Carvacrol alleviates CUMS-induced depressive-like behaviors and cognitive impairment by reducing oxidative stress and neuroinflammation in mice.

The present study aimed to evaluate the protective potential of carvacrol against depressive-like behavior and cognitive impairment prompted by chronic unpredictable mild stress (CUMS) in mice. The animals were divided into six groups: Control (non-stressed), CARV (carvacrol at 50 mg/kg, p.o.), FLU (fluoxetine at 10 mg/kg, p.o.), CUMS (stressed), CUMS + CARV and CUMS + FLU, and the groups with CUMS were subjected to different stressors for 28 days. After treatment, mice underwent behavioral testing (open field, forced swimming, sucrose preference, social interaction, novel object recognition and Y-maze) and brain areas were removed for oxidative stress (MDA, nitrite/nitrate and GSH levels) and cytokine (IL-1ß and TNF-α) content assays. The results revealed that CARV administration reversed depressive-like behavior and significantly ameliorated the cognitive deficit induced by CUMS, as well as was able to attenuate oxidative stress (decreased MDA and nitrite/nitrate levels and increased GSH levels). In addition, a significant reduction in hippocampal IL-1ß and TNF-α levels was observed, demonstrating a potential anti-neuroinflammatory activity. Taken together, the antioxidant and anti-inflammatory activities observed in this study indicate that CARV is a promising drug for antidepressant treatment.

Long-term Environmental Enrichment Normalizes Schizophrenia-like Abnormalities and Promotes Hippocampal Slc6a4 Promoter Demethylation in Mice Submitted to a Two-hit Model.

Here, we explored the impact of prolonged environmental enrichment (EE) on behavioral, neurochemical, and epigenetic changes in the serotonin transporter gene in mice subjected to a two-hit schizophrenia model. The methodology involved administering the viral mimetic PolyI:C to neonatal Swiss mice as a first hit during postnatal days (PND) 5-7, or a sterile saline solution as a control. At PND21, mice were randomly assigned either to standard environment (SE) or EE housing conditions. Between PND35-44, the PolyI:C-treated group was submitted to various unpredictable stressors, constituting the second hit. Behavioral assessments were conducted on PND70, immediately after the final EE exposure. Following the completion of behavioral assessments, we evaluated the expression of proteins in the hippocampus that are indicative of microglial activation, such as Iba-1, as well as related to neurogenesis, including doublecortin (Dcx). We also performed methylation analysis on the serotonin transporter gene (Slc6a4) to investigate alterations in serotonin signaling. The findings revealed that EE for 50 days mitigated sensorimotor gating deficits and working memory impairments in two-hit mice and enhanced their locomotor and exploratory behaviors. EE also normalized the overexpression of hippocampal Iba-1 and increased the expression of hippocampal Dcx. Additionally, we observed hippocampal demethylation of the Slc6a4 gene in the EE-exposed two-hit group, indicating epigenetic reprogramming. These results contribute to the growing body of evidence supporting the protective effects of long-term EE in counteracting behavioral disruptions caused by the two-hit schizophrenia model, pointing to enhanced neurogenesis, diminished microglial activation, and epigenetic modifications of serotonergic pathways as underlying mechanisms.

Vaccine adherence and adverse events of the SARS-COV vaccine in patients with inflammatory bowel disease.

OBJECTIVE: To assess adherence to and the adverse effects of the SARS-COV vaccine in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: This is an observational, analytical, cross-sectional study. Sociodemographic and clinical data, SARS-COV vaccine data, medications for IBD with use during the vaccination period, and adverse events during the vaccination period were collected. Carried out logistic regressions with robust variance estimation to estimate the odds ratio with the respective 95% confidence intervals (95%CI) to assess the factors associated with non-serious adverse effects following vaccine doses as outcome variables. RESULTS: 194 patients participated, with vaccine compliance of 78.3% for three doses of any vaccine (n=152). Local symptoms and mild systemic symptoms predominated, regardless of the type of vaccine. The first dose of the SARS-COV vaccine with AstraZeneca had a higher percentage of patients with vaccine symptoms. AstraZeneca vaccine increased the chance of non-serious adverse effects in IBD patients by 2.65 times (95% CI: 1.38-5.08; p=0.003), regardless of age, gender, physical activity, excess weight, use of disease-modifying drugs, immunobiological and corticosteroids. CoronaVac vaccine was associated with asymptomatic patients at the first dose and reduced the chance of adverse effects by 0.28 times (OR: 0.284; 95%CI: 0.13-0.62; p=0.002). CONCLUSION: Local symptoms and mild systemic symptoms predominated, regardless of the type of vaccine. Using CoronaVac in the first dose reduced the chances of adverse effects, while AstraZeneca increased the risk of adverse effects.

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.

Cyclooxygenase-2 inhibitors alleviated depressive and anxious-like behaviors in mice exposed to lipopolysaccharide: Involvement of oxidative stress and neuroinflammation.

Depression and anxiety disorders have their pathophysiologies linked to inflammation and oxidative stress. In this context, celecoxib (CLX) and etoricoxib (ETR) inhibit cyclooxygenase 2 (COX-2), an enzyme expressed by cells involved in the inflammatory process and found in the brain. Studies have been using CLX as a possible drug in the treatment of depression, although its mechanisms at the central nervous system level are not fully elucidated. In this study, the effects of CLX and ETR on behavioral, oxidative, and inflammatory changes induced by systemic exposure to Escherichia coli lipopolysaccharide (LPS) were evaluated in adult male swiss mice. For ten days, the animals received intraperitoneal injections of LPS at 0.5 mg/kg. From the sixth to the tenth day, one hour after LPS exposure, they were treated orally with CLX (15 mg/kg), ETR (10 mg/kg), or fluoxetine (FLU) (20 mg/kg). Twenty-four hours after the last oral administration, the animals underwent evaluation of locomotor activity (open field test), predictive tests for depressive-like behavior (forced swim and tail suspension tests), and anxiolytic-like effect (elevated plus maze and hole board tests). Subsequently, the hippocampus, prefrontal cortex and striatum were dissected for the measurement of oxidative and nitrosative parameters (malondialdehyde, nitrite, and glutathione) and quantification of pro-inflammatory cytokines (IL-1ß and IL-6). LPS induced depressive and anxious-like behavior, and treatment with CLX or ETR was able to reverse most of the behavioral changes. It was evidenced that nitrosative stress and the degree of lipid peroxidation induced by LPS were reduced in different brain areas after treatment with the drugs, as well as the endogenous defense system against free radicals was strengthened. CLX and ETR also significantly reduced LPS-induced cytokine levels. These data are expected to expand information on the role of inflammation in depression and anxiety and provide insights into possible mechanisms of COX-2 inhibitors in psychiatric disorders with a neurobiological basis in inflammation and oxidative stress.

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.

Long-term administration of omeprazole in mice: a study of behavior, inflammatory, and oxidative stress alterations with focus on central nervous system.

Chronic use of omeprazole has been linked to central effects alongside with the global concern of increasing appearance of neuropsychiatric disorders. This study aimed to identifying behavioral, inflammatory, and oxidative stress alterations after long-term administration of omeprazole. C57BL/6 mice were divided in groups: OME and Sham, each received either solutions of omeprazole or vehicle, administered for 28 days by gavage. Results observed in the omeprazole-treated mice: Decrease in the crossing parameter in the open field, no change in the motor performance assessed by rotarod, an immobility time reduction in the forced swimming test, improved percentage of correct alternances in the Ymaze and an exploration time of the novel object reduction in the novel object recognition. Furthermore, a reduced weight gain and hippocampal weight were observed. There was an increase in the cytokine IL1-ß levels in both prefrontal cortex (PFC) and serum, whereas TNF-α increased only in the PFC. Nitrite levels increased in the hippocampus (HP) and PFC, while malondialdehyde (MDA) and glutathione (GSH) levels decreased. These findings suggest that omeprazole improves depressive-like behavior and working memory, likely through the increase in nitrite and reduction in MDA levels in PFC and HP, whereas, the impairment of the recognition memory is more likely to be related to the reduced hippocampal weight. The diminished weight gain might be associated with the IL-1ß increased levels in the peripheral blood. Altogether, omeprazole showed to have the potential to impact at central level and inflammatory and oxidative parameters might exert a role between it.

Nutritional strategies, performance, digestibility, and carcass traits of Santa Ines and Rabo Largo breeds in a tropical climate.

The aim of this study was to compare the performance, intake, digestibility, ruminal parameters, carcass traits, and the yield of commercial cuts of Santa Ines (SI) and Rabo Largo (RL) breeds fed diets with high or low roughage-to-concentrate ratio (R:C) under a tropical climate. Twenty lambs from each breed were individually housed in covered pens and fed the experimental diets for 58 days. The diets were formulated to meet the growth requirements of lambs with a roughage-to-concentrate ratio of 70:30 and 30:70. Significant interactions of breed × diet for nutrient intake were observed (P < 0.05), with SI lambs fed low R:C diet showing higher intake of dry matter, organic matter, crude protein, and total carbohydrates compared to RL lambs fed the same diet. SI lambs fed high R:C diet had higher intake of neutral detergent fiber than RL lambs (P < 0.05). SI lambs displayed better average daily gain and feed efficiency, regardless of diet (P < 0.05). Carcass traits and gastrointestinal components were influenced by breed and diet (P < 0.05). SI lambs fed low R:C diet showed higher subcutaneous fat thickness and better carcass finishing compared to RL lambs (P < 0.05). SI breed lambs exhibited better growth performance, carcass traits, and gastrointestinal characteristics, even when fed diets with a high roughage-to-concentrate ratio.

Social and health vulnerability of homeless people.

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.

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.

The evening crepuscular host-seeking activity of Anopheles mosquitoes in northeast Brazil.

Studies on the timing of anopheline host-seeking are important for understanding mosquito ecology, behaviors, and possible role in disease transmission. To study the evening crepuscular host-seeking activity of anophelines and the effects of moonlight, anopheline mosquitoes were collected with light traps settled in a livestock area in the Brazilian Cerrado region. Traps (Silva traps) were placed next to animal enclosures at 1.5 m asl. The research was divided in 2 experiments: the first experiment (12 nights) comprised 2 trapping periods, one from 6 PM to 7 PM and one from 7 PM to 6 AM, and the second experiment (16 evenings) divided in three 20-min intervals based on the 3 twilight phases (civil: 6-6:20 PM; nautical: 6:20-6:40 PM; and astronomical: 6:40-7 PM). A total of 2,815 anopheline mosquitoes and 9 species were found. The main species were Anopheles triannulatus s.l., An. argyritarsis, An. goeldii, and An. evanse. Host-seeking mosquitoes were more frequently active during the first hour after sunset, with a significant peak in the second 20-min interval. After that, a decrease in the number of individuals was observed from the astronomical twilight onwards. Moonlight did not affect the evening flight activity of anophelines. By using LED-based passive light traps, the evening arrival time of anophelines at blood-feeding sites was demonstrated, and it may be a key time window for malaria vector control interventions.

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

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.

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.

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.

Power of mortality prediction in patients awaiting liver transplantation according to the Global Leadership Initiative on Malnutrition criteria and Subjective Global Assessment and Royal Free Hospital Global Assessment scores.

OBJECTIVES: This study aimed to analyze the performance of the Global Leadership Initiative on Malnutrition (GLIM) criteria and Subjective Global Assessment (SGA) and Royal Free Hospital Global Assessment (RFH-GA) scores in predicting 12-mo mortality in patients awaiting liver transplantation. METHODS: This is a longitudinal observational study, carried out between March 2019 and November 2021. Clinical data were collected and nutritional assessment was performed through anthropometry and application of validated instruments, such as the SGA, GLIM criteria, and RFH-GA. A Cox regression model was carried out, in which the dependent variable was mortality in 1 y, and the independent variables were the classifications of nutritional status by the different methods. RESULTS: The sample consisted of 126 patients, most of them male (56.35%). Malnutrition was diagnosed in 85.71% of the patients according to the RFH-GA, 62.70% according to the SGA, and 56.31% according to the GLIM criteria. Malnutrition assessed by GLIM was related to a 3.79-fold increase in the chance of mortality over time in patients awaiting liver transplantation. Moreover, the GLIM criteria had good discriminatory power in identifying mortality in patients awaiting liver transplantation, compared with the initial and final SGA and RFH-GA scores and the Model for End-stage Liver Disease-Sodium (MELD-Na) index. CONCLUSIONS: The GLIM criteria were a good predictor of increased risk of mortality in malnourished patients with chronic liver disease awaiting liver transplantation, compared with the SGA and RFH-GA scores and the MELD-Na index.

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.

Development and Characterization of Symbiotic Buffalo Petit Suisse Cheese Utilizing Whey Retention and Inulin Incorporation.

This study presents the development and characterization of a novel buffalo Petit Suisse cheese, enhanced with symbiotic properties through an innovative whey retention method and incorporating inulin and xanthan gum. The research focused on assessing the cheese's physicochemical properties, shelf life, lactic acid bacteria viability, syneresis behavior, and the impact of varying concentrations of functional ingredients. The addition of inulin and xanthan gum, following a design of experiments, significantly influenced the cheese's texture and consistency. Higher inulin concentrations were associated with increased fermentation activity, as indicated by total titratable acidity, which showed an increase from 1.22% to 1.50% over a 28-day period, and pH levels that decreased from 3.33 to 2.96. The syneresis index varied across trials, with the highest reduction observed in trials with increased xanthan gum concentrations, effectively reducing syneresis to 0%. Lactic acid bacteria viability also showed notable variations, with the highest cell survival percentage reaching 107.89% in formulations with higher inulin and xanthan gum concentrations. These results underscore the importance of inulin and xanthan gum in enhancing the cheese's microbial stability and textural quality. The study concludes that the strategic use of inulin and xanthan gum improves the nutritional profile of buffalo Petit Suisse cheese and optimizes its textural and sensory attributes.