Systematic screening of synthetic organochalcogen compounds with anticancer activity using human lung adenocarcinoma spheroids.

Lung adenocarcinoma stands as a leading global cause of cancer-related fatalities, with current therapeutic approaches remaining unsatisfactory. Given the association between elevated oxidative markers and the aggressive nature of cancer cells (including multidrug resistance and metastatic potential) that can predict poor outcome of lung adenocarcinoma patients, any compounds that interfere with their aberrant redox biology should be rationally explored as innovative intervention strategies. This study was designed to screen potential anticancer activities within nine newly synthesized organochalcogen - compounds characterized by the presence of oxygen, sulfur, or selenium elements in their structure and exhibiting antioxidant activity - and systematically evaluated their performance against cisplatin, the cornerstone therapeutic agent for lung adenocarcinoma. Our methodology involved the establishment of optimal conditions for generating single tumor spheroids using A549 human lung adenocarcinoma cell line. The initiation interval for spheroid formation was determined to be four days in vitro (DIV), and these single spheroids demonstrated sustained growth over a period of 20 DIV. Toxic dose-response curves were subsequently performed for each compound after 24 and 48 h of incubation at the 12th DIV. Our findings reveal that at least two of the synthetic organochalcogen compounds exhibited noteworthy anticancer activity, surpassing cisplatin in key parameters such as lower LD (Lethal Dose) 50, larger drug activity area, and maximum amplitude of effect, and are promising drugs for futures studies in the treatment of lung adenocarcinomas. Physicochemical descriptors and prediction ADME (absorption, distribution, metabolism, and excretion) parameters of selected compounds were obtained using SwissADME computational tool; Molinspiration server was used to calculate a biological activity score, and possible molecule targets were evaluated by prediction with the SwissTargetPrediction server. This research not only sheds light on novel avenues for therapeutic exploration but also underscores the potential of synthetic organochalcogen compounds as agents with superior efficacy compared to established treatments.

Percepção dos profissionais da saúde no enfrentamento da covid-19: principais desafios no processo de trabalho / Healthcare providers' perception of COVID-19: main challenges in the work process / Percepción de los profesionales de la salud sobre el afrontamiento de la COVID-19: principales retos en el proceso de trabajo

O cenário advindo como consequência da pandemia de covid-19 acarretou diversas mudanças na vida dos profissionais de saúde. A percepção desse grupo torna-se indispensável para a compreensão do contexto, visto que esses trabalhadores são figuras essenciais no enfrentamento da doença. O objetivo deste estudo foi analisar a percepção de gestores e profissionais que atuaram durante a primeira onda da pandemia de covid-19 no município de Sobral (CE). Trata-se de uma pesquisa exploratório-descritiva, com abordagem qualitativa, feita por meio da aplicação de um instrumento de coleta de dados. O estudo foi realizado com gestores e trabalhadores que atuaram de março a dezembro de 2020 no município. A coleta foi feita no formato híbrido, com auxílio da plataforma Google Meet, fundamentada na metodologia snowball sampling e no método de saturação. Após a coleta, os discursos foram transcritos ­ utilizando a ferramenta Microsoft Word ­ e analisados ­ com suporte do software NVivo11. Foram contactados 68 profissionais. Identificou-se predominância final de enfermeiros, sexo feminino e atuantes na atenção terciária. Após análise e categorização, identificaram-se 12 unidades de registro. Foram dispostos os principais desafios e dificuldades acarretados para os processos de trabalho e suas subcategorias: a sobrecarga de trabalho e o desgaste físico; a reorganização dos serviços em resposta à nova realidade; o desconhecimento sobre a doença e seu impacto psicológico no fazer profissional; e o fator social e a dificuldade de seguimento da assistência na atenção primária. Por fim, conclui-se que os desafios identificados se inter-relacionam, repercutindo uns nos outros, e constata-se a importância de conhecer esses entraves para ações mais bem direcionadas e estratégicas.

The scenario that has arisen in response to COVID-19 has led to a variety of changes in the lives of healthcare providers. The perception of this group is essential to understanding this context since they are key figures in coping with the disease. This study aimed to analyze the perception of managers and professionals who worked during the first wave of the COVID-19 pandemic in the municipality of Sobral/CE. This is an exploratory-descriptive study with a qualitative approach that applied a collection instrument with managers and workers who worked from March to December 2020 in the municipality. Data were collected using the Snowball Smapling and the saturation method in a hybrid format using the Google Meet platform. After the collection, responses were transcribed using Microsoft Word and analyzed with the aid of NVivo11. In total, 68 professionals were contacted, with a final predominance of female nurses working in tertiary care. After analysis and categorization, 12 recording units were identified. The main challenges and difficulties for work processes and their subcategories include work overload and physical exhaustion; reorganization of services in response to the new reality; lack of knowledge about the disease and its psychological impact on professional practice; and the social factor and the difficulty of following up care in primary care. Finally, we conclude that the identified challenges are interrelated and have repercussions on each other, and that it is important to understand these obstacles to take more targeted and strategic actions.

El escenario que ha surgido en respuesta a la pandemia de la COVID-19 ha provocado diversos cambios en la vida de los profesionales de la salud. La percepción de este grupo es indispensable para comprender el contexto, ya que estos trabajadores son figuras esenciales en el enfrentamiento a la enfermedad. El objetivo de este estudio fue analizar la percepción de gestores y profesionales que actuaron durante la primera ola de la pandemia de la COVID-19 en el municipio de Sobral (Ceará, Brasil). Se trata de un estudio exploratorio-descriptivo, con enfoque cualitativo, realizado mediante la aplicación de una herramienta de recolección de datos. En esta investigación participaron gestores y trabajadores que actuaron de marzo a diciembre de 2020 en el municipio. Se realizó la recolección en formato híbrido, con ayuda de la plataforma Google Meet, basada en el método bola de nieve y en el método de saturación. Después, se transcribieron los discursos, utilizando la herramienta Microsoft Word, y se analizaron con el apoyo del software NVivo11. Se contactaron 68 profesionales. Se identificó predominio de enfermeros, mujeres y trabajadores de atención terciaria. Después del análisis y de la categorización, se identificaron 12 unidades de registro. Se presentaron los principales retos y dificultades que generan los procesos de trabajo y sus subcategorías: la sobrecarga de trabajo y el agotamiento físico; la reorganización de los servicios en respuesta a la nueva realidad; el desconocimiento de la enfermedad y su impacto psicológico en la práctica profesional; y el factor social y la dificultad de seguimiento de los cuidados en atención primaria. Finalmente, se concluye que los retos identificados están interrelacionados, impactándose entre sí, y se señala la importancia de conocer estos obstáculos para emprender acciones más específicas y estratégicas.

Association of Cytokine Gene Polymorphisms and Their Impact on Active and Latent Tuberculosis in Brazil's Amazon Region.

Some genetic variations in cytokine genes can alter their expression and influence the evolution of Mycobacterium tuberculosis (Mtb) infection. This study aimed to investigate the association of polymorphisms in cytokine genes and variability in plasma levels of cytokines with the development of tuberculosis (TB) and latent tuberculosis infection (LTBI). Blood samples from 245 patients with TB, 80 with LTBI, and healthy controls (n = 100) were included. Genotyping of the IFNG +874A/T, IL6 -174G/C, IL4 -590C/T, and IL10 -1082A/G polymorphisms was performed by real-time PCR, and cytokine levels were determined by flow cytometry. Higher frequencies of genotypes AA (IFNG +874A/T), GG (IL6 -174G/C), TT (IL4 -590C/T), and GG (IL10 -1082A/G) were associated with an increased risk of TB compared to that of LTBI (p = 0.0027; p = 0.0557; p = 0.0286; p = 0.0361, respectively) and the control (p = <0.0001, p = 0.0021; p = 0.01655; p = 0.0132, respectively). In combination, the A allele for IFNG +874A/T and the T allele for IL4 -590C/T were associated with a higher chance of TB (p = 0.0080; OR = 2.753 and p < 0.0001; OR = 3.273, respectively). The TB group had lower levels of IFN-γ and higher concentrations of IL-6, IL-4, and IL-10. Cytokine levels were different between the genotypes based on the polymorphisms investigated (p < 0.05). The genotype and wild-type allele for IFNG +874A/T and the genotype and polymorphic allele for IL4 -590C/T appear to be more relevant in the context of Mtb infection, which has been associated with the development of TB among individuals infected by the bacillus and with susceptibility to active infection but not with susceptibility to latent infection.

Quantum biochemistry description of PI3Kα enzyme bound to selective inhibitors.

The PI3K class I is composed of four PI3K isoforms that serve as regulatory enzymes governing cellular metabolism, proliferation, and survival. The hyperactivation of PI3Kα is observed in various types of cancer and is linked to poor prognosis. Unfortunately, the development inhibitors selectively targeting one of the isoforms remains challenging, with only few agents in clinical use. The main difficulty arises from the high conservation among residues at the ATP-binding pocket across isoforms, which also serves as target pocket for inhibitors. In this work, molecular dynamics and quantum calculations were performed to investigate the molecular features guiding the binding of selective inhibitors, alpelisib and GDC-0326, into the ATP-binding pocket of PI3Kα. While molecular dynamics allowed crystallographic coordinates to relax, the interaction eergy between each amino acid residues and inhibitors was obtained by combining the Molecular Fractionation with Conjugated Caps scheme with Density Functional Theory calculations. In addition, the atomic charge of ligands in the bound and unbound (free) was calculated. Results indicated that the most relevant residues for the binding of alpelisib are Ile932, Glu859, Val851, Val850, Tyr836, Met922, Ile800, and Ile848, while the most important residues for the binding of GDC-0326 are Ile848, Ile800, Ile932, Gln859, Glu849, and Met922. In addition, residues Trp780, Ile800, Tyr836, Ile848, Gln859 Val850, Val851, Ile932 and Met922 are common hotspots for both inhibitors. Overall, the results from this work contribute to improving the understanding of the molecular mechanisms controlling selectivity and highlight important interactions to be considered during the rational design of new agents.Communicated by Ramaswamy H. Sarma.

Natural and Synthetic Peptides to Control Drug-resistant Pathogens.

Due to the excessive and inappropriate use of antibiotics in farming and clinic, pathogens developed resistance mechanisms to currently used drugs. Thus, because of this resistance, drugs become ineffective, leading to public health problems worldwide. According to the World Health Organization (WHO), microbial resistance to drugs is one of the most threats that humanity must face. Therefore, it is imperative to seek alternative methods to overcome microbial resistance. Here, the potential of natural or synthetic antimicrobial peptides to overcome microbial resistance will be discussed, and how peptides could be a source for new therapeutics molecules. In this context, antimicrobial peptides (natural or synthetic) are considered promising molecules based on their antifungal, antiviral, and antibacterial properties, making them eligible for developing new drugs. In addition, they can act synergistically with existing drugs on the market, revealing a broad spectrum of applications.

Qualificação interprofissional da atenção pré-natal no contexto da atenção primária à saúde / Interprofessional qualification of prenatal care in the context of primary health care

Resumo O objetivo deste artigo é descrever e analisar intervenção educativa interprofissional para a qualificação da atenção pré-natal no contexto da atenção primária à saúde. Trata-se de uma pesquisa-ação cujo processo de intervenção teve como cenário a qualificação pré-natal, a partir de um curso sistematizado em atividades síncronas e assíncronas, com a participação de 65 profissionais que atuam em Unidades Básicas de Saúde. Da análise temática do tipo reflexive, que possibilitou o registro de ideias, insights e a significação da intervenção, resultaram três categorias: qualidade da atenção pré-natal - concepções e significados; aprendizagem colaborativa - estratégia para transcender a atenção linear e pontual; necessidade de evoluir do agir local ao pensar global. A análise da intervenção educativa interprofissional para a qualificação da atenção pré-natal no contexto da atenção primária à saúde demonstrou que percursos construtivistas, participativos e interprofissionais são relevantes e pertinentes para ampliar percepções teóricas e ressignificar o processo de trabalho nos diversos pontos da rede de saúde.

Abstract This study aims to describe and analyze an interprofessional educational intervention for the qualification of prenatal care in the context of primary health care. Method: action-research comprising a prenatal care qualification course with 65 primary health care professionals. Collaborative learning activities were conducted in synchronous and asynchronous meetings. Results: the reflexive thematic analysis of participants' experiences, views and perceptions on the meanings of the intervention revealed three categories: quality of prenatal care: conceptions and meanings; collaborative learning: strategy to overcome linear and isolated care; the need to evolve from acting locally to thinking globally. Conclusion: the analysis of the interprofessional educational intervention for the qualification of prenatal care in the context of primary health care showed that constructivist, participatory and interprofessional approaches are relevant and pertinent to broaden theoretical perceptions and give new meanings to the work process at different settings of the health network.

Low levels of TNFA gene expression seem to favor the development of pulmonary tuberculosis in a population from the Brazilian Amazon.

TNF-α is a Th1 cytokine profile active in the control of Mycobacterium tuberculosis infection, IL-10 is associated with persistence of bacterial infection. The aim of the study was to investigate the association of TNFA -308G/A and IL10 -819C/T polymorphisms and TNFA and IL10 gene expression levels with pulmonary and extrapulmonary tuberculosis (n = 200) and control (n = 200). The individuals were submitted to genotyping and quantification of gene expression performed by real-time quantitative polymerase chain reaction (qPCR). No association was observed between the frequencies of polymorphisms evaluated and pulmonary tuberculosis. The frequency of polymorphic genotypes for TNFA -308G/A were associated with the extrapulmonary tuberculosis (p = 0.0445). The levels of TNFA expression were lower in the pulmonary tuberculosis group than in the control (p = 0.0009). There was a positive correlation between the levels of TNFA and IL10 in patients with pulmonary tuberculosis (r = 0.560; p = 0.0103). Reduced levels of TNFA expression may promote the formation of an anti-inflammatory microenvironment, favoring the persistence of the bacillus in the host, contributing to the establishment of pulmonary tuberculosis.

Binding site hotspot map of PI3Kα and mTOR in the presence of selective and dual ATP-competitive inhibitors.

The PI3K/Akt/mTOR signaling pathway plays a pivotal role in cellular metabolism, growth and survival. PI3Kα hyperactivation impairs downstream signaling, including mTOR regulation, and are linked to poor prognosis and refractory cancer treatment. To support multi-target drug discovery, we took advantage from existing PI3Kα and mTOR crystallographic structures to map similarities and differences in their ATP-binding pockets in the presence of selective or dual inhibitors. Molecular dynamics and MM/PBSA calculations were employed to study the binding profile and identify the relative contribution of binding site residues. Our analysis showed that while varying parameters of solute and solvent dielectric constant interfered in the absolute binding free energy, it had no effect in the relative per residue contribution. In all complexes, the most important interactions were observed within 3-3.5 Å from inhibitors, responding for ∼75-100% of the total calculated interaction energy. While closest residues are essential for the strength of the binding of all ligands, more distant residues seem to have a larger impact on the binding of the dual inhibitor, as observed for PI3Kα residues Phe934, Lys802 and Asp805 and, mTOR residues Leu2192, Phe2358, Leu2354, Lys2187 and Tyr2225. A detailed description of individual residue contribution in the presence of selective or dual inhibitors is provided as an effort to improve the understanding of molecular mechanisms controlling multi-target inhibition. This work provides key information to support further studies seeking the rational design of potent PI3K/mTOR dual inhibitors for cancer treatment.Communicated by Ramaswamy H. Sarma.

Social and health vulnerability of homeless people / Vulnerabilidad social y sanitaria de personas en situación de calle / Vulnerabilidade social e de saúde de pessoas em situação de rua

ABSTRACT The objective is to conduct a theoretical reflection on the social and health vulnerability of homeless people, from the perspective of complexity thinking. Study with a theoretical and reflective approach that accessed bibliographical sources of contemporary authors who seek to understand the phenomenon of homeless populations and, at the same time, attribute theoretical support from the reference of complexity, under a critical and analytical bias. Health is conceived as a subsystem of the social system that transcends any linear and punctual diagnostic perspective. Theoretical reflection on the social and health vulnerability of homeless people sparks a unique and multidimensional apprehension of the human being - a complex unit par excellence, which demands equally complex interventions.

RESUMEN El objetivo es realizar una reflexión teórica sobre la vulnerabilidad social y sanitaria de las personas en situación de calle desde la perspectiva del pensamiento de la complejidad. Se trata de un estudio con enfoque teórico y reflexivo basado en fuentes bibliográficas de autores contemporáneos que buscan comprender el fenómeno de las poblaciones sin hogar y, paralelamente, aportar sustento teórico desde el marco de la complejidad, bajo un sesgo crítico y analítico. La salud está concebida como un subsistema del medio social que trasciende cualquier perspectiva diagnóstica, lineal y puntual. La reflexión teórica sobre la vulnerabilidad social y sanitaria de las personas en situación de calle suscita una percepción singular y multidimensional del ser humano, unidad compleja por excelencia, que exige intervenciones igualmente complejas.

RESUMO Objetiva-se conduzir reflexão teórica sobre a vulnerabilidade social e de saúde de pessoas em situação de rua, na perspectiva do pensamento da complexidade. Estudo de abordagem teórico-reflexiva que acessou fontes bibliográficas de autores contemporâneos que buscam compreender o fenômeno das populações em situação de rua e, paralelamente, aprofundar a temática à luz do referencial da complexidade, sob um viés crítico e analítico. Concebe-se a saúde como subsistema do sistema social que transcende qualquer perspectiva diagnóstica linear e pontual. A reflexão teórica acerca da vulnerabilidade social e de saúde de pessoas em situação de rua acende uma apreensão singular e multidimensional de ser humano - unidade complexa por excelência, que demanda intervenções, igualmente, complexas.

Intensificação laboral e gênero profissional de professoras da educação infantil / Intensification of labor and professional gender of female teachers of early childhood education

As reformas neoliberais levaram à intensificação do trabalho, dada a exigência de maiores e melhores resultados em contextos laborais cujas condições eram insuficientes para realizá-lo. Este artigo visa compreender, a partir do referencial teórico da Clínica da Atividade, a relação entre intensificação do trabalho docente e gênero profissional. Trata-se de um estudo de caso derivado de uma intervenção com seis professoras da Educação Infantil que utilizou o método de instrução ao sósia. Os registros de áudio produzidos ao longo das instruções ao sósia foram transcritos e submetidos à análise construtivo-interpretativa. O número de alunos por sala, fator inerente à organização do trabalho, mostrou-se promotor dessa intensificação, uma vez que exigia mais dos profissionais, sem a contrapartida necessária das condições de trabalho. Nesse cenário, ocorreu a construção coletiva do que era chamado de "domínio de sala", norma de proceder não oficializada relativa às habilidades necessárias à atuação docente para lidar com a intensificação laboral. Desenvolveu-se, assim, uma cultura profissional que orientou a ação das docentes, de modo a viabilizar a atividade e preservar o poder de agir

Neoliberal reforms have led to the intensification of work, given the demand for greater and better results in labor contexts whose conditions were insufficient to realize it. This article aims to understand based on the theoretical framework of the Clinic of Activity the relationship between intensification of the teaching work and professional genre. This is a case study derived from an intervention with six children's education teachers that used the method of instruction to the look-alike. The audio recordings produced during the instruction to the look-alike were transcribed and submitted to constructive-interpretative analysis. The number of students per classroom, a factor inherent to the work organization, proved to be a promoter of this intensification, since it demanded more from professionals, without the necessary counterpart of working conditions. In this scenario there was a collective construction of what was called "classroom mastery," an unofficial rule of thumb related to the necessary skills for teaching to deal with work intensification. Thus, a professional culture was developed that guided the teachers' action to make the activity viable and preserve the power to act

Aortic Valve Surgery in Patients with Infective Endocarditis: Mid-Term Follow-up of Patients Treated With the ST. Jude Medical Trifecta Valve.

BACKGROUND: It is particularly difficult to choose the appropriate prosthesis to treat infective endocarditis. OBJECTIVES: To investigate the outcomes after aortic valve replacement with a stented bioprosthesis (Trifecta) in patients with active or previous infective endocarditis. METHODS: We performed a single-centre, retrospective study including consecutive patients with infective endocarditis who underwent aortic valve replacement between July 2011 and June 2019. Survival and reintervention were assessed as of December 2021. Hospital mortality was defined as death in-hospital or within 30-days of surgery. Kaplan-Meier method was used for time-to-event outcome assessment (all-cause mortality and reoperation). Data are median (minimum and maximum) or absolute (relative) frequencies. RESULTS: We included 51 patients, median age of 69 (40 to 87) years, 78% male. The median follow-up time was 5.4 years and the maximum was 10 years. Most patients (71%) had native valve infective endocarditis and 16% had previous endocarditis. Surgery was urgent in 82%. Hospital mortality occurred in 10 patients (20%). After excluding these patients, 1-, 3-, 6-, and 9-years cumulative survival rates were 93%, 78%, 72%, and 72%, respectively. There were five bioprosthesis-related reoperations: 4 due to endocarditis at 1-year, 3-years, and 5-years on follow-up (n=1, 1 and 2, respectively) and 1 due to non-structural deterioration, 6-years after surgery. CONCLUSIONS: Despite the small sample size, this report supports a satisfactory performance profile of the Trifecta bioprosthesis in the treatment of infective endocarditis.

Neuroprotective effects of dimethyl fumarate against depression-like behaviors via astrocytes and microglia modulation in mice: possible involvement of the HCAR2/Nrf2 signaling pathway.

We postulated that dimethyl fumarate (DMF) exerts neuroprotective effects against depression-like behaviors through astrocytes and microglia modulation. To ascertain our hypothesis and define the mechanistic pathways involved in effect of DMF on neuroinflammation, we used the depression model induced by chronic unpredictable mild stress (CUMS), in which, the mice were exposed to stressful events for 28 days and from the 14th day they received DMF in the doses of 50 and 100 mg/kg or fluoxetine 10 mg/kg or saline. On the 29th day, the animals were subjected to behavioral tests. Microglia (Iba1) and astrocyte (GFAP) marker expressions were evaluated by immunofluorescence analyzes and the cytokines TNF-α and IL-Iß by immunoenzymatic assay. In addition, computational target prediction, 3D protein structure prediction, and docking calculations were performed with monomethyl fumarate (DMF active metabolite) and the Keap1 and HCAR2 proteins, which suggested that these could be the probable targets related protective effects. CUMS induced anxiety- and depressive-like behaviors, cognitive deficit, decreased GFAP, and increased Iba1, TNF-α, and IL-Iß expression in the hippocampus. These alterations were reversed by DMF. Thus, it is suggested that one of the mechanisms involved in the antidepressant effect of DMF is neuroinflammatory suppression, through the signaling pathway HCAR2/Nrf2. However, more studies must be performed to better understand the molecular mechanisms of this drug.

Protocolo de Avaliação de Sensibilidade Dermatológica para Pessoas com Estomias de Eliminação / Dermatological Sensitivity Assessment Protocol for People With Elimination Stomas / Protocolo de Evaluación de Sensibilidad Dermatológica para Personas con Stomos de Eliminación

Objetivo:Construir e validar um protocolo clínico direcionado à avaliação de sensibilidade dermatológica ocasionada por dispositivos coletores e adjuvantes utilizados por pessoas com estomias. Metodologia:Pesquisa metodológica, desenvolvida entre os anos de 2020 e 2021, para construção e validação de um protocolo de avaliação dermatológica para pessoas com estomias de eliminação. A construção do protocolo percorreu as etapas: diagnóstico situacional teórico, levantamento do referencial teórico e desenvolvimento do protocolo. Resultados: Para validação foram recrutados 21 juízes, enfermeiros, com experiência na área de Estomaterapia, cujo instrumento para validação do conteúdo avaliou objetivos, estrutura e relevância da tecnologia, sendo disponibilizado via e-mail por formulário eletrônico na plataforma Google Forms. Para análise dos dados utilizou-se a estatística descritiva e o cálculo de índice de validade de conteúdo (IVC). Obteve-se escore global de concordância entre os juízes de 0,92. Conclusão: Conclui-se que o protocolo criado possui fundamentação e validação prática, versatilidade de aplicação, viabilizando um processo assistencial mais congruente com a realidade da pessoa com estomia de eliminação.

Objective:To build and validate a clinical protocol aimed at evaluating the dermatological sensitivity caused by collection devices and adjuvants used by people with stomas. Methodology: Methodological research, developed between 2020 and 2021, for the construction and validation of a dermatological evaluation protocol for people with elimination stomas. The construction of the protocol went through the steps: theoretical situational diagnosis, survey of the theoretical framework and development of the protocol. Results: For validation, 21 judges, nurses, with experience in the area of enterostomal therapy, were recruited, whose instrument for content validation evaluated objectives, structure and relevance of the technology, being made available via e-mail through an electronic form on the Google Forms platform. For data analysis, descriptive statistics and the calculation of content validation index were used. A global score of agreement between the judges of 0.92 was obtained. Conclusion: It is concluded that the protocol created has a practical basis and validation, application versatility, enabling a care process that is more congruent with the reality of the person with an elimination stoma.

Objetivo:Construir y validar un protocolo clínico dirigido a la evaluación de la sensibilidad dermatológica provocada por los dispositivos colectores y adyuvantes utilizados por personas con ostomías. Metodología: Investigación metodológica, desarrollada entre 2020 y 2021, para la construcción y validación de un protocolo de evaluación dermatológica para personas con estomas de eliminación. La construcción del protocolo pasó por las etapas: diagnóstico situacional teórico, levantamiento del marco teórico y desarrollo del protocolo. Resultados: Para la validación fueron reclutados 21 jueces, enfermeros, con experiencia en el área de Estomaterapia, cuyo instrumento para validación de contenido evaluó objetivos, estructura y pertinencia de la tecnología, estando disponible vía e-mail a través de formulario electrónico en Google Plataforma de formularios. Para el análisis de los datos se utilizó la estadística descriptiva y el cálculo del Índice de Validación de Contenido. Se obtuvo una puntuación global de concordancia entre los jueces de 0,92. Conclusión: Se concluye que el protocolo creado tiene base práctica y validación, versatilidad de aplicación, posibilitando un proceso de atención más congruente con la realidad de la persona con ostomía de eliminación.

Implantação de um serviço para pessoas com distúrbios do assoalho pélvico / Implementation of a service for people with pelvic floor disorders / Implementación de un servicio para personas con trastornos del suelo pélvico

Objetivo:objetivou-se descrever os procedimentos técnicos operacionais e dados clínicos relacionados à implantação de um programa de atenção à saúde das pessoas com distúrbios do assoalho pélvico em um serviço público de atenção secundária. Método: trata-se de um relato de experiência, baseado em vivências relacionadas à assistência acadêmico-profissional na implantação de serviço voltado aos distúrbios do assoalho pélvico na região do Cariri cearense, realizado de maio a julho de 2021. Resultados: para a implantação do serviço, adotaram-se as seguintes estratégias: rastreamento da rede de atenção à saúde da pessoa com distúrbios do assoalho pélvico; estruturação organizacional do serviço; captação de pessoas com disfunções pélvicas; início dos atendimentos; e seguimento terapêutico. Conclusão: face ao exposto, evidencia-se que o programa de atenção à saúde das pessoas com distúrbios do assoalho pélvico pôde ser implantado satisfatoriamente, tendo em vista a infraestrutura, ao expressivo quantitativo de atendimentos realizados e ao seguimento terapêutico alcançado. Assim, com este relato, espera-se contribuir para o desenvolvimento de novos serviços ambulatoriais voltados a essa área de atuação do enfermeiro estomaterapeuta e da equipe multidisciplinar.

Objective:the objective was to describe the technical operational procedures and clinical data related to the implementation of a health care program for people with pelvic floor disorders in a public secondary care service. Method: this is an experience report, based on experiences related to academic and professional assistance in the implementation of a service aimed at pelvic floor disorders in the Cariri region of Ceará, carried out from May to July 2021. Results: for the implementation of the service, the following strategies were adopted: tracking the health care network for people with pelvic floor disorders; organizational structuring of the service; capturing people with pelvic dysfunctions; start of care; and therapeutic follow-up. Conclusion: in view of the above, it is evident that the health care program for people with pelvic floor disorders could be implemented satisfactorily, considering the infrastructure, the significant amount of care provided and the therapeutic follow-up achieved. Thus, with this report, it is expected to contribute to the development of new outpatient services aimed at this area of work of the stomatherapist nurse and the multidisciplinary team.

Objetivo:El objetivo es describir los procedimientos técnicos operativos y datos clínicos relacionados a la implementación de un programa de atención a la salud de las personas con trastornos del suelo pélvico en un servicio público de atención secundaria. Método: se trata de un reporte de experiencia, basado en vivencias relacionadas a la asistencia académico-profesional en la implementación de servicio destinado a los trastornos del suelo pélvico en la región del Cariri cearense, realizado de mayo a julio de 2021. Resultados: para la implementación del servicio, se adoptaron las siguientes estrategias: rastreo de la red de atención a la salud de personas con trastornos del suelo pélvico; estructuración organizacional del servicio; captación de personas con disfunciones pélvicas; inicio de la atención; y seguimiento terapéutico. Conclusión: frente a lo expuesto, queda evidente que el programa de atención a la salud de las personas con trastornos del suelo pélvico puede ser implementado satisfactoriamente, teniendo en cuenta la infraestructura, el importante número de atenciones realizadas y al seguimiento terapéutico alcanzado. Así, con este informe, se espera contribuir al desarrollo de nuevos servicios ambulatorios destinados a esta área de trabajo del enfermero estomaterapeuta y del equipo multidisciplinario.

Animal Model of Neonatal Immune Challenge by Lipopolysaccharide: A Study of Sex Influence in Behavioral and Immune/Neurotrophic Alterations in Juvenile Mice.

INTRODUCTION: The prenatal/perinatal exposure to infections may trigger neurodevelopmental alterations that lead to neuropsychiatric disorders such as autism spectrum disorder (ASD). Previous evidence points to long-term behavioral consequences, such as autistic-like behaviors in rodents induced by lipopolysaccharide (LPS) pre- and postnatal (PN) exposure during critical neurodevelopmental periods. Additionally, sex influences the prevalence and symptoms of ASD. Despite this, the mechanisms underlying this influence are poorly understood. We aim to study sex influences in behavioral and neurotrophic/inflammatory alterations triggered by LPS neonatal exposure in juvenile mice at an approximate age of ASD diagnosis in humans. METHODS: Swiss male and female mice on PN days 5 and 7 received a single daily injection of 500 µg/kg LPS from Escherichia coli or sterile saline (control group). We conducted behavioral determinations of locomotor activity, repetitive behavior, anxiety-like behavior, social interaction, and working memory in animals on PN25 (equivalent to 3-5 years old of the human). To determine BDNF levels in the prefrontal cortex and hippocampus, we used animals on PN8 (equivalent to a human term infant) and PN25. In addition, we evaluated iba-1 (microglia marker), TNFα, and parvalbumin expression on PN25. RESULTS: Male juvenile mice presented repetitive behavior, anxiety, and working memory deficits. Females showed social impairment and working memory deficits. In the neurochemical analysis, we detected lower BDNF levels in brain areas of female mice that were more evident in juvenile mice. Only LPS-challenged females presented a marked hippocampal expression of the microglial activation marker, iba-1, and increased TNFα levels, accompanied by a lower parvalbumin expression. DISCUSSION/CONCLUSION: Male and female mice presented distinct behavioral alterations. However, LPS-challenged juvenile females showed the most prominent neurobiological alterations related to autism, such as increased microglial activation and parvalbumin impairment. Since these sex-sensitive alterations seem to be age-dependent, a better understanding of changes induced by the exposure to specific risk factors throughout life represents essential targets for developing strategies for autism prevention and precision therapy.

A 2-Step Strategy Combining FIB-4 With Transient Elastography and Ultrasound Predicted Liver Cancer After HCV Cure.

INTRODUCTION: Despite the direct-acting antiviral therapy has dramatically decreased the likelihood of having liver-related complications and extrahepatic outcomes, the risk of developing hepatocellular carcinoma (HCC) is not totally eliminated after sustained virological response (SVR). We aimed to develop an easy-to-apply strategy to be adopted in clinical practice for accurately classifying the HCC risk in hepatitis C virus patients after SVR. METHODS: Prospective and multicenter study enrolling hepatitis C virus patients with advanced fibrosis (transient elastography [TE] > 10 kPa) or cirrhosis by ultrasound showing SVR. They were followed up until HCC, liver transplantation, death, or until October 2020, which occurred first, with a minimum follow-up period of 6 months after SVR (follow-up: 49 [interquartile range 28-59] months). RESULTS: Patients with cirrhosis by ultrasound represented 58% (611/1,054) of the overall cohort. During the study, HCC occurrence was 5.3% (56/1,054). Multivariate analyses revealed that Fibrosis-4 (FIB-4) > 3.25 (hazard ratio [HR] 2.26 [1.08-4.73]; P = 0.030), TE (HR 1.02 [1.00-1.04]; P = 0.045) and cirrhosis by ultrasound (HR 3.15 [1.36-7.27]; P = 0.007) predicted HCC occurrence. Baseline HCC screening criteria (TE > 10 kPa or cirrhosis) identified patients at higher risk of HCC occurrence in presence of FIB-4 > 3.25 (8.8%; 44/498) vs FIB-4 < 3.25 (2.4%; 12/506), while those with only FIB > 3.25 had no HCC (0%; 0/50) (logRank 22.129; P = 0.0001). A combination of baseline FIB-4 > 3.25 and HCC screening criteria had an annual incidence >1.5 cases per 100 person-years, while the rest of the groups remained <1 case. Patients who maintained post-treatment FIB-4 > 3.25 and HCC screening criteria remained at the highest risk of HCC occurrence (13.7% [21/153] vs 4.9% [9/184]; logRank 7.396, P = 0.007). DISCUSSION: We demonstrated that a two-step strategy combining FIB-4, TE, and ultrasound could help stratify HCC incidence risk after SVR.

Plasma Levels of sFas-sFasL and FASL Gene Expression Are Associated with Tuberculosis.

Apoptosis of macrophages infected by Mycobacterium tuberculosis via Fas-FasL is an important immune mechanism against infection. This study investigated the association of tuberculosis (TB) with the presence of the polymorphisms FAS -670A/G and FASL -124A/G, the levels of sFas and sFasL, and the gene expression of FASL and cytokines. Samples of 200 individuals diagnosed with TB and 200 healthy controls were evaluated. Real-time PCR (genotyping and gene expression) and ELISA (dosages of sFas, sFasL, IFN-γ, and IL-10) tests were performed. There was no association of FAS -670A/G and FASL -124A/G polymorphisms with TB. The TB group exhibited high plasma levels of sFas and reduced plasma levels of sFasL (p < 0.05). The correlation analysis between these markers revealed a positive correlation between the levels of sFas and sFasL, sFasL and FASL expression, and between sFas and FASL expression (p < 0.05). In the TB group, there was a positive correlation between FASL expression and IFN-γ levels and higher levels of IL-10 compared to IFN-γ (p < 0.05). High levels of sFas and reduced levels of sFasL and FASL expression may contribute to the inhibition of apoptosis in infected cells and represent a possible bacterial resistance resource to maintain the infection.

Tyramine exerts hypolipidemic and anti-obesity effects in vivo

Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine

Prevalence and predisponent factors of molar-incisor hypomineralization in primary dentition

Aim: To evaluate the prevalence and predisposing factors for hypomineralization of second molars in children in primary dentition. Methods: A questionnaire was applied to parents to analyze predisposing factors and to assist in the diagnosis of hypomineralization in children between 2 and 6 years old, followed by an intraoral examination based on indices of non-fluorotic enamel defects in the primary dentition, according to the "Modified Index DDE" to determine demarcated opacity and HSPM presence / severity index to assess hypomineralization. Children from public and private schools were dived into two groups: if they presented HSPM-Group 1 (G1) and if they did not have HSPM-Control group (CG). Results: The most frequent predisposing factors associated with the child were Illness in the first year of life (X2= 6.49; p=0.01) and antibiotic use in the first year of life (X2= 41.82; p= 0.01). The factors associated with the mother were hypertension (X2= 9.36; p=0.01), infections during pregnancy (X2=14.80; p=0.01) and alcohol consumption during pregnancy (X2=97.33; p=0.01). There was a prevalence of 3.9% of HSPM in 14 children, with statistical difference regarding gender (X2 = 4.57; p <0.05), with boys presenting a higher frequency. In G1 hypomineralization was of the type with demarcated opacity, with more prevalent characteristics the yellowish spot, with moderate post-eruptive fracture and acceptable atypical restorations. All lesions were located in the labial region with 1/3 of extension. Conclusion: The prevalence of HSPM in children between 2 and 6 years old was 3.9%, with a predominance in males, with tooth 65 being the most affected. There was an association between HSPM and infection in the first year of life, as well as the use of antibiotics and sensitivity in the teeth affected by the lesion. There was an association between HSPM and hypertension, infection and mothers' alcohol use during pregnancy