Genomic analysis of Oceanotoga teriensis strain UFV_LIMV02, a multidrug-resistant thermophilic bacterium isolated from an offshore oil reservoir.

Bacteria of the species Oceanotoga teriensis belong to the family Petrotogaceae, are Gram-negative bacilli, are moderately thermophilic and are included in the group of thiosulfate-reducing bacteria, being capable of significantly accelerating corrosion in metallic structures. However, no in-depth study on the genome, antibiotic resistance and mobile elements has been carried out so far. In this work, the isolation, phenotypic and genotypic characterization of the multi-resistant O. teriensis UFV_LIMV02 strain was carried out, from water samples from an offshore oil extraction platform in Rio de Janeiro (Brazil). We determined that the isolate has a genome of 2 812 778 bp in size, with 26 % GC content, organized into 34 contigs. Genomic annotation using Rapid Annotation using Subsystem Technology revealed the presence of genes related to resistance to antibiotics and heavy metals. By evaluating the antimicrobial resistance of the isolate using the disc diffusion technique, resistance was verified for the classes of antibiotics, beta-lactams, fluoroquinolones, aminoglycosides, sulfonamides, lincosamides and rifamycins, a total of 14 antibiotics. The search for genomic islands, prophages and defence systems against phage infection revealed the presence of five genomic islands in its genome, containing genes related to resistance to heavy metals and antibiotics, most of which are efflux pumps and several transposases. No prophage was found in its genome; however, nine different defence systems against phage infection were detected. When analysing the clustered regularly interspaced short palindromic repeat (CRISPR) systems, four CRISPR arrays, classified as types I-B and III-B, with 272 spacers, can provide the strain with immunity to different mobile genetic elements and bacteriophage infection. The results found in this study show that the isolate UFV_LIVM02 is an environmental bacterium, resistant to different classes of antibiotics, and that the proteins encoded by the predicted genomic islands may be associated with the development of greater resistance to antibiotics and heavy metals. They provide evidence that environmental bacteria found in offshore oil exploration residues may pose a risk for the spread of antibiotic resistance genes. More comprehensive studies on the microbial community present in oil waste are needed to assess the risks of horizontal gene transfer.

GDP-mannose pyrophosphorylase is an efficient target in Xanthomonas citri for citrus canker control.

Xanthomonas citri subsp. citri (Xcc) is a bacterium that causes citrus canker, an economically important disease that results in premature fruit drop and reduced yield of fresh fruit. In this study, we demonstrated the involvement of XanB, an enzyme with phosphomannose isomerase (PMI) and guanosine diphosphate-mannose pyrophosphorylase (GMP) activities, in Xcc pathogenicity. Additionally, we found that XanB inhibitors protect the host against Xcc infection. Besides being deficient in motility, biofilm production, and ultraviolet resistance, the xanB deletion mutant was unable to cause disease, whereas xanB complementation restored wild-type phenotypes. XanB homology modeling allowed in silico virtual screening of inhibitors from databases, three of them being suitable in terms of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties, which inhibited GMP (but not PMI) activity of the Xcc recombinant XanB protein in more than 50%. Inhibitors reduced citrus canker severity up to 95%, similarly to copper-based treatment. xanB is essential for Xcc pathogenicity, and XanB inhibitors can be used for the citrus canker control. IMPORTANCE: Xcc causes citrus canker, a threat to citrus production, which has been managed with copper, being required a more sustainable alternative for the disease control. XanB was previously found on the surface of Xcc, interacting with the host and displaying PMI and GMP activities. We demonstrated by xanB deletion and complementation that GMP activity plays a critical role in Xcc pathogenicity, particularly in biofilm formation. XanB homology modeling was performed, and in silico virtual screening led to carbohydrate-derived compounds able to inhibit XanB activity and reduce disease symptoms by 95%. XanB emerges as a promising target for drug design for control of citrus canker and other economically important diseases caused by Xanthomonas sp.

Perfil profissional dos egressos do curso de Odontologia de uma universidade do interior da Bahia / Perfil profesional de los egresados de la carrera de Odontología en una universidad del interior de Bahía / Professional profile of the dentistry school graduates from a university in the interior of the state of Bahia

O objetivo desse estudo foi conhecer o perfil profissional dos egressos do Curso de Odontologia da Universidade Estadual do Sudoeste da Bahia e o grau de satisfação em relação ao âmbito de trabalho. Foi realizado um estudo quali-quantitativo e transversal por meio de questionário onlineautoaplicável enviado por meio das redes sociais para os cirurgiões-dentistas que colaram grau entre 2009 e 2020. Os dados obtidos foram tabulados em planilha Excel e submetidos à análise descritiva e ao teste Qui-quadrado de Pearson com nível de significância de 5%. Quando a frequência esperada foi menor que cinco (n<5), utilizou-se o teste exato de Fisher. Para a questão discursiva foi utilizada a técnica de análise de conteúdo proposta por Bardin. Dos 383 egressos, 124 (32%) participaram da pesquisa. Observou-se que 74,2% são do sexo feminino e 44,6% realizaram especialização. A maioria (84,6%) se inseriu no mercado de trabalho em até um mês após a formatura e atuavam como profissional liberal (30,2%). Houve diferença significativa quando associadas as variáveis satisfação com a profissão e valorização financeira. A insegurança em atuar na profissão foi relacionada a não ter mais a supervisão do docente. Ademais, foram apontadas pouca exploração nos conteúdos de gestão e empreendedorismo durante a graduação. Conclui-se que os egressos conseguiram uma rápida inserção no mercado de trabalho após a colação de grau e que um elevado percentual dos cirurgiões-dentistas se sente satisfeito com a profissão (AU).

El objetivo de este estudio fue comprender el perfil profesional de los egresados de la Carrera de Odontología de la Universidad Estadual del Suroeste de Bahía y el grado de satisfacción en relación al ámbito de trabajo. Se realizóun estudio cuali-cuantitativo y transversal mediante un cuestionario en línea autoadministrado enviado a través de redes sociales a cirujanos dentistas egresados entre 2009 y 2020. Los datos obtenidos fueron tabulados en una hoja de cálculo Excel y sometidos a análisis descriptivo y prueba de Pearson. chi-cuadrado con un nivel de significancia del 5%. Cuando la frecuencia esperada fue menor de cinco (n<5), se utilizó la prueba exacta de Fisher. Para la pregunta discursiva se utilizó la técnica de análisis de contenido propuesta por Bardin. De los 383 graduados, 124 (32%) participaron de la investigación. Se observó que el 74,2% son mujeres y el 44,6% completó la especialización. La mayoría (84,6%) ingresó al mercado laboral dentro del mes posterior a su graduación y trabajó como profesionales independientes (30,2%). Hubo diferencia significativa cuando se asociaron las variables satisfacción con la profesión y apreciación financiera. La inseguridad en el trabajo en la profesión estaba relacionada con la falta de supervisión docente. Además, se destacó poca exploración de contenidos de gestión y emprendimiento durante la graduación. Se concluye que los egresados lograron insertarse rápidamente al mercado laboral luego de graduarse y que un alto porcentaje de los cirujanos dentistas se sienten satisfechos con su profesión (AU).

The objective of this study was to review the profile of the Dentistry School graduates from a State University in Southwest Bahia and the degree of satisfaction in relation to their work. A qualitative-quantitative and cross-sectional study was carried out using an online self-administered questionnaire forwarded through the social networks WhatsApp and Instagram to dental surgeons who graduated between 2009 and 2020. The data obtained were tabulated in an Excel spreadsheet and subjected to descriptive analysis and Pearson's Chi-square test with a significance level of 5%. For the open-ended question, the content analysis technique proposed by Bardin was used. Out of the 383 graduates, 124 (32%) participated in the survey. The majority (84.6%) entered the job market within one month after graduation and had been working as independent professionals (30.2%). There was a significant difference with regard to job satisfaction and financial appreciation. The insecurity in the professional endeavor was associated with the fact that a teacher's guidance was no more available. Furthermore, little exploration of management and entrepreneurship matters had been addressed during the graduation course. It is concluded that graduates were able to quickly enter the job market after graduating and that extracurricular activities are crucial in guiding their future profession and in contributing to professional qualification (AU).

Development of a low-cost congenital abdominal wall defect simulator (wall-go) for undergraduate medical education: a validation study.

BACKGROUND: Congenital Anomalies were responsible for 303,000 deaths in the neonatal period, according to the WHO, they are among the world's top 20 causes of morbidity and mortality. Expensive simulators demonstrate several diseases, but few are related to congenital anomalies. This study aims to develop, validate, and evaluate low-cost simulator models (WALL-GO) of the most common abdominal wall defects, gastroschisis, and omphalocele, to enable diagnosis through an accessible tool with study value and amenable to replication. METHODS: Market research was conducted to find materials to build low-cost models. The researchers built the model and underwent validation assessment of the selected experts who scored five or more in the adapted Fehring criteria. The experts were assessed through a 5-point Likert scale to 7 statements (S1-7). Statements were assigned values according to relevance in face and transfer validities. Concomitantly, the model was also evaluated by students from 1st to 5th year with the same instruments. Content Validity Indexes (CVIs) were considered validated between groups with concordance greater than 90%. Text feedback was also collected. Each statement was subjected to Fisher's Exact Test. RESULTS: Gastroschisis and omphalocele model costs were US $15 and US $27, respectively. In total, there were 105 simulator evaluators. 15 experts were selected. Of the 90 students, there were 16 (1st year), 22 (2nd), 16 (3rd), 22 (4th), and 14 (5th). Students and experts obtained CVI = 96.4% and 94.6%, respectively. The CVIs of each statement were not significantly different between groups (p < 0,05). CONCLUSIONS: The WALL-GO models are suitable for use and replicable at a manufacturable low cost. Mannequins with abdominal wall defects are helpful in learning to diagnose and can be applied in teaching and training health professionals in developing and low-income countries.

Intervenção educativa multiprofissional para conservação de energia em paciente idosa com insuficiência cardíaca: relato de experência / Multidisciplinary educational intervention for energy conservation in elderly patients with heart failure: experience report

INTRODUÇÃO: A insuficiência cardíaca (IC) é a via final das cardiopatias, causando nos acometidos congestão pulmonar, dispneia, ortopneia, fadiga e edema, comprometendo a qualidade de vida dos portadores de IC. OBJETIVO: Relatar a experiência de desenvolvimento e implementação de um plano terapêutico individualizado destinado à atenção a paciente com IC hospitalizada. METODOLOGIA: Trata-se de um relato de caso que traz menção à intervenção educativa realizada durante um cenário de atuação Multiprofissional do Programa de Residência Multiprofissional em Saúde Cardiovascular em instituição pública da cidade de São Paulo especializada em cardiologia. O grupo realizou a coleta de dados e reunião com familiares e pessoas de referência envolvidas no cuidado de uma paciente com IC internada em uma enfermaria, afim de esclarecimento de dados que direcionassem a conduta profissional. Foram estabelecidas as necessidades por meio de uma coleta de dados com uso de escalas e questionários validados e foi estabelecido como diagnóstico de enfermagem prioritário tolerância à atividade diminuída, de acordo com a Taxonomia NANDA-I. Todo o processo foi pautado na Teoria Holística de Myra Levine para compreender e embasar os processos adaptativos incluídos no processo saúde-doença, além de planejar os cuidados transicionais. RESULTADOS: Paciente idosa, portadora de IC de etiologia valvar, Classe Funcional NYHA III e verbalizava sua insatisfação com a sua situação clínica. A partir das necessidades levantadas, traçou-se uma intervenção educativa com o objetivo de favorecer o autocuidado frente às novas situações vivenciadas a partir do adoecimento, respeitando os desejos e o sentido atribuído à vida da paciente e de auxiliá-la com orientações baseadas em evidências científicas sobre métodos para conservação de energia, a fim de melhorar os sintomas apresentados. Sendo assim, optou-se pela construção de um livro contendo um breve resumo da história do sujeito, orientações sobre os cuidados necessários, sobretudo sobre medidas de conservação de energia, e um espaço para que este possa se expressar. Com isso, o vínculo entre paciente- -profissional foi aprimorado e, ainda na internação, apresentou melhora importante dos sintomas, evoluindo para Classe Funcional NYHA II. CONCLUSÃO: Durante a intervenção da equipe multiprofissional pautada em modelos teóricos, foi possível o estabelecimento de vínculo entre paciente, rede de apoio e equipe. Ademais, houve melhora dos sintomas apresentados, caracterizando um avanço no processo de adaptação da paciente frente à sua nova realidade.

Ligand-based virtual screening, molecular dynamics, and biological evaluation of repurposed drugs as inhibitors of Trypanosoma cruzi proteasome.

Chagas disease is a well-known Neglected Tropical Disease, mostly endemic in continental Latin America, but that has spread to North America and Europe. Unfortunately, current treatments against such disease are ineffective and produce known and undesirable side effects. To find novel effective drug candidates to treat Chagas disease, we uniquely explore the Trypanosoma cruzi proteasome as a recent biological target and, also, apply drug repurposing through different computational methodologies. For this, we initially applied protein homology modeling to build a robust model of proteasome ß4/ß5 subunits, since there is no crystallographic structure of this target. Then, we used it on a drug repurposing via a virtual screening campaign starting with more than 8,000 drugs and including the methodologies: ligand-based similarity, toxicity predictions, and molecular docking. Three drugs were selected concerning their favorable interactions at the protein binding site and subsequently submitted to molecular dynamics simulations, which allowed us to elucidate their behavior and compare such theoretical results with experimental ones, obtained in biological assays also described in this paper.Communicated by Ramaswamy H. Sarma.

Responses Triggered by the Immune System in Hypertensive Conditions and Repercussions on Target Organ Damage: A Review.

BACKGROUND: Hypertension is a chronic, multifactorial clinical condition characterized by sustained high blood pressure levels. It is often associated with functional-structural alterations of target organs, which include heart, brain, kidneys, and vasculature. OBJECTIVE: This study highlights the recent correlation between the immune system and hypertension and its repercussions on target-organ damage. METHODS: The descriptors used for the search of the study were "hypertension", "immunity", and "target organs". The methodology of the study followed the main recommendations of the PRISMA statement. RESULTS: The damage to the vasculature arises mainly from the migration of T cells and monocytes that become pro-inflammatory in the adventitia, releasing TNF-α, IFN-γ, and IL-17, which induce endothelial damage and hinder vascular relaxation. In the renal context, the inflammatory process associated with hypertension culminates in renal invasion by leukocytes, which contribute to the injury of this organ by mechanisms of intense sympathetic stimulation, activation of the reninangiotensin system, sodium retention, and aggravation of oxidative stress. In the cardiac context, hypertension increases the expression of pro-inflammatory elements, such as B, T, and NK cells, in addition to the secretion of IFN-γ, IL-17, IL-23, and TNF-α from angiotensin II, reactive oxygen species, and aldosterone. This pro-inflammatory action is also involved in brain damage through SphK1. In view of the above, the participation of the immune system in hypertension-induced injuries seems to be unequivocal. CONCLUSION: Therefore, understanding the multifactorial mechanisms related to hypertension will certainly allow for more efficient interventions in this condition, preventing target organ damage.

Sensitivity of eucalyptus (Eucalyptus urograndis) plants to subdoses of the herbicide dicamba / Sensibilidade de plantas de eucalipto (Eucalyptus urograndis) à subdoses do herbicida dicamba

In view of the widespread increase in herbicide-resistant weeds, biotechnology companies have developed dicamba-tolerant soybean and cotton cultivars. This technology can, however, increase the risk of the productdrifting to adjacent areas.This study was developed with the objective of the to evaluate the phytotoxicity and biometric variables of young eucalyptus plants exposed to subdoses of the herbicide dicamba. The experiment was carried out under field conditions in Rio Verde, state of Goiás, Brazil. The treatments were represented by the application of 0 (control), 7.5, 15, 30, 60, 120 or 240 g ae ha-1of dicamba 45 days after the seedlings were planted in the field. In terms of phytotoxicity, the dicamba doses of 120 and 240 g ae ha-1caused greater damage to the eucalyptus plants in all periods of evaluation. The predominant symptoms were epinasty, increased number of shoots and necrosis and senescence of young branches and leaves. The herbicide doses of 120 and 240 g ae ha-1 significantly compromised plant height and diameter, number of branches and dry mass of leaves and roots, interfering with the growth and development of the eucalyptus crop. The results indicate that the effect of subdoses of the herbicide dicamba can interfere with the proper development of young eucalyptus plants, which may cause losses in the initial plantingphase and future losses for producers.(AU)

Em decorrência do aumento generalizado de plantas daninhas com resistência a herbicidas, empresas de biotecnologia desenvolveram cultivares de soja e algodão tolerantes ao herbicida dicamba. Essa tecnologia pode, no entanto, aumentar o risco do produto ser deslocado para áreas adjacentes às aplicadas. Neste trabalho objetivou-seavaliar a fitotoxicidade evariáveis biométricas de plantas jovens de eucalipto tratadas com subdoses do herbicida dicamba. O experimento foi realizado em condições de campo em Rio Verde, Goiás, Brasil. Os tratamentos foram representados pela aplicação de 0 (testemunha), 7,5, 15,30, 60, 120 ou 240 g ea ha-1de dicamba aos 45 dias após o plantio das mudas no campo. Em termos de fitotoxicidade, as doses de dicamba de 120 e 240 g ea ha-1causaram maiores danos às plantas de eucalipto em todos os períodos de avaliação. Os sintomas predominantes foram epinastia, aumento do número de brotações e necrose e senescência de ramos e folhas jovens. As doses de herbicidas de 120 e 240 g ea ha-1comprometeram significativamente a altura e diâmetro das plantas, número de ramos e massa seca de folhas, caules e raízes, interferindo no crescimento e desenvolvimento da cultura do eucalipto. Os resultados indicam que o efeito de subdoses do herbicida dicamba pode interferir no bom desenvolvimento de plantas jovens de eucalipto, podendo causar prejuízos na fase inicial de plantio e prejuízos futuros para os produtores.(AU)

Componente curricular projeto de vida: perspectivas de professoras da rede estadual de São Paulo / Curricular component life purpose: perspectives of teachers of the São Paulo state network / Componente curricular proyecto de vida: perspectivas de profesores de la red estadual de São Paulo

O objetivo deste estudo foi conhecer a experiência de alguns professores ao lecionar projeto de vida durante a implementação do componente curricular Projeto de Vida no estado de São Paulo. Realizou-se uma pesquisa qualitativa, de caráter exploratório. Participaram do estudo sete professoras que lecionavam o componente curricular Projeto de Vida em duas escolas públicas, de uma cidade do interior do estado de São Paulo, escolhidas por conveniência. Foram utilizados o Questionário de Dados Sociodemográficos e o Protocolo de Entrevista Semiestruturada para Projeto de Vida de Professores, elaborados para este estudo. As professoras foram entrevistadas individualmente, on-line, e as entrevistas foram gravadas em áudio e vídeo. Os dados foram analisados por meio de análise temática. Os resultados indicaram possibilidades e desafios em relação à implementação do componente curricular Projeto de Vida. Constatou- se que a maioria das docentes afirmou que escolheu esse componente curricular devido à necessidade de atingir a carga horária exigida na rede estadual. As professoras criticaram a proposta, os conteúdos e os materiais desse componente curricular. As críticas apresentadas pelas professoras estão em consonância com aquelas presentes na literatura em relação à reforma do Ensino Médio e ao Inova Educação. Esses resultados sugerem a necessidade de formação tanto nos cursos de licenciatura quanto em ações de formação continuada, para que os professores se sintam mais seguros e preparados para lecionar o componente curricular Projeto de Vida na Educação Básica. Propõe-se uma perspectiva de formação pautada na reflexão e na troca entre os pares para a construção de um projeto coletivo da escola para o componente Projeto de Vida.(AU)

This study aimed to know the experience of some teachers when teaching life purpose during the implementation of the curricular component "Life Purpose" (Projeto de Vida) in the state of São Paulo. A qualitative, exploratory research was carried out. Seven teachers who taught the curricular component "Life Purpose" (Projeto de Vida) in two public schools in a city in the inland state of São Paulo, chosen for convenience, participated in the study. The Sociodemographic Data Questionnaire and the Semi-structured Interview Protocol for Teachers' Life Purposes, developed for this study, were used. The teachers were interviewed individually, online, and the interviews were recorded in audio and video. Data were analyzed using thematic analysis. The results indicated possibilities and challenges regarding the implementation of the Life Purpose curricular component. It was found that most teachers chose this curricular component due to the need to reach the required workload in the state network. The teachers criticized the proposal, the contents and the materials of this curricular component. Teacher's critics are in line with the criticisms present in the literature regarding the reform of High School and Inova Educação. Therefore, training is essential, both in undergraduate courses and in continuing education actions, so that teachers can teach the curricular component Life Purpose in Basic Education. A training perspective based on reflection and exchange between peers is proposed for the construction of a collective school project for the Life Purpose component.(AU)

El objetivo de este estudio fue conocer la experiencia de algunos profesores al enseñar proyecto de vida durante la implementación del componente curricular Proyecto de Vida en el estado de São Paulo. Se realizó una investigación cualitativa, exploratoria. Participaron en el estudio siete profesores que impartían el componente curricular Proyecto de Vida en dos escuelas públicas en un municipio del estado de São Paulo, elegidos por conveniencia. Los instrumentos utilizados fueron el cuestionario de datos sociodemográficos y el protocolo de entrevista semiestructurada para proyectos de vida de profesores, desarrollados para este estudio. Las entrevistas a los profesores fueron en línea, de manera individual, y fueron grabadas en audio y video. Los datos se sometieron a un análisis temático. Los resultados indicaron posibilidades y desafíos en relación a la implementación del componente curricular Proyecto de Vida. La mayoría de los profesores declararon elegir este componente curricular por la necesidad de alcanzar la carga horaria requerida en la red estatal. Los profesionales criticaron la propuesta, los contenidos y los materiales de este componente curricular. Las críticas presentadas están en línea con las críticas presentes en la literatura respecto a la reforma de la educación básica e Inova Educação. Por lo tanto, la formación es fundamental, tanto en los cursos de grado como en las acciones de educación permanente, para que los profesores puedan impartir el componente curricular Proyecto de Vida en la educación básica. Se propone una formación basada en la reflexión y el intercambio entre pares para la construcción de un proyecto escolar colectivo en el componente Proyecto de Vida.(AU)

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling.

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infections in infants. Currently, ribavirin, a nucleoside analog containing a 1,2,4-triazole-3-carboxamide moiety, is a first-line drug for its treatment, however, its clinical use has been limited due to its side effects. Here, we designed two new nitroaryl-1,2,3-triazole triterpene derivatives as novel anti-RSV drugs. Their anti-RSV and cytotoxic activity were evaluated in vitro, RSV protein F gene effects by RT-PCR and molecular modeling with inosine monophosphate dehydrogenase (IMPDH) were performed. Compound 8 was the best performing compound, with an EC50 value of 0.053 µM, a TI of 11160.37 and it inhibited hRSV protein F gene expression by approximately 65%. Molecular docking showed a top-ranked solution located in the same region occupied by crystallographic ligands in their complex with IMPDH. The results obtained in this study suggest that compound 8 might be a new anti-RSV candidate.

In silico Study of Acetylcholinesterase and Beta-secretase Inhibitors: Potential Multitarget Anti-Alzheimer's Agents.

BACKGROUND: Alzheimer's disease is a progressive neurodegenerative process with multifactorial characteristics. This disease follows the natural aging process, affecting mainly people over 65 years. Pharmacotherapeutic treatment currently combats symptoms related to cognitive function. Several targets have begun to attract the interest of the scientific community to develop new drug candidates which have better pharmacokinetic and lower toxicity parameters. OBJECTIVE: The present study aims to design new candidates for acetylcholinesterase/ß-secretase (AChE/BACE1) multitarget inhibitor drugs. METHODS: 17 natural products were selected from the literature with anticholinesterase activity and 1 synthetic molecule with inhibitory activity for BACE1. Subsequently, the molecular docking study was performed, followed by the derivation of the pharmacophoric pattern and prediction of pharmacokinetic and toxicological properties. Finally, the hybrid prototype was designed. RESULTS: All selected molecules showed interactions with their respective target enzymes. Derivation of the pharmacophoric pattern from molecules that interacted with the AChE enzyme resulted in 3 pharmacophoric regions: an aromatic ring, an electron-acceptor region and a hydrophobic region. The molecules showed good pharmacokinetic and toxicological results, showing no warnings of mutagenicity and/or carcinogenicity. After the hybridization process, three hybrid molecules were obtained, which showed inhibitory activity for both targets. CONCLUSION: It is concluded that research in the field of medicinal chemistry is advancing towards the discovery of new drug candidates that bring a better quality of life to patients with AD.

Chromatographic profile, in silico and in vivo study of the pharmacokinetic and toxicological properties of major constituent present in kefir, the kefiran.

Kefiran is a polysaccharide present in kefir grains that have been widely explored due to its potential health benefits. The objective of this work was to characterize and quantify the components present in the ethanolic extract of milk kefir grains; to study its pharmacokinetic and toxicological properties in silico and evaluate the acute toxicity of the kefiran in zebrafish. The prediction of pharmacokinetic properties was performed by QikProp software. In silico toxicity assessment was performed using the DEREK (deductive estimate of risk from existing knowledge) software. In the chromatographic, kefiran was identified as the major component. Results showed that the kefiran had low human oral absorption and intestinal absorption its due poor solubility profile; low logP value, indicating its lipophilicity and the low MDCK and Caco-2 cells permability, and unable to cross the blood-brain barrier. Kefiran did not present any structural warning for in silico toxicity. In zebrafish, the dose of 2,000 mg/kg of kefiran produced nonsignificant alterations in the analyzed organs. It can be said then that kefiran has an acceptable degree of safety for use in the development of drugs or functional foods. Further research such as in vivo testing to confirm its pharmacological potential is currently underway.

Design of Multitarget Natural Products Analogs with Potential Anti-Alzheimer's Activity.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition and the most common type of dementia among the elderly. The enzymes acetylcholinesterase (AChE) and nitric oxide synthase (NOS) have a pivotal role in the pathophysiology of this disease. OBJECTIVE: This study aimed to select medicinal plant-derived molecules with reported inhibition of AChE and design optimized molecules that could inhibit not only AChE, but also NOS, potentially increasing its efficacy against AD. METHODS: 24 compounds were selected from the literature based on their known AChE inhibitory activity. Then, we performed molecular orbital calculations, maps of electrostatic potential, molecular docking study, identification of the pharmacophoric pattern, evaluation of pharmacokinetic and toxicological properties of these molecules. Next, ten analogs were generated for each molecule to optimize their effect where the best molecules of natural products had failed. RESULTS: The most relevant correlation was between HOMO and GAP in the correlation matrix of the molecules' descriptors. The pharmacophoric group's derivation found the following pharmacophoric features: two hydrogen bond acceptors and one aromatic ring. The studied molecules interacted with the active site of AChE through hydrophobic and hydrogen bonds and with NOS through hydrogen interactions only but in a meaningful manner. In the pharmacokinetic and toxicological prediction, the compounds showed satisfactory results. CONCLUSION: The design of natural products analogs demonstrated good affinities with the pharmacological targets AChE and NOS, with satisfactory pharmacokinetics and toxicology profiles. Thus, the results could identify promising molecules for treating Alzheimer's disease.

Evaluation of diagnostic tests' sensitivity, specificity and predictive values in bovine carcasses showing brucellosis suggestive lesions, condemned by Brazilian Federal Meat Inspection Service in the Amazon Region of Brazil.

Cervical bursitis is a suggestive lesion of bovine brucellosis. Diagnostic sensitivity and specificity of two brucellosis serological tests, Rose Bengal (RB) and serum agglutination test with 2-mercaptoethanol (SAT/2-ME), and of isolation and identification (bacteriology) were evaluated through Bayesian latent class analysis (BLCA). A total of 165 paired serum and cervical bursitis samples detected at inspection by Brazilian federal meat inspection services were analyzed. The best model fit to the data occurred when accounting for the conditional dependence between serological tests. According to this model, RB and SAT/2-ME had almost the same sensitivity, 0.960 [0.903 - 0.992] and 0.963 [0.906 - 0.994] with 95 % Credible Interval (95 %CrI), respectively. Specificities were 0.9068 [0.562 - 0.997] and 0.875 [0.546 - 0.990] for RB and SAT/2-ME, respectively, also with 95 %CrI. Bacteriology had lower sensitivity than serological tests, 0.594 (95 %CrI: [0.525 - 0.794]) and the highest specificity of all evaluated tests, 0.992 (95 %CrI: [0.961-1.00]). Prevalence of infected animals was 0.829 (95 %CrI: [0.700-0.900]). BLCA showed that both RB and SAT/2-ME fitted to the purpose of initial screening the brucellosis suspect in carcasses with cervical bursitis in a reliable way. The results of RB or SAT/2-ME can guide the sanitary actions for brucellosis control and help the implementation of a risk-based surveillance system in the meat production chain. This strategy is especially true in remote areas with large beef cattle herds, raised extensively, where in vivo tests are rarely performed due to logistic and management constraints, as in the Northern region of Brazil.

O ensino remoto no curso de Medicina de uma universidade brasileira em tempos de pandemia / Remote education at Brazilian university medical school during the pandemic

Resumo: Introdução: O processo de ensino-aprendizagem passou por grandes mudanças tecnológicas ao longo das décadas, com importante impacto nos cursos de Medicina. Uma dessas mudanças foi o uso dos ambientes virtuais de aprendizagem (AVA). Objetivo: Este estudo teve como objetivo avaliar a qualidade do processo de ensino-aprendizagem remoto no curso de Medicina durante a pandemia da Covid-19. Método: É um estudo de caráter descritivo com abordagem quantitativa e qualitativa. Seu desenvolvimento foi dividido em quatro fases: revisão da literatura, desenvolvimento do protocolo de avaliação, coleta e análise dos dados. A coleta de dados foi realizada por meio de um formulário on-line, e a análise dos dados, por análise estatística em três eixos: a avaliação do perfil tecnológico, a avaliação da aceitação da tecnologia e a experiência do usuário. Resultado: Foi constatado que a maioria dos estudantes (65%) e docentes (88.2%) possuía infraestrutura para participar do semestre suplementar. A maior parte dos alunos relatou sentir segurança em utilizar as ferramentas tecnológicas e estava satisfeita com o ensino remoto, porém 53% dos alunos relataram não ter um rendimento tão grande quanto teriam em um período presencial comum, além de terem mencionado dificuldades na adaptação ao ensino remoto, e 40,2% citaram uma alta taxa de problemas psicológicos entre eles. Os docentes em sua maioria se sentiam seguros em lecionar on-line e também tiveram uma avaliação em geral bastante positiva do semestre remoto, tendo apenas algumas discordâncias em relação ao tempo para preparação das aulas e da criação de materiais didáticos para seus alunos. Conclusão: Os diversos fatores relacionados à tecnologia, organização e saúde mental dos estudantes e docentes devem ser levados em consideração no planejamento dos próximos semestres, pois, até que a situação de saúde volte ao normal, os próximos semestres letivos terão todos os componentes teóricos do curso de Medicina trabalhados remotamente, ao menos com a maioria na modalidade híbrida. É provável que alunos e professores desenvolvam uma curva de aprendizagem e consequente adaptação, o que pode atenuar algumas das dificuldades observadas. É preciso que o processo de adaptação seja catalisado por normas, orientações e também inovações da universidade.

Abstract: Introduction: Introduction: The teaching-learning process has undergone major technological changes over the decades, with a significant impact on medical courses. One of these changes has been the use of virtual learning environments (VLEs). Objective: to evaluate the quality of the remote teaching-learning process in the medical course during the COVID-19 pandemic. Method: This is a descriptive study with a quantitative and qualitative approach. Its development was divided into 4 phases: literature review, development of the assessment protocol, data collection and analysis. Data collection was through an online form and data analysis was by statistical analysis on three axes: assessment of the technological profile, assessment of the acceptance of the technology and the user experience. Result: It was found that most students (65%) and teachers (88.2%) had the infrastructure to participate in the supplementary semester. Most students reported feeling safe in using technological tools and were satisfied with the remote teaching, however, 53% of students reported underachievement in relation to their performance in an ordinary classroom period and reported difficulties in adapting to remote learning, and 40.2% reported a high rate of psychological problems. Most teachers felt secure in teaching online and had a very positive overall evaluation of the remote semester, with only a few disagreements regarding the time to prepare classes and create teaching materials for their students. Conclusion: The various factors related to technology, organization and mental health of students and teachers must be taken into account in the planning of the next semesters, because until the health situation returns to normal, the forthcoming academic semesters will provide all the theoretical components of the medical course remotely, or at least the majority provided in a hybrid modality. It is likely that students and teachers will develop a learning curve and consequent adaptation, which may alleviate some of the difficulties observed. The adaptation process needs to be catalyzed by standards, guidelines and innovations from the university.

Synthesis, antitumor activity and in silico analyses of amino acid derivatives of artepillin C, drupanin and baccharin from green propolis.

Breast cancer has the highest incidence and mortality in females, while prostate cancer has the second-highest incidence in males. Studies have shown that compounds from Brazilian green propolis have antitumor activities and can selectively inhibit the AKR1C3 enzyme, overexpressed in hormone-dependent prostate and breast tumors. Thus, in an attempt to develop new cytotoxic inhibitors against these cancers, three prenylated compounds, artepillin C, drupanin and baccharin, were isolated from green propolis to synthesize new derivatives via coupling reactions with different amino acids. All obtained derivatives were submitted to antiproliferative assays against four cancer cells (MCF-7, MDA MB-231, PC-3, and DU145) and two normal cell lines (MCF-10A and PNT-2) to evaluate their cytotoxicity. In general, the best activity was observed for compound6e, derived from drupanin, which exhibited half-maximal inhibitory concentration (IC50) of 9.6 ± 3 µM and selectivity index (SI) of 5.5 against MCF-7 cells.In silicostudies demonstrated that these derivatives present coherent docking interactions and binding modes against AKR1C3, which might represent a possible mechanism of inhibition in MCF-7 cells.

Identification of known drugs as potential SARS-CoV-2 Mpro inhibitors using ligand- and structure-based virtual screening.

Background: The new coronavirus pandemic has had a significant impact worldwide, and therapeutic treatment for this viral infection is being strongly pursued. Efforts have been undertaken by medicinal chemists to discover molecules or known drugs that may be effective in COVID-19 treatment - in particular, targeting the main protease (Mpro) of the virus. Materials & methods: We have employed an innovative strategy - application of ligand- and structure-based virtual screening - using a special compilation of an approved and diverse set of SARS-CoV-2 crystallographic complexes that was recently published. Results and conclusion: We identified seven drugs with different original indications that might act as potential Mpro inhibitors and may be preferable to other drugs that have been repurposed. These drugs will be experimentally tested to confirm their potential Mpro inhibition and thus their effectiveness against COVID-19.

Potential beneficial effects of kefir and its postbiotic, kefiran, on child food allergy.

Food allergies are known as the public health problem, affecting people of all age groups, but more commonly in babies and children, with consequences for nutritional status and quality of life. The increase in the consumption of healthy foods has consequently led to an increased demand for functional foods with specific health benefits. Thus, the pharmaceutical industry's interest in natural products has grown every time and is therefore considered as an alternative to synthetic drugs. Kefir has been outstanding for several years as promising in the manufacture of various pharmaceutical products, due to its nutritional and therapeutic properties for the treatment of many diseases. Currently, a wide variety of new functional foods are appearing on the market, representing an important segment. Postbiotics, for example, has stood out for being a product with action similar to probiotics, without offering side effects. The kefiran is the postbiotic from kefir that promotes potential beneficial effects on food allergy from the intestinal microbiome to the immune system. In this context, it is necessary to know the main promoting component of this functional effect. This review compiles the benefits that kefir, and especially its postbiotic, kefiran, can bring to food allergy. In addition, it serve as a subsidy for studies on the development of innovative nutraceutical products, including the use of kefiran as an alternative therapy in food allergy.

The first trimester uterine artery Doppler: comparison between sagittal and transverse techniques.

CONTEXT: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide, affecting about 2-3% of all pregnancies. There is consistent evidence today that starting to take aspirin before the 16th week of gestation manages to halve the prevalence of PE and also reduces the incidence of fetal growth restriction, hence the importance of being able to identify early high-risk pregnant women regarding those outcomes and thus finding candidates for the use of that medication. Therefore, interest in methods of PE screening and prediction has increased in recent years. MATERIALS AND METHODS: A retrospective study was carried out by means of a review of the medical records of pregnant women submitted to the first trimester morphological examination at Mater Dei Healthcare Network from August 2017 to January 2018, which included the Doppler study of the uterine arteries performed using longitudinal and transverse insonation techniques, for calculating PE risk in the way recommended by the Fetal Medicine Foundation. Then, a comparative analysis of uterine artery mean pulsatility index (PI) measured transversally and longitudinally was performed. RESULTS: The value for the PI in the sagittal plane (1.634 ± 0.52) was highly correlated (ICC = 0.85) and similar to the value found for the cross-section (1.633 ± 0.54), with no statistically significant differences between them (p = .93). Bland Altman's analysis highlighted the existence of a very tight agreement between both methods of measuring PI. CONCLUSION: The pulsatility index of uterine arteries can be measured in a reliable and easily reproducible way using both the sagittal and transverse techniques, with no change in the final outcome of preeclampsia screening through the Fetal Medicine Foundation (FMF) algorithm.

Molecular Docking, Physicochemical Properties, Pharmacokinetics and Toxicity of Flavonoids Present in Euterpe oleracea Martius.

BACKGROUND: Euterpe oleracea Martius, popularly known as açaí, is a fruit rich in α- tocopherols, fibers, lipids, mineral ions, and polyphenols. It is believed that the high content of polyphenols, especially flavonoids, provides several health-promoting effects to the açaí fruit, including anti-inflammatory, immunomodulatory, antinociceptive and antioxidant properties. Most of the flavonoids are antioxidant molecules of plant origin that act as a trap for free radicals, reacting and neutralizing them, thus offering perspectives in preventing oxidative damage. OBJECTIVE: In this study, we aim to perform an in silico evaluation of flavonoids present in the pulp and the oil of Euterpe oleracea Martius, evaluating their potential to serve as antioxidant agents. METHODS: Firstly, we selected 16 flavonoids present in Euterpe oleracea Martius pulp and oil, and then their physicochemical properties were analyzed concerning the Lipinski's Rule of Five. Moreover, we evaluated their pharmacokinetic properties using the QikProp module of the Schrödinger software as well as their toxicity profile, using the DEREK software. Docking simulations, using the GOLD 4.1 software, as well as pharmacophoric hypotheses calculation of molecules were also performed. RESULTS: Flavonoids present in the açaí pulp including catechin, epicatechin, luteolin, chrisoeriol, taxifolin, apigenin, dihydrokaempferol, isovitexin, and vitexin presented good oral bioavailability. Regarding the pharmacokinetic properties, the compounds catechin, epicatechin, isovitexin, luteolin, chrisoeriol, taxifolin, and isorhamnetin rutinoside presented the best results, besides high human oral absorption. Regarding the prediction of toxicological properties, compounds isorhamnetin rutinoside and rutin presented mutagenicity for hydroxynaphthalene or derivate, and regarding the docking simulations, all the compounds investigated in this study presented key interactions with the corresponding targets. CONCLUSION: The flavonoids catechin, chrysoeriol, and taxifolin presented the best results according to the evaluation conducted in this study. These computational results can be used as a theoretical basis for future studies concerning the development of drug candidates, as well as to enlighten biological tests in vitro and in vivo, which can contribute to the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.