Ligand-functionalized nanoparticles for targeted therapy of melanoma in situ

Diretores de Tese : Dra. Patrícia Rijo ; Dra. Catarina Reis ; Dr. Jesús MolpeceresEl melanoma cutáneo es un tipo de cáncer con origen en los melanocitos que se vuelven malignos. El tratamiento del melanoma cutáneo ha evolucionado mucho en los últimos treinta años, sin embargo, no ha conseguido incrementar significativamente la supervivencia de los pacientes con cáncer avanzado. Además, el tratamiento presenta muchas limitaciones, como una reducida especificidad, efectos secundarios graves y multi-resistencia a los fármacos. De hecho, un paso importante para el éxito del tratamiento del melanoma es su detección precoz. En el caso de que no haya metástasis, el cáncer puede ser extirpado por cirugía, pero hay casos en que el riesgo de la intervención, así como el elevado riesgo de recurrencia, obligan a un tratamiento adyuvante. Actualmente, sólo está aprobado un tratamiento adyuvante, con interferón alfa, para estos casos. De este modo, el principal objetivo de esta tesis es el estudio de alternativas para tratamientos adyuvantes, más eficientes y menos agresivos, del melanoma cutáneo. En este contexto, se han estudiado dos estrategias para aplicación de sistemas de nanopartículas. La primera estrategia consiste en el desarrollo de nanopartículas de oro, cubiertas con polímeros naturales y péptidos, con absorción en la región del infrarojo próximo, para terapia fototérmica. La segunda estrategia incluye el desarrollo de nanopartículas hibridas, para encapsulación de compuestos antitumorales, cubiertas con polímeros naturales y péptidos, capaces de una acción química local en el tumor. Conjuntamente, hemos investigado el comportamiento físico-químico y la estabilidad de las nanopartículas para cada aplicación. Reconociendo la importancia de un tratamiento eficaz y específico, ambas las estrategias se basan en un direccionamiento específico hacia las células de melanoma, que sobre-expresan múltiples receptores en su superficie. Por fin, se utilizaron modelos animales de melanoma humano para evaluación de la eficacia de las dos formulaciones propuestas. En conclusión, es posible desarrollar nanosistemas que comprenden diferentes estrategias terapéuticas, basadas en núcleos con estructuras distintas y funcionalización de superficies con múltiples ligandos, para una aplicación amplia y exitosa en los cánceres heterogéneos, tales como el melanoma cutáneo.Cutaneous melanoma occurs on the skin and is the most common type of melanoma. Treatment of cutaneous melanoma has improved over the last thirty years; however, without demonstrating a significant increase on survival of patients with advanced disease. Indeed, conventional treatment generally shows several limitations, such as reduced target specificity, severe adverse effects and multiple drug resistance. In fact, an important step for the success of melanoma treatment is its early detection. In cases where there are no metastases, this cancer can be removed by surgery, but in some cases the risk of intervention has to be measured, as well as the high risk of recurrence, which impose the use of an adjuvant treatment. Currently, there is only one adjuvant treatment approved, with interferon alpha, in these cases. Therefore, the main objective of this thesis was the study of alternatives as adjuvant treatments, more efficient and less aggressive, for cutaneous melanoma. In this context, two strategies have been studied for application of nanoparticles systems. The first strategy is focused on the development of gold nanoparticles, coated with natural polymers and peptides, with absorption at the near infrared range, for photothermal therapy. The second strategy includes the development of hybrid nanoparticles, for encapsulation of anti-tumor compounds, coated with natural polymers and peptides, capable of a local chemotherapy at the tumor site. Overall, the physico-chemical behavior and stability of both nanoparticles for each application were investigated. Recognizing the importance of an efficient and specific treatment, both strategies were based on a specific targeting to melanoma cells, which overexpressed multiple receptors at their surface. At last, animal models for human melanoma were used for evaluation of the efficiency of both proposed strategies. In conclusion, it is possible to develop nanosystems comprising different therapeutic strategies, based on distinct core structures and surface functionalization with multiple targeting ligands, for a broad and potential application in heterogeneous cancers, such as cutaneous melanoma

Estresse no trabalho relacionado ao exercício da docência no ensino superior / Work stress related ated to the exercise of teaching in higher education

Objetivo: Avaliar o nível de estresse de docentes atuantes no ensino superior público. Realizou-se um estudo epidemiológico, transversal e analítico, com docentes atuantes em cursos de graduação da área de saúde da Universidade Federal dos Vales do Jequitinhonha e Mucuri no ano de 2019. Métodos:  Como instrumento, utilizou-se a Escala de Estresse no Trabalho (EET) associada a um questionário para investigar as características sociodemográficas, de formação, trabalho e saúde. Foi realizada a análise descritiva e bivariada por meio do teste qui-quadrado. Resultados: Os resultados encontrados pela classificação dos escores totais na Escala de Estresse no Trabalho evidenciaram preponderância de baixo nível de estresse em todas as variáveis analisadas. Os docentes do estudo possuíam baixos níveis de estresse. Conclusão: Conclui-se que os docentes deste estudo apresentaram baixo nível de estresse, entretanto, é indispensável considerar os fatores estressantes desses profissionais a fim de produzir um ambiente favorável à qualidade de vida e do trabalho docente

Hexapoda Yearbook (Arthropoda: Mandibulata: Pancrustacea) Brazil 2020: the first annual production survey of new Brazilian species

This paper provided a list of all new Brazilian Hexapoda species described in 2020. Furthermore, based on the information extracted by this list, we tackled additional questions regarding the taxa, the specialists involved in the species descriptions as well as the journals in which those papers have been published. We recorded a total of 680 new Brazilian species of Hexapoda described in 2020, classified in 245 genera, 112 families and 18 orders. These 680 species were published in a total of 219 articles comprising 423 different authors residing in 27 countries. Only 30% of these authors are women, which demonstrates an inequality regarding sexes. In relation to the number of authors by species, the majority of the new species had two authors and the maximum of authors by species was five. We also found inequalities in the production of described species regarding the regions of Brazil, with Southeast and South leading. The top 10 institutions regarding productions of new species have four in the Southeast, two at South and with one ate North Region being the outlier of this pattern. Out of the total 219 published articles, Zootaxa dominated with 322 described species in 95 articles. The average impact factor was of 1.4 with only seven articles being published in Impact Factors above 3, indicating a hardship on publishing taxonomic articles in high-impact journals.The highlight of this paper is that it is unprecedent, as no annual record of Hexapoda species described was ever made in previous years to Brazil.Fil: Silva Neto, Alberto Moreira. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Lopes Falaschi, Rafaela. Universidade Estadual do Ponta Grossa; BrasilFil: Zacca, Thamara. Universidade Federal Do Rio de Janeiro. Museu Nacional; BrasilFil: Hipólito, Juliana. Universidade Federal da Bahia; BrasilFil: Costa Lima Pequeno, Pedro Aurélio. Universidade Federal de Roraima; BrasilFil: Alves Oliveira, João Rafael. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Oliveira Dos Santos, Roberto. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Heleodoro, Raphael Aquino. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Jacobina, Adaiane Catarina Marcondes. Universidade Federal do Paraná; BrasilFil: Somavilla, Alexandre. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Camargo, Alexssandro. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: de Oliveira Lira, Aline. Universidad Federal Rural Pernambuco; BrasilFil: Sampaio, Aline Amanda. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: da Silva Ferreira, André. Universidad Federal Rural Pernambuco; BrasilFil: Martins, André Luis. Universidade Federal do Paraná; BrasilFil: Figueiredo de Oliveira, Andressa. Universidade Federal do Mato Grosso do Sul; BrasilFil: Gonçalves da Silva Wengrat , Ana Paula. Universidade do Sao Paulo. Escola Superior de Agricultura Luiz de Queiroz; BrasilFil: Batista Rosa, Augusto Henrique. Universidade Estadual de Campinas; BrasilFil: Dias Corrêa, Caio Cezar. Universidade Federal Do Rio de Janeiro. Museu Nacional; BrasilFil: Costa De-Souza, Caroline. Museu Paraense Emilio Goeldi; BrasilFil: Anjos Dos Santos, Danielle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Pacheco Cordeiro, Danilo. Instituto Nacional Da Mata Atlantica; BrasilFil: Silva Nogueira, David. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Almeida Marques, Dayse Willkenia. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Nunes Barbosa, Diego. Universidade Federal do Paraná; BrasilFil: Mello Mendes, Diego Matheus. Instituto de Desenvolvimento Sustentável Mamirauá; BrasilFil: Galvão de Pádua, Diego. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Silva Vilela, Diogo. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Gomes Viegas, Eduarda Fernanda. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Carneiro dos Santos, Eduardo. Universidade Federal do Paraná; BrasilFil: Rodrigues Fernandes, Daniell Rodrigo. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; Brasi

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Os principais tipos e manifestações da Cirrose Hepática: uma atualização clínica

Introdução: A cirrose hepática é um processo patológica crônico, considerado a hepatopatia mais comum, definido como a conversão difusa morfoestrutural por nódulos de arquitetura anômalo envoltos por fibrose. Objetivou-se descrever os tipos mais relevantes de cirrose e suas devidas manifestações. Metodologia: Trata-se de uma revisão bibliográfica, fundamentada nas plataformas do SciELO, PubMed, Scopus, utilizando os termos “hepatical cirrhosis”, “liver disease” e “hepatocellular insufficiency” a qual através da revisão narrativa, abordou amplamente a respeito da contextualização da cirrose e as principais etiologias. Resultados e Discussão: Foi analisado que tal condição afeta qualquer faixa etária, sexo, etnia e independe da classe socioeconômica, mas as diversas etiologias impõem um perfil epidemiológico específico conforme a aparição. As principais origens abordam o tipo alcoólico, hepatite, aplicação crônica de alguns fármacos e esteatose gordurosa ou não. Ademais, estima-se que estas afetam a anatomofuncionalidade do órgão responsável por grande parte da homeostase, culminando em diversas manifestações clínicas.  Conclusão: A cirrose é uma consequência grave de fatores de base em estágio avançado, a qual devido ao seu curso geralmente silencioso culmina no desenvolvimento e progressão clínica. Neste contexto, a atenção aos fatores predisponentes como alimentação rica em lipídios, estilismo, negligência a exames de rotina, sedentarismo e obesidade contribuem constituem medidas eficazes de prevenção primária.&nbsp

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

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