The chemistry of Vernonanthura nudiflora (Less.) H. Rob. flowers and its antimicrobial activities.

Twenty-one known specialised metabolites were isolated from the flowers of Vernonanthura nudiflora (Less.) H. Rob., the structures of the compounds were established based on 1 D and 2 D NMR spectroscopic experiments. Others 28 compounds were putatively identified using the dereplication technique by UHPLC-HRMS/MS. Twenty-three of the compounds are being reported for the first time in this species. The mixture of sesquiterpene lactones piptocarphins A and B (17 + 18), and the flavone velutin (14) were tested against several microorganisms and showed promising activity against Mycobacterium tuberculosis with MIC of 15.6 µg/mL and 31.2 µg/mL, respectively. Furthermore, 17 + 18 showed greater cytotoxicity against VERO cells (IC50 = 7.0 ± 1.73) compared to compound 14 (IC50 85.0 ± 10.6 µg/mL). These findings reveal the feasibility of using the UHPLC-ESI-HRMS/MS-based dereplication strategy in complex fractions to identify specialised metabolites, moreover to V. nudiflora flowers being a source of compounds with antimycobacterial potential.

Decrease in compulsory notifications registered by the Brazilian National Hospital Epidemiological Surveillance Network during the COVID-19 pandemic: a descriptive study, 2017-2020. / Decréscimo nas notificações compulsórias registradas pela Rede Nacional de Vigilância Epidemiológica Hospitalar do Brasil durante a pandemia da COVID-19: um estudo descritivo, 2017-2020.

OBJECTIVE: To describe compulsorily notifiable diseases, health conditions and public health events (DAEs as per the Brazilian acronym) registered by the National Hospital Epidemiological Surveillance Network (RENAVEH as per the Brazilian acronym), before and during the COVID-19 pandemic. METHODS: This was a descriptive ecological study using records held on the Notifiable Health Conditions Information System (SINAN as per the Brazilian acronym) between Epidemiological Week (EW) 1 of 2017 (January 1st, 2017) and 52 of 2020 (December 26, 2020). RESULTS: Between 2017 and 2020, RENAVEH notified 1,258,455 DAE form records, with only 225,081 (17.9%) notifications in 2020, representing a decrease of 146,340 records compared to 2019. The temporal analysis showed a decrease per EW of more than 1,000 notified records with effect from EW 12. CONCLUSION: There was a decrease in compulsorily notifiable DAEs registered by RENAVEH in Brazil taking the period analyzed as a whole, in particular in 2020.

Decréscimo nas notificações compulsórias registradas pela Rede Nacional de Vigilância Epidemiológica Hospitalar do Brasil durante a pandemia da COVID-19: um estudo descritivo, 2017-2020 / Disminución de las notificaciones obligatorias registradas por la Red Nacional de Vigilancia Epidemiológica Hospitalaria de Brasil durante la pandemia de COVID-19: un estudio descriptivo, 2017-2020 / Decrease in compulsory notifications registered by the Brazilian National Hospital Epidemiological Surveillance Network during the COVID-19 pandemic: a descriptive study, 2017-2020

Objetivo: Descrever as notificações compulsórias de doenças, agravos e eventos de saúde pública (DAEs) registradas pela Rede Nacional de Vigilância Epidemiológica Hospitalar (Renaveh) do Brasil antes e durante a pandemia de COVID-19. Métodos: Estudo ecológico descritivo, com registros do Sistema de Informação de Agravos de Notificação (Sinan) no período correspondente às Semanas Epidemiológicas (SEs) 1 de 2017 (1º de janeiro de 2017) a 52 de 2020 (26 de dezembro de 2020). Resultados: No período de 2017 a 2020, a Renaveh notificou 1.258.455 fichas de DAEs, das quais apenas 225.081 (17,9%) foram notificadas em 2020, representando um decréscimo de 146.340 registros em relação às notificações de 2019. Na análise temporal por SE, houve decréscimo maior que mil registros nas notificações a partir da SE 12. Conclusão: Houve decréscimo nas notificações compulsórias de DAEs registradas pela Renaveh em todo o período analisado, com destaque para o ano de 2020.

Objetivo: Describir las notificaciones obligatorias de Enfermedades y Eventos de Salud Pública (DAEs), registradas por la Red Nacional de Vigilancia Epidemiológica Hospitalaria (RENAVEH), antes y durante la pandemia de COVID-19 e n Brasil. Métodos: Estudio ecológico descriptivo, con registros del Sistema de Información de Agravamientos de Notificación (Sinan) en el período de las Semanas Epidemiológicas (SEs) 1 de 2017 (1 de enero de 2017) a 52 de 2020 (26 de diciembre de 2020). Resultados: En el período 2017 a 2020, la RENAVEH notificó 1.258.455 registros de DAE, y solo se notificaron 225.081 (17,9%) registros en 2020, lo que representa una disminución de 146.340 registros con respecto a las notificaciones de 2019. En el análisis temporal por SE, hubo una disminución superior a mil registros en las notificaciones de la SE 12. Conclusión: Hubo una disminución en las notificaciones de DAEs registradas por la RENAVEH a lo largo del período analizado, con énfasis en el año 2020.

Objective: To describe compulsorily notifiable diseases, health conditions and public health events (DAEs as per the Brazilian acronym) registered by the National Hospital Epidemiological Surveillance Network (RENAVEH as per the Brazilian acronym), before and during the COVID-19 pandemic. Methods: This was a descriptive ecological study using records held on the Notifiable Health Conditions Information System (SINAN as per the Brazilian acronym) between Epidemiological Week (EW) 1 of 2017 (January 1st, 2017) and 52 of 2020 (December 26, 2020). Results: Between 2017 and 2020, RENAVEH notified 1,258,455 DAE form records, with only 225,081 (17.9%) notifications in 2020, representing a decrease of 146,340 records compared to 2019. The temporal analysis showed a decrease per EW of more than 1,000 notified records with effect from EW 12. Conclusion: There was a decrease in compulsorily notifiable DAEs registered by RENAVEH in Brazil taking the period analyzed as a whole, in particular in 2020.

In Vitro and In Silico Evaluations of Anti-Mycobacterium tuberculosis Activity of Benzohydrazones Compounds.

Tuberculosis is a disease caused by Mycobacterium tuberculosis, with high mortality rates and an extended treatment that causes severe adverse effects, besides the emergence of resistant bacteria. Therefore, the search for new compounds with anti-M. tuberculosis activity has considerably increased in recent years. In this context, benzohydrazones are significant compounds that have antifungal and antibacterial action. This study aimed at evaluating the in vitro activity of 18 benzohydrazones against M. tuberculosis. Compounds' cytotoxicity, inhibition of M. tuberculosis efflux pumps, and in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) assays were also performed. In general, the minimum inhibitory concentration values for the standard M. tuberculosis H37Rv strain ranged from 7.8 to 250 µg/mL, and some compounds were not toxic to any of the cells tested (IC50 ranged from 18.0 to 302.5 µg/mL). In addition, compounds (4) and (7) showed to be possible efflux pump inhibitors. In ADMET assays, all benzohydrazones had high gastrointestinal absorption. Most of the compounds were able to overcome the blood-brain barrier, and no compounds had irritant or tumorigenic effects. Compounds (1), (3), (9), (12), and (15) stood out for showing good activities, both in vitro and in silico assays.

Antituberculosis Activities of Lapachol and ß-Lapachone in Combination with Other Drugs in Acidic pH.

Background: The treatment of multidrug-resistant tuberculosis (MDR-TB) is a challenge to be overcome. The increase of resistant isolates associated with serious side effects during therapy leads to the search for substances that have anti-TB activity, which make treatment less toxic, and also act in the macrophage acidic environment promoted by the infection. Objective: The aim of this study was to investigate lapachol and ß-lapachone activities in combination with other drugs against Mycobacterium tuberculosis at neutral and acidic pH and its cytotoxicity. Design: Inhibitory and bactericidal activities against M. tuberculosis and clinical isolates were determined. Drug combination and cytotoxicity assay were carried out using standard TB drugs and/or N-acetylcysteine (NAC). Results: Both naphthoquinones presented activity against MDR clinical isolates. The combinations with the first-line TB drugs demonstrated an additive effect and ß-lapachone+NAC were synergic against H37Rv. Lapachol activity at acidic pH and its association with NAC improved the selectivity index. Lapachol and ß-lapachone produced cell morphological changes in bacilli at pH 6.0 and 6.8, respectively. Conclusion: Lapachol revealed promising anti-TB activity, especially associated with NAC.

RDRioMycobacterium tuberculosis lineage in the Brazil/Paraguay/Argentina triple border.

The high tuberculosis (TB) incidence rates, the closeness of the cities and the high migration flux on the Brazil/Paraguay/Argentina border deserves an in-depth study, using Mycobacterial Interspersed Repetitive Unit (MIRU) and Spoligotyping genetic markers to explore the impact of the Mycobacterium tuberculosis RDRio lineage on disease transmission and resistance to anti-TB drugs in this setting. Although without the totality of M. tuberculosis isolates causing TB in this studied setting, a number of 97 isolates obtained from sputa samples culture of patients with confirmed TB, from 2013 to 2015, were submitted to 24 loci MIRU, Spoligotyping, detection of RDRio lineage and detection of mutation related to isoniazid and rifampicin resistance by MTBDRplus/DNA STRIP. In this sample, it was observed high clonal variability of circulating M. tuberculosis isolates causing TB in Brazilian cities bordering Paraguay and Argentina. The percentage of RDRio lineage causing TB in this setting was 15.46%, and lower than the detected in different areas of Brazil. According to 24 loci MIRU, the major MIRU International Type (MIT) related with RDRio lineage were MIT 26, MIT 738, MIT 601 with four, two and one isolates, respectively. Eight isolates with RDRio marker were classified as orphans. The mainly Spoligofamily related with RDRio lineage was LAM1 and LAM9 and no relationship between RDRio lineage and resistance in M. tuberculosis isolates circulating in this setting could be established. This work is pioneer in studying the dynamics of RDRio lineage transmission on the Brazil/Paraguay/Argentina border and deserves further studies to analyze the real contribution of the RDRio lineage in outbreaks and the risk of significant development of MDR-TB in the setting studied.