Florestas plantadas de eucalipto em sistemas silvipastoris e o impacto da entrada do componente animal

Neste trabalho objetivou-se fazer um levantamento sobre estudos que mostram os impactos ambientais e econômicos da entrada dos animais em sistema silvipastoril de florestas plantadas de eucalipto. O cultivo de florestas plantadas de eucalipto contribui para a diminuição dos impactos ambientais, causado pelo manejo inadequado de florestas naturais e promove o desenvolvimento econômico e social sustentável. Com base em tecnologias avançadas de gestão e controle, as empresas de celulose e papel visam alcançar práticas de excelência em sustentabilidade na área ambiental. Para seu desenvolvimento satisfatório como monocultura, são necessárias tecnologias modernas e, para transpô-la para sistemas silvipastoris, é necessária inteligência, criatividade e muita observação de produtores e técnicos. Os componentes que o homem pode manejar dentro do sistema silvipastoril são as árvores, o sub-bosque (pasto) e o rebanho animal, que requerem cuidados e manejo específico. A interação entre os componentes é de grande importância, pois respondem pelo êxito do sistema e fornecem os pontos de intervenção para o manejo da floresta e dos animais. Os sistemas silvipastoris têm-se mostrado viáveis para suprir a demanda de produtos derivados da madeira, trazendo receitas adicionais, no entanto, não deve ser esperada produtividade máxima dos componentes desses sistemas, mas a sustentabilidade do ecossistema como um todo

Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner

Paracoccidioides brasiliensis, a causative agent of paracoccidioidomycosis (PCM), should be able to adapt to dramatic environmental changes inside the infected host after inhalation of air-borne conidia and transition to pathogenic yeasts. Proteins with antioxidant functions may protect fungal cells against reactive oxygen (ROS) and nitrogen (RNS) species generated by phagocytic cells, thus acting as potential virulence factors. Ras GTPases are involved in stress responses, cell morphology, and differentiation in a range of organisms. Ras, in its activated form, interacts with effector proteins and can initiate a kinase cascade. in lower eukaryotes, Byr2 kinase represents a Ras target. the present study investigated the role of Ras in P. brasiliensis after in vitro stimulus with ROS or RNS. We have demonstrated that low concentrations of H2O2 (0.1 mM) or NO2 (0.1-0.25 mu M) stimulated P. brasiliensis yeast cell proliferation and that was not observed when yeast cells were pre-incubated with farnesyltransferase inhibitor. We constructed an expression plasmid containing the Byr2 Ras-binding domain (RBD) fused with GST (RBD-Byr2-GST) to detect the Ras active form. After stimulation with low concentrations of H2O2 or NO2, the Ras active form was observed in fungal extracts. Besides, NO2 induced a rapid increase in S-nitrosylated Ras levels. This alternative posttranslational modification of Ras, probably in residue Cys123, would lead to an exchange of GDP for GTP and consequent GTPase activation in P. brasiliensis. in conclusion, low concentrations of H2O2 or NO2 stimulated P. brasiliensis proliferation through Ras activation.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenacao Aperfeicoamento de Pessoal de Nivel SuperiorUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Dept Bioquim Biol Mol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Dept Bioquim Biol Mol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, BrazilFAPESP: 2011/14392-2CNPq: 477764/2009-6Web of Scienc

The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Intracellular targets and mechanism of action of copper (II) or zinc (II) oxindoliminic complexes with antitumor activity

No presente trabalho foram realizados estudos da atividade biológica de complexos imínicos de Cu(II) e Zn(II) derivados da isatina, principalmente frente a células tumorais HeLa. Sabe-se que estes complexos se ligam ao DNA, podendo causar clivagens simples e duplas na sua estrutura, em presença de peróxido de hidrogênio, através de um mecanismo predominantemente oxidativo. Os complexos de Cu(II) geram espécies reativas de oxigênio (EROs) e, além disto, atuam sobre a mitocôndria como agentes desacopladores. Sabe-se ainda que esses compostos interagem com proteínas específicas, como por exemplo a topoisomerase humana IB e as quinases dependentes de ciclinas (CDKs), inibindo significativamente sua atividade, ou a proteassoma, frente à qual apenas uma inibição moderada foi observada. Os ensaios in vitro desenvolvidos nesta tese, permitiram evidenciar a capacidade de os complexos de intercalar no DNA e RNA, além de clivar o primeiro biopolímero. Os resultados obtidos in celullo, evidenciaram a dependência do cobre para a citotoxicidade dos complexos sendo estes compostos capazes de estimular a necrose das células HeLa. Além disso, os resultados demonstraram que estes compostos são capazes de interferir no ciclo celular, interrompendo-o em fase G2/M e de desencadear um desequilíbrio oxidativo. Os principais alvos intracelulares dos complexos, em células HeLa, são a Mitocôndria, pois interferem em seu funcionamento diminuindo o seu potencial de membrana, e o DNA clivando-o. Ademais, pretendeu-se, através de um estudo sistemático por microscopia Raman confocal, identificar danos celulares provocados pelos complexos, especialmente uma grande alteração no núcleo celular de células HeLa após o tratamento com o complexo [Cu(isaepy)]+. Através de ensaios de viabilidade, também foi possível demonstrar que a superexpressão de glicoproteína-P para linhagem MES-AS/Dx5 não resulta na resistência dessas células frente aos compostos testados, e que os complexos não interferem no funcionamento desta glicoproteína. Também foi observado, através dos experimentos com células HaCaT, que o complexo [Zn(isaepy)]2+ é capaz de interferir no ciclo autofágico celular.In the present work, the synthesis and characterization of oxindolimine complexes of Cu(II) and Zn(II) were carried out. R is known that these complexes bind to DNA and can cause single and double cleavages in their structure, in the presence or absence of hydrogen peroxide, through a predominantly oxidative mechanism. Cu(II) complexes generate reactive oxygen species (ROS) and, in addition, act on mitochondria as decoupling agents. These compounds are also known to interact with specific proteins, such as human topoisomerase IB and cyclin-dependent kinases (CDKs), inhibiting significantly their activity, or the proteasome, against which only moderate inhibition has been observed. The in vitro assays developed in this thesis have demonstrated the ability of these complexes in intercalating at DNA and RNA, in addition to cleaving the first biopolymer. The results in cellulo evidenced the dependence on the copper for the cytotoxicity of the complexes, that can stimulate the necrosis in HeLa cells. In addition, the results demonstrated that these compounds are capable of interfering in the cell cycle, stopping it at G2/M phase and triggering an oxidative imbalance. The main intracellular targets of the complexes, in HeLa cells, are the Mitochondria, where they interfere in its function, diminishing its membrane potential, and the DNA, causing its cleavage. Further, it was intended, through a systematic study by confocal Raman microscopy, to identify cellular damage triggered by the complexes. Particularly, a large change in the cell nucleus of HeLa cells was demonstrated after treatment with the \'[Cu(isaepy)] POT.+\' complex. Through viability assays, it was also demonstrated that overexpression of P-glycoprotein in MES-SA/Dx5 lineage does not result in the resistance of these cells to the tested compounds, and that the complexes do not interfere in the functioning of this glycoprotein. Finally, it was observed, in experiments with HaCaT cells, that \'[Zn(isaepy)] POT.2+\' complex can interfere in the autophagic cell cycle

Florestas plantadas de eucalipto em sistemas silvipastoris e o impacto da entrada do componente animal

This work aimed to make a survey of studies that show the environmental and economic impacts of the entry of animals in silvopastoral system of planted forests of Eucalyptus. Eucalyptus planted forests contributes to the reduction of environmental impacts caused by inappropriate management of natural forests and promotes economic and social development. Based on advanced technologies of management and control, pulp and paper companies aim to achieve best practices in sustainability in the environmental area. For their satisfactory development as monoculture, modern technologies are needed and to transpose it to silvopastoral systems, it is necessary intelligence, creativity and much notice of producers and technicians. The components that man can handle within the silvopastoral system are the trees, the understory (pasture) and the animal herd that require specific care and management. The interaction between the components is of great importance because they respond by the system successfully and provide intervention points for the management of forest and animals. The silvopastoral systems has proven viable to meet the demand for wood products, bringing additional revenue, however, should not be expected maximum productivity components of such systems, but the sustainability of the ecosystem as a whole.Neste trabalho objetivou-se fazer um levantamento sobre estudos que mostram os impactos ambientais e econômicos da entrada dos animais em sistema silvipastoril de florestas plantadas de eucalipto. O cultivo de florestas plantadas de eucalipto contribui para a diminuição dos impactos ambientais, causado pelo manejo inadequado de florestas naturais e promove o desenvolvimento econômico e social sustentável. Com base em tecnologias avançadas de gestão e controle, as empresas de celulose e papel visam alcançar práticas de excelência em sustentabilidade na área ambiental. Para seu desenvolvimento satisfatório como monocultura, são necessárias tecnologias modernas e, para transpô-la para sistemas silvipastoris, é necessária inteligência, criatividade e muita observação de produtores e técnicos. Os componentes que o homem pode manejar dentro do sistema silvipastoril são as árvores, o sub-bosque (pasto) e o rebanho animal, que requerem cuidados e manejo específico. A interação entre os componentes é de grande importância, pois respondem pelo êxito do sistema e fornecem os pontos de intervenção para o manejo da floresta e dos animais. Os sistemas silvipastoris têm-se mostrado viáveis para suprir a demanda de produtos derivados da madeira, trazendo receitas adicionais, no entanto, não deve ser esperada produtividade máxima dos componentes desses sistemas, mas a sustentabilidade do ecossistema como um todo