Automatic characterization of drug/amino acid interactions by energy decomposition analysis

The computational study of drug/protein interactions is fundamental to understand the mode of action of drugs and design new ones. In this study, we have developed a python code aimed at characterizing the nature of drug/amino acids interactions in an accurate and automatic way. Specifically, the code is interfaced with different software packages to compute the interaction energy quantum mechanically, and obtain its different contributions, namely, Pauli repulsion, electrostatic and polarisation terms, by an energy decomposition analysis based on one-electron and two-electron deformation densities. The code was tested by investigating the nature of the interaction between the glycine amino acid and 250 drugs. An energy-structure relationship analysis reveals that the strength of the electrostatic and polarisation contributions is related with the presence of small and large size heteroatoms, respectively, in the structure of the drugLR and JJN acknowledge the Comunidad de Madrid for funding through the Attraction of Talent Program (Grant ref 2018-T1/BMD-10261) and the Spanish Ministry of Science and Innovation (Project PID2020-117806GA-I00). MM thanks Xunta de Galicia for fnancial support through the project GRC2019/2

Effect of the QM size, basis set, and polarization on QM/MM interaction energy decomposition analysis

Herein, an Energy Decomposition Analysis (EDA) scheme extended to the framework of QM/MM calculations in the context of electrostatic embeddings (QM/MM-EDA) including atomic charges and dipoles is applied to assess the effect of the QM region size on the convergence of the different interaction energy components, namely, electrostatic, Pauli, and polarization, for cationic, anionic, and neutral systems interacting with a strong polar environment (water). Significant improvements are found when the bulk solvent environment is described by a MM potential in the EDA scheme as compared to pure QM calculations that neglect bulk solvation. The predominant electrostatic interaction requires sizable QM regions. The results reported here show that it is necessary to include a surprisingly large number of water molecules in the QM region to obtain converged values for this energy term, contrary to most cluster models often employed in the literature. Both the improvement of the QM wave function by means of a larger basis set and the introduction of polarization into the MM region through a polarizable force field do not translate to a faster convergence with the QM region size, but they lead to better results for the different interaction energy components. The results obtained in this work provide insight into the effect of each energy component on the convergence of the solute−solvent interaction energy with the QM region size. This information can be used to improve the MM FFs and embedding schemes employed in QM/MM calculations of solvated systems.Agencia Estatal de Investigación | Ref. PID2020-117806GA-I00Comunidad de Madrid | Ref. 2018-T1/BMD-10261Xunta de Galicia | Ref. GRC2019/24Universidade de Vigo/CISU

CARACTERIZAÇÃO AMBIENTAL DE SANTA QUITÉRIA, CEARÁ: A NOVA CIDADE URANÍFERA DO BRASIL.

A busca desmedida por recursos naturais para atender às crescentes necessidades humanas temproporcionado na natureza um balanço deficitário no que diz respeito aos seus limites de tolerância.As evidências estão expostas na crise ambiental que tem se configurado nos últimos quarenta anos.Nesse contexto destaca-se a implantação da atividade mineradora de fosfato e urânio no município deSanta Quitéria, Ceará, com o objetivo de mapear e caracterizar os sistemas ambientais maisexpressivos. A pesquisa está baseada em fundamentos sistêmicos e holísticos subsidiada peloconjunto de geotecnologias e dados de sensoriamento remoto. Os principais sistemasambientais delimitados e caracterizados foram a depressão sertaneja, os maciços residuais, asplanícies fluviais e lacustres

BACIAS HIDROGRÁFICAS COSTEIRAS: IMPORTÂNCIA E CENÁRIO DEGRADACIONAL NO SETOR LESTE METROPOLITANO DE FORTALEZA, ESTADO DO CEARÁ

Adotar a bacia hidrográfica como uma entidade espacial de análise compreende um esforço que se encontra atrelado ao tripé ambiental, social e econômico, tendo em vista que em sua morfologia são agregadas, sistematicamente, às ações da natureza e da sociedade. O estudo em apreço objetiva avaliar as condições ambientais e socioeconômicas das bacias hidrográficas costeiras dos rios Catú, Caburé, Caponga Funda, Caponga Roseira e Mal Cozinhado, as quais envolvem no todo ou em partes os municípios de Aquiraz, Cascavel, Horizonte, Pacajus e Pindoretama, no estado do Ceará, com vista a diagnosticar sua importância hídrica e os principais cenários degradacionais. A fundamentação teórico-metodológica encontra-se nos estudos sistêmicos, baseada no viés da concepção e percepção das relações indissociáveis entre natureza e sociedade. Diante dos problemas diagnosticados no que se refere aos impactos ambientais negativos configurados no conjunto das bacias hidrográficas costeiras, destacam-se os elevados níveis de degradação da cobertura vegetal e contaminação/ poluição dos corpos hídricos, tanto do ponto de vista industrial quanto residencial, devido às precárias e/ou inexistentes ações de saneamento básico. Por sua vez, as características degradacionais podem ser consideradas tensores desencadeadores para o atual cenário de degeneração dos sistemas ambientais outrora naturais, hoje antropizados. Conclui-se que critérios subjetivos devem ser substituídos por análises mais abrangentes e consistentes que deem subsídios concretos ao planejamento territorial no âmbito metropolitano

Vaginal lipidomics of women with vulvovaginal candidiasis and cytolytic vaginosis: a non-targeted LC-MS pilot study

sem informaçãoTo characterize the lipid profile in vaginal discharge of women with vulvovaginal candidiasis, cytolytic vaginosis, or no vaginal infection or dysbiosis. Design. Cross-sectional study. Setting. Genital Infections Ambulatory, Department of Tocogynecology,138sem informaçãosem informaçãosem informaçãoThe supervision of the laboratory studies by Gustavo Henrique Bueno Duarte at Thomson Mass Spectrometry Laboratory–Campinas State Universit

An analysis of the injury severity of pedestrians in Brazil using random parameters logit models

In Brazil, pedestrians represent the third largest group of crash victims, after motorcyclists and car occupants. Implementing measures to ensure pedestrian safety and prioritization requires an understanding of the risk factors associated with crash injuries. In this study, a random-parameter logit model was estimated to investigate factors influencing the severity of crashes with pedestrians in urban roads in Fortaleza, Brazil. A sample of 2,660 observations of crashes with pedestrians in the city from 2017 to 2019 was used. The injury severity levels adopted by the Crash Information System (SIAT) were grouped into three categories: mild/moderate, severe and fatal. From the investigated factors, only the variable related to the pedestrian's age over 60 years old obtained a significant random parameter. In this case, the heterogeneity in the observations may be associated, among other factors, to the body’s physical fragility and the cognitive function that may differ among individuals in this group. The results showed that the driver’s gender and age, the crash site, the motorcycle use, and the presence of speed cameras did not have a significant impact on the severity of crashes with pedestrians. On the other hand, crashes occurring at night, with heavy vehicles, on weekends, and located on roads with higher traffic classification are associated with more severe injuries. The incorporation of unobserved heterogeneity in the estimation of the model's parameters stands out as one of the main contributions of this work

Intracavernous injection in the treatment of erectile dysfunction after radical prostatectomy: an observational study

CONTEXT: Despite the recent improvements in performing radical retropubic prostatectomy that have led to a considerable decrease in the complication rate, erectile dysfunction still represents a major problem. Moreover, less invasive treatment options that are emerging for erectile dysfunction have not shown satisfactory results in managing these patients. OBJECTIVE: To study the efficacy and side effects of self-injection therapy in the treatment of men who had become impotent after undergoing radical prostatectomy due to prostate cancer, over a study period of 96 months. DESIGN: Observational study. SETTING: University Referral Center. PARTICIPANTS: 168 patients with erectile dysfunction, aged 43 to 78 years old, who underwent radical retropubic prostatectomy due to localized prostate cancer. PROCEDURES: The patients were treated with self-injection therapy using papaverine, phentolamine and prostaglandin E1, at home. RESULTS: This study showed an acceptable 94.6% success rate, with no life-threatening complications. In addition to this, our series presented a 13.1% cure rate with this therapy. CONCLUSION: Self-injection therapy with papaverine, phentolamine and prostaglandin E1 is effective and safe in the treatment of erectile dysfunction after radical prostatectomy.CONTEXTO: Apesar do recente avanço técnico na realização da prostatectomia radical retropúbica, que levou a queda no índice de complicações, a disfunção erétil ainda é um problema importante. Além disso, as novas opções (menos invasivas) de tratamento da disfunção erétil não mostram resultados satisfatórios nesse grupo de pacientes. OBJETIVO: Avaliar a eficácia e efeitos colaterais da auto-injeção no tratamento da disfunção erétil causada pela prostatectomia radical, durante 96 meses. TIPO DE ESTUDO: Estudo observacional. LOCAL: Universidade Federal de São Paulo (UNIFESP)/Escola Paulista de Medicina. PARTICIPANTES: 168 pacientes com disfunção erétil, entre 43 e 78 anos, submetidos a prostatectomia radical retropúbica, devido a câncer localizado da próstata. PROCEDIMENTOS: Os pacientes foram tratados com auto-injeção utilizando a associação de papaverina, fentolamina e prostaglandina E1 em casa. RESULTADOS: O índice de sucesso foi de 94,6% com complicações bastante discretas. Além disso, tivemos um índice de cura de 13,1% nesse estudo. CONCLUSÕES: A auto-injeção com papaverina, fentolamina e prostaglandina E1 é eficaz e segura no tratamento da disfunção erétil causada pela prostatectomia radical.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Urology DepartmentUNIFESP, EPM, Urology DepartmentSciEL