Post Market Monitoring: Legal Framework in Brazil and First Results(Contribution to the 4th International Workshop on PMEM of Genetically Modified Plants, Quedlinburg)

Brasilien war 2010 der zweitgrößte Anbauer von gentechnisch veränderten Pflanzen. Die rechtliche Basis für die Forschung und kommerzielle Freisetzung von gentechnisch veränderten Organismen geht zurück auf das Jahr 2005. Nach der notwendigen Risikobewertung durch die nationale Technische Kommission für Biologische Sicherheit (CTNBio), kann eine Genehmigung für die kommerzielle Verwertung einer gentechnisch veränderten Pflanze erteilt werden. Allerdings erfordert die Normregel Nr. 5 (NR-5) aus dem Jahre 2008 ein begleitendes Monitoring. Allerdings wurde bereits im Jahre 2005 die erste transgene Pflanze, eine Herbizid-tolerante Sojabohne, in Brasilien angebaut. CTNBio forderte die Ausarbeitung eines Monitoringplanes, dem die Antragsteller mit einem komplexen, fallspezifisch fokussierten Monitoringdesign nachkamen. Nach vier Jahren detaillierter Feldstudien konnten keine Schäden durch den Anbau der transgenen Pflanzen nachgewiesen werden. Der Kostenaufwand war jedoch enorm. Im Juni 2010 waren bereits 23 gentechnisch veränderte Pflanzen mit verschiedenen transgenen Merkmalen für die kommer­zielle Nutzung in Brasilien zugelassen: Soja (6 Zulassungen), Baumwolle (8) und Mais (9). Einzelne oder gekoppelte Merkmale für Herbizidtoleranz und Insektenresistenz werden derzeit genutzt. Müsste für jedes einzelne Merkmal oder gekoppelte Merkmale ein eigenständiges Monitoringprogramm durchgeführt werden, wären die Kosten praktisch untragbar. Die Antragsteller sind nach brasilianischem Recht für die Planung und Durchführung des Monitoring verantwortlich. Da die Normregel Nr. 5 keine klaren Vorgaben macht, reichen die Antragsteller entweder sehr detaillierte, fallspezifisch orientierte oder sehr einfache, allgemeine Monitoringpläne ein, die sich auf einfach nachzuweisende, mögliche Effekte im kommerziellen Anbau beziehen. Im Gegensatz zum euro­päischen Recht unterscheidet weder das brasilianische Biosicherheitsgesetz noch Normregel Nr. 5 ein fallspezi­fisches Monitoring und eine Allgemeine Beobachtung. Sollte ein fallspezifischer Monitoringplan schwer herzuleiten sein, gibt es keine verbindlichen Vorgaben für eine Allgemeine Beobachtung. Hier kann ein zukünftiges brasilianisches Informationssystem für Biosicherheit wertvolle Unterstützung bieten. Derzeit jedoch ist eine Allgemeine Beobachtung gar nicht oder nur sehr begrenzt in den Monitoringplänen vorgesehen. Es ist zu beachten, dass die Antragsteller in jedem Fall für das Monitoring verantwortlich bleiben. Dies kann jedoch bei zunehmendem Anbau transgener Pflanzen mit verschiedenen (ähnlichen), einzelnen oder gekoppelten Merkmalen auf benachbarten Feldern zu großen Schwierigkeiten bei der Interpretation der einzelnen Monitoringdaten führen. Deshalb ist es notwendig, eine breit angelegte und mit verschiedenen Interessengruppen kommunizierte Monitoringstrategie zu entwickeln. CTNBio ist sich dieser Herausforderungen bewusst und hat in einem ersten Schritt die Normregel Nr. 5 überarbeitet, um den Antragstellern klarere Vorgaben für den Entwurf von Monitoringplänen zu bieten.    Brazil is presently (2010) the second largest producer of genetically modified (GM) crops. The legal framework to support both research activities and the commercial release of Genetically Modified Organisms (GMOs) is, however, very recent, as the Biosafety Law dates back from 2005. After the indispensable risk analysis, done by National Technical Commission for Biosafety (CTNBio), a GM plant can be approved for commercial release. Nevertheless, as stated in the Normative Resolution Nr. 5 (NR-5), of 2008, the post-market monitoring is mandatory. However, the first GM crop in Brazil, the herbicide tolerant soybean, was harvested in 2005. The CTNBio then asked for a monitoring plan and the applicant designed a complex study focused on case-specific monitoring. After four years the detailed field studies proved that no harm derived from this crop. The costs, nevertheless, were enormous. In June 2010, 21 GM plants were already approved for commercial release in Brazil, corresponding to different events in soybean (6), cotton (8) and maize (9). Single and stacked events tolerant to herbicides or insect-resistant are presently been planted. If, for each single event and for the stacks, a laborious post market monitoring plan were to be executed, the total costs would be unbearably high. The applicant is legally and financially responsible for the monitoring in Brazil. It is also responsible to produce an adequate monitoring plan. Since the NR-5 rules are far from being clear, the applicants either proposed an elabo­rated plan for case-specific monitoring or, conversely, submitted a very simple plan, targeting some potential adverse effect that can be more easily evaluated in commercial fields. It is not clearly stated either in the Biosafety Law or in the NR-5 that monitoring should be split in case-specific monitoring and general surveillance, as adopted in Europe. If case-specific monitoring plans are difficult to design, a sensible suggestion for the general surveillance was not yet achieved. Never­theless, the info-concentrating Brazilian Biosafety Infor­mation System may be a valuable source for the general surveillance, once it starts to operate. The general surveillance is presently either not contemplated in the monito­ring plans or only minimally treated. It is important to keep in mind that the applicants are responsible to produce most of the data, even for the general surveillance, and this can be extremely difficult in a scenario where many different events are cultivated, frequently in neighbouring fields. A conceptual framework for post market monitoring must therefore be established following a dia­log with all stakeholders. CTNBio is aware of these challenges and has already started to adjust the NR-5 to better guide the applicants in their writing of monitoring plans.   &nbsp

Post-market monitoring: legal framework in Brazil and first results

Brazil is presently (2010) the second largest producer of Genetically Modified (GM) crops. The legal framework to support both research activities and the commercial release of Genetically Modified Organisms (GMOs) is, however, very recent, as the Biosafety Law dates back from 2005. After the indispensable risk analysis, done by National Technical Committee for Biosafety (CTNBio), a GM plant can be approved for commercial release. Nevertheless, as stated in the Normative Resolution nr. 5 (NR-5), 2008, the post-market monitoring is mandatory. However, the first GM crop in Brazil, the herbicide tolerant soybean, was harvested in 2005. The CTNBio asked, then, for a monitoring plan and the applicant designed a complex study focused on case-specific monitoring. After four years the detailed field studies proved that no harm derived from this crop. The costs, nevertheless, were enormous. In May 2010, 21 GM plants were already approved for commercial release in Brazil, corresponding to different events in soybean (6), cotton (8) and maize (9). Single and stacked events tolerant to herbicides or insect-resistant are presently been planted for all three crops. If, for each single event and for the stacks, a laborious post market monitoring plan were to be executed, the total costs would be unbearably high. The applicant, i.e. the seed company in the case of the three common crops, is legally responsible for the monitoring in Brazil. It is also responsible to produce an adequate monitoring plan. Since the rules in the Normative Resolution nr. 5 are far from being clear, the applicants either propose an elaborated plan for case-specific monitoring or, conversely, submit a very simple plan, targeting some potential adverse effect that can be more easily evaluated in commercial fields. All data generated must be reported to federal agencies belonging to at least three different ministries. Monitoring is also a responsibility of some federal agencies, as stated in the Biosafety Law, like registration and inspection agencies and other entities, which are responsible for, among other duties, keep updated information in the Biosafety Information Systems (SIB) of institutions and technical responsible individuals that carry out activities and projects related to GMOs and their by products. It is not clearly stated either in the Biosafety Law or in the NR-5 that monitoring should be split in case-specific monitoring and general surveillance, as adopted in Europe. If case-specific monitoring plans are difficult to design, a sensible suggestion for the general surveillance was not yet achieved. Nevertheless, the info-concentrating SIB may be a valuable source for the general surveillance, once it starts to operate. In conclusion, due to the lack of clear information about how to produce an adequate monitoring plan, stakeholders either tend to unnecessarily enlarge the monitoring scope or shorten it to a few objectives. The general surveillance is either not contemplated in the monitoring plans or minimally treated. It is important to keep in mind that the applicants are responsible to produce most of the data, even for the general surveillance, and this can be extremely difficult in a scenario where 20 or more different events are cultivated, frequently in neighboring fields. The EuropaBio approach to general surveillance for cultivation of GM crops (available from Nature Precedings "doi:10.1038/npre.2010.4451.1":http://dx.doi.org/10.1038/npre.2010.4451.1) is difficult to be largely adopted: farmers may be unable to meaningfully answer the questionnaire and the network has a very restricted number of potential participants. CTNBio is aware of these challenges and has already started to adjust the NR-5 to better guide the applicants in their writing of monitoring plans

Congenital hip dislocation: an initial approach

This bibliographic study aimed to identify and analyse scientific publications about Congenital Hip Dislocation (CHD). 41 articles were found. The analysis resealed that, in spite of the diversity and distinct parameters used by authors, complications entrailed by this disease result from deficient detection and late diagnosis. For nurses, knowledge about this disease can contribute to patient care and follow-up, as well as to training aimed at family members.O objetivo do presente estudo foi identificar e analisar as publicações científicas acerca da Luxação Congênita do Quadril (LCQ) através de uma pesquisa bibliográfica. Foram encontrados 41 artigos e constatou-se pela análise que apesar da diversidade e dos distintos parâmetros utilizados pelos autores, as complicações da patologia resultam da deficiência da detecção e do diagnóstico tardio. Considera-se que o conhecimento dessa patogenia pela enfermeira possa contribuir com os cuidados e acompanhamento aos portadores, além do treinamento de seus familiares

Lutzomyia longipalpis s.l. in Brazil and the impact of the Sao Francisco River in the speciation of this sand fly vector

Lutzomyia longipalpis s.l. (Diptera: Psychodidae) is the principal vector of Leishmania infantum chagasi in the Americas, and constitutes a complex of species. Various studies have suggested an incipient speciation process based on behavioral isolation driven by the chemotype of male sexual pheromones. It is well known that natural barriers, such as mountains and rivers can directly influence population divergence in several organisms, including insects. In this work we investigated the potential role played by the Sao Francisco River in eastern Brazil in defining the current distribution of Lu. longipalpis s.l. Our studies were based on analyses of polymorphisms of the cytochrome b gene (cyt b) sequences from Lu. longipalpis s.l. available in public databases, and from additional field-caught individuals. Altogether, 9 distinct populations and 89 haplotypes were represented in the analyses. Lu. longipalpis s.l. populations were grouped according to their distribution in regards to the 10°S parallel: north of 10°S (<10°S); and south of 10°S (>10°S). Our results suggest that although no polymorphisms were fixed, moderate genetic divergences were observed between the groups analyzed (i.e., FST = 0.184; and Nm = 2.22), and were mostly driven by genetic drift. The population divergence time estimated between the sand fly groups was about 0.45 million years (MY), coinciding with the time of the change in the course of the Sao Francisco River, during the Mindel glaciation. Overall, the polymorphisms on the cyt b haplotypes and the current speciation process detected in Lu. longipalpis s.l. with regards to the distribution of male sexual pheromones suggest a role of the Sao Francisco River as a significant geographical barrier in this process

Morbidity study of the orthopedic unit

Modelo de estudo: Estudo retrospectivo e descritivo. Objetivo: Descrever a clientela hospitalizada na Unidade de Internação de Ortopedia do HCRP, segundo as variáveis do diagnóstico principal, idade e sexo. Metodologia: Foram analisadas as saídas hospitalares codificadas pela Classificação Internacional de Doenças, 9ª revisão, 1975, ocorridas no período de 1992 a 1996. Os dados foram obtidos através do Serviço de Arquivo Médico (SAME) da instituição, a partir de programa de registro de altas da Companhia de Processamento de Dados do Estado de São Paulo- PRODESP e decodificados a partir da elaboração especial de um programa de computador desenvolvido em linguagem C++.&nbsp;Resultados: Encontram-se 5819 saídas hospitalares, sendo o Capítulo XVII – Lesões e Envenenamentos – responsável pelo maior número,correspondendo a 2.345 saídas (40,30%). Em seguida, o Capítulo XIII – Doenças do Sistema Osteomuscular e do Tecido Conjuntivo - foi o responsável por 1.904 saídas (32,72%). O Capítulo VI – Doenças do Sistema Nervoso e dos Órgãos dos Sentidos - foi responsável por 433 saídas (7,44%). Especificamente, o diagnóstico de Síndrome do Túnel do Carpo representou 310 casos. O Capítulo II – Neoplasma - foi o responsável por 479 saídas (8,23). O Capítulo XIV – Anomalias Congênitas foi o responsável por 333 saídas (5,72%). Os demais capítulos apresentaram freqüência menor de saídas. Em todos os capítulos notou-se distribuição nas diversas faixas etárias, predominando a de 20 a 49 anos de idade (48,44%). Considerações: Acredita-se que o conhecimento da morbidade hospitalar, pelos enfermeiros, possa orientar o uso de recursos dos serviços de saúde, de modo a garantir a qualidade da assistência prestada.Study Design:&nbsp;Retrospective and descriptive research.&nbsp;Objective: the purpose of this study is to describe the clientele hospitalized at the Orthopedic Unit of the University of São Paulo at Ribeirão Preto Faculty of Medicine Hospital, according to variables such as the main diagnosis, age and sex.&nbsp;Method:&nbsp;Authors analyzed hospital discharge codified by the International Classification of Diseases, 9th review, 1975, occurred from 1992 to 1996. Data were collected through the Service of Medical Files of the Institution, through a program of registries of discharges from Data Process Company of São Paulo (PRODESP) and coded from a special software developed ein C++.&nbsp;Results: The authors found 5819 hospital discharge and the Chapter XVII - Lesions and poisoning was the responsible for the highest number of hospital discharge, corresponding to 2.345 (40.30%). Following, the Chapter XIII - Diseases of the osteomuscular and conjunctive tissue was responsible for 1.904 hospital discharge (32.72%). The Chapter VI - Diseases of the nervous system was the responsible for 433 hospital discharge (7.44%). In specific, the diagnostic of Carpal tunnel syndrome represented 310 cases. The Chapter II - Neoplasm was responsible for 479 hospital discharge (8.23). Chapter XIV - Congenital anomalies was responsible for 333 hospital discharge (5.72%). The other chapters presented a lower frequency. In all chapters, authors found a distribution of several age groups, mainly from 20 to 49 years of age (48.44%).&nbsp;Final Considerations: They believe that knowledge on hospital morbidity will orient the use of health services resources, in order to garantee the quality of care

Defluorination of Sodium Fluoroacetate by Bacteria from Soil and Plants in Brazil

The aim of this work was to isolate and identify bacteria able to degrade sodium fluoroacetate from soil and plant samples collected in areas where the fluoroacetate-containing plants Mascagnia rigida and Palicourea aenofusca are found. The samples were cultivated in mineral medium added with 20 mmol L−1 sodium fluoroacetate. Seven isolates were identified by 16S rRNA gene sequencing as Paenibacillus sp. (ECPB01), Burkholderia sp. (ECPB02), Cupriavidus sp. (ECPB03), Staphylococcus sp. (ECPB04), Ancylobacter sp. (ECPB05), Ralstonia sp. (ECPB06), and Stenotrophomonas sp. (ECPB07). All seven isolates degraded sodium-fluoroacetate-containing in the medium, reaching defluorination rate of fluoride ion of 20 mmol L−1. Six of them are reported for the first time as able to degrade sodium fluoroacetate (SF). In the future, some of these microorganisms can be used to establish in the rumen an engineered bacterial population able to degrade sodium fluoroacetate and protect ruminants from the poisoning by this compound

Alternative transmission routes in the malaria elimination era: an overview of transfusion-transmitted malaria in the Americas

Submitted by Janaína Nascimento ([email protected]) on 2019-02-21T11:59:00Z No. of bitstreams: 1 ve_Alho_Regina_etal_INI_2017.pdf: 1190158 bytes, checksum: 8937322faefa31c89eb1bbd2f7d134a3 (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-02-25T11:34:33Z (GMT) No. of bitstreams: 1 ve_Alho_Regina_etal_INI_2017.pdf: 1190158 bytes, checksum: 8937322faefa31c89eb1bbd2f7d134a3 (MD5)Made available in DSpace on 2019-02-25T11:34:33Z (GMT). No. of bitstreams: 1 ve_Alho_Regina_etal_INI_2017.pdf: 1190158 bytes, checksum: 8937322faefa31c89eb1bbd2f7d134a3 (MD5) Previous issue date: 2017Universidade do Estado do Amazonas. Manaus, AM, Brasil / Fundação de Hematologia e Hemoterapia do Amazonas. Manaus, AM, Brasil.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil.Universidade do Estado do Amazonas. Manaus, AM, Brasil / Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil.Fundação de Hematologia e Hemoterapia do Amazonas. Manaus, AM, Brasil.Universidade do Estado do Amazonas. Manaus, AM, Brasil.Universidade do Estado do Amazonas. Manaus, AM, Brasil / Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil.Sem afiliação.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Pesquisas Leônidas e Maria Deane. Manaus, AM, Brasil.Universidade do Estado do Amazonas. Manaus, AM, Brasil / Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil.Universidade do Estado do Amazonas. Manaus, AM, Brasil / Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil / Fundação Oswaldo Cruz. Instituto de Pesquisas Leônidas e Maria Deane. Manaus, AM, Brasil.Background: Transfusion-transmitted (TT) malaria is an alternative infection route that has gained little attention from authorities, despite representing a life-threatening condition. There has been no systematic review of this health problem in American countries. The aim of this study was to describe the clinical and epidemiological characteristics of TT malaria in the Americas and identify factors associated with lethality based on the studies published in the literature. Methods: Potentially relevant papers in all languages were retrieved from MEDLINE and LILACS. Additional articles were obtained from reviews and original papers. Publications on screening of candidate blood donors and on surveillance of TT malaria cases were included. Odds ratios with respective 95% confidence intervals (95% CI) were calculated. Epidemiological characteristics of blood donors of TT malaria cases, including a pooled positivity of different tests for malaria diagnosis, were retrieved. Results: A total of 63 publications regarding TT malaria from seven countries were included, from 1971 to 2016. A total of 422 cases of TT malaria were recorded. Most TT malaria cases were in females (62.0%) and 39.5% were in the ≥61 years-old age group. About half of all cases were from Mexico (50.7%), 40.3% from the United States of America (USA) and 6.6% from Brazil. Gyneco-obstetrical conditions (67.3%), surgical procedures (20.6%) and complications from neoplasias (6.1%) were the most common indications of transfusion. Packed red blood cells (RBCs) (50.7%) and whole blood (43.3%) were the blood products mostly associated with TT malaria. Cases were mostly caused by Plasmodium malariae (58.4%), followed by Plasmodium vivax (20.7%) and Plasmodium falciparum (17.9%). A total of 66.6% of cases were diagnosed by microscopy. Incubation period of 2–3 weeks was the most commonly observed (28.6%). Lethality was seen in 5.3% of cases and was associated with living in non-endemic countries, P. falciparum infection and concomitant neoplastic diseases. Conclusion: There is an important research and knowledge gap regarding the TT malaria burden in Latin American countries where malaria remains endemic. No screening method that is practical, affordable and suitably sensitive is available at blood banks in Latin American countries, where infections with low parasitaemia contribute greatly to transmission. Lethality from TT malaria was not negligible. TT malaria needs to be acknowledged and addressed in areas moving toward elimination

Impairment of peroxisomal APX and CAT activities increases protection of photosynthesis under oxidative stress

Retrograde signalling pathways that are triggered by changes in cellular redox homeostasis remain poorly understood. Transformed rice plants that are deficient in peroxisomal ascorbate peroxidase APX4 (OsAPX4-RNAi) are known to exhibit more effective protection of photosynthesis against oxidative stress than controls when catalase (CAT) is inhibited, but the mechanisms involved have not been characterized. An in-depth physiological and proteomics analysis was therefore performed on OsAPX4-RNAi CAT-inhibited rice plants. Loss of APX4 function led to an increased abundance of several proteins that are involved in essential metabolic pathways, possibly as a result of increased tissue H2O2 levels. Higher photosynthetic activities observed in the OsAPX4-RNAi plants under CAT inhibition were accompanied by higher levels of Rubisco, higher maximum rates of Rubisco carboxylation, and increased photochemical efficiencies, together with large increases in photosynthesis-related proteins. Large increases were also observed in the levels of proteins involved in the ascorbate/glutathione cycle and in other antioxidant-related pathways, and these changes may be important in the protection of photosynthesis in the OsAPX4-RNAi plants. Large increases in the abundance of proteins localized in the nuclei and mitochondria were also observed, together with increased levels of proteins involved in important cellular pathways, particularly protein translation. Taken together, the results show that OsAPX4-RNAi plants exhibit significant metabolic reprogramming, which incorporates a more effective antioxidant response to protect photosynthesis under conditions of impaired CAT activity.</p

Incidence and risk factors for Preeclampsia in a cohort of healthy nulliparous pregnant women: a nested case-control study

The objective of this study is to determine the incidence, socio-demographic and clinical risk factors for preeclampsia and associated maternal and perinatal adverse outcomes. This is a nested case-control derived from the multicentre cohort study Preterm SAMBA, in five different centres in Brazil, with nulliparous healthy pregnant women. Clinical data were prospectively collected, and risk factors were assessed comparatively between PE cases and controls using risk ratio (RR) (95% CI) plus multivariate analysis. Complete data were available for 1,165 participants. The incidence of preeclampsia was 7.5%. Body mass index determined at the first medical visit and diastolic blood pressure over 75 mmHg at 20 weeks of gestation were independently associated with the occurrence of preeclampsia. Women with preeclampsia sustained a higher incidence of adverse maternal outcomes, including C-section (3.5 fold), preterm birth below 34 weeks of gestation (3.9 fold) and hospital stay longer than 5 days (5.8 fold) than controls. They also had worse perinatal outcomes, including lower birthweight (a mean 379 g lower), small for gestational age babies (RR 2.45 [1.52-3.95]), 5-minute Apgar score less than 7 (RR 2.11 [1.03-4.29]), NICU admission (RR 3.34 [1.61-6.9]) and Neonatal Near Miss (3.65 [1.78-7.49]). Weight gain rate per week, obesity and diastolic blood pressure equal to or higher than 75 mmHg at 20 weeks of gestation were shown to be associated with preeclampsia. Preeclampsia also led to a higher number of C-sections and prolonged hospital admission, in addition to worse neonatal outcomes9CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ401636/2013-5Bill and Melinda Gates FoundationGates Foundation [OPP1107597]; CNPqNational Council for Scientific and Technological Development (CNPq) [401636/2013-5