherent cells were removed by washing. Next, adherent cells were cultured with macrophage-colony stimulating factor (M-CSF) for 7 days to induce macrophage differentiation. We suggest plating 2 x 106 cells per well on 24-well plates in order to obtain 2 x 105 macrophages. Fully differentiated macrophages can then be infected with Lb for 4 or 24 hours. This protocol results in a significant percentage of infected cells, which can be assessed by optical or fluorescence microscopy. In addition to infection index, parasite load can be measured by counting the numbers of parasites inside each cell. Further molecular and functional assays can also be performed in culture supernatants or within the macrophages themselves, which allows this protocol to be applied in a variety of contexts and also adapted to other intracellular parasite species.

Cell Migration and Cell Adhesion Assays to Investigate Leishmania-Host Cell Interaction.

Leishmania is an intracellular protozoan parasite that causes a broad spectrum of clinical manifestations, ranging from self-resolving localized cutaneous lesions to a highly fatal visceral form of the disease. An estimated 12 million people worldwide are currently infected, and another 350 million face risk of infection. It is known that host cells infected by Leishmania parasites, such as macrophages or dendritic cells, can migrate to different host tissues, yet how migration contributes to parasite dissemination and homing remains poorly understood. Therefore, assessing these parasites' ability to modulate host cell response, adhesion, and migration will shed light on mechanisms involved in disease dissemination and visceralization. Cellular migration is a complex process in which cells undergo polarization and protrusion, allowing them to migrate. This process, regulated by actin and tubulin-based microtubule dynamics, involves different factors, including the modulation of cellular adhesion to the substrate. Cellular adhesion and migration processes have been investigated using several models. Here, we describe a method to characterize the migratory aspects of host cells during Leishmania infection. This detailed protocol presents the differentiation and infection of dendritic cells, the analysis of host cell motility and migration, and the formation of adhesion complexes and actin dynamics. This in vitro protocol aims to further elucidate mechanisms involved in Leishmania dissemination within vertebrate host tissues and can also be modified and applied to other cell migration studies.

LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes.

Diabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19), the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. We aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of patients with and without diabetes hospitalized for COVID-19. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of the SARS-CoV-2 main receptor system (ACE2/TMPRSS2), and for the main molecule of the leukotriene B4 (LTB4) pathway (ALOX5). We found that diabetes activates the LTB4 pathway and that during COVID-19 it increases ACE2/TMPRSS2 as well as ALOX5 expression. Diabetes was also associated with COVID-19-related disorders, such as reduced oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen (FiO2) and arterial partial pressure of oxygen/FiO2 levels, and increased disease duration. In addition, the expressions of ACE2 and ALOX5 are positively correlated, with increased expression in patients with diabetes and COVID-19 requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB4 is significantly increased in individuals with diabetes. In addition, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB4 and IL-6 systemic levels, as well as ACE2/ALOX5 blood expression, could be early markers of severe COVID-19 in individuals with diabetes.

Oral Tolerance Induced by Heat Shock Protein 65-Producing Lactococcus lactis Mitigates Inflammation in Leishmania braziliensis Infection.

Cutaneous leishmaniasis caused by L. braziliensis induces a pronounced Th1 inflammatory response characterized by IFN-γ production. Even in the absence of parasites, lesions result from a severe inflammatory response in which inflammatory cytokines play an important role. Different approaches have been used to evaluate the therapeutic potential of orally administrated heat shock proteins (Hsp). These proteins are evolutionarily preserved from bacteria to humans, highly expressed under inflammatory conditions and described as immunodominant antigens. Tolerance induced by the oral administration of Hsp65 is capable of suppressing inflammation and inducing differentiation in regulatory cells, and has been successfully demonstrated in several experimental models of autoimmune and inflammatory diseases. We initially administered recombinant Lactococcus lactis (L. lactis) prior to infection as a proof of concept, in order to verify its immunomodulatory potential in the inflammatory response arising from L. braziliensis. Using this experimental approach, we demonstrated that the oral administration of a recombinant L. lactis strain, which produces and secretes Hsp65 from Mycobacterium leprae directly into the gut, mitigated the effects of inflammation caused by L. braziliensis infection in association or not with PAM 3CSK4 (N-α-Palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-L-cysteine, a TLR2 agonist). This was evidenced by the production of anti-inflammatory cytokines and the expansion of regulatory T cells in the draining lymph nodes of BALB/c mice. Our in vitro experimental results suggest that IL-10, TLR-2 and LAP are important immunomodulators in L. braziliensis infection. In addition, recombinant L. lactis administered 4 weeks after infection was observed to decrease lesion size, as well as the number of parasites, and produced a higher IL-10 production and decrease IFN-γ secretion. Together, these results indicate that Hsp65-producing L. lactis can be considered as an alternative candidate for treatment in both autoimmune diseases, as well as in chronic infections that cause inflammatory disease.

Metformin promotes susceptibility to experimental Leishmania braziliensis infection.

BACKGROUND: Metformin (MET) is a hypoglycemic drug used for the treatment of diabetes, despite interference in host immunity against microorganisms. Cutaneous infection caused by pathogens such as Leishmania braziliensis (Lb), the agent responsible for cutaneous leishmaniasis (CL) in Brazil, represents an interesting model in which to evaluate the effects associated with MET. OBJECTIVE: To evaluate the modulatory effect of MET in Lb infection. MATERIAL AND METHODS: Experimental study of Lb infection and MET treatment in BALB/c mice and Raw 264.7 macrophages. FINDINGS: MET treatment interfered with lesion kinetics, increased parasite load and reduced macrophage proliferation. Low concentrations of MET in Lb culture allow for the maintenance of stationary parasite growth phase. Lb-infected cells treated with MET exhibited increased parasite load. While both MET and Lb infection alone promoted the production of intracellular reactive oxygen species (ROS), reduced levels of ROS were seen in MET-treated Lb-infected macrophages. MAIN CONCLUSION: Experimental treatment with MET interfered with the kinetics of cutaneous ulceration, increased Lb parasite load, altered ROS production and modulated cellular proliferation. Our experimental results indicate that MET interfere with the evolution of CL.

Leukotriene B4 licenses inflammasome activation to enhance skin host defense.

The initial production of inflammatory mediators dictates host defense as well as tissue injury. Inflammasome activation is a constituent of the inflammatory response by recognizing pathogen and host-derived products and eliciting the production of IL-1ß and IL-18 in addition to inducing a type of inflammatory cell death termed "pyroptosis." Leukotriene B4 (LTB4) is a lipid mediator produced quickly (seconds to minutes) by phagocytes and induces chemotaxis, increases cytokine/chemokine production, and enhances antimicrobial effector functions. Whether LTB4 directly activates the inflammasome remains to be determined. Our data show that endogenously produced LTB4 is required for the expression of pro-IL-1ß and enhances inflammasome assembly in vivo and in vitro. Furthermore, LTB4-mediated Bruton's tyrosine kinase (BTK) activation is required for inflammasome assembly in vivo as well for IL-1ß-enhanced skin host defense. Together, these data unveil a new role for LTB4 in enhancing the expression and assembly of inflammasome components and suggest that while blocking LTB4 actions could be a promising therapeutic strategy to prevent inflammasome-mediated diseases, exogenous LTB4 can be used as an adjuvant to boost inflammasome-dependent host defense.

Condições clínicas de pacientes com hemofilia assistidos em um hemocentro regional: um estudo transversal / Clinical conditions of patients with hemophilia assisted in a regional hemocenter: a cross-section study / Condiciones clínicas de pacientes con hemofilia asistidos en hemocentro regional: estudio transversal

O objetivo do estudo foi caracterizar o perfil sociodemográfico e clínico de pacientes com hemofilia acompanhados em um Hemocentro Regional. Estudo epidemiológico de delineamento transversal com coleta de dados por análise documental com 30 prontuários de um Hemocentro Regional da região Centro-Sul do Ceará. Realizou-se análise estatística através do software Microsoft Office Excel® 2016. O trabalho foi aprovado pelo Comitê de Ética de Pesquisa. Predominou o sexo masculino (27), com idade de 20 a 59 anos, estado civil solteiro, ensino fundamental incompleto, residência em zona rural e renda inferior a 01 salário mínimo. Quanto ao perfil clínico, a hemofilia A na forma grave, apresentam sedentarismo, com histórico de procedimentos transfusionais. A maioria com duas ou mais manifestações clínicas associadas. Com a prevalência apontada entre os participantes, evidencia-se a necessidade de uma assistência integral e equânime, com ênfase nas ações de enfermagem.(AU)

The aim of the study was to characterize the sociodemographic and clinical profile of patients with hemophilia followed at a Regional Blood Center. Epidemiological cross-sectional study with data collection by document analysis with 30 records from a Regional Blood Center in the Center-South region of Ceará. Statistical analysis was performed using Microsoft Office Excel® 2016 software. The work was approved by the Research Ethics Committee. There was a predominance of males (27), aged 20 to 59 years, single marital status, incomplete elementary education, residing in rural areas and income below 01 minimum wage. As for the clinical profile, hemophilia A in severe form, has a sedentary lifestyle, with a history of transfusion procedures. Most have two or more associated clinical manifestations. With the prevalence pointed out among the participants, the need for comprehensive and equitable assistance is evident, with an emphasis on nursing actions.(AU)

El objetivo del estudio fue caracterizar el perfil sociodemográfico y clínico de los pacientes con hemofilia seguidos en un Centro Regional de Sangre. Estudio epidemiológico de diseño transversal con recolección de datos por análisis documental con 30 registros de un Centro Regional de Sangre de la región Centro-Sur de Ceará. El análisis estadístico se realizó con el software Microsoft Office Excel® 2016. El trabajo fue aprobado por el Comité de Ética en Investigación. Predominó el sexo masculino (27), de 20 a 59 años, estado civil soltero, educación primaria incompleta, residente en área rural e ingresos por debajo de 01 salario mínimo. En cuanto al perfil clínico, la hemofilia A en forma severa, tiene un estilo de vida sedentario, con antecedentes de procedimientos transfusionales. La mayoría tiene dos o más manifestaciones clínicas asociadas. Con la prevalencia señalada entre los participantes, se evidencia la necesidad de una atención integral y equitativa, con énfasis en las acciones de enfermería.(AU)

Unbalanced production of LTB4/PGE2 driven by diabetes increases susceptibility to cutaneous leishmaniasis.

Poorly controlled diabetes mellitus leads to several comorbidities, including susceptibility to infections. Hyperglycemia increases phagocyte responsiveness, however immune cells from people with diabetes show inadequate antimicrobial functions. We and others have shown that aberrant production of leukotriene B4 (LTB4) is detrimental to host defense in models of bacterial infection. Here, we will unveil the consequences of high glucose in the outcome of Leishmania braziliensis skin infection in people with diabetes and determine the role of LTB4 in human phagocytes. We show that diabetes leads to higher systemic levels of LTB4, IL-6 and TNF-α in cutaneous leishmaniasis. Only LTB4 correlated with blood glucose levels and healing time in diabetes comorbidity. Skin lesions of people with leishmaniasis and diabetes exhibit increased neutrophil and amastigote numbers. Monocyte-derived macrophages from these individuals showed higher L. braziliensis loads, reduced production of Reactive Oxygen Species and unbalanced LTB4/PGE2 ratio. Our data reveal a systemic inflammation driven by diabetes comorbidity in opposition to a local reduced capacity to resolve L. braziliensis infection and a worse disease outcome.

Participação universitária em defesa do Sistema Único de Saúde / University participation in defense of the Unified Health System

RESUMO Uma das conquistas essenciais da Reforma Sanitária foi a participação social, o principal motor para promoção da igualdade, haja vista que, por meio desta, diferentes grupos na saúde obtiveram voz, preceito valioso da base democrática. No contexto universitário, a temática tem sido incorporada sob diversos aspectos, conformando um ambiente que polariza opiniões e proporciona reflexões que corroboram, ou destoam, os da reforma e consolidação do Sistema Único de Saúde (SUS). Dessa forma, este estudo teve por objetivo investigar e discutir a participação dos universitários visando à defesa e ao fortalecimento do SUS. Trata-se de um estudo de campo, do tipo exploratório descritivo com abordagem qualitativa, sendo utilizada uma entrevista semiestruturada para coleta de dados, e o software IRaMuTeQ para o processamento. Para a apreciação, seguiu-se a análise categorial temática proposta por Minayo. Observou-se um conhecimento satisfatório quanto à importância da participação social em um contexto de movimentos sociais, porém, a participação ativa não ocorre de forma desejada ainda que seja em conferências e conselhos de saúde. Apesar das fragilidades, vislumbra-se um novo horizonte no qual a universidade seja um espaço que consolide este princípio do SUS.

ABSTRACT One of the essential achievements of Health Reform was social participation, the main driver for promoting equality, given that, through this, different groups in health have gained a voice, a valuable precept of the democratic base. In the university context, the theme has been incorporated in several aspects, forming an environment that polarizes opinions and provides reflections that corroborate, or contradict, those of the reform and consolidation of the Unified Health System (SUS). Thus, this study aimed to investigate and discuss the participation of university students in order to defend and strengthen the SUS. This is a field study, of the exploratory descriptive type with a qualitative approach, using a semi-structured interview for data collection, and the IRaMuTeQ software for processing. For the appreciation, the thematic categorical analysis proposed by Minayo was followed. Satisfactory knowledge was observed regarding the importance of social participation in a context of social movements, however, active participation does not occur in a desired way even if it is at conferences and health councils. Despite the weaknesses, a new horizon is envisaged in which the university is a space that consolidates this principle of SUS.