Phenotypical characterization of regulatory T cells in acute Zika infection.

Zika virus (ZIKV), alongside Dengue virus (DENV), Chikungunya virus (CHIKV), and Yellow Fever Virus (YFV) are prevalent arboviruses in the Americas. Each of these infections is associated with the development of associated disease immunopathology. Immunopathological processes are an outcome of counter-balancing impacts between effector and regulatory immune mechanisms. In this context, regulatory T cells (Tregs) are key in modulating the immune response and, therefore, in tissue damage control. However, to date, Treg phenotypes and mechanisms during acute infection of the ZIKV in humans have not been fully investigated. The main aim of this work was to characterize Tregs and their immunological profile related to cytokine production and molecules that are capable of controlling the exacerbated inflammatory profile in acute Zika infected patients. Using whole blood analyses of infected patients, an ex vivo phenotypical characterization of Tregs, circulating during acute Zika virus infection, was conducted by flow cytometry. We found that though there are no differences in absolute Treg frequency between infected and healthy control groups. However, pro-inflammatory cytokine up-regulation such as IFN-γ and LAP was observed in the acute disease. Furthermore, acute ZIKV patients expressed increased levels of CD39/CD73, perforin/granzyme B, PD-1, and CTLA-4, all markers involved in mechanisms used by Tregs to attempt to control strong inflammatory responses. Thus, the data indicates a potential contribution of Tregs during the inflammatory ZIKV infection response.

Human CD8 T-cell activation in acute and chronic chikungunya infection.

There is a need for more detailed elucidation of T-cell immunity in chikungunya infection. CD8 T cells are one of main actors against viruses. Here, we analysed CD8+ T lymphocytes from patients in the acute and chronic phases of chikungunya disease (CHIKD). Our results demonstrate that CD8+ T cells expressed higher ex vivo granzyme B, perforin and CD107A expression in patients in the acute phase of CHIKD compared with healthy individuals and higher ex vivo expression of CD69, interleukin-17A, interleukin-10 and CD95 ligand, and co-expression of CD95/CD95 ligand. These results elucidate the importance of these lymphocytes, demonstrating immune mechanisms mediated in human chikungunya infection.

New cost-effective bioconversion process of palm kernel cake into bioinsecticides based on Beauveria bassiana and Isaria javanica.

The present study aimed to add value to palm oil by-products as substrates to efficiently produce conidia of Beauveria bassiana and Isaria javanica (Hypocreales: Cordycipitaceae) for biological control of the whitefly Bemisia tabaci (Hemiptera: Aleyrodidae), through a solid-state fermentation process using palm kernel cake and palm fiber as nutrient source and solid matrix, respectively. The optimum culture conditions yielded high concentrations of viable conidia after air-drying, when the fungi were grown on palm kernel cake (B. bassiana 7.65 × 109 and I. javanica 2.91 × 109 conidia g-1 dry substrate) after 6 days under optimal growth conditions set to 60% substrate moisture and 32 °C. Both fungal strains exhibited high efficacy against third-instar whitefly nymphs, inducing mortality up to 62.9 and 56.6% by B. bassiana and I. javanica, respectively, assessed after 9 days post-application in a screenhouse. Furthermore, we noted that insect mortality was strongly correlated with high atmospheric moisture, while B. bassiana appeared to require shorter accumulative hours under high moisture to kill whitefly nymphs compared to I. javanica. Our results underpin a feasible and cost-effective mass production method for aerial conidia, using palm kernel as the main substrate in order to produce efficacious fungal bioinsecticides against an invasive whitefly species in Brazil. Finally, our fermentation process may offer a sustainable and cost-effective means to produce eco-friendly mycoinsecticides, using an abundant agro-industrial by-product from Brazil that will ultimately assist in the integrated management of agricultural insect pests.

Enhancing pulmonary delivery and immunomodulation of respiratory diseases through virus-mimicking nanoparticles.

This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycol-coated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 ± 24 nm, a neutral zeta potential, osmolarity of 358 ± 28 mOsmol/kg, and a pH of 6.5. Nebulizing without leakage and showing no toxicity to epithelial cells, NBL display mucoadhesive properties with a 60% mucin-binding efficiency. They effectively traverse the dense mucus layer of Calu-3 cultures in an air-liquid interface, as supported by a 55% decrease in MUC5AC density and a 29% increase in nanoparticles internalization compared to non-exposed cells. In assessing immunomodulatory effects, NBL treatment in SARS-CoV-2-infected lung cells leads to a 40-fold increase in anti-inflammatory MUC1 gene expression, a proportional reduction in pro-inflammatory IL-6 expression, and elevated anti-inflammatory IL-10 expression. These findings suggest a potential mechanism to regulate the excessive IL-6 expression triggered by virus infection. Therefore, the NBL platform demonstrates promising potential for efficient pulmonary drug delivery and immunomodulation, offering a novel approach to addressing mucus permeation and inflammation in pulmonary diseases.

Primary care in supplementary health: assessment of costs in the care of older adult patients with heart diseases.

OBJECTIVES: to identify whether implementing a supplementary Primary Health Care (PHC) system makes it possible to reduce care costs for older adults with heart diseases. METHODS: a retrospective cohort of 223 patients with heart disease aged ≥ 60 years. Data were obtained from medical records and cost databases, assessed for a period of one year before and after PHC implementation. The results were expressed as mean absolute frequencies for number of hospitalizations and as average annual expenses expressed in dollars (US$) in relation to cost data. RESULTS: there was a reduction in hospitalization expenses after implementing supplementary PHC (p=0.01) and a decrease in the frequency of hospitalizations for the entire sample (p=0.006). There was a reduction in the frequency of consultations at the Emergency Room among frail older adults (p=0.011). CONCLUSIONS: there was a reduction in hospitalization costs and frequency of visits to the Emergency Room after supplementary PHC.

Downregulation of CD73 on CD4+ T cells from patients with chronic Chikungunya infection.

Chikungunya is an important mosquito-borne disease caused by the arthritogenic chikungunya virus, characterized by sporadic outbreaks all around the world. Although CD4+ T cells seem to have an important role in the pathogenesis of chikungunya, the mechanisms involved in this process are not yet fully elucidated. The ectoenzymes CD39 and CD73, also expressed by CD4 T lymphocytes, are involved in the hydrolysis of pro-inflammatory extracellular ATP and generation of immunosuppressive adenosine and seem to be modulated in some arthritogenic pathologies. However, their involvement in Chikungunya disease is unclear. Thus, using flow cytometry, we investigated peripheral CD4+ T cells from patients with acute and chronic chikungunya to assess the expression of ectonucleotidases CD39 and CD73 and coinhibitory receptors and production of cytokine and cytolytic granules. Patients in the acute phase displayed increased levels of PD-1, CTLA-4, IL-10, and IFN-γ compared to healthy individuals and patients in the chronic phase. Moreover, during chronic Chikungunya, analyses of Mean Fluorescent Intensity (MFI) demonstrated a reduced density of LAP, Perforin and Granzyme B compared to the healthy control. Finally, reduced levels of the ectoenzymes CD39 and CD73 expression was found during the chronic phase suggesting a possible modulation of extracellular ATP and adenosine by CD4+ T cells that may be involved in the persistence of arthritogenic symptoms.

Regulatory T cells in acute and chronic human Chikungunya infection.

Chikungunya virus (CHIKV) infection generates strong immune responses that are associated with the disease pathophysiology. Regulatory T cells (Treg-cluster of differentiation (CD)-4+CD25highforkhead box P3 (FOXP3+)) are essential for the induction and maintenance of peripheral tolerance. Thus, they play key roles in determining the patient prognosis by preventing excessive immune responses via different suppression immune mechanisms. However, the regulatory mechanisms involved in human CHIKV infection are still poorly understood. Here, we characterize for the first time the Treg cell molecule-associated-mechanism during acute and chronic human Chikungunya disease. Here, we assessed the Treg cell population and molecule-associated mechanism in the peripheral blood samples of acute and chronic patients with Chikungunya. Our results indicate that CHIKV infection is associated with reduced frequency of Tregs, along with the impaired expression and production of Treg functional markers, including CD39, CD73, perforin, granzyme, programmed death 1 (PD-1), cytotoxic T lymphocyte antigen (CTLA)-4, and transforming growth factor (TGF)-ß. This observation suggests that Treg cells possess the poor regulatory capacity in both acute and chronic phases of the disease. Taken together, these data provide significant evidence that the imbalanced response of Treg cells plays an essential role in establishing the pathogenesis of Chikungunya.

Predictors and reference equations for augmentation index, an arterial stiffness marker, in healthy children and adolescents.

OBJECTIVES: To investigate predictors and propose reference equations for the augmentation index normalized to 75 bpm heart rate (AIx@75) in healthy children and adolescents. METHODS: This was a cross-sectional, observational study involving 134 healthy children and adolescents aged 9 to 19 years old. Participants were categorized into child (n=53) and adolescent (n=81) groups, as well as into male (n=69) and female (n=65) groups. We evaluated AIx@75, vascular and hemodynamic parameters, anthropometric data, physical activity profile, and quality of life (Peds-QL4.0; physical, emotional, social and school domains). RESULTS: The predictors of AIx@75 in the whole sample were age, peripheral diastolic blood pressure (pDBP), mean arterial pressure, pulse pressure amplification (PPA), systolic volume (SV), cardiac index (CI), and pulse wave velocity (PWV; R2=80.47%). In the male group, the predictors of AIx@75 were SV, CI, total vascular resistence (TVR), and PWV (R2=78.56%), while in the female group, they were pDBP, PPA, SV, and PWV (R2=82.45%). In the children, they were pDBP, PPA, SV, and PWV (R2=79.17%), while in the adolescents, they were body mass index, pDBP, PPA, SV, TVR, and PWV (R2=81.57%). CONCLUSION: In the present study, we used a representative sample from Belo Horizonte to establish normality values of AIx@75. We also identified, for the first time, independent predictors of AIx@75 in healthy children and adolescents categorized by sex and age. Determining AIx@75 reference equations may facilitate the early diagnosis of preclinical atherosclerosis and allow an objective measure of the vascular effects of therapeutic interventions aimed at modifying cardiovascular risk factors.

Evaluation of the enantioselective in vitro metabolism of the chiral pesticide fipronil employing a human model: Risk assessment through in vitro-in vivo correlation and prediction of toxicokinetic parameters.

The chiral pesticide fipronil is employed as a racemic mixture to control pests. Although there are no enantioselective differences in the fipronil enantiomer activities toward target organisms, fipronil enantiomers may exhibit enantioselective differences in their bioaccumulation, toxicity, and metabolism toward non-target organisms, including humans. The present work aims to provide significant reliable enantioselective information concerning fipronil risk assessment in humans. For that, the in vitro metabolism of rac-fipronil, S-fipronil, and R-fipronil by human liver microsomes was evaluated, the in vivo enantioselective toxicokinetic parameters were predicted and the main CYP450 isoforms involved in the enantioselective metabolism were determined. The obtained results demonstrated that fipronil may undergo a clearance by the liver and it is exclusively metabolized by the CYP3A4 isoform. Although no significative stereoselective differences were observed, the results provide reliable information on fipronil risk assessment for humans.

Correlation of dengue incidence and rainfall occurrence using wavelet transform for João Pessoa city.

Dengue, a reemerging disease, is one of the most important viral diseases transmitted by mosquitoes. In this study, 55,680 cases of dengue between 2007 and 2015 were reported in Paraíba State, among which, 30% were reported in João Pessoa city, with peaks in 2015, 2011 and 2013. Weather is considered to be a key factor in the temporal and spatial distribution of vector-transmitted diseases. Thus, the relationship between rainfall occurrence and dengue incidences reported from 2007 to 2015 in João Pessoa city, Paraíba State, Brazil, was analyzed by means of wavelet transform, when a frequency analysis of both rainfall and dengue incidence signals was performed. To determine the relationship between rainfall and the incidence of dengue cases, a sample cross correlation function was performed to identify lags in the rainfall and temperature variables that might be useful predictors of dengue incidence. The total rainfall within 90 days presented the most significant association with the number of dengue cases, whereas temperature was not found to be a useful predictor. The correlation between rainfall and the occurrence of dengue cases showed that the number of cases increased in the first few months after the rainy season. Wavelet analysis showed that in addition to the annual frequency presented in both time series, the dengue time series also presented the 3-year frequency from 2010. Cross wavelet analysis revealed that such an annual frequency of both time series was in phase; however, after 2010, it was also possible to observe 45° up phase arrows, which indicated that rainfall in the present year led to an increased dengue incidence the following year. Thus, this approach to analyze surveillance data might be useful for developing public health policies for dengue prevention and control.

Cryptogenic Acute Ischemic Stroke: Assessment of the Performance of a New Continuous Long-Term Monitoring System in the Detection of Atrial Fibrillation.

BACKGROUND: Long-term monitoring has been advocated to enhance the detection of atrial fibrillation (AF) in patients with stroke. OBJECTIVE: To evaluate the performance of a new ambulatory monitoring system with mobile data transmission (PoIP) compared with 24-hour Holter. We also aimed to evaluate the incidence of arrhythmias in patients with and without stroke or transient ischemic attack. METHODS: Consecutive patients with and without stroke or TIA, without AF, were matched by propensity score. Participants underwent 24-hour Holter and 7-day PoIP monitoring. RESULTS: We selected 52 of 84 patients (26 with stroke or TIA and 26 controls). Connection and recording times were 156.5 ± 22.5 and 148.8 ± 20.8 hours, with a signal loss of 6,8% and 11,4%, respectively. Connection time was longer in ambulatory (164.3 ± 15.8 h) than in hospitalized patients (148.8 ± 25.6 h) (p = 0.02), while recording time did not differ between them (153.7 ± 16.9 and 143.0 ± 23.3 h). AF episodes were detected in 1 patient with stroke by Holter, and in 7 individuals (1 control and 6 strokes) by PoIP. There was no difference in the incidence of arrhythmias between the groups. CONCLUSIONS: Holter and PoIP performed equally well in the first 24 hours. Data transmission loss (4.5%) occurred by a mismatch between signal transmission (2.5G) and signal reception (3G) protocols in cell phone towers (3G). The incidence of arrhythmias was not different between stroke/TIA and control groups.

A Compreensão da Intersubjetividade Entre um Adolescente Suicida e seus Pais Através da Combinação de Métodos na Análise do Discurso / La Comprensión dela intersubjetividadentre un adolescente suicida y sus padres mediante la combinación de métodos en el análisis del discurso / Understanding Intersubjectivity Between a Suicidal Adolescent and His Parents Through the Combination of Methods in Discourse Analysis

Trata-se de um recorte de pesquisa de doutorado em que se intencionou estudar o vínculo intersubjetivo familiar em um adolescente com histórico de tentativa de suicídio, pautando-se nos desejos e defesas. Utilizou-se a combinação de três instrumentos (ADL-AH, ADL-R e o Genograma) para a análise do discurso. Após exame individual dos dados apontados por cada instrumento, realizou-se asanálises comparativas. Inicialmente, confrontou-se os resultados do ADL-AH com o ADL-R conforme a descrição do caso. Em seguida, o Genograma propiciou o entendimento intergeracional da família estudada, confirmou aspectos já levantados e elucidou pontos dos quais o ADL não poderia ter alcançado, embora esse último tenha encontrado discrepâncias no discurso, isto é, aquilo que se pretendia disfarçar ou esconder de forma consciente ou inconsciente. A combinaçãodos três instrumentos trouxe consistência para a investigação no sentido de uma melhor compreensão da intersubjetividade do adolescente, sua família e do comportamento suicida AU

Este es un extracto de una investigación doctoral que tuvo como objetivo estudiar el vínculo familiar intersubjetivo en un adolescente con antecedentes de intento de suicidio, basado en deseos y defensas. Para el análisis del discurso se utilizó una combinación de tres instrumentos (ADL-AH, ADL-R y Genograma). Luego de examinar individualmente los datos indicados por cada instrumento, se realizaron comparaciones. Inicialmente se confrontaran los resultados del ADL-AH con el ADL-R según la descripción del caso. Luego, el Genograma proporcionó una comprensión intergeneracional de la familia estudiada, confirmó aspectos ya planteados y aclaró puntos que la ADL no podría haber logrado, aunque este último tenga encontrado discrepancias en el discurso, es decir, lo que se pretendía disfrazar u ocultar consciente o inconscientemente. Esta combinación aportó consistencia a la investigación y con ella fue posible tener una mejor comprensión de la intersubjetividad, del adolescente, su familia y la conducta suicida AU

Primary care in supplementary health: assessment of costs in the care of older adult patients with heart diseases / Atención primaria en salud complementaria: evaluación de costos en el cuidado de ancianos con enfermedades del corazón / Atenção primária na saúde suplementar: avaliação de custos no cuidado de pacientes idosos com cardiopatias

ABSTRACT Objectives: to identify whether implementing a supplementary Primary Health Care (PHC) system makes it possible to reduce care costs for older adults with heart diseases. Methods: a retrospective cohort of 223 patients with heart disease aged ≥ 60 years. Data were obtained from medical records and cost databases, assessed for a period of one year before and after PHC implementation. The results were expressed as mean absolute frequencies for number of hospitalizations and as average annual expenses expressed in dollars (US$) in relation to cost data. Results: there was a reduction in hospitalization expenses after implementing supplementary PHC (p=0.01) and a decrease in the frequency of hospitalizations for the entire sample (p=0.006). There was a reduction in the frequency of consultations at the Emergency Room among frail older adults (p=0.011). Conclusions: there was a reduction in hospitalization costs and frequency of visits to the Emergency Room after supplementary PHC.

RESUMEN Objetivos: identificar si la implementación de un sistema complementario de Atención Primaria de Salud (APS) permite reducir los costos de atención a los ancianos con enfermedades del corazón. Métodos: cohorte retrospectiva de 223 pacientes con cardiopatía de edad ≥ 60 años. Los datos fueron obtenidos de prontuarios y bases de datos de costos, evaluados por un período de un año antes y después de la implementación de la APS. Los resultados se expresaron como frecuencias absolutas medias por número de hospitalizaciones y como gasto anual medio expresado en dólares (US$) en relación con los datos de costes. Resultados: hubo reducción de los gastos de hospitalización después de la implementación de la APS complementaria (p=0,01) y disminución de la frecuencia de hospitalizaciones para toda la muestra (p=0,006). Hubo reducción en la frecuencia de consultas en Emergencia entre los ancianos frágiles (p=0,011). Conclusiones: hubo una reducción en los costos de hospitalización y frecuencia de visitas a la Sala de Emergencia después de la APS complementaria.

RESUMO Objetivos: identificar se a implementação de um sistema de Atenção Primária à Saúde (APS) suplementar possibilita a redução dos custos assistenciais de idosos com cardiopatias. Métodos: coorte retrospectiva de 223 pacientes cardiopatas com idade ≥ 60 anos. Os dados foram obtidos em registros médicos e banco de dados de custos, avaliados por período de um ano antes e após a implementação da APS. Os resultados foram expressos como media das frequências absolutas para número de internações e como gasto médio anual expressos em dólares (US$) em relação aos dados de custos. Resultados: houve redução nas despesas de internação após a implementação da APS suplementar (p=0,01) e diminuição da frequência de internação para toda a amostra (p=0,006). Houve redução na frequência de consultas no Pronto Atendimento entre os idosos frágeis (p=0,011). Conclusões: houve redução nos custos de internação e frequência de consulta no Pronto Atendimento após a APS suplementar.

Quando édipo encontra Lábdaco: Sobre o complexo de édipo entre um avô e uma neta à luz da psicanálise vincular / When oedipus meets Lábdaco: About the oedipus complex between a grandfather and a granddaughter in the light of Links Psychoanalysis / Cuando edipo encuentra Lábdaco: Sobre el complejo de edipo entre un abuelo y una nieta a la luz de Psicoanálisis Vincular

O complexo de Édipo é até hoje um dos conceitos mais centrais no campo da psicanálise e se refere a uma dada situação familiar prototípica que supostamente atravessa todo sujeito no decorrer de seu desenvolvimento emocional. Tendo o conceito passado por diversas revisões, complementações e críticas ao longo do tempo, e, embora tenha perdido seu caráter universal, não ocorrendo necessariamente entre pai, mãe e criança, como acreditava Freud, ainda assim tem sua importância. Entretanto, são poucos os trabalhos que abordam outras dinâmicas relacionais na família, para além do relacionamento pais e filhos. Este artigo se propõe a contribuir para o estudo específico do vínculo entre avós e netos, por meio de um relato de caso bastante particular acerca de um complexo edípico envolvendo esse tipo de dupla. O aporte teórico da psicanálise vincular foi eleito por ser um referencial que enfatiza o âmbito intersubjetivo e o todo familiar, podendo, assim, melhor abarcar uma reflexão aprofundada sobre essa temática.

The Oedipus complex is to this day one of the most central concepts in the field of psychoanalysis and refers to a given prototypical family situation that supposedly crosses every subject in the course of his emotional development. Since the concept has undergone several revisions, complements and criticisms over time, and although it has lost its universal character, not necessarily occurring between father, mother and child, as Freud believed, it still has its importance. However, few studies deal with other relational dynamics in the family, in addition to the relationship between parents and children. This article proposes to contribute to the specific study of the bond between grandparents and grandchildren, through a very particular case report about an oedipal complex involving this type of pair. The theoretical contribution of the links psychoanalysis was chosen because it is a reference that emphasizes the intersubjective scope and the family, and, therefore, better to include a deep reflection on this theme.

El complejo de Edipo es hasta hoy uno de los conceptos más centrales en el campo del psicoanálisis y se refiere a una determinada situación familiar prototípica que supuestamente atraviesa a todo sujeto en el transcurso de su desarrollo emocional. Con el concepto pasado por diversas revisiones, complementaciones y críticas a lo largo del tiempo, y, aunque ha perdido su carácter universal, no ocurriendo necesariamente entre padre, madre y niño, como creía Freud, todavía tiene su importancia. Sin embargo, son pocos los trabajos que abordan otras dinámicas relacionales en la familia, además de la relación padres e hijos. Este artículo se propone contribuir al estudio específico del vínculo entre abuelos y nietos, por medio de un relato de caso bastante particular acerca de un complejo edípico envolviendo ese tipo de doble. El aporte teórico del psicoanálisis vincular fue elegido por ser un referencial que enfatiza el ámbito intersubjetivo y el todo familiar, pudiendo así mejor abarcar una reflexión profundizada sobre esa temática.

PREVALENCE OF SMALL INTESTINE BACTERIAL OVERGROWTH IN PATIENTS WITH GASTROINTESTINAL SYMPTOMS.

BACKGROUND: Small intestine bacterial overgrowth is a heterogeneous syndrome characterized by an increase in the number and/or the presence of atypical microbiota in the small intestine. The symptoms of small intestine bacterial overgrowth are unspecific, encompassing abdominal pain/distension, diarrhea and flatulence. Due to the increased cost and complexity for carrying out the jejunal aspirate, the gold standard for diagnosis of the syndrome, routinely the hydrogen (H 2 ) breath test has been used, utilizing glucose or lactulose as substrate, which is able to determine, in the exhaled air, the H 2 concentration produced from the intestinal bacterial metabolism. However, due to a number of individuals presenting a methanogenic microbiota, which does not produce H 2 , the testing on devices capable of detecting, concurrently, the concentration of exhaled H 2 and methane (CH 4 ) is justified. OBJECTIVE: This study aimed to determine the prevalence of small intestine bacterial overgrowth in patients with digestive symptoms, through a comparative analysis of breath tests of H 2 or H 2 and CH 4 associated, using glucose as substrate . METHODS: A total of 200 patients of both sexes without age limitation were evaluated, being directed to a Breath Test Laboratory for performing the H 2 test (100 patients) and of exhaled H 2 and CH 4 (100 patients) due to gastrointestinal complaints, most of them patients with gastrointestinal functional disorders. RESULTS: The results indicated a significant prevalence of small intestine bacterial overgrowth in the H 2 test and in the test of exhaled H 2 and CH 4 (56% and 64% respectively) in patients with gastrointestinal symptoms, and higher prevalence in females. It found further that methane gas was alone responsible for positivity in 18% of patients. CONCLUSION: The data found in this study is consistent with the findings of the current literature and underscores the need for using devices capable of capturing the two gases (exhaled H 2 and CH 4 ) to improve the sensitivity and hence the accuracy of small intestine bacterial overgrowth diagnosis in daily medical practice.

Epidemiological Profile of Patients with Infective Endocarditis at three Tertiary Centers in Brazil from 2003 to 2017

Abstract Background Infective endocarditis (IE) is a disease with high morbimortality and an increasing incidence. With improved diagnosis and treatment, a number of epidemiological changes have been reported over time. Objectives We sought to describe the epidemiological profile, mortality predictors, and analysis of a possible microbiological transition in patients admitted to three tertiary centers in Brazil. Methods In this cross-sectional retrospective study, data from 211 patients with definite or probable IE were analyzed according to the modified Duke criteria between 2003 and 2017. The association between categorical variables was assessed using the chi-square or Fisher's exact test, and binary logistic models were built to investigate mortality. We considered p <0.05 statistically significant. Results The median age of the sample was 48 (33-59) years old, 70.6% were men, and the most prevalent pathogen was Staphylococcus spp. (19%). Mortality was 22.3%, with increasing age being the leading risk factor for death (p = 0.028). Regarding the location of the disease, native valves were the most affected site, with the aortic valve being more affected in men than women (p = 0.017). The mean number of cases of Staphylococcus spp. (τ = 0.293, p = 0.148) and Streptococcus spp. (τ = -0.078, p = 0.727) has remained stable over the years. Conclusion No trend towards reduced or increased mortality was evident between 2003 and 2017. Although Staphylococcus spp. were the most prevalent pathogen, the expected epidemiological transition could not be observed.

Availability of essential medicines in primary health care of the Brazilian Unified Health System.

OBJECTIVE: To characterize the availability of tracer medicines in pharmaceutical services in primary health care of the Brazilian Unified Health System (SUS). METHODS: This is a cross-sectional and evaluative study, part of the Pesquisa Nacional Sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos - Serviços, 2015 (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines - Services, 2015). To analyze the availability of medicines, we verified 50 items selected from the Relação Nacional de Medicamentos Essenciais (Rename - National List of Essential Medicines) of 2012. Observation scripts were applied to medicine dispensing services in the primary health care. Interviews were carried out with patients, health care professionals, and public managers, using semi-structured questionnaires. The availability index was presented as the percentage of health units where the medicines were available. For statistical analysis, absolute, relative, and mean frequencies were presented (with 95% confidence intervals). The comparison of groups was carried out by Pearson Chi-square tests or variance analysis, when needed. RESULTS: One thousand, one hundred, and seventy-five observation scripts were filled in a national representative sample composed by 273 cities. Statistically significant differences were observed regarding the type of unit, infrastructure, and presence of a pharmacist between regions of Brazil. The average availability of tracer medicines in primary health care was 52.9%, with differences between regions and sampling strata. This index increased to 62.5% when phytotherapic medicines were excluded. We found limited availability of medicines for treatment of chronic and epidemiological diseases, such as tuberculosis and congenital syphilis. CONCLUSIONS: The low availability of essential medicines purchased centrally by the Brazilian Ministry of Health indicates deficiencies in supply chain management. The different views on the availability of tracer medicines in SUS confirm the general availability verified in this study. Among patients, about 60% said they obtain medicines in SUS units, data consistent with the lack of medicines reported by medicine dispensers and in line with physicians' evaluations.

Polypharmacy: a challenge for the primary health care of the Brazilian Unified Health System.

OBJECTIVE: To characterize the polypharmacy in primary health care patients and to identify its associated factors. METHODS: This is a cross-sectional, exploratory, and evaluative study, part of the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos - Serviços, 2015 (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines - Services, 2015). The variable of interest was polypharmacy, defined as the use of five or more medicines. We sought to identify the association of sociodemographic variables and indicators of health conditions to polypharmacy. For group comparison, the Pearson's Chi-square test was used. The association between polypharmacy and explanatory variables was evaluated by logistic regression model (p < 0.05). The quality of the adjustment was verified by Hosmer-Lemeshow test. RESULTS: The prevalence of polypharmacy among medicine users was 9.4% (95%CI 7.8-12.0) in the general population and 18.1% (95%CI 13.6-22.8) in older adults above 65 years old. We found statistically significant association between polypharmacy and age above 45 years, lower self-perception of health, presence of chronic diseases, having health insurance, care in emergency services, and region of the Country. South users presented the highest chances to polypharmacy. The most used medicines were those of the cardiovascular system, being compatible with the national epidemiological profile. CONCLUSIONS: Polypharmacy is a reality in the population met within the primary care of Brazilian Unified Health System and may be related to excessive or inappropriate use of medicines. The main challenge to qualify health care is to ensure that prescription of multiple medicines be appropriate and safe.

Molecular and clinical epidemiological surveillance of dengue virus in Paraíba, Northeast Brazil.

INTRODUCTION:: Despite being the most prevalent arboviral disease worldwide, dengue has been neglected lately. However, recent epidemics of arboviruses such as Zika and chikungunya in locations throughout the world have alerted health authorities to these diseases. This study evaluated the incidence pattern of dengue, its clinical characteristics, and co-circulation of serotypes from 2007 to 2015 in Paraiba State, Northeast Brazil. METHODS:: Data on dengue cases from 2007 to 2015 were extracted from clinical reports of the National System for Notifiable Diseases [Sistema Nacional de Agravos de Notificação (SINAN)] of Brazil provided by the Paraiba Health Department. Reverse transcription polymerase chain reaction (RT-PCR) assays for dengue serotypes were carried out on plasma samples obtained from patients with suspected dengue. The data were analysed using descriptive statistics. RESULTS:: According to clinical features, dengue fever [n = 39,083 (70.2%)] and dengue without warning signs [n = 15,365 (27.7%)] were the most common classifications of dengue. On RT-PCR, DENV 1 was the most commonly identified serotype (80.5%) in all years studied. Co-circulation of all four DENV serotypes was observed in 2013 and 2014. Furthermore, we observed an increase in dengue notifications in 2015, possibly due to the rise of Zika and chikungunya. CONCLUSIONS:: Our findings support the hypothesis that co-circulation of the four DENV serotypes may be a reason for the increased prevalence of severe forms of dengue in the years studied. This study may contribute to directing research, health policy, and financial resources toward reducing poorly controlled epidemic diseases.

Trabalhando o vínculo, trabalhando no vínculo: considerações sobre o papel da transferência no atendimento de crianças e jovens que sofreram rupturas familiares / Working the bond, working in the bond: considerations about the role of transfer in the care of children and young people who have suffered family breaks / Trabajar el vínculo, trabajar en el vínculo: consideraciones sobre el papel de la transferencia en el cuidado de los niños y jóvenes que han sufrido descansos familiares

O objetivo deste trabalho é refletir acerca de situações de rupturas familiares, que geram consequências importantes para a formação do self, e sobre a possibilidade de elaboração frente a esperança produzida pela construção de novos vínculos. Quais as reverberações dessas rupturas familiares no processo de constituição da identidade e no desenrolar da própria transferência num atendimento de orientação psicanalítica? Numa tentativa de responder a essa pergunta, será destacado aqui o vínculo transferencial como promotor de uma potencialidade terapêutica.

The main objective of the present paper is, based on the psychoanalytic theory (specially Winnicott's considerations), to reflect about situations regarding the rupture of family links, which cause relevant consequences to the construction of the self of a child, and about the possibility of elaboration with the development of new links. Considering those ruptures, what are the reverberations in the process of identity constitution and, considering the analysis environment, in the outcome of the transference itself? To answer this question, it will be highlighted in the present paper the bond between analyst and patient as a promoter of a therapeutic potentiality.

El objetivo desto trabajo es refletir acerca de situaciones de rupturas familiares y las consecuencias que estas tienen en la formación del self, y acerca de la posibilidad de elaboración frente a la esperanza producida por la construcción de novos vinculos. ¿Quales son las reverberaciones de esas rupturas familiares en los procesos de constitución de la identidad y en el desenvolvimiento de la propia transferencia en un atendimiento de orientación psicoanalítica? En una tentativa de responder a essa pregunta, será destacado aqui el vínculo transferencial como promotor de una potencialidad terapeutica.