Biotransformation of Hydroxychloroquine to Evaluate the Cytotoxicity of its Metabolites and Mimic Mammalian Metabolism

Hydroxychloroquine (HCQ) displays attractive anti-inflammatory and antiviral effects. Because of that, such a drug made part of some clinical trials for combating Sars-CoV-2 during the COVID-19 pandemic. The present study aimed to conduct the biotransformation of HCQ by filamentous fungi reported as microbial models of mammalian drug metabolism to evaluate its cytotoxic after metabolization. Cunninghamella echinulata var. elegans ATCC 8688a could efficiently biotransform HCQ into one main metabolite identified as the new 4-(1,2,3,4-tetrahydroquinolin-4-ylamino)pentan-1-ol (HCQ-M). The microbial transformation occurred through N-dealkylation, 7-chloro-elimination, and reduction of the two conjugated double-bond from the quinoline system of HCQ. The cytotoxicities of HCQ and its metabolite were evaluated using CCD1059SK cells (human fibroblasts) through sulforhodamine B, trypan blue, and Live/Dead assays. Both HCQ and HCQ-M displayed toxicities in human fibroblasts, but HCQ-M was significantly more toxic. The reported findings should be considered for further clinical studies of HCQ and will be important for guidance in achieving new derivatives from it.

Biotransformation of hydroxychloroquine to evaluate the cytotoxicity of its metabolites and mimic mammalian metabolism.

Hydroxychloroquine (HCQ) displays attractive anti-inflammatory and antiviral effects. Because of that, such a drug made part of some clinical trials for combating Sars-CoV-2 during the COVID-19 pandemic. The present study aimed to conduct the biotransformation of HCQ by filamentous fungi reported as microbial models of mammalian drug metabolism to evaluate its cytotoxic after metabolization. Cunninghamella echinulata var. elegans ATCC 8688a could efficiently biotransform HCQ into one main metabolite identified as the new 4-(1,2,3,4-tetrahydroquinolin-4-ylamino)pentan-1-ol (HCQ-M). The microbial transformation occurred through N-dealkylation, 7-chloro-elimination, and reduction of the two conjugated double-bond from the quinoline system of HCQ. The cytotoxic profiles of HCQ and its metabolite were evaluated using CCD-1059Sk cells (human fibroblasts) through sulforhodamine B, trypan blue, and Live/Dead assays. Both HCQ and HCQ-M displayed cytotoxic activities in human fibroblasts, but HCQ-M was significantly more toxic than HCQ. The reported findings should be considered for further clinical studies of HCQ and will be important for guidance in achieving new derivatives from it.

Involvement of political and socio-economic factors in the spatial and temporal dynamics of COVID-19 outcomes in Brazil: A population-based study.

Background: Brazil has been severely impacted by COVID-19 pandemics that is aggravated by the absence of a scientifically-driven coordinated informative campaign and the interference in public health management, which ultimately affected health measures to avoid SARS-CoV2 spread. The decentralization and resultant conflicts in disease control activities produced different protection behaviours and local government measures. In the present study, we investigated how political partisanship and socio-economic factors determined the outcome of COVID-19 at the local level in Brazil. Methods: A retrospective study of COVID-19 deaths was carried out using mortality databases between Feb 2020, and Jun 2021 for the 5570 Brazilian municipalities. Socio-economic parameters including city categories, income and inequality indexes, health service quality and partisanship, assessed by the result of the second round of the 2018 Brazilian presidential elections, were included. Regression tree analysis was carried out to identify the statistical significance and conditioning relationships of variables. Findings: Municipalities that supported then-candidate Jair Bolsonaro in the 2018 elections were those that had the worst COVID-19 mortality rates, mainly during the second epidemic wave of 2021. This pattern was observed even considering structural inequalities among cities. Interpretation: In general, the first phase of the pandemic hit large and central cities hardest, while the second wave mostly impacted Bolsonarian municipalities, where scientific denialism among the population was stronger. Negative effects of partisanship towards the right-wing on COVID-19 outcomes counterbalances favourable socioeconomic indexes in affluent Brazilian cities. Our results underscore the fragility of public health policies which were undermined by the scientific denialism of right-wing supporters in Brazil. Funding: International joint laboratories of Institute de Recherche pour le Développement, a partnership between the University of Brasília and the Oswaldo Cruz Foundation (LMI-Sentinela - UnB - Fiocruz - IRD), Coordination for the Improvement of Higher Education Personnel (CAPES), National Council for Scientific and Technological Development (CNPq).

AVALIAÇÕES DOCENTES SOBRE O ENSINO REMOTO NA PANDEMIA À LUZ DA LINGUÍSTICA SISTÊMICO-FUNCIONAL: RECURSOS TECNOLÓGICOS, MATERIAIS DIDÁTICOS E AVALIATIVIDADE EM FOCO

Diante da pandemia que impactou o trabalho docente em todo o Brasil, buscamos valorizar a voz de professores responsáveis por dar continuidade ao processo educacional via ensino remoto. Nosso enfoque recai sobre professores de línguas de diversos contextos de ensino que migraram para o ensino remoto ainda no primeiro semestre de 2020. O objetivo da pesquisa apresentada neste artigo foi investigar como professores de línguas avaliam o uso de materiais didáticos e recursos tecnológicos digitais de comunicação a distância em aulas remotas durante o isolamento social imposto pela pandemia de Covid-19, bem como as condutas institucionais e pessoais envolvidas naquele momento. A pesquisa contou com 130 docentes brasileiros, que responderam um questionário em que expressaram suas avaliações acerca dos recursos tecnológicos e dos materiais utilizados, bem como sobre a implementação e a experiência do ensino remoto em suas instituições de trabalho. Em termos teóricos, adotamos a perspectiva da Linguística Sistêmico-Funcional visando um enfoque linguístico e social, e especificamente utilizamos o sistema de Avaliatividade (MARTIN;WHITE, 2005;MARTIN;ROSE, 2007) para análise dos dizeres docentes. A análise linguística revela atitudes de afeto, demonstrando insegurança mediante a incerteza decorrente do momento e das mudanças no trabalho, julgamentos sobre as capacidades dos docentes, revelando certo despreparo para a situação, e apreciações da precariedade dos recursos e materiais disponíveis, além dos sentimentos de cansaço e angústia.Alternate :Faced with the pandemic that impacted teaching work throughout Brazil, we seek to value the voice of teachers responsible for continuing the educational process via remote teaching. Our focus is on language teachers from different teaching contexts who migrated to remote teaching in the first half of 2020. The objective of the research presented in this article was to investigate how language teachers assess the use of teaching materials and digital communication technology resources in remote classes during the social isolation imposed by the COVID-19 pandemic, as well as the institutional and personal conduct involved at that time. The research included 130 Brazilian professors who answered a questionnaire in which they expressed their evaluations about the technological resources and materials used, as well as about the implementation and experience of remote teaching in their work institutions. In theoretical terms, we adopt Systemic-Functional Linguistics perspective aiming at a linguistic and social focus, and specifically we use the Appraisal System (MARTIN;WHITE, 2005;MARTIN;ROSE, 2007) to analyze the teachers' sayings. The linguistic analysis reveals attitudes of affect, demonstrating insecurity due to the uncertainty resulting from the moment and changes at work, judgment on the teachers’ abilities, revealing a certain lack of preparation for the situation, and the appreciations of the precariousness of available resources and materials, in addition to feelings of tiredness, and anguish. 

A simple mathematical model for the evaluation of the long first wave of the COVID-19 pandemic in Brazil.

We propose herein a mathematical model to predict the COVID-19 evolution and evaluate the impact of governmental decisions on this evolution, attempting to explain the long duration of the pandemic in the 26 Brazilian states and their capitals well as in the Federative Unit. The prediction was performed based on the growth rate of new cases in a stable period, and the graphics plotted with the significant governmental decisions to evaluate the impact on the epidemic curve in each Brazilian state and city. Analysis of the predicted new cases was correlated with the total number of hospitalizations and deaths related to COVID-19. Because Brazil is a vast country, with high heterogeneity and complexity of the regional/local characteristics and governmental authorities among Brazilian states and cities, we individually predicted the epidemic curve based on a specific stable period with reduced or minimal interference on the growth rate of new cases. We found good accuracy, mainly in a short period (weeks). The most critical governmental decisions had a significant temporal impact on pandemic curve growth. A good relationship was found between the predicted number of new cases and the total number of inpatients and deaths related to COVID-19. In summary, we demonstrated that interventional and preventive measures directly and significantly impact the COVID-19 pandemic using a simple mathematical model. This model can easily be applied, helping, and directing health and governmental authorities to make further decisions to combat the pandemic.