Structural assessment, toxicity, and increased antimicrobial activity

Scorpion venom is a rich source of biologically active components and various peptides with high-potential therapeutic use that have been characterized for their antimicrobial and antiproliferative activities. Stigmurin is a peptide identified from the Tityus stigmurus venom gland with high antibacterial and antiproliferative activities and low toxicity. Amino acid substitutions in peptides without a disulfide bridge sequence have been made with the aim of reducing their toxicity and increasing their biological activities. The purpose of this study was to evaluate the structural conformation and structural stability, as well as antimicrobial, antiproliferative, and hemolytic activities of two peptide analogs to Stigmurin, denominated StigA6 and StigA16. In silico analysis revealed the α-helix structure for both analog peptides, which was confirmed by circular dichroism. Data showed that the net charge and hydrophobic moment of the analog peptides were higher than those for Stigmurin, which can explain the increase in antimicrobial activity presented by them. Both analog peptides exhibited activity on cancerous cells similar to the native peptide; however, they were less toxic when tested on the normal cell line. These results reveal a potential biotechnological application of the analog peptides StigA6 and StigA16 as prototypes to new therapeutic agents.publishersversionpublishe

The Text Mining Technique Applied to the Analysis of Health Interventions to Combat Congenital Syphilis in Brazil: The Case of the "Syphilis No!" Project

Congenital syphilis (CS) remains a threat to public health worldwide, especially in developing countries. To mitigate the impacts of the CS epidemic, the Brazilian government has developed a national intervention project called "Syphilis No." Thus, among its range of actions is the production of thousands of writings featuring the experiences of research and intervention supporters (RIS) of the project, called field researchers. In addition, this large volume of base data was subjected to analysis through data mining, which may contribute to better strategies for combating syphilis. Natural language processing is a form of knowledge extraction. First, the database extracted from the "LUES Platform" with 4,874 documents between 2018 and 2020 was employed. This was followed by text preprocessing, selecting texts referring to the field researchers' reports for analysis. Finally, for analyzing the documents, N-grams extraction (N = 2,3,4) was performed. The combination of the TF-IDF metric with the BoW algorithm was applied to assess terms' importance and frequency and text clustering. In total, 1019 field activity reports were mined. Word extraction from the text mining method set out the following guiding axioms from the bigrams: "confronting syphilis in primary health care;" "investigation committee for congenital syphilis in the territory;" "municipal plan for monitoring and investigating syphilis cases through health surveillance;" "women's healthcare networks for syphilis in pregnant;" "diagnosis and treatment with a focus on rapid testing." Text mining may serve public health research subjects when used in parallel with the conventional content analysis method. The computational method extracted intervention activities from field researchers, also providing inferences on how the strategies of the "Syphilis No" Project influenced the decrease in congenital syphilis cases in the territory

AVASUS’ Contributions to Promoting Lifelong Learning in Health: Toward Achieving the SDGs and Strengthening Global Health Security

The Virtual Learning Environment of the Brazilian Health System (AVASUS) was developed by the Laboratory for Technological Innovation in Health (LAIS) and the Secretariat of Distance Education (SEDIS) at the Federal University of Rio Grande do Norte (UFRN) in partnership with Brazil’s Ministry of Health (MoH). AVASUS provides open educational resources in the health field and has emerged as the third largest platform for massive health education globally, with more than one million students. Among the various learning pathways AVASUS offers, some specifically focus on meeting the educational needs to address public health emergencies and overlooked health contexts. The main argument in this study is that technology-mediated lifelong learning in health is an effective strategy for achieving the Sustainable Development Goals (SDGs) of the 2030 Agenda. This chapter analyzes the pathways related to COVID-19, syphilis, and prison health, focusing on the contributions towards achieving SDGs 3, 4, 5, 10, 11, 16, and 17 and fulfilling the Global Health Security Agenda. Our analysis revealed two key findings. Lifelong learning in health (i) prompts decision-making on public health policies and (ii) contributes towards implementing the SDGs. Ultimately, AVASUS should be recognized as a tool to improve health services and support policy-making

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

N-4-Phenyl-substituted 2-acetylpyridine thiosemicarbazones: Cytotoxicity against human tumor cells, structure-activity relationship studies and investigation on the mechanism of action

N-4-Phenyl 2-acetylpyridine thiosemicarbazone (H2Ac4Ph; N-(phenyl)-2-(1-(pyridin-2-yl)ethylidene) hydrazinecarbothioamide) and its N-4-ortho-, -meta- and -para-fluorophenyl (H2Ac4oFPh, H2Ac4mFPh, H2Ac4pFPh), N-4-ortho-, -meta- and -para-chlorophenyl (H2Ac4oClPh, H2Ac4mClPh, H2Ac4pClPh), N-4-ortho-, -meta- and -para-iodophenyl (H2Ac4oIPh, H2Ac4mIPh, H2Ac4pIPh) and N-4-ortho-, -meta- and -para-nitrophenyl (H2Ac4oNO(2)Ph, H2Ac4mNO(2)Ph, H2Ac4pNO(2)Ph) derivatives were assayed for their cytotoxicity against human malignant breast (MCF-7) and glioma (T98G and U87) cells. The compounds were highly cytotoxic against the three cell lineages (IC50: MCF-7, 52-0.16 nM; T98G, 140-1.0 nM; U87, 160-1.4 nM). All tested thiosemicarbazones were more cytotoxic than etoposide and did not present any haemolytic activity at up to 10(-5) M. The compounds were able to induce programmed cell death. H2Ac4pClPh partially inhibited tubulin assembly at high concentrations and induced cellular microtubule disorganization. (C) 2012 Elsevier Ltd. All rights reserved.CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)CNEN (Comissao Nacional de Energia Nuclear)CNEN (Comissao Nacional de Energia Nuclear)FAPEMIG (Fundacao de Amparo a Pesquisa do Estado de Minas Gerais)Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)INCTINOFAR (Instituto Nacional de Ciencia e Tecnologia de Farmacos e Medicamentos)INCT-INOFAR (Instituto Nacional de Ciencia e Tecnologia de Farmacos e Medicamentos) [Proc. CNPq 573.364/2008-6]INCTMM (Instituto Nacional de Ciencia e Tecnologia de Medicina Molecular)INCT-MM (Instituto Nacional de Ciencia e Tecnologia de Medicina Molecular) [Proc. FAPEMIG: CBB-APQ-00075-09/CNPq 573646/2008-2]INCT-Catalise (Instituto Nacional de Ciencia e Tecnologia de Catalise em Sistemas Moleculares e Nanoestruturados)INCTCatalise (Instituto Nacional de Ciencia e Tecnologia de Catalise em Sistemas Moleculares e Nanoestruturados)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo