Docking and Electronic Structure of Rutin, Myricetin, and Baicalein Targeting 3CLpro.

Understanding the role of 3CLpro protease for SARS-CoV-2 replication and knowing the potential of flavonoid molecules like rutin, myricetin, and baicalein against 3CLpro justify an investigation into their inhibition. This study investigates possible bonds and reactivity descriptors of rutin, myricetin, and baicalein through conformational and electronic properties. Density functional theory was used to determine possible interactions. Analyses were carried out through the molecular electrostatic potential, electron localization function, Fukui function descriptors based on frontier orbitals, and non-covalent interactions. A docking study was performed using a resolution of 1.55 Å for 3CLpro to analyze the interactions of rutin, myricetin, and baicalein. Scores of structures showed that rutin is the best ligand, followed by myricetin and baicalein. Docking studies showed that baicalein and rutin can establish effective interactions with residues of the catalytic dyad (Cys145 and His41), but just rutin forms a hydrogen bond. Myricetin, in turn, could not establish an effective interaction with Cys145. Baicalein interaction arose with active residues such as Arg188, Val186, Gln189, and Gln192. Interactions of rutin and myricetin with Arg188 and Gln189 were also found. A critical interaction was observed only for rutin with the hydroxyls of ring A with His41, and also for Cys145 with rings B and C, which is probably related to the highest score of rutin.

Comparative analysis of the reactivity of anthocyanidins, leucoanthocyanidins, and flavonols using a quantum chemistry approach.

Anthocyanidins, leucoanthocyanidins, and flavonols are natural compounds mainly known due to their reported biological activities, such as antiviral, antifungal, anti-inflammatory activities, and antioxidant activity. In the present study, we performed a comparative structural, conformational, electronic, and nuclear magnetic resonance analysis of the reactivity of the chemical structure of primary anthocyanidins, leucoanthocyanidins, and flavonoids. We focused our analysis on the following molecular questions: (i) differences in cyanidin catechols ( +)-catechin, leucocyanidin, and quercetin; (ii) the loss of hydroxyl presents in the R1 radical of leucoanthocyanidin in the functional groups linked to C4 (ring C); and (iii) the electron affinity of the 3-hydroxyl group (R7) in the flavonoids delphinidin, pelargonidin, cyanidin, quercetin, and kaempferol. We show unprecedented results for bond critical point (BCP) of leucopelargonidin and leucodelphirinidin. The BCP formed between hydroxyl hydrogen (R2) and ketone oxygen (R1) of kaempferol has the same degrees of covalence of quercetin. Kaempferol and quercetin exhibited localized electron densities between hydroxyl hydrogen (R2) and ketone oxygen (R1). Global molecular descriptors showed quercetin and leucocyanidin are the most reactive flavonoids in electrophilic reactions. Complementary, anthocyanidins are the most reactive in nucleophilic reactions, while the smallest gap occurs in delphinidin. Local descriptors indicate that anthocyanidins and flavonols are more prone to electrophilic attacks, while in leucoanthocyanidins, the most susceptible to attack are localized in the ring A. The ring C of anthocyanidins is more aromatic than the same found in flavonols and leucoanthocyanidins. METHODS: For the analysis of the molecular properties, we used the DFT to evaluate the formation of the covalent bonds and intermolecular forces. CAM-B3LYP functional with the def2TZV basis set was used for the geometry optimization. A broad analysis of quantum properties was performed using the assessment of the molecular electrostatic potential surface, electron localization function, Fukui functions, descriptors constructed from frontier orbitals, and nucleus independent chemical shift.

Neurosurgical Emergencies in the Amazon: An Epidemiologic Study of Patients Referred by Air Transport for Neurosurgical Evaluation at a Referral Center in Amazonas.

BACKGROUND: Amazonas is the largest state in Brazil, covering an area of 1,559,159.148 km2 and primarily occupied by the Amazon rainforest. Fluvial and aerial transport are the primary means of transportation. Studying the epidemiologic profile of patients transported by neurologic emergencies is essential because there is only 1 referral center hospital serving approximately 4 million inhabitants in Amazonas. METHODS: This work studies the epidemiologic profile of patients referred by air transport for evaluation by the neurosurgery team at a referral center in the Amazon. RESULTS: Of the 68 patients transferred, 50 (75.53%) were men. The study covered 15 municipalities in Amazonas. Of the patients, 67.64% had a traumatic brain injury due to various causes, and 22.05% had had a stroke. Of all patients, 67.65% did not undergo surgery and 43.9% evolved with good evolution and without complications. CONCLUSIONS: Air transportation for neurologic evaluation is essential in Amazonas. However, most patients did not require neurosurgical intervention, indicating that investments in medical infrastructures, such as computed tomography scanners and telemedicine, may optimize health costs.

Analysis of Conformational, Structural, Magnetic, and Electronic Properties Related to Antioxidant Activity: Revisiting Flavan, Anthocyanidin, Flavanone, Flavonol, Isoflavone, Flavone, and Flavan-3-ol.

Understanding the antioxidant activity of flavonoids is important to investigate their biological activities as well as to design novel molecules with low toxicity and high activity. Aromaticity is a chemical property found in cyclic structures that plays an important role in their stability and reactivity, and its investigation can help us to understand the antioxidant activity of some heterocyclic compounds. In the present study, we applied the density functional theory (DFT) to investigate the properties of seven flavonoid structures with well-reported antioxidant activity: flavan, anthocyanidin, flavanone, flavonol, isoflavone, flavone, and flavan-3-ol. Conformational, structural, magnetic, and electronic analyses were performed using nuclear magnetic resonance, ionization potentials, electron affinity, bond dissociation energy, proton affinity, frontier molecular orbitals (highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO)), and aromaticity through nucleus-independent chemical shifts to analyze these seven flavonoid structures. We revised the influence of hydroxyl groups on the properties of flavonoids and also investigated the influence of the aromaticity of these seven flavonoids on the antioxidant activity.

Os efeitos do memorando de entendimento nas Unidades Locais de Saúde: o caso da Unidade Local de Saúde de Castelo Branco / The effects of the memorandum of understanding in the Local Health Units: the case of the Local Health Unit of Castelo Branco

Objetivo: Verificar se o Memorando de Entendimento sobre Condicionalismos Específicos de Política Económica (MECPE), imposto em Portugal em período de crise pelo Fundo Monetário Internacional, Banco Central Europeu e Comissão Europeia, gerou melhoria nos resultados de eficiência no sector da Saúde. Métodos: Foi realizado um estudo de caso para avaliação dos resultados de eficiência nos departamentos clínicos da Unidade Local de Saúde de Castelo Branco (ULSCB), localizada em uma das áreas economicamente mais desfavorecidas Recorreu-se à técnica da Análise Envoltória de Dados, levando em consideração como insumos os custos e como resultados a produção registada de cada departamento clínico em três períodos de tempo antes (2002-2010), durante (2011-2014) e após a austeridade (2015-2017). Os dados referentes ao custo e produção foram fornecidos pelo Gabinete de Apoio à Gestão e pelo Gabinete de Contabilidade do hospital. Em complemento da análise quantitativa, utilizou-se o método qualitativo de análise do conteúdo das entrevistas semiestruturadas, aos diretores e administradores do hospital, que permitiu avaliar a informação que detém e que é resultado do seu treinamento e sua experiência. Resultados: Durante o período de austeridade e execução do MECPE, a unidade hospitalar estudada obteve eficiência técnica média de 0,84, que significou um aumento de 16% em relação ao período anterior. Em particular, apenas um departamento clínico (neurologia) não registou essa melhoria em sua eficiência técnica. Na análise qualitativa do estudo, a maioria dos entrevistados sentiu que a austeridade teve impacto negativo na eficiência de seus departamentos e de seu hospital, o que não se confirma pelos resultados obtidos. Conclusões: O MECPE não apenas aumentou a eficiência técnica, mas também incentivou medidas inovadoras para aumentar os ganhos nos anos subsequentes.

Objective: To verify that the Memorandum of Understanding (MuO), imposed on Portugal in the period of crisis by the International Monetary Fund, the European Central Bank and the European Commission, generated an improvement in the efficiency results in the Health area. Methods: To evaluate the results of efficiency carried out a case study in the hospital clinical services Local Health Unit Castelo Branco (ULSCB), located in one of the areas with more economic constraints. Resorted to the technique of Data Envelopment Analysis, considering as input costs and as a result the recorded production of each clinical service in three time periods before (2002-2010) during (2011-2014) and after the crisis (2015-2017). The data relating to cost and production were provided by the Office of Support and the Hospital Accountability Office. In addition to the quantitative analysis, the qualitative method of content analysis of the semi-structured interviews was used, to the directors and administrators of the hospital, which allowed the evaluation of the information that it holds and which is the result of its training and experience. Results: During the period of austerity and execution of the MoU, the hospital unit under study obtained a technical efficiency average of 0.84, which meant an increase of 16% over the previous period. In particular, only one clinical service has failed to record this improvement in its technical efficiency. In the qualitative analysis of the study, most interviewees felt that austerity had a negative impact on the efficiency of their departments and their hospital, which is not confirmed by the results obtained. Conclusions: The Memorandum of Understanding not only increased technical efficiency but also promoted innovative measures that allowed for increased gains in subsequent years.

Inovação na gestão hospitalar: análise dos resultados de eficiência de um hospital português integrado em uma unidade local de saúde / Innovation in hospital management: analysis of efficiency results of an portuguese hospital in a local health unit

Objetivo: Verificar se a alteração do formato jurídico do hospital Amato Lusitano e a simultânea integração com a atenção primária gerou melhoria dos resultados de eficiência em seus serviços clínicos. Metodologia: Para avaliar os resultados de eficiência, utilizou-se à técnica da análise envoltória de dados, considerando como insumos os custos e como resultados a produção registrada de cada serviço clínico ao longo de um período de 15 anos. Os dados de custo e produção foram obtidos através do Gabinete de Apoio à Gestão e do Gabinete de Contabilidade do hospital. A amostra incluiu todos os serviços clínicos de internação, imagem e patologia clínica. Resultados: A mudança da gestão pública para a condição corporativa resultou em melhoria nos resultados de eficiência em 16 dos 17 serviços analisados apresentando um aumento médio de 19,0%. Conclusões: A adoção da gestão empresarial e do modelo de unidade de saúde local tem sido benéfica para o desempenho dos serviços clínicos, com melhoria geral nos resultados de eficiência técnica.

Objective: Verify that the change of the legal form of the Amato Lusitano Hospital and the simultaneous integration with primary care led to improved results in efficiency in their clinical services. Methodology: For evaluate the efficiency results, we used the technique of data envelopment analysis, considering as inputs the costs and as results the recorded production of each clinical service over a period of 15 years. Cost and production data were obtained through the Office of Management Support and the Accounting Office of the hospital. The sample included all clinical inpatient services, imagiology and clinical pathology. Results: The change of public management for corporate condition resulted in improvement in efficiency results, with 16 of the 17 services analyzed with an average increase of 19.0%. Conclusions: The adoption of business management and the local health unit model has been beneficial to the performance of clinical services, overall improvement in technical efficiency results.

Structure and electronic properties of azadirachtin.

We performed a combined DFT and Monte Carlo (13)C NMR chemical-shift study of azadirachtin A, a triterpenoid that acts as a natural insect antifeedant. A conformational search using a Monte Carlo technique based on the RM1 semiempirical method was carried out in order to establish its preferred structure. The B3LYP/6-311++G(d,p), wB97XD/6-311++G(d,p), M06/6-311++G(d,p), M06-2X/6-311++G(d,p), and CAM-B3LYP/6-311++G(d,p) levels of theory were used to predict NMR chemical shifts. A Monte Carlo population-weighted average spectrum was produced based on the predicted Boltzmann contributions. In general, good agreement between experimental and theoretical data was obtained using both methods, and the (13)C NMR chemical shifts were predicted highly accurately. The geometry was optimized at the semiempirical level and used to calculate the NMR chemical shifts at the DFT level, and these shifts showed only minor deviations from those obtained following structural optimization at the DFT level, and incurred a much lower computational cost. The theoretical ultraviolet spectrum showed a maximum absorption peak that was mainly contributed by the tiglate group.

CO2 adsorption on polar surfaces of ZnO.

Physical and chemical adsorption of CO2 on ZnO surfaces were studied by means of two different implementations of periodic density functional theory. Adsorption energies were computed and compared to values in the literature. In particular, it was found that the calculated equilibrium structure and internuclear distances are in agreement with previous work. CO2 adsorption was analyzed by inspection of the density of states and electron localization function. Valence bands, band gap and final states of adsorbed CO2 were investigated and the effect of atomic displacements analyzed. The partial density of states (PDOS) of chemical adsorption of CO2 on the ZnO(0001) surface show that the p orbitals of CO2 were mixed with the ZnO valence band state appearing at the top of the valence band and in regions of low-energy conduction band.

Alternativa de manejo con bromocriptina (BEC) en pacientes con prolactinoma e intolerancia a BEC oral / An alternative for management with bromocriptine (BEC) in patients with prolactinoma and intolerance to tal BEC

En la actualidad, el tratamiento de elección en los casos de prolactinoma, es el empleo de mesilato de bromocriptina (BEC) por vía oral, con lo cual, en la mayoría de los casos se obtiene una evolución satisfactoria. Sin embargo, existen pacientes que presentan una intolerancia franca al medicamento por vía oral, a pesar de emplear dosis muy bajas y otras estrategias, lo cual deja como única opción de manejo, a la cirugía hipofisiaria (transesfenoidal) ya que no se tiene un fácil acceso a otros medicamentos dopaminérgicos y/o al preparado de BEC parenteral. El presente trabajo, muestra la evolución de once pacientes que presentan intolerancia fraca a BEC oral y eran portadoras de prolactinoma (9 micros, 2 macros) y no aceptaban o en sus casos, no era conveniente la cirugía hipofisiaria; en estas pacientes, se utilizó una vía alterna de administración de BEC; la vía vaginal. Esta vía resulta efectiva y puede ser fácilmente empleada en nuestro medio ante situaciones similares. La edad promedio de las pacientes fué de 32 años, con edades mínimas y máximas de 26 y 44 respectivamente; cuatro con esterilidad primaria, una con esterilidad secundaria asociadas a su problema y en seis pacientes no había problema de esterilidad; todas las pacientes mostraron una redución importante en sus niveles de prolactinemia, desde los 7 días de administración vaginal, ya que el promedio de prolactinemia previo, con BEC oral era de 121.3 + - 21.2, y posteriormente a la vía vaginal el nivel promedio obtenido fue de 21.2 + - 4.7 mh/ml (a los 7 días), persistiendo un nivel bajo (normal) a los 10 días (14.7 + - 4.7) y 30 días (15.7 mg/ml + - 3.7). Con resultados similares a lo largo de 12 meses en 6 pacientes; 4 presentaron embarazo durante el tratamiento, con evolución satisfactoria y una paciente rechazó finalmente la vía vaginal. En todos los casos, cedieron las molestias de intolerancia que motivó el empleo de esta vía alterna de administración; predominando en dichas molestias adversas con la vía oral, las de índole gastrointestinal.