Saturated Iso-Type Fatty Acids from the Marine Bacterium Mesoflavibacter zeaxanthinifaciens with Anti-Trypanosomal Potential.

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new anti-trypanosomal compounds, we investigated the potential of the metabolites from the bacteria living in the corals and sediments of the southeastern Brazilian coast. Three corals, Tubastraea coccinea, Mussismilia hispida, Madracis decactis, and sediments yielded 11 bacterial strains that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera-Vibrio, Shewanella, Mesoflavibacter, Halomonas, Bacillus, and Alteromonas. To conduct this study, EtOAc extracts were prepared and tested against Trypanosoma cruzi. The crude extracts showed IC50 values ranging from 15 to 51 µg/mL against the trypomastigotes. The bacterium Mesoflavibacter zeaxanthinifaciens was selected for fractionation, resulting in an active fraction (FII) with IC50 values of 17.7 µg/mL and 23.8 µg/mL against the trypomastigotes and amastigotes, respectively, with neither mammalian cytotoxicity nor hemolytic activity. Using an NMR and ESI-HRMS analysis, the FII revealed the presence of unsaturated iso-type fatty acids. Its lethal action was investigated, leading to a protein spectral profile of the parasite altered after treatment. The FII also induced a rapid permeabilization of the plasma membrane of the parasite, leading to cell death. These findings demonstrate that these unsaturated iso-type fatty acids are possible new hits against T. cruzi.

Saturated iso-type fatty acids from the marine bacterium Mesoflavibacter zeaxanthinifaciens with anti-Trypanosomal potential

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new anti-trypanosomal compounds, we investigated the potential of the metabolites from the bacteria living in the corals and sediments of the southeastern Brazilian coast. Three corals, Tubastraea coccinea, Mussismilia hispida, Madracis decactis, and sediments yielded 11 bacterial strains that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera—Vibrio, Shewanella, Mesoflavibacter, Halomonas, Bacillus, and Alteromonas. To conduct this study, EtOAc extracts were prepared and tested against Trypanosoma cruzi. The crude extracts showed IC50 values ranging from 15 to 51 μg/mL against the trypomastigotes. The bacterium Mesoflavibacter zeaxanthinifaciens was selected for fractionation, resulting in an active fraction (FII) with IC50 values of 17.7 μg/mL and 23.8 μg/mL against the trypomastigotes and amastigotes, respectively, with neither mammalian cytotoxicity nor hemolytic activity. Using an NMR and ESI-HRMS analysis, the FII revealed the presence of unsaturated iso-type fatty acids. Its lethal action was investigated, leading to a protein spectral profile of the parasite altered after treatment. The FII also induced a rapid permeabilization of the plasma membrane of the parasite, leading to cell death. These findings demonstrate that these unsaturated iso-type fatty acids are possible new hits against T. cruzi.

Avaliação de risco agudo à exposição dietética a resíduos de agrotóxicos em tomate / Acute risk assessment of dietary exposure to pesticide residues in tomato

A utilização de agrotóxicos ao redor do mundo é elevada, estimada em mais 2 milhões de toneladas e somente o continente americano emprega 1,2 milhão de toneladas de produtos. O Brasil possui na agricultura a sua principal atividade econômica e utilizou em 2021 aproximadamente 700 mil toneladas de agrotóxicos. O tomate é um dos vegetais mais cultivados e consumidos no mundo e o Brasil figura como o 10º maior produtor. O consumo anual médio de tomate do brasileiro é de 4,2 kg, é um vegetal nutritivo e com propriedades associadas à prevenção de câncer. O tomate é uma das culturas com maior uso de agrotóxicos e durante o período desse estudo, era autorizado o uso de 123 agrotóxicos. Os resíduos desses produtos nos alimentos podem acarretar em diversos problemas à saúde, mesmo em curta exposição (< 24h). Desse modo, uma das maneiras de garantir a segurança alimentar da população é a realização da avaliação de risco de contaminação dietética. No processo de validação 73 ingredientes ativos respeitaram os critérios do protocolo adotado. Para a realização da estimativa de risco de exposição dietética aguda, foram coletadas 30 amostras de tomate in natura e 11 de tomate pelado, entre setembro de 2021 e março de 2022. Para a extração dos compostos de interesse foi utilizado o método QuEChERS e para avaliação dos resíduos, a cromatografia líquida acoplada à espectrometria de massas. Das amostras de tomate in natura, somente seis (20 %) estavam isentas dos compostos pesquisados; 18 (60 %) apresentaram resíduo(s) abaixo do limite (LMR) estabelecido e seis amostras (20 %) foram consideradas impróprias ao consumo. Das amostras de tomate pelado, três estavam isentas dos agrotóxicos pesquisados e oito (72 %) apresentaram resíduo de carbendazim abaixo do LMR. Nenhuma das amostras mostrou potencial de contaminação aguda por agrotóxicos, apesar disso não é possível afirmar que não há risco, pois não há como estimar os potenciais efeitos adversos provenientes do consumo de um alimento com múltiplos compostos.

More than 2 million tons of pesticide products are used annually through the world and only the America continent was used 1,2 million tons of these products. The agriculture is the main economic activity in Brazil, this way in 2021 approximately 700 thousand tons of pesticide were applied in its crops. Tomato is one of the most cultivated and consumed vegetables in the world and Brazil is the 10th largest producer. The Brazilian people consumes an average of 4.2 kg of tomatoes by year, it is a nutritious vegetable with anti-cancer properties. Tomato crop is one of the which highest pesticide usages, during this study 123 compounds were permitted for this crop. Pesticide residues in food may causes several health problems, even in short-term exposition (< 24h), thus one of the ways to ensure the food safety to population is performing the dietary contamination risk assessment. In the validation process 73 active ingredients were within the established criteria. To perform the acute risk assessment of dietary exposure, were collected samples of: fresh tomato (30) and whole peeled tomato (11) in between September of 2021 and March of 2022. To extraction of interest substances was used the QuEChERS method and to residue evaluation the liquid chromatography coupled to mass spectrometry. Of the fresh tomato samples, only six (20 %) were free of searched analytes; 18 (60 %) showed residue(s) bellow the established limits (MRL) and six (20 %) were considered unfit to consumption. Of the whole peeled tomato samples, three were free of searched substances and eight (72 %) showed residue of carbendazim bellow the MRL. None of the samples showed potential for acute contamination by pesticide, however it is not possible to say that there is no risk, as there is no way to estimate the potential adverse effects on health arising from the consumption of a food with several compounds.

Correlation of serological and molecular markers in the screening for hepatitis B virus in blood bank in northern Brazil

ABSTRACT Introduction: In Brazil, the blood donor screening for hepatitis B virus (HBV) includes laboratory testing for serological (HBsAg and Anti-HBc) and molecular (HBV DNA) markers. This study aims to correlate serology reactive results with HBV DNA detection among blood donors with at least one HBV infection marker detected in a blood bank in northern Brazil. Method: A retrospective search for HBV reactive blood donor data from January 2017 to December 2019 was performed. Serological screening was performed by chemiluminescent microparticle immunoassays Architect HBsAg and Architect Anti-HBc, whereas molecular screening was performed by the HBV nucleic acid test (HBV NAT). Main results: A total of 556 HBsAg reactive results were detected, between positive (47.66%) and inconclusive (52.34%). A total of 3,658 Anti-HBc reactive results were detected, between positive (83.71%) and inconclusive (16.29%). None of the inconclusive results were associated with HBV DNA detection. The HBV DNA detection rates were 47.55% among HBsAg positive samples and 4.08% among Anti-HBc positive samples. The signal-to-cutoff (S/CO) ratio median of HBV NAT positive samples was superior in comparison to HBV NAT negative samples (p < 0.0001). The thresholds found to optimize sensitivity and specificity were 404.15 for Architect HBsAg and 7.77 for Architect Anti-HBc. Three blood donors were in the window period and 1 occult HBV infection case was detected. Conclusion: High S/CO ratios were more predictive of HBV DNA detection. However, a number of HBV NAT positive samples gave low values, while some HBV NAT negative samples showed high values, reaffirming the significance of molecular testing to enhance transfusion safety.

Perspectivas para a Prática Avançada de Enfermagem em Unidades de Terapia Intensiva: uma reflexão / Perspectives for Advanced Practice Nursing in Intensive Care Units: a reflection

OBJETIVO: Refletir sobre as ações de práticas avançadas de enfermagem no contexto das Unidades de Terapia Intensiva. MÉTODO: Trata-se de um estudo teórico-reflexivo embasado em literatura internacional, cujos artigos apontem ações do enfermeiro de prática avançada no ambiente de terapia intensiva, além do guideline de Prática Avançada de Enfermagem do International Council of Nurses. RESULTADOS: A união de informações acerca das ações de práticas avançadas de enfermagem no ambiente de terapia intensiva permitiu a reflexão que gerou nove categorias de ações: educação continuada, educação em saúde, ser referência especializada em terapia intensiva, atividade de pesquisa, gerenciamento do cuidado, liderança de equipe, cuidado com a família, atuação em equipe multidisciplinar e assistência direta ao paciente. CONCLUSÃO: A reflexão evidenciou que educação, gestão e assistência são eixos de competências encontradas nas práticas avançadas de enfermagem na terapia intensiva.

OBJECTIVE: To reflect on the actions of advanced practice nursing in the context of intensive care units. METHOD: This is a theoretical-reflective study based on international literature whose articles refer to the actions of advanced practice nurses in the intensive care environment. It is also based on the International Council of Nurses' Advanced Practice Nursing Guideline. RESULTS: The union of information about the actions of advanced practice nursing in the intensive care environment allowed a reflection that generated nine categories of actions: continuing education, patient education, being a specialized reference in intensive care, research activity, care management, team leadership, family care, multidisciplinary teamwork, and direct patient care. CONCLUSION: The reflection showed that education, management, and care are the axes of competencies in advanced practice nursing in intensive care.

First report of Rhodnius stali Lent, Jurberg & Galvão, 1993 (Hemiptera: Reduviidae: Triatominae), vector of Trypanosoma cruzi (TcI) and Trypanosoma rangeli (TrA), in Rondônia, Southwestern Brazilian Amazonia.

Triatomines are hematophagous insects of epidemiological importance as they are vectors of Chagas disease. The first report of Rhodnius stali Lent, Jurberg & Galvão, 1993 in Rondônia, Brazil, is described. The insects were captured on palm trees of the genus Oenocarpus sp. Two adult male specimens of R. stali were identified and were found to be infected with Trypanosoma cruzi and Trypanosoma rangeli. The confirmation of this Rhodnius species in Rondônia increases the number of triatomines from nine to ten species in this state.

A quantitative textual analysis of the subjective effects of ayahuasca in naïve users with and without depression.

Ayahuasca is a brew with psychoactive properties that has been used as an entheogen for centuries, with more recent studies suggesting it is a promising treatment for some clinical disorders. Although there is an emerging scientific literature on its effects, to the best of our knowledge no study has explored the self-reported experiences of first-time ayahuasca users with quantitative textual analysis tools. Accordingly, the current study aimed to analyze the subjective experience of naive individuals with depression and healthy controls after consuming ayahuasca. For this purpose, responses from a subsample of participants from a previous clinical trial to open-ended questions regarding their experience with ayahuasca underwent textual analysis. Data from nine patients with treatment-resistant depression and 20 healthy individuals were included, and quantitative textual analysis was performed using IRaMuTeQ 0.7 alpha 2 and R 3.1.2. The analysis identified five clusters: alterations in the state of consciousness, cognitive changes, somatic alterations, auditory experiences, and visual perceptual content. Additionally, findings suggest specific features of the experience of people with depression with ayahuasca, such as increased aversive bodily reactions. The results are consistent with previous findings indicating central axes of the psychedelic experience, and may inform therapeutic approaches using ayahuasca.

Acute purulent diverticulitis in the cecum: case report.

A 40-year-old female with a 24-hour course of abdominal pain suggestive of acute appendicitis. An emergency laparotomy was performed, finding plastron in the cecum and ascending colon, color changes, with purulent liquid and 5 cm in diameter, fixed to Toldt's. It was decided to perform a right hemicolectomy with an ileotransverse end-to-side anastomosis with adequate postsurgical evolution. The histopathological report showed acute purulent diverticulitis of the cecum, which is very low incidence in the Mexican population, that's why this case report is carried out.

Mujer de 40 de años con cuadro de dolor abdominal de 24 h de evolución clínicamente sugestiva de apendicitis aguda. Se realiza laparotomía de urgencia, encontrando plastrón en ciego y colon ascendente, irregular, pétreo, con cambios de coloración, de 5 cm de diámetro, fijo a la fascia de Toldt, con líquido purulento. Se decide realizar hemicolectomía derecha con ileotransverso anastomosis terminolateral, con adecuada evolución posquirúrgica. El reporte histopatológico mostró diverticulitis aguda purulenta de ciego, lo cual es de baja incidencia en la población mexicana, motivo por el que se realiza este reporte de caso.

Barbellatanic acid, a new antitrypanosomal pseudo-disesquiterpenoid isolated from Nectandra barbellata, displayed interaction with protozoan cell membrane.

As part of our ongoing studies involving the discovery of new natural prototypes with antiprotozoal activity against Trypanosoma cruzi from Brazilian plant species, the chromatographic fractionation of hexane extract from leaves of Nectandra barbellata afforded one new pseudo-disesquiterpenoid, barbellatanic acid. The structure of this compound was elucidated by NMR and HR-ESIMS data analysis. Barbellatanic acid displayed a trypanocidal effect with IC50 of 13.2 µM to trypomastigotes and no toxicity against NCTC cells (CC50 > 200 µM), resulting in an SI value higher than 15.1. The investigation of the lethal mechanism of barbellatanic acid in trypomastigotes, using both fluorescence microscopy and spectrofluorimetric analysis, revealed a time-dependent permeation of the plasma membrane. Based on these results, this compound was incorporated in cellular membrane models built with lipid Langmuir monolayers. The interaction of barbellatanic acid with the models was inferred by tensiometric, rheological, spectroscopical, and morphological techniques, which showed that this compound altered the thermodynamic, viscoelastic, structural, and morphological properties of the film. Taking together, these results could be employed when this prodrug interacts with lipidic interfaces, such as protozoa membranes or liposomes for drug delivery systems.

Health Benefits and Positive Acute Effects of Psilocybin Consumption: A Quantitative Textual Analysis of User Self-Reported Data.

There has been growth in the use of psychedelics by the global population in recent years. In addition to recreational and ritualistic use, recent research into psychedelics has brought advances for treating mental disorders. Understanding the specific circumstances in which psilocybin leads to positive outcomes may have important implications for the future of its clinical use and for harm reduction initiatives. This study aimed to investigate the positive effects from the consumption of psilocybin through public online self-reports. We sought to investigate health benefits promoted by the consumption of the substance, positive acute effects, and contextual details of these experiences. We analyzed 846 reports with the assistance of the IRaMuTeQ textual analysis software, adopting the procedures of Descending Hierarchical Classification, Correspondence Factor Analysis, and Specificities Analysis. The texts were grouped in 5 clusters, describing the content of mental experiences, cognitive processes, somatic experiences, perceptual alterations, and context of administration. The findings of this study reinforce central axes of the psychedelic experience, such as the presence of somatic and visual alterations, connectedness and feeling one with the world and effects of setting, as well as the beneficial character of mystical experiences this substance promotes, and the importance of the ego-dissolution phenomenon.

Characterization of polyphenols in the methanol leaf extract of Bathysa gymnocarpa (Rubiaceae) by HPLC-DAD-ESI-MS/MS.

The species Bathysa gymnocarpa K.Schum is a tree belonging to the Rubiaceae family, endemic in Brazil. So far, there are reports neither of phytochemical work nor of biological evaluation of it. The analysis by High Performance Liquid Chromatography coupled to a Diode Array Detector and a tandem Mass Spectrometer with an Electrospray Ionization source (HPLC-DAD-ESI-MS/MS) of its crude extract allowed to characterize in a complex mixture, without isolation, fourteen compounds, being two as cinnamic acid derivatives, and the others as mono-, di- and triglycosilated derivatives of the flavonols quercetin and kaempferol. These compounds are reported for the first time in Bathysa spp.

Correlation of serological and molecular markers in the screening for hepatitis B virus in blood bank in northern Brazil.

INTRODUCTION: In Brazil, the blood donor screening for hepatitis B virus (HBV) includes laboratory testing for serological (HBsAg and Anti-HBc) and molecular (HBV DNA) markers. This study aims to correlate serology reactive results with HBV DNA detection among blood donors with at least one HBV infection marker detected in a blood bank in northern Brazil. METHOD: A retrospective search for HBV reactive blood donor data from January 2017 to December 2019 was performed. Serological screening was performed by chemiluminescent microparticle immunoassays Architect HBsAg and Architect Anti-HBc, whereas molecular screening was performed by the HBV nucleic acid test (HBV NAT). MAIN RESULTS: A total of 556 HBsAg reactive results were detected, between positive (47.66%) and inconclusive (52.34%). A total of 3,658 Anti-HBc reactive results were detected, between positive (83.71%) and inconclusive (16.29%). None of the inconclusive results were associated with HBV DNA detection. The HBV DNA detection rates were 47.55% among HBsAg positive samples and 4.08% among Anti-HBc positive samples. The signal-to-cutoff (S/CO) ratio median of HBV NAT positive samples was superior in comparison to HBV NAT negative samples (p < 0.0001). The thresholds found to optimize sensitivity and specificity were 404.15 for Architect HBsAg and 7.77 for Architect Anti-HBc. Three blood donors were in the window period and 1 occult HBV infection case was detected. CONCLUSION: High S/CO ratios were more predictive of HBV DNA detection. However, a number of HBV NAT positive samples gave low values, while some HBV NAT negative samples showed high values, reaffirming the significance of molecular testing to enhance transfusion safety.

A comparative study of telephone and face-to-face use of phone screening interview for autistic spectrum disorder symptoms (PSI-ASD) / Estudo comparativo da aplicação por telefone e presencial da entrevista de triagem por telefone de sintomas do espectro autista (PSI-TEA)

ABSTRACT Objective: Describe reliabilities evidence of the Phone Screening Interview (PSI), a telephone screening interview for autism spectrum disorder (ASD) symptoms, capable of investigating mild to moderate ASD symptoms. Moreover, the PSI also works for verbal and non-verbal children and is consistent with the DSM-5 diagnostic criteria. Methods: An interview was performed with sixty-eight parents of children between 2 and 15 years old attended by the Psychiatry Ambulatory of Santa Casa de Misericórdia do Rio de Janeiro through the PSI in person and by telephone. Results: No significant differences in comparison between averages of the total score of the face-to-face and telephone applications were observed. The agreement analysis between the items indicated three items with lower values, leading to the modification of some questions, culminating in a new interview version for further studies. Given the disagreement in the values found, the order of application of the interviews seems to not impact the results, demonstrating strong correlations between both interviews, even with a different order of application. Aiming to facilitate the use of the scale by different examiners, the interobserver reliability was investigated, which did not show significant differences in the means. Conclusion: The study suggests that the telephone interview can be used similarly to the face-to-face interview, by different evaluators, with no impact on its efficiency in detecting ASD symptoms.

RESUMO Objetivo: Descrever evidências de confiabilidade da Phone Screening Interview (PSI), uma entrevista para rastreio telefônico de sintomas do Transtorno do Espectro Autista (TEA) de fácil aplicação, capaz de investigar sintomas de TEA leve a moderado, aplicável a crianças verbais e não verbais e consistente com os critérios diagnósticos do DSM-5. Métodos: Sessenta e oito pais de crianças com idade entre 2 e 15 anos atendidas pelo Ambulatório de Psiquiatria da Santa Casa de Misericórdia do Rio de Janeiro foram entrevistados por meio da PSI, tanto de maneira presencial quanto telefônica. Resultados: As médias da pontuação total da aplicação presencial e telefônica foram comparadas, não sendo obtidas diferenças significativas. A análise de concordância entre os itens apontou três itens com valores muito baixos, levando à modificação de algumas perguntas, culminando em uma nova versão, para estudos posteriores. Diante da discordância de valores encontrada, foi verificado que a ordem de aplicação das entrevistas não impactaria os resultados, demonstrando fortes correlações entre as entrevistas, mesmo com ordem de aplicação diferente. Para viabilizar o uso da escala por diferentes examinadores, investigou-se a confiabilidade interobservadores, que não mostrou diferenças significativas nas médias. Conclusão: O estudo sugere que a entrevista telefônica pode ser utilizada de forma semelhante à presencial, por diferentes avaliadores, sem impacto em sua eficiência na detecção de sintomas de TEA.

Adaptation and latent structure of the Brazilian version of the Ego Dissolution Inventory (EDI-BR): An exploratory study.

INTRODUCTION: Existing scales that seek to measure alterations in self-experience were based on studies conducted in developed countries. Therefore, the aim of this study was to evaluate the psychometric properties of the Ego-Dissolution Inventory (EDI), translate and adapt it to the Brazilian context. METHODS: Translation of the measure was made by two translators fluent in both English and Portuguese, with back-translation into English to ensure there was no loss of meaning. The scale was included in an online survey exploring substance use. A total of 528 participants answered the full scale. We calculated the Kaiser-Meyer-Olkin (KMO) measure to evaluate sampling adequacy, then ran Exploratory Analysis Factor (EFAs) to investigate the factor structure of the EDI. RESULTS: The scale showed acceptable psychometric properties, with excellent internal consistency and sampling adequacy for a factor analysis. Kaiser-Gutman's criteria and Hull's method pointed to a three-factor solution, while Parallel Analysis suggested a two-factor solution. All items showed salient loadings, with two items exhibiting cross-loading. Positive but weak correlations were found between EDI factors 1 and 2 and nature-relatedness. CONCLUSIONS: The validated scale showed solid psychometric properties, with potential differences in factor structure in relation to the English version. Considering validation as ongoing process, it is recommended to conduct studies comparing the scores of ego dissolution across distinct substances and different regions of the country.

Mitochondrial Imbalance of Trypanosoma cruzi Induced by the Marine Alkaloid 6-Bromo-2'-de-N-Methylaplysinopsin.

Chagas disease, caused by Trypanosoma cruzi, affects seven million people worldwide and lacks effective treatments. Using bioactivity-guided fractionation, NMR, and electrospray ionization-high resolution mass spectrometry (ESI-HRMS) spectral analysis, the indole alkaloid 6-bromo-2'-de-N-methylaplysinopsin (BMA) was isolated and chemically characterized from the marine coral Tubastraea tagusensis. BMA was tested against trypomastigotes and intracellular amastigotes of T. cruzi, resulting in IC50 values of 62 and 5.7 µM, respectively, with no mammalian cytotoxicity. The mechanism of action studies showed that BMA induced no alterations in the plasma membrane permeability but caused depolarization of the mitochondrial membrane potential, reducing ATP levels. Intracellular calcium levels were also reduced after the treatment, which was associated with pH alteration of acidocalcisomes. Using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)/MS analysis, alterations of mass spectral signals were observed after treatment with BMA, suggesting a different mechanism from benznidazole. In silico pharmacokinetic-pharmacodynamic (PKPD) parameters suggested a drug-likeness property, supporting the promising usefulness of this compound as a new hit for optimizations.

A new reduced chalcone-derivative affects the membrane permeability and electric potential of multidrug-resistant Enterococcusfaecalis.

The emergence and spread of multidrug-resistant (MDR) enterococci and other Gram-positive bacteria represents a severe problem due to the lack of effective therapeutic alternatives. Natural products have long been an important source of new antibacterial scaffolds and can play a key role in the current antibiotic crisis. Enterococci are predominantly non-pathogenic gastrointestinal commensal bacteria, but among them, Enterococcus faecalis and Enterococcus faecium represent the species that account for most clinically relevant infections. The emergence of MDR enterococci has reduced the available antibiotic treatment options and highlights the need to develop new antimicrobial compounds. In the search for new hit compounds against MDR Enterococcus spp., natural-derived compounds represent inspiring scaffolds for drug design studies. In this work, the antimicrobial activity of a fully synthetic chalcone derivative (r4MB) was determined on a clinical panel of 34 MDR Gram-positive bacteria, mostly constituted by E. faecalis and E. faecium, along with Staphylococcus spp., amongst others. Compound r4MB showed activity against 100% of the tested strains, with the minimum inhibitory concentration (MIC) in the range of 5-20 µM. The lethal action of the compound was evaluated using different fluorescent-based assays. The compound showed a time-dependent permeabilisation of the membrane of a vancomycin-resistant E. faecalis, detected by the fluorescent probe SYTOX Green, and digital fluorescent microscopy corroborated the spectrofluorimetric analysis within 6 min of incubation. Flow cytometry analysis of the membrane electric potential demonstrated a significant depolarization, confirming the target of the compound towards the bacterial membrane. No cytotoxic haemolysis was observed with mammalian erythrocytes, and a 99% cytotoxic concentration of 118 µM on NCTC cells demonstrated a promising antimicrobial selectivity. In silico studies using SwissADME and ADMETLabs servers suggest that compound r4MB displayed adequate ADME properties, with no alerts for pan-assay interference compounds (PAINS). Future hit-to-lead optimization of this chalcone derivative can contribute to developing a more potent derivative against infections caused by MDR enterococci.

Avaliação de resíduos de agrotóxicos em amostras de farinha de trigo por espectrometria de massas / Evaluation of pesticide residues in wheat flour by mass spectrometry

Os cereais são uma importante fonte alimentícia e econômica, dentre eles se destaca o trigo e sua farinha. Durante o cultivo, visando o controle de pragas, frequentemente são utilizados os agrotóxicos, porém seu uso abusivo pode acarretar danos à saúde humana e ao meio ambiente. O trabalho teve como objetivo avaliar a presença de resíduos de agrotóxicos em amostras de farinha de trigo comercializadas no estado de São Paulo, utilizando o método QuEChERS (Rápido, Fácil, Barato, Efetivo, Robusto e Seguro) modificado, seguido de análise por CG-EM/EM e CLUE-EMAR para identificação e quantificação. No total, 124 ingredientes ativos (i.a.) estavam dentro dos critérios de aceitação para linearidade, limites de detecção e quantificação, exatidão e precisão (intervalo de confiança de 95%; k = 2). Os resultados de 25 amostras indicaram a presença de bifentrina, fenitrotiona, clorpirifós, deltametrina, lambda-cialotrina e pirimifós-metílico em farinha de trigo comum e os quatro últimos i.a. também foram detectados em farinha de trigo orgânica. O pirimifósmetílico foi detectado em 92% das amostras. Os i.a. encontrados nas amostras estavam abaixo do Limite Máximo de Resíduos (LMR) estabelecidos pela Agência Nacional de Vigilância Sanitária (Anvisa) para farinha de trigo e as amostras foram consideradas próprias para o consumo (AU).

Cereals are an important economic factor and food source, which wheat and its flour stand out. Pesticides are often employed to control harmful organisms, but their abusive use can cause damage to human health and the environment. This study aimed to evaluate the presence of pesticide residues in wheat flour samples commercialized in the state of São Paulo ­ Brazil, using the modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method, followed by GC-MS/MS and UHPLC-HRMS analysis for identification and quantification. Thus, 124 active ingredients (a.i.) were within acceptable criteria for linearity, limits of detection and quantification, accuracy (trueness), and precision (95% confidence level; k = 2). The results for 25 wheat flour samples showed the presence of bifenthrin, fenitrothion, chlorpyrifos, deltamethrin, lambda-cyhalothrin, and pirimiphos-methyl, and the last four a.i. were also detected in organic wheat flour. Pirimiphos-methyl was detected in 92% of all samples. All compounds were found below the Maximum Residue Levels (MRL) established by Brazilian Health Regulatory Agency (Anvisa) for wheat flour and the samples were considered suitable for consumption (AU).

Aproximações com a educação libertadora de Paulo Freire: o caso de uma professora de Educação Física no "chão da escola" / Approaches to the liberating education of Paulo Freire: the case of a Physical Education teacher on the "school floor" / Aproximaciones a la educación liberadora de Paulo Freire: el caso de una profesora de Educación Física en el "piso de la escuela"

O presente ensaio é um texto autorreflexivo sobre qual a função social da escola e do professor de educação física a partir de questionamentos que surgiram ao longo da prática docente. Compreendendo a educação como um processo com vias à conscientização dos educandos, buscamos alinhar as expectativas entre a função da instituição escola, a função do professor de educação física e a nossa prática enquanto sujeitos sociais. Considerando o papel do professor frente a instituição escolar, apresentamos atravessamentos que confluíram para que a prática se ampare em uma relação horizontalizada com os educandos no intuito de que eles possam ser protagonistas, sujeitos da construção do seu conhecimento e ter uma visão ampliada de sua realidade, buscando assim uma educação libertadora.

This essay is a self-reflective text about the social function of the school and the physical education teacher from questions that arose throughout the teaching practice. Understanding education as a process with ways to raise the awareness of students, I seek to align expectations between the role of the school institution, the role of physical education teacher and my practice as a social subject. Considering the role of the teacher in the school institution, I present crossings that converged so that my practice is supported in a horizontal relationship with the students so that they can be protagonists, subjects of the construction of their knowledge and have an expanded view of their reality, thus seeking a liberating education.

Este ensayo es un texto autorreflexivo sobre la función social de la escuela y el docente de educación física a partir de preguntas que surgieron a lo largo de la práctica docente. Entendiendo la educación como un proceso con formas de sensibilizar a los estudiantes, busco alinear expectativas entre el rol de la institución escolar, el rol del docente de educación física y mi práctica como sujeto social. Considerando el rol del docente en la institución escolar, presento cruces que confluyeron para que mi práctica se apoye en una relación horizontal con los estudiantes para que puedan ser protagonistas, sujetos de la construcción de su conocimiento y tener una visión ampliada de su realidad, buscando así una educación liberadora.

Results of a sample-to-cutoff ratio using Abbott Architect rHTLV-I/II assay allow to predict detection of HTLV-1 and HTLV-2 proviral DNA by real-time PCR / Resultados da razão sinal da amostra sobre o cutoff da reação no ensaio Abbott Architect rHTLV-I/II permite prever a detecção de DNA proviral por PCR em tempo real

The present study aims to correlate the sample-to-cutoff ratios (S/CO) distributions of reactive results for HTLV-1/2 antibodies with the detection of proviral DNA in a population of blood donor candidates. It was carried out a retrospective data search of 632 HTLV-1/2 reactive samples, submitted to confirmatory testing from January 2015 to December 2019. Serological screening was performed by chemiluminescent microparticle immunoassay Architect rHTLV-I/II, whereas confirmatory testing was performed by in-house real-time polymerase chain reaction method. 496 out of 632 samples (78%) had undetectable HTLV-1/2 proviral DNA and 136 (22%) had detectable proviral DNA. HTLV infection was not confirmed in any individual for whom the S/CO ratio value was <4, and proviral DNA detection rates gradually escalated as S/CO ratio values increased. The sensitivity and predictive positive value found for the Architect rHTLV-I/II was 100% and 22%, respectively. The receiver operating characteristic (ROC) curve analysis showed that the optimal S/CO ratio value for predicting the presence of HTLV-1/2 was 18.11. High S/CO ratios were more associated with the detection of proviral DNA. The S/CO ratio value <4 suggests excluding true HTLV infection and the risk of blood transmission (AU).

O estudo tem como objetivo correlacionar às distribuições das razões sample-to-cutoff (S/CO) de resultados reagentes para anticorpos HTLV-1/2 com a detecção de DNA proviral em uma população de candidatos à doação de sangue. Realizou-se uma busca retrospectiva de dados de 632 amostras reagentes para HTLV-1/2 submetidas à testagem confirmatória entre janeiro de 2015 a dezembro de 2019. A triagem sorológica foi realizada pelo imunoensaio quimioluminescente de micropartículas Architect rHTLV-I/II, enquanto o teste confirmatório foi realizado pelo método de PCR em tempo real in-house. 496 de 632 amostras (78%) apresentaram DNA proviral indetectável e 136 (22%) apresentaram DNA proviral detectável. A infecção por HTLV não foi confirmada em nenhum indivíduo com valor de S/CO <4 e as taxas de detecção de DNA proviral escalonaram gradualmente à medida que as razões S/CO aumentaram. A sensibilidade e valor preditivo positivo encontrados para o Architect rHTLV-I/II foram 100% e 22%, respectivamente. Utilizando análise de curva ROC, o valor de razão S/CO ideal para predizer a presença de DNA proviral foi de 18,11. Razões S/CO elevadas foram mais associadas à detecção de DNA proviral. Em suma, o valor de S/CO <4 sugere a exclusão de infecção por HTLV e o risco de transmissão pelo sangue (AU).

Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes.

Ubiquitination represents a post-translational modification (PTM) essential for the maintenance of cellular homeostasis. Ubiquitination is involved in the regulation of protein function, localization and turnover through the attachment of a ubiquitin molecule(s) to a target protein. Ubiquitination can be reversed through the action of deubiquitinating enzymes (DUBs). The DUB enzymes have the ability to remove the mono- or poly-ubiquitination signals and are involved in the maturation, recycling, editing and rearrangement of ubiquitin(s). Ubiquitin-specific proteases (USPs) are the biggest family of DUBs, responsible for numerous cellular functions through interactions with different cellular targets. Over the past few years, several studies have focused on the role of USPs in carcinogenesis, which has led to an increasing development of therapies based on USP inhibitors. In this review, we intend to describe different cellular functions, such as the cell cycle, DNA damage repair, chromatin remodeling and several signaling pathways, in which USPs are involved in the development or progression of cancer. In addition, we describe existing therapies that target the inhibition of USPs.