Over the years the study of the quantitative structure-activity relationship (QSAR) has transformed from a simple regression analysis to the implementation of machine learning (ML) with multiple statistics. Today ML-based QSAR models are quite important and play a notable role in drug design and screening, property prediction, biological activity, etc. ML methods applied to QSAR build classification or regression models to describe/predict the complex relationships between the chemical structure of molecules and biological activity. Even with the increase in scientific publications addressing this topic written in Portuguese, there is still a shortage of scientific articles explaining ML techniques applied to QSAR, how to build models, the types of models, algorithms, for the Brazilian scientific community. And to fill this need, we intend to approach the subject in a simple and didactic way for students and researchers who are starting in this very promising and important area. We will describe the fully explained theory of machine learning by applying QSAR, abstracting the complexity, and well-illustrated. structureactivity activity (QSAR (ML statistics MLbased based screening prediction etc describepredict predict Portuguese algorithms community need area complexity wellillustrated. wellillustrated well illustrated. illustrated well-illustrated

Chagas disease, caused by the parasite Trypanosoma cruzi, occurs most commonly in Latin America. As the treatment is highly toxic and ineffective in the chronic phase of the disease, alternative treatments are needed. Through quantitative structure-activity relationship modeling (QSAR) analysis using ligand-based and structure-based virtual screening methods, we predicted the trypanocidal potential of 47 neolignans against three targets, the enzymes cruzain, trypanothione reductase, and sterol 14-alpha demethylase. A combined analysis allowed for the selection of potent inhibitors against Trypanosoma cruzi. Of these compounds, two were isolated and shown to inhibit the growth of epimastigotes at concentrations of 9.64 and 8.72 µM, and trypomastigote forms at 4.88 and 2.73 µM. Therefore, the compounds (2R, 3R)-2,3-dihydro-2 (4 methoxyphenyl)-3-methyl-5-(E)-propenylbenzofuran (46) and ottomentosa (47) may be a good option of growth inhibitors for the parasite stages and warrant additional study. disease cruzi America needed structureactivity structure activity QSAR (QSAR ligandbased ligand based structurebased methods 4 targets cruzain reductase 14alpha alpha 14 demethylase 964 9 64 9.6 872 8 72 8.7 µM 488 88 4.8 273 2 73 2.7 Therefore 2R, 2R R (2R 3R2,3dihydro2 3R23dihydro2 Rdihydro 3R 2,3 dihydro 3 3R)-2,3-dihydro- ( methoxyphenyl3methyl5Epropenylbenzofuran methoxyphenylmethylEpropenylbenzofuran methoxyphenyl methyl 5 E propenylbenzofuran 46 (46 (47 study 1 96 6 9. 87 7 8. 48 4. 27 2. 3R2 3dihydro2 3R2,3dihydro 3R23dihydro 23 2, 3R)-2,3-dihydro Epropenylbenzofuran 3dihydro

Abstract This study evaluated the orofacial antinociceptive effect of (S)-(-)-perillyl alcohol (PA) associated with codeine (C) and investigated the possible molecular anchorage mechanisms of PA. Mice (n = 5 per group) were treated with PA alone and associated with codeine and assigned to the following groups: 75.0 mg/kg PA; 75.0 mg/kg PA + C 30 mg/kg; PA 37.5 mg/kg + C 15.0 mg/kg; C 30.0 mg/kg; and control. Nociception was induced by formalin, capsaicin, and glutamate, and was quantified based on the duration (in seconds) of face grooming. The possible mechanisms of action were evaluated by molecular docking study. In the formalin test, PA75/C30 presented an effect in the neurogenic (p < 0.0001) and inflammatory (p < 0.005) phases. Mice treated with PA75 (p < 0.0001) and PA75/C30 (p < 0.0005) showed a reduced nociceptive behavior in the capsaicin test. Glutamate-induced nociception also was blocked by PA75 (p < 0.0005) and C30 (p < 0.0005). The molecular anchorage analysis indicated high negative binding energy values for the evaluated receptors, especially glutamate receptors (AMPA -79.57 Kcal/mol, mGLUR6 -71.25, and NMDA -66.33 Kcal/mol). PA associated with codeine showed orofacial antinociceptive activity, with theoretical evidence of interaction with glutamate receptors.

Resumen: Todas las familias esperan contar con la protección de sus derechos más allá de las fronteras territoriales, buscarán poder disponer de ellos en otros países y, en su caso, acudirán a las autoridades para que brinden justicia. En este sentido, es labor de los Estados garantizar la continuidad de las relaciones jurídicas como respeto a la multiculturalidad. Las “uniones convivenciales” fueron una realidad social que logró un reconocimiento normativo traído en el derecho argentino. En el presente trabajo, nos proponemos analizar su tratamiento desde el Derecho Internacional Privado y el impacto de ellas en el derecho de familia.

Abstract: All families hope to count on the protection of their rights beyond territorial borders, they will seek to have them in other countries and, where appropriate, they will go to the authorities to provide justice. In this sense, it is the task of the States to guarantee the continuity of legal relations as respect for multiculturalism. The "convivial unions" were a social reality that achieved a normative recognition brought in Argentine law. In this paper, we propose to analyze their treatment from Private International Law and their impact on family law.

Resumo: Todas as famílias esperam contar com a proteção de seus direitos além das fronteiras territoriais, buscarão tê-los em outros países e, quando for o caso, recorrerão às autoridades para fazer justiça. Nesse sentido, cabe aos Estados garantir a continuidade das relações jurídicas no respeito ao multiculturalismo. As “uniões conviviais” foram uma realidade social que alcançou um reconhecimento normativo trazido pelo direito argentino. Neste trabalho, nos propomos a analisar seu tratamento a partir do Direito Internacional Privado e seu impacto no direito de família.

The Annonaceae family of plants is one of the most anatomically and structurally uniform families. Chemotaxonomy is a common practice to determine the chemical patterns within these families at different phylogenetic levels. The aim of this study was to build a dataset of all the secondary metabolites isolated within the Annonaceae family and to perform the respective chemotaxonomic analysis using self-organizing maps (SOMs). This dataset is composed of 5321botanical occurrences and 1860 unique molecules present in all subfamilies of the Annonaceae. Diterpenes account for 366 unique compounds and 533 botanical occurrences seen in both Annonoideae and Malmeoideae subfamilies. The Annoneae, Xylopieae and Miliuseae tribes had the highest number of botanical occurrences and were therefore selected for the analysis. Molecular descriptors of the diterpenes and their respective botanical occurrences were used to generate the SOMs. These SOMs demonstrated clear and indicative tribe separations, with a match rate higher than 70%. Our results corroborate with the morphological and molecular data. These models can be used to predict the phylogenetic location of certain diterpenes and to accelerate the research of Annonaceae secondary metabolites and their biological potentials.

This study describes a virtual screening performed for two series of selenides (28 compounds), derived from N-phenylacetamides chlorides and 7-chloro-quinoline, to determine their potential for leishmanicidal activity against Leishmania amazonensis and Leishmania donovani. Seven compounds were predicted as potential leishmanicides; therefore, they were synthesized from elemental selenium, as a precursor for the production of NaHSe, and subsequent reactions with 4,7-dichloro-quinoline and N-phenylacetamides chlorides were performed. The compounds were characterized by infrared (IR), 1H and 13C nuclear magnetic resonance (NMR), and sent for in vitro cytotoxicity tests against L. amazonensis and were found to be active and selective, and two compounds presented half-maximal inhibitory concentrations (IC50) of 5.67 and 10.81 µg mL-1. They also presented good interaction energies in the docking study, suggesting that may exert their effects by inhibiting the N-myristoyltransferase and O-acetylserine sulfhydrylase enzymes in parasites.

Abstract Aspergillus genus causes many diseases, and the species Aspergillus flavus is highly virulent. Treatment of aspergillosis involves azole derivatives such as voriconazole and polyenes such as amphotericin B. Due to an increase in fungal resistance, treatments are now less effective; the search for new compounds with promising antifungal activity has gained importance. The aims of this study were to evaluate the effects of the synthetic amide 2-chloro-N-phenylacetamide (A1Cl) against strains of Aspergillus flavus and to elucidate its mechanism of action. Thus, the minimum inhibitory concentration, minimum fungicidal concentration, conidial germination, associations with antifungal agents, cell wall activities, membrane activities and molecular docking were evaluated. A1Cl presented antifungal activity against Aspergillus flavus strains with a minimum inhibitory concentration of between 16 and 256 μg/mL and a minimum fungicidal concentration between 32 and 512 μg/mL. The minimum inhibitory concentration of A1Cl also inhibited conidial germination, but when associated with amphotericin B and voriconazole, it promoted antagonistic effects. Binding to ergosterol on the fungal plasma membrane is the likely mechanism of action, along with possible inhibition of DNA synthesis through the inhibition of thymidylate synthase. It is concluded that the amide 2-chloro-N-phenylacetamide has promising antifungal potential.

The objective of this work was to carry out a bibliographic survey of secondary metabolites isolated from the Velloziaceae family, creating a bank of compounds. After the bank was created, four prediction models for potentially active compounds against pathogenic microorganisms (Candida albicans, Escherichia coli, Pseudomonas aeruginosa and Salmonella sp.) were obtained trying to identify which metabolites would be more active against the strains. Four sets of compounds with known activity for microorganisms were selected for the construction of predictive models from the CHEMBL database. Another bank with 163 unique molecules isolated from the Velloziaceae family was built. The Volsurf+ v.1.0.7 software obtained the molecular descriptors and Knime 3.5 generated the in silico model. The performances of the internal and external tests were also analyzed. The study contributed through the virtual screening of a bank of metabolites to select several compounds with potential antimicrobial activity, highlighting the biflavonoid amentoflavone which showed potential activity against the four strains.

The present study investigated the activity of pyrimidine derivatives against Aedes aegypti. Two compounds, 3c and 3d showed excellent larvicide activity. Additionally, quantitative structure-activity relationship (QSAR) models were built using multiple-linear regression and partial least squares with descriptors generated from Dragon and VolSurf+ software, respectively. The best model is obtained with multiple linear regression (MLR), leading to a robust model. Moreover, the QSAR model is validated by means of some internal validation techniques in order to check its reliability, quality and robustness for predicting the larvicidal activity against A. aegypti. The models confirmed that the three-dimensional structure of molecules, steric properties, hydrophobic polar surface area, log partition (logP) and a simple pattern of substituent groups as methyl, methoxy, and succinimide in the pyrimidine derivatives are responsible for the larvicidal activity of the pyrimidine derivatives. Even more, the activity decreases by an electron-withdrawing group in R1 and increases when it is replaced by an aromatic ring activator group. These findings will aid in further studies of new pyrimidine derivatives active against Aedes aegypti.

Abstract We aimed to evaluate the orofacial antinociceptive effect of geraniol in mice and its molecular anchorage mechanism. Seven mice per group (probabilistic sample) were treated with geraniol (12.5, 25 and 50 mg/kg, i.p.), morphine (6 mg/kg, i.p.) and vehicle (saline + Tween 80 at 0.2%, i.p.) 30 minutes prior to the beginning of the experiment. Injecting glutamate (25 μM), capsaicin (2.5 μg) and formalin (2%) into the right upper lip (perinasal) of the mouse induced nociception. Behavioral analysis of the animals considered the friction time (in seconds) of the mentioned region using hind or front paws by a researcher blinded to the treatment groups. The statistical analysis was performed blindly, considering α = 5%. The results showed that in the glutamate and capsaicin tests, concentrations of 25 mg/kg and 50 mg/kg presented antinociceptive activity (p < 0.005, power> 80%). In the formalin test, geraniol was able to reduce nociception at a concentration of 50 mg/kg (p < 0.005, power> 80%). In the molecular anchorage study, high values of binding between the evaluated substance and receptors of glutamate were observed (metabotropic glutamate receptor, -87.8501 Kcal/mol; N-methyl-D-aspartate, -86.4451 Kcal/mol; α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, -85.6755 Kcal/mol). Geraniol presented orofacial antinociceptive activity, probably by interacting with glutamate-related receptors.

Abstract OBJECTIVE To describe the implantation of a care quality indicator associated to the nursing diagnosis of patients at high risk of bleeding, based on the alarming results of prothrombin time (PT), partially activated thromboplastin time (aPTT) and platelets. METHODS Retrospective experience report of multidisciplinary actions developed in a university hospital. The stages of the study involved team meetings, search for effective communication strategies and creation of a new indicator of quality of care. RESULTS The indicator was called "Compliance of Nursing Diagnosis Risk for bleeding", monitored monthly since June 2016. The technical file includes the characteristics and attributes of the indicator. Based on the analyzes of the indicator, action plans are established for its qualification. CONCLUSION The implementation of the quality of care indicator associated to the nursing diagnosis improved the communication process, the monitoring and the nursing care to patients at risk of bleeding.

Resumen OBJETIVO Describir la implementación de un indicador de calidad asistencial asociado al diagnóstico de enfermería de pacientes con alto riesgo de sangrado, con base en los resultados alarmantes de tiempo de protombina (Tp), tiempo de tromboplastina parcialmente activada (TTPa) y plaquetas. MÉTODO Relato de experiencia retrospectiva de acciones multidisciplinares desarrolladas en un hospital universitario. Las etapas del estudio involucraron reuniones de equipos, búsqueda de estrategias de comunicación efectiva y creación de un nuevo indicador de calidad asistencial. RESULTADOS El indicador se denominó "Conformidad del Diagnóstico de Enfermería Riesgo de Sangrado", y se monitoreó mensualmente desde junio de 2016. La ficha técnica contempla las características y atributos del indicador. Con base en los análisis del indicador se establecen planes de acción para su cualificación. CONCLUSIÓN La implementación del indicador de calidad asistencial asociado al diagnóstico de enfermería mejoró el proceso de comunicación, el monitoreo y el cuidado de enfermería a pacientes con riesgo de sangrado.

Resumo OBJETIVO Descrever a implantação de um indicador de qualidade assistencial associado ao diagnóstico de enfermagem de pacientes com alto risco de sangramento, com base nos resultados alarmantes de tempo de protombina (TP), tempo de tromboplastina parcialmente ativada (TTPa) e plaquetas. MÉTODOS Relato de experiência retrospectivo de ações multidisciplinares desenvolvidas em um hospital universitário. As etapas do estudo envolveram reuniões de equipes, busca de estratégias de comunicação efetiva e criação de um novo indicador de qualidade assistencial. RESULTADOS O indicador foi denominado “Conformidade do Diagnóstico de Enfermagem Risco de Sangramento”, monitorado mensalmente desde junho de 2016. A ficha técnica contempla as características e atributos do indicador. Com base nas suas análises são estabelecidos planos de ações para sua qualificação. CONCLUSÃO A implantação do indicador de qualidade assistencial associado ao diagnóstico de enfermagem aprimorou o processo de comunicação, monitoramento e cuidado de enfermagem a pacientes com risco de sangramento.

Resumo OBJETIVO Descrever a implantação de um indicador de qualidade assistencial associado ao diagnóstico de enfermagem de pacientes com alto risco de sangramento, com base nos resultados alarmantes de tempo de protombina (TP), tempo de tromboplastina parcialmente ativada (TTPa) e plaquetas. MÉTODOS Relato de experiência retrospectivo de ações multidisciplinares desenvolvidas em um hospital universitário. As etapas do estudo envolveram reuniões de equipes, busca de estratégias de comunicação efetiva e criação de um novo indicador de qualidade assistencial. RESULTADOS O indicador foi denominado “Conformidade do Diagnóstico de Enfermagem Risco de Sangramento”, monitorado mensalmente desde junho de 2016. A ficha técnica contempla as características e atributos do indicador. Com base nas suas análises são estabelecidos planos de ações para sua qualificação. CONCLUSÃO A implantação do indicador de qualidade assistencial associado ao diagnóstico de enfermagem aprimorou o processo de comunicação, monitoramento e cuidado de enfermagem a pacientes com risco de sangramento.

Abstract OBJECTIVE To describe the implantation of a care quality indicator associated to the nursing diagnosis of patients at high risk of bleeding, based on the alarming results of prothrombin time (PT), partially activated thromboplastin time (aPTT) and platelets. METHODS Retrospective experience report of multidisciplinary actions developed in a university hospital. The stages of the study involved team meetings, search for effective communication strategies and creation of a new indicator of quality of care. RESULTS The indicator was called "Compliance of Nursing Diagnosis Risk for bleeding", monitored monthly since June 2016. The technical file includes the characteristics and attributes of the indicator. Based on the analyzes of the indicator, action plans are established for its qualification. CONCLUSION The implementation of the quality of care indicator associated to the nursing diagnosis improved the communication process, the monitoring and the nursing care to patients at risk of bleeding.

Resumen OBJETIVO Describir la implementación de un indicador de calidad asistencial asociado al diagnóstico de enfermería de pacientes con alto riesgo de sangrado, con base en los resultados alarmantes de tiempo de protombina (Tp), tiempo de tromboplastina parcialmente activada (TTPa) y plaquetas. MÉTODO Relato de experiencia retrospectiva de acciones multidisciplinares desarrolladas en un hospital universitario. Las etapas del estudio involucraron reuniones de equipos, búsqueda de estrategias de comunicación efectiva y creación de un nuevo indicador de calidad asistencial. RESULTADOS El indicador se denominó "Conformidad del Diagnóstico de Enfermería Riesgo de Sangrado", y se monitoreó mensualmente desde junio de 2016. La ficha técnica contempla las características y atributos del indicador. Con base en los análisis del indicador se establecen planes de acción para su cualificación. CONCLUSIÓN La implementación del indicador de calidad asistencial asociado al diagnóstico de enfermería mejoró el proceso de comunicación, el monitoreo y el cuidado de enfermería a pacientes con riesgo de sangrado.

ABSTRACT Infectious diseases are a health problem today and have high mortality rates with a wide diversity of potentially pathogenic microorganisms. Research that is based either on the search for new drugs from plants or on the improvement of phytotherapeutics is prominent and continues to play an important role nowadays. From this perspective, use of in silico studies to carry out investigations of new molecules potentially active for methicillin-resistant Staphylococcus aureus and Escherichia coli using an in-house database with 421 different secondary metabolites selected from the literature from Solanum genus was performed. We also realized an in vitro study with strains of S. aureus and E. coli and compared the results. Two databases from ChEMBL were selected, the first one with activity against methicillin-resistant S. aureus and another against E. coli. The compounds were classified according to the pIC50 values to generate and validate the model using a "Random Forest". The "Random Forest" prediction model for methicillin-resistant S. aureus obtained an accuracy of 81%, area under the Receiver Operating Characteristic curve of 0.885, selecting eight molecules with an active potential above 60%. The prediction model for E. coli obtained an accuracy rate of 88%, area under the Receiver Operating Characteristic curve of 0.932, selecting four molecules with potential probability above 84%. Rutin proved to be potentially active in the in silico study for S. aureus and E. coli. Microbiological tests have shown that rutin has activity only for E. coli. An interaction study with strains of S. aureus ATCC 25923, a standard strain sensitive to all antibiotics, and SAM-01, a multidrug-resistant strain, was designed. There was interaction only between rutin and oxacillin, one of the three antibiotics studied in the interaction, for the strain SAM-01, reducing the resistance of this strain.

ABSTRACT Background: Due to laboratory logistic issues, our center has traditionally scheduled peripheral blood stem cell harvests based on timing from the start of mobilization. This has proved to be useful in some cases, but also resulted in many fruitless harvests due to poor mobilization. In order to improve the efficiency of collections and compare the effectiveness of peripheral blood CD34+ cells as a predictor with data from other reports, this study analyzed the implementation of this routine. Methods: Peripheral blood and leukapheresis samples were quantified by flow cytometry and the association between these parameters was assessed. Results: Sixty-six consecutive leukapheresis samples were collected from 34 patients after the collection of peripheral blood samples for CD34+ quantification. A moderate positive correlation was observed between peripheral blood CD34+ cell count and total CD34+ cell count/kg (r = 0.596; p-value < 0.001). A multivariable regression model also confirmed this association and allowed the estimation that for every increase in five CD34+ cells/µL in the peripheral blood, a mean increase of 0.38 × 106 CD34+ cells/kg could be predicted. Demographic characteristics, baseline comorbidities and mobilization regimen did not influence final CD34+ cell count in this sample. Conclusions: As observed in other centers, quantification of peripheral blood CD34+ progenitor cells is a strong predictor of effectiveness to guide stem cell harvesting. Due to the results of this study, a modification in the peripheral blood stem cell harvesting logistics was implemented at our center in order to incorporate this routine.

The pharmaceutical industry is increasingly joining chemoinformatics in the search for the development of new drugs to be used in the treatment of diseases. These computational studies have the advantage of being less expensive and optimize the study time, and thus the interest in this area is increasing. Among the techniques used is the development of multitarget directed ligands (MTDLs), which has become an ascending technique, mainly due to the improvement in the quality of treatment involving several drugs. Multitarget therapy is more effective than traditional drug therapy that emphasizes maximum selectivity for a single target. In this review a multitarget drug survey was carried out as a promising strategy in several important diseases: neglected diseases, neurodegenerative diseases, AIDS, and cancer. In addition, we discuss Computer-Aided Drug Design (CADD) techniques as a tool in the projection of multitarget compounds against these diseases.