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The assessment of renal function is performed using the glomerular filtration rate (GFR) whose measurement by creatinine clearance (ClCr) and is dependent on a 24-hour urine sample, hindering it use in primary healthcare. The equations that estimate GFR from serum creatinine make the test more accessible, however, their adjustments by race/color have been questioned in mixed populations. To test the agreement between CrCl and GFR estimated by formulas (Modification of Diet in Renal Disease [MDRD-4] and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]), with or without adjusting for race/color, data were used from a sub-study of the National Health Survey (NHS) including 272 adults from Vitória/Espírito Santo who underwent a 24-hour urinary sampling. Analysis of variance (ANOVA) and the Bland-Altman method were adopted. There was adequate agreement between ClCr and equations, but the adjustment by race/color decreases the accuracy of both equations. In the race/color factor, there was similarity between groups for CrCl (p=0.21), suggesting that there is no difference in creatinine metabolism induced by skin color. It is concluded that MDRD and CKD-EPI equations perform satisfactorily in the evaluation of renal function, and the use of corrections for race/color is not recommended.

A avaliação da função renal é feita por meio da taxa de filtração glomerular (TFG), que pode ser determinada pelo clearance de creatinina (CrCl) e é dependente da coleta urinária de 24 horas (h), o que dificulta o seu uso na atenção primária. As equações que estimam a TFG a partir da creatinina sérica tornam o exame mais acessível, contudo, os seus ajustes por raça/cor têm sido questionados em populações miscigenadas. Para verificar a concordância entre o ClCr e a TFG estimada por fórmulas (Modification of Diet in Renal Disease [MDRD-4] e Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]), com ou sem ajuste por raça/cor, foram utilizados dados de subestudo da Pesquisa Nacional de Saúde (PNS) com inclusão de 272 adultos de Vitória, Espírito Santo, que fizeram coleta urinária de 24h. Adotou-se análise de variância (ANOVA) e método de Bland-Altman. Houve concordância adequada entre o ClCr e as equações, mas o ajuste por raça/cor diminui a acurácia destas últimas. No fator raça/cor, houve semelhança entre grupos para o ClCr (p=0,21) sugerindo não haver diferença no metabolismo da creatinina em função da cor da pele. Conclui-se que MDRD-4 e CKD-EPI apresentam desempenho satisfatório na avaliação da função renal, não sendo recomendado o uso de correções para raça/cor.

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Resumo A avaliação da função renal é feita por meio da taxa de filtração glomerular (TFG), que pode ser determinada pelo clearance de creatinina (CrCl) e é dependente da coleta urinária de 24 horas (h), o que dificulta o seu uso na atenção primária. As equações que estimam a TFG a partir da creatinina sérica tornam o exame mais acessível, contudo, os seus ajustes por raça/cor têm sido questionados em populações miscigenadas. Para verificar a concordância entre o ClCr e a TFG estimada por fórmulas (Modification of Diet in Renal Disease [MDRD-4] e Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]), com ou sem ajuste por raça/cor, foram utilizados dados de subestudo da Pesquisa Nacional de Saúde (PNS) com inclusão de 272 adultos de Vitória, Espírito Santo, que fizeram coleta urinária de 24h. Adotou-se análise de variância (ANOVA) e método de Bland-Altman. Houve concordância adequada entre o ClCr e as equações, mas o ajuste por raça/cor diminui a acurácia destas últimas. No fator raça/cor, houve semelhança entre grupos para o ClCr (p=0,21) sugerindo não haver diferença no metabolismo da creatinina em função da cor da pele. Conclui-se que MDRD-4 e CKD-EPI apresentam desempenho satisfatório na avaliação da função renal, não sendo recomendado o uso de correções para raça/cor.

Abstract The assessment of renal function is performed using the glomerular filtration rate (GFR) whose measurement by creatinine clearance (ClCr) and is dependent on a 24-hour urine sample, hindering it use in primary healthcare. The equations that estimate GFR from serum creatinine make the test more accessible, however, their adjustments by race/color have been questioned in mixed populations. To test the agreement between CrCl and GFR estimated by formulas (Modification of Diet in Renal Disease [MDRD-4] and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]), with or without adjusting for race/color, data were used from a sub-study of the National Health Survey (NHS) including 272 adults from Vitória/Espírito Santo who underwent a 24-hour urinary sampling. Analysis of variance (ANOVA) and the Bland-Altman method were adopted. There was adequate agreement between ClCr and equations, but the adjustment by race/color decreases the accuracy of both equations. In the race/color factor, there was similarity between groups for CrCl (p=0.21), suggesting that there is no difference in creatinine metabolism induced by skin color. It is concluded that MDRD and CKD-EPI equations perform satisfactorily in the evaluation of renal function, and the use of corrections for race/color is not recommended.

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OBJECTIVE: To evaluate accuracy and agreement between creatinine clearance (CrCl) measured in 12-h urine and glomerular filtration rate (GFR) calculated by the Modification of Diet in Renal Disease (MDRD-4) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas, with and without adjustment for race/color. METHODS: Baseline data from the Longitudinal Study of Adult Health (ELSA-Brazil) in adults (35-74 years of age) of both genders were used. Serum creatinine was measured in fasting blood and urinary creatinine was measured in an overnight 12-h urine collect. The agreement between CrCl and the calculated GFR was analyzed by the Bland-Altman method. One-way analysis of variance (ANOVA) with race/color factor was used to verify differences between means of CrCl and GFR with and without correction for race/color. Statistical significance was accepted for p<0.05. RESULTS: From 15,105 participants in the ELSA-Brazil, 12,813 had a validated urine collect. The Bland-Altman diagrams showed that formulas and CrCl agree with each other with a better accuracy for GFR <90 mL/.min x 1.73m2. The adjustment by race/color increased data dispersion. In this range, one-way ANOVA of CrCl with race/color factor showed similarity between groups (p=0.27). CONCLUSION: MDRD-4 and CKD-EPI are useful formulas for screening cases of chronic kidney disease, and correction by race/color, only in blacks or in black and brown subjects, proved to be unnecessary and reduced the reliability of the equations.

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Azithromycin (AZM) is a macrolide-type antibiotic used to prevent and treat serious infections (mycobacteria or MAC) that significantly inhibit bacterial growth. Knowledge of the predominant conformation in solution is of fundamental importance for advancing our understanding of the intermolecular interactions of AZM with biological targets. We report an extensive density functional theory (DFT) study of plausible AZM structures in solution considering implicit and explicit solvent effects. The best match between the experimental and theoretical nuclear magnetic resonance (NMR) profiles was used to assign the preferred conformer in solution, which was supported by the thermodynamic analysis. Among the 15 distinct AZM structures, conformer M14, having a short intramolecular C6-OH … N H-bond, is predicted to be dominant in water and dimethyl sulfoxide (DMSO) solutions. The results indicated that the X-ray structure backbone is mostly conserved in solution, showing that large flexible molecules with several possible conformations may assume a preferential spatial orientation in solution, which is the molecular structure that ultimately interacts with biological targets.

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Thalidomide (TLD) was used worldwide as a sedative, but it was revealed to cause teratogenicity when taken during early pregnancy. It has been stated that the (R) enantiomer of TLD has therapeutic effects, while the (S) form is teratogenic. Clinical studies, however, demonstrated the therapeutic efficacy of thalidomide in several intractable diseases, so TLD and its derivatives have played an important role in the development and therapy of anticancer drugs. Therefore, it is important to know the molecular mechanism of action of the TLD, although this is still not clear. In what molecular interactions are concerned, it is known that drug molecules can interact with DNA in different ways, for example, by intercalation between base pairs. Furthermore, the ability of the TLD to interact with DNA has been confirmed experimentally. In this work, we report a theoretical investigation of the interaction of the R and S enantiomers of TLD, in its monomeric, dimeric, trimeric, and tetrameric forms, with guanine (GUA) DNA nucleotide basis in solution using density functional theory (DFT). Our initial objective was to evaluate the interaction of TLD-R/S with GUA through thermodynamic and spectroscopic study in dimethyl sulfoxide (DMSO) solvent and an aqueous solution. Comparison of the experimental 1H nuclear magnetic resonance (NMR) spectrum in DMSO-d6 solution with calculated DFT-PCM-DMSO chemical shifts revealed that TLD can undergo molecular association in solution, and interaction of its dimeric form with a DNA base ((TLD)2-GUA and (TLD)2-2GUA, for example) through H-bond formation is likely to take place. Our results strongly indicated that we must consider the plausibility of the existence of TLD associations in solution when modeling the complexation of the TLD with biological targets. This is new information that may provide further insight into our understanding of drug binding to biological targets at the molecular level.

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ABSTRACT Objective: To evaluate accuracy and agreement between creatinine clearance (CrCl) measured in 12-h urine and glomerular filtration rate (GFR) calculated by the Modification of Diet in Renal Disease (MDRD-4) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas, with and without adjustment for race/color. Methods: Baseline data from the Longitudinal Study of Adult Health (ELSA-Brazil) in adults (35-74 years of age) of both genders were used. Serum creatinine was measured in fasting blood and urinary creatinine was measured in an overnight 12-h urine collect. The agreement between CrCl and the calculated GFR was analyzed by the Bland-Altman method. One-way analysis of variance (ANOVA) with race/color factor was used to verify differences between means of CrCl and GFR with and without correction for race/color. Statistical significance was accepted for p<0.05. Results: From 15,105 participants in the ELSA-Brazil, 12,813 had a validated urine collect. The Bland-Altman diagrams showed that formulas and CrCl agree with each other with a better accuracy for GFR <90 mL/.min x 1.73m2. The adjustment by race/color increased data dispersion. In this range, one-way ANOVA of CrCl with race/color factor showed similarity between groups (p=0.27). Conclusion: MDRD-4 and CKD-EPI are useful formulas for screening cases of chronic kidney disease, and correction by race/color, only in blacks or in black and brown subjects, proved to be unnecessary and reduced the reliability of the equations.

RESUMO Objetivo: Avaliar a acurácia e a concordância entre o clearance de creatinina (ClCr) medido na urina de 12 h e a taxa de filtração glomerular (TFG) calculada pelas fórmulas Modification of Diet in Renal Disease (MDRD-4) e Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), com e sem ajuste por raça/cor. Métodos: Foram usados dados da linha de base do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil), em adultos (35-74 anos) de ambos os sexos. A creatinina sérica foi medida no sangue em jejum e a creatinina urinária foi medida na urina de 12 h coletada no período noturno. A concordância entre o ClCr e a TFG calculada pelas fórmulas foi analisada pelo método de Bland-Altman. Análise de variância (ANOVA) de uma via com fator raça/cor foi usada para comparar médias do ClCr e da TFG calculadas com e sem ajuste por raça/cor. A significância estatística foi aceita para p<0,05. Resultados: Dos 15.105 participantes do ELSA-Brasil, 12.813 tiveram a coleta urinária de 12 h validada. Os diagramas de Bland-Altman mostraram que as fórmulas e o ClCr concordam entre si e têm melhor acurácia para TFG <90 mL/min/1,73m2, e que o ajuste por raça/cor aumenta a dispersão dos dados. Nessa faixa, a ANOVA de uma via do ClCr com fator raça/cor mostrou semelhança entre grupos (p=0,27). Conclusão: MDRD-4 e CKD-EPI são fórmulas adequadas para rastreamento da doença renal crônica na população brasileira, sendo desnecessário o ajuste por raça/cor para o uso desses instrumentos, uma vez que a introdução do ajuste tanto em pretos quanto em pretos e pardos diminuiu a acurácia dos métodos.

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Two different products were obtained by the regiodivergent reaction of benzoquinone derivatives with phenolates and anilines: 3-aryloxybenzoquinone and 2-phenylamino-3-bromobenzoquinone. Calculated density functional theory free energies of reaction values corroborate the experimental observation of the formation of the substitution product in the reaction with phenolates in acetonitrile and the product of addition/oxidation for the reaction with aniline in water. Calculated charges and Fukui functions are similar for C2 and C3 atoms, indicating an equal possibility to suffer a nucleophilic attack. The calculated energy barriers for nucleophilic attack steps indicated that the first steps of the substitution with phenolates and addition/oxidation with anilines are faster, which justifies the formation of the respective products. The natural bond order analysis for the transition states revealed that there is a strong interaction between lone pairs of N and O atoms and the πC2C3 * for the O → C2 and N → C3 attacks and a weak interaction for the O → C3 and N → C2 attacks, which also agrees with experimental observations.

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Azithromycin (AZM) is a well-known macrolide-type antibiotic that has been used in the treatment of infections and inflammations. Knowledge of the predominant molecular structure in solution is a prerequisite for an understanding of the interactions of the drug in biological media. Experimental structural determination can be carried out for samples in solid-state (X-ray diffraction technique) and gas phase (electron diffraction experiment). In solution, spectroscopic methods can be used to extract valuable information which combined with quantum chemical calculations can lead to the determination of the preferred molecular structures to be observed when a given solute is dissolved in each solvent. That is precisely the aim of this work. We used experimental NMR chemical shift data (in CDCl3) as a reference for comparison with Density Functional Theory (DFT) NMR calculations, with geometry optimized having as guess input two crystallographic structures available in the literature with the configuration of all chiral carbon atoms inverted, named here A and B. The Polarizable Continuum Model (PCM) was used to describe the solvent effects (chloroform) including five explicit CHCl3 solvent molecules, which we believe can account for short and long-range solute-solvent interactions. Analysis of calculated thermodynamic, NMR chemical shift, MAE (Mean Absolute Error), and spin-spin coupling constant values revealed that both supposable C3R-C5S (named M2-A) and C3S-C5R (named M2-B) structures are equally probable to exist in chloroform solution. In addition, we found that the heavy atoms' conformation is reasonably similar in the solid-state and chloroform solution; however, regarding the OH groups, the spatial orientations are rather different with intramolecular OH⋯N and OH⋯O hydrogen bonds present in solution and with some of them being absent in the X-ray structure probably due to crystal packing effects.

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Este estudo teve por objetivo reunir evidências científicas sobre o papel dos fatores sociodemográficos na adesão aos anti-hipertensivos na Atenção Primária à Saúde (APS) no Brasil. Trata-se de uma revisão integrativa com estudos publicados entre 2015 e 2019 em periódicos nacionais. Foram incluídos artigos originais desenvolvidos com hipertensos usuários da APS no Brasil e foram excluídos artigos publicados fora do intervalo temporal citado, bem como revisões de literatura, e os que não tinham como foco os elementos de interesse nesta revisão. Foram selecionados 5 estudos que investigaram variáveis sociodemográficas no contexto da adesão a esta classe de medicamentos na APS. Embora alguns estudos tenham encontrado uma possível interferência de algumas variáveis sociodemográficas na adesão aos anti-hipertensivos na Atenção Básica, há, para cada uma dessas variáveis, resultados divergentes, mostrando que a dimensão sociodemográfica pode ou não interferir na adesão à medicação em um determinado grupo populacional. Nesse sentido, há também resultados sugestivos de que, com oferta efetiva de assistência aos usuários, tais variáveis parecem perderem capacidade de interferirem nesta adesão, em consonância com a hipótese de que características organizacionais dos serviços de saúde têm impacto muito maior na adesão do que diferenças sociodemográficas.

This study aimed to gather scientific evidence on the role of sociodemographic factors in adherence to antihypertensive drugs in Primary Health Care (PHC)_in Brazil. This is an integrative review with studies published between 2015 and 2019 in national journals. Original studies developed with hypertensive PHC users in Brazil were included and articles published outside the time range were excluded, as well as literature reviews, and those that did not focus on the elements of interest of this review. A total of 5 studies that investigated sociodemographic variables in the context of adherence to this class of drugs in PHC were selected. Although some studies have found a possible interference of some sociodemographic variables in adherence to antihypertensive drugs in Primary Care, there are, for each of these variables, divergent results, showing that the sociodemographic dimension may or may not interfere with medication adherence in a given population group. In this sense, there are also results suggesting that, with effective provision of assistance to users, such variables seem to lose their interference capacity in user adherence, in line with the hypothesis that organizational characteristics of health services have a much greater impact on adherence than sociodemographic differences.

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Chloroquine (CQ) and hydroxychloroquine (HCQ) have been standard antimalarial drugs since the early 1950s, and very recently, the possibility of their use for the treatment of COVID-19 patients has been considered. To understand the drug mode of action at the submicroscopic level (atoms and molecules), molecular modeling studies with the aid of computational chemistry methods have been of great help. A fundamental step in such theoretical investigations is the knowledge of the predominant drug molecular structure in solution, which is the real environment for the interaction with biological targets. Our strategy to access this valuable information is to perform density functional theory (DFT) calculations of 1H NMR chemical shifts for several plausible molecular conformers and then find the best match with experimental NMR profile in solution (since it is extremely sensitive to conformational changes). Through this procedure, after optimizing 30 trial distinct molecular structures (ωB97x-D/6-31G(d,p)-PCM level of calculation), which may be considered representative conformations, we concluded that the global minimum (named M24), stabilized by an intramolecular N-H hydrogen bond, is not likely to be observed in water, chloroform, and dimethyl sulfoxide (DMSO) solution. Among fully optimized conformations (named M1 to M30, and MD1 and MD2), we found M12 (having no intramolecular H-bond) as the most probable structure of CQ and HCQ in water solution, which is a good approximate starting geometry in drug-receptor interaction simulations. On the other hand, the preferred CQ and HCQ structure in chloroform (and CQ in DMSO-d6) solution was assigned as M8, showing the solvent effects on conformational preferences. We believe that the analysis of 1H NMR data in solution can establish the connection between the macro level (experimental) and the sub-micro level (theoretical), which is not so apparent to us and appears to be more appropriate than the thermodynamic stability criterion in conformational analysis studies.

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RESUMO O Aterro Controlado do Jóquei Clube (ACJC), localizado no Distrito Federal, operou como área de disposição final inadequada de resíduos sólidos desde 1960 até o início de 2018. O principal objetivo desta pesquisa consistiu em avaliar o potencial de contaminação desse aterro, em razão da produção de chorume e biogás. Inicialmente, foram identificadas as áreas mais suscetíveis à contaminação nas sub-bacias hidrográficas do Bananal e do Riacho Fundo, onde o aterro está situado, por meio da produção de um mapa de vulnerabilidade natural à contaminação dos aquíferos. Para tanto, utilizou-se a metodologia DRASTIC, que consiste em uma combinação linear ponderada de sete parâmetros hidrogeológicos, com o auxílio da ferramenta de análise multicritério AHP (Análise Hierárquica de Processos) e de algoritmos de álgebra de mapas implementados em ambiente de Sistema de Informação Geográfica (SIG). Esse mapa evidenciou que o ACJC está localizado em áreas de moderada a elevada vulnerabilidade natural à contaminação. Simulou-se também o balanço hídrico no aterro por meio do modelo Hydrologic Evaluation of Landfill Performance (HELP), o qual possibilitou a identificação de áreas com maior potencial de contaminação em razão do maior volume de chorume produzido. Por fim, realizou-se uma análise da temperatura de cobertura do solo na região do aterro, por meio de imagens sazonais do sensor orbital TM/Landsat entre os anos de 1986 e 2016, as quais evidenciaram aumento gradual da temperatura, servindo de possível indicador da distribuição subsuperficial de biogás presente no aterro.

ABSTRACT The Jockey Club Landfill is a solid waste disposal site located at Brazil's Federal District, which operated inadequately from 1960 until the beginning of 2018. The main objective of this paper was to assess the contamination potential of the Jockey Club Landfill due to leachate and biogas production. Initially, the most susceptible areas to contamination were identified within the two hydrographic sub-basins of Bananal and Riacho Fundo, where the landfill is located, by producing a map of the aquifer's natural vulnerability to contamination. This map was produced based on the DRASTIC methodology, which consists in a weighted linear combination of seven important hydrogeological parameters, with support of the multicriteria Analytic Hierarchy Process (AHP) and map algebra tools implemented in a Geographic Information System (GIS) environment. This map evidenced that Jockey Club Landfill is located in areas of moderate to high natural vulnerability to contamination. The water balance throughout the landfill profile was also simulated using the Hydrologic Evaluation of Landfill Performance model (HELP), whose results evidenced that the contamination potential is higher in some portions of the landfill due to greater volumes of leachate produced. Lastly, an analysis of ground cover temperature in the landfill region was undertaken, using TM/Landsat seasonal images between the years 1986 to 2016, which indicated a gradual increase in ground temperature, evidencing a possible occurrence of subsurface biogas distribution in the landfill.

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Among 20 compounds isolated from the extracts of Ouratea ferruginea the 5,4'-dihydroxy-7,5',3'-trimethoxyisoflavone (9) showed the best inhibitory effect on glutathione S-transferase (GST) and so deserves our attention. In this work we investigated the preferred molecular structure of 9 in chloroform solution using the density functional theory (DFT) and molecular dynamics simulation. Comparison between experimental 1H NMR data in CDCl3 solution and calculated chemical shifts enabled us to precisely determine the conformation adopted by 9 in solution, which can be used in further theoretical studies involving interaction with biological targets. Moreover, the experimental NMR data were used as reference to assess the ability of DFT based methods to predict 1H NMR spectrum in solution for organic compounds. Among various DFT functionals the hybrid B3LYP was the most adequate for the calculation of chemical shifts in what CHn protons are concerned. Regarding the OH hydrogen, inclusion of explicit CHCl3 solvent molecules adequately placed around the solute led to good agreement with the experimental chemical shifts (in CDCl3). It is a well-known fact that theoretical prediction of chemical shifts for OH hydrogens poses as a challenge and also revealed that the way the solvent effects are included in the DFT calculations is crucial for the right prediction of the whole 1H NMR spectrum. It was found in this work that a supermolecule solute-solvent calculation with a minimum of four CHCl3 molecules is enough to correctly reproduce the 1H NMR experimental profile observed in solution, revealing that the calculated solvated structure used to reproduce the NMR chemical shifts is not unique.

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Coordination compounds formed by flavonoid ligands are recognized as promising candidates as novel drugs with enhanced antioxidant and anticancer activity. Zn(II)-Rutin complexes have been described in the literature and distinct coordination modes proposed based on 1H NMR/MS and IR/UV-VIS experimental spectroscopic data: 1:1/1:2 (Zn(II) binding to A-C rings) and 2:1 (Zn(II) binding to A-C-B rings) stoichiometry. Aiming to clarify these experimental findings and provide some physical insights into the process of complex formation in solution, we carried out density functional theory calculations of NMR and UV-VIS spectra for 25 plausible Zn(II)-Rutin molecular structures including solvent effect using the polarizable continuum model approach. The studied complexes in this work have 1:1, 1:2, 2:1, and 3:1 metal-ligand stoichiometry for all relevant Zn(II)-Rutin configurations. The least deviation between theoretical and experimental spectroscopic data was used as an initial criterion to select the probable candidate structures. Our theoretical spectroscopic results strongly indicate that the experimentally suggested modes of coordination (1:2 and 2:1) are likely to exist in solution, supporting the two distinct experimental findings in DMSO and methanol solution, which may be seen as an interesting result. Our predicted 1:2 and 2:1 metal complexes are in agreement with the experimental stoichiometry; however, they differ from the proposed structure. Besides the prediction of the coordination site and molecular structure in solution, an important contribution of this work is the determination of the OH-C5 deprotonation state of rutin due to metal complexation at the experimental conditions (pH = 6.7 and 7.20). We found that, in the two independent synthesis of metal complexes, distinct forms of rutin (OH-C5 and O(-)-C5) are present, which are rather difficult to be assessed experimentally.

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Carbon nanohorns (CNH) have been considered potential anticancer drug carriers, such as the cisplatin drug (cddp), due to their low toxicity, high purity, drug-loading capacity, and biodegradation routes. However, when it comes to nanomedicine applications, chemical functionalization is an essential step in order to overcome undesirable properties of these nanomaterials, such as the high hydrophobicity, low reactivity, and low dispersibility in polar solvents. In this context, the present study involved the modeling of new CNH topologies based on chemical oxidation and reduction mechanisms and the investigation of the influence of these modified structures on the dynamics and stability of inclusion complexes with cddp. The results indicated that these functionalization strategies lead to the opening of nanowindows on the CNH surfaces, which would constitute the main route for drug release, as reported by experimentalists. Also, our results showed that the insertion of polar functional groups on the oxidized CNH (CNHox-N) contributed to an improvement of the cddp@CNHox-N biocompatibility due to the greater number of hydrogen bonds formed with the solvent. Despite the favorable formation of all complexes, the binding free energies pointed out that the oxidation process made the cddp@CNHox-N complexes slightly less stable than the ones with pristine and reduced CNH. Besides, the results suggest the possibility to tune the complex stability by controlling the oxidation degree, which could be explored by the experimentalists in order to design controlled drug delivery systems based on CNH nanocarriers.

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The medication with Pt-based antitumor drug cisplatin has demonstrated effective results against cancer cells, despite the severe side effects due to the high toxicity associated with the low selectivity of these anticancer agents. An alternative to overcome or decrease the side effects is to use drug delivery systems, which can carry high doses of the anticancer drug and promote its slow and targeted release to the tumor sites. Herein, we used molecular dynamics to study prototypes of the complexes formed by the encapsulated cisplatin and carbon nanohorns (CNH), with the purpose to characterize its structures and dynamical behavior in aqueous solution, an important feature to assess the potentiality of using CNH as carrier systems. The results indicated the presence of up to 36 water molecules inside the empty CNH cavity, depending on the cone angle and the presence of the cisplatin. Some of these solvent molecules are expelled out to the bulk upon cisplatin inclusion, although more than 10 molecules remain even for the narrow structures. Moreover, the calculated binding free energy (ΔbG) pointed out that the inclusion complexes formation between CNH structures and up to two cisplatin molecules was thermodynamically favorable in aqueous media, which suggests the potentiality of these carbon nanostructures as drug carriers. For the most likely and narrow host structure the average ΔbG was -92.0 kcal mol-1 for inclusion of two cisplatin, with most of the complex stability coming from the van der Waals contribution.

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Major depressive disorder (MDD), also known as unipolar depression, is one of the leading causes of disability and disease worldwide. The signs and symptoms are low self­esteem, anhedonia, feeling of worthlessness, sense of rejection and guilt, suicidal thoughts, among others. This review focuses on studies with molecular-based approaches involving MDD to obtain an integrated, more detailed and comprehensive view of the brain changes produced by this disorder and its treatment and how the Central Nervous System (CNS) produces neuroplasticity to orchestrate adaptive defensive behaviors. This article integrates affective neuroscience, psychopharmacology, neuroanatomy and molecular biology data. In addition, there are two problems with current MDD treatments, namely: 1) Low rates of responsiveness to antidepressants and too slow onset of therapeutic effect; 2) Increased stress vulnerability and autonomy, which reduces the responses of currently available treatments. In the present review, we encourage the prospection of new bioactive agents for the development of treatments with post-transduction mechanisms, neurogenesis and pharmacogenetics inducers that bring greater benefits, with reduced risks and maximized access to patients, stimulating the field of research on mood disorders in order to use the potential of preclinical studies. For this purpose, improved animal models that incorporate the molecular and anatomical tools currently available can be applied. Besides, we encourage the study of drugs that do not present "classical application" as antidepressants, (e.g., the dissociative anesthetic ketamine and dextromethorphan) and drugs that have dual action mechanisms since they represent potential targets for novel drug development more useful for the treatment of MDD.

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Resumo Introdução: Um dos maiores problemas de saúde no Brasil é a prevalência de doenças crônicas. A WHO sugere que pacientes com essas doenças recebam cuidados paliativos (CP) desde o diagnóstico. O terapeuta ocupacional pode colaborar no cuidado de pessoas hospitalizadas com ações que promovam dignidade e qualidade de vida ao paciente. Objetivos: Compreender a abordagem de cuidados paliativos adotada por terapeutas ocupacionais no cuidado de pessoas com doenças crônicas; e, conhecer a organização dos cuidados paliativos nos hospitais gerais de Curitiba. Método: É um estudo qualitativo cuja coleta de dados realizou-se através de entrevistas semiestruturadas gravadas para posterior transcrição, categorização, análise e discussão dos resultados. Para tratamento e análise dos dados, utilizou-se a técnica de análise de conteúdo. Resultados: Foram identificadas e discutidas as categorias: "cuidados paliativos nos hospitais gerais de Curitiba: organização do serviço" e "Intervenção do terapeuta ocupacional baseada na abordagem dos cuidados paliativos". Na primeira abrangeu-se a organização dos CP e as dificuldades enfrentadas pelas entrevistadas na prática dessa abordagem; na segunda, foram incluídas as avaliações utilizadas, objetivos e intervenções realizadas. Conclusão: Os relatos demonstraram que a abordagem estava associada à fase final da vida. O tipo de avaliação realizada dependia da organização do serviço de terapia ocupacional da instituição. Os objetivos das intervenções eram condizentes com os princípios dos CP. A realização de atividades significativas foi a principal intervenção citada e todas elas buscavam a promoção da qualidade de vida, bem-estar e manutenção da vida ativa.

Abstract Introduction: One of the worst issues of Brazilian public health is the prevalence of chronic diseases. The WHO suggests that patients who have these diseases should receive Palliative Care (PC) since the diagnostic. The occupational therapist can help in the cares of this hospitalized people, with actions which improve their life quality as well as dignity. Objectives: Comprehend the approach of PC adopted by occupational therapists on the care of hospitalized people with chronicle diseases and know about the structure of palliative care on Curitiba's General Hospitals. Method: It's a qualitative study which collects data from a semi-structured recorded interview for posterior transcription, categorization, analysis and discussion of the results. For the treatment and analysis of data a analysis of content technique was used. Results: It was identified and discussed these following categories: "Palliative Cares inside Curitiba's hospitals: service organization" and "The occupational therapist intervention based in the Palliative Care approach". In the first one the organizations and the struggle that the interviewers have based in this approach experience were included; the second one included the assessments used, objectives and interventions performed. Conclusion: The reports show that the approach was associated with life's final stage. The type of assessment realized depended on the organization of the institution occupational therapy service. The objectives of the interventions were in keeping with the PC principles. The execution of significant activities was the main related intervention and all of them looked for the improvement of life quality, well being and active life conservation.

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A theoretical (1)H NMR spectroscopy and thermodynamic analysis of the host-guest inclusion process involving the norfloxacin (NFX) into ß-cyclodextrin (ß-CD) was carried out. DFT structure and stabilization energies were obtained in both gas and aqueous phases. We could establish that the complex formation is enthalpy driven, and the hydrogen bonds established between NFX and ß-CD play a major role in the complex stabilization. Besides, a theoretical (1)H NMR analysis has shown to be a supplementary proceeding to predict appropriately the inclusion mode of norfloxacin molecule into the ß-CD. In this work, a theoretical study of the NFX@ß-CD complex is reported for the first time, seeking a deep understanding of topology and thermodynamics of the inclusion complex formation. Graphical Abstract Topology, thermodynamic and (1)H NMR analysis of NFX@ß-CD host-guest complexes.

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Thermodynamic properties for ß-cyclodextrin-Sertraline inclusion process was calculated at the density functional theory (DFT) level using the PBE0 functional with 6-31G(d,p), 6-31++G(d,p) and 6-311++G(2df,p) basis sets. Electron correlation was evaluated through Møller-Plesset second-order perturbation theory (MP2). The standard statistical thermodynamic approach was used to assess the entropic contribution to the Gibbs free energy value. According to our results, inclusion of hydration waters to describe the reactants and products in the complex formation reaction model is crucial in order to reproduce the experimental data and seems very coherent with basics thermodynamics yielding good agreement with experiment.

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Recent studies have shown that only quinones with a 2-methoxy group can act simultaneously as the primary (QA) and secondary (QB) electron acceptors in photosynthetic reaction centers from purple bacteria such as Rb. sphaeroides. 13C HYSCORE measurements of the 2-methoxy group in the semiquinone states, SQA and SQB, were compared with DFT calculations of the 13C hyperfine couplings as a function of the 2-methoxy dihedral angle. X-ray structure comparisons support 2-methoxy dihedral angle assignments corresponding to a redox potential gap (ΔEm) between QA and QB of 175-193 mV. A model having a methyl group substituted for the 2-methoxy group exhibits no electron affinity difference. This is consistent with the failure of a 2-methyl ubiquinone analogue to function as QB in mutant reaction centers with a ΔEm of ∼160-195 mV. The conclusion reached is that the 2-methoxy group is the principal determinant of electron transfer from QA to QB in type II photosynthetic reaction centers with ubiquinone serving as both acceptor quinones.