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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.

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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

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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