Agronomic efficiency of organomineral fertilizer in onion cultivation

Onions has high nutritional and nutraceutical value. In the last decade the bulbs have gained increasingrelevance due their compounds linked to anti-cancer effects. The fertilization managment is relevant to thiscrop because the mineral’s influence beyond productivity, interfering in several aspects of quality. Organicsources despite available, adoption is still cautious and seen as an expense, rather than investment in soilquality. Therefore, the objective was to evaluate the use of organomineral fertilizer on the development andproductivity of Akamaru hybrid. The experiment was carried out in Cristalina-GO, in a randomized block design,with 4 replications and 5 treatments: organomineral fertilizer (NPK) with the formula 02-20-05. The rates wereadjusted to approximately the same amounts, where 3,680 kg ha-1 was considered the 100% rate, 2,944 kg ha-1as 80%, 2,208 kg ha-1 as 60% and 1,472 kg ha-1 as 40% of the rate established. The rate of 2,300 kg ha-1 of theformulated 03-35-06 referred to 100% of the mineral source. The total yield of onion was not affected when theorganomineral source was used, therefore, it is a viable source for use in onion culture. A rate reduction of upto 20% of the recommended mineral rate allows good performance (85.5 t ha-1), with 7.5 t ha-1 higher than the60% reduction of the recommended rate.Onions has high nutritional and nutraceutical value. In the last decade the bulbs have gained increasingrelevance due their compounds linked to anti-cancer effects. The fertilization managment is relevant to thiscrop because the mineral’s influence beyond productivity, interfering in several aspects of quality. Organicsources despite available, adoption is still cautious and seen as an expense, rather than investment in soilquality. Therefore, the objective was to evaluate the use of organomineral fertilizer on the development andproductivity of Akamaru hybrid. The experiment was carried out in Cristalina-GO, in a randomized block design,with 4 replications and 5 treatments: organomineral fertilizer (NPK) with the formula 02-20-05. The rates wereadjusted to approximately the same amounts, where 3,680 kg ha-1 was considered the 100% rate, 2,944 kg ha-1as 80%, 2,208 kg ha-1 as 60% and 1,472 kg ha-1 as 40% of the rate established. The rate of 2,300 kg ha-1 of theformulated 03-35-06 referred to 100% of the mineral source. The total yield of onion was not affected when theorganomineral source was used, therefore, it is a viable source for use in onion culture. A rate reduction of upto 20% of the recommended mineral rate allows good performance (85.5 t ha-1), with 7.5 t ha-1 higher than the60% reduction of the recommended rate

Office paper decorated with silver nanostars-an alternative cost effective platform for trace analyte detection by SERS

FCT (Portuguese Foundation for Science and Technology) under the project DISERTOX number PTDC/CTM-NAN/2912/2014 and CENIMAT/i3N by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT under the project number POCI-01-0145-FEDER- 007688, Reference UID/CTM/50025/2013. Unidade de Ciencias Biomoleculares Aplicadas-UCIBIO was financed by Portuguese national funds from FCT/MEC (UID/Multi/04378/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728). LAQV-Laboratorio associado para a Quimica Verde was partly financed by the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia), under the Partnership Agreement PT2020 through project UID/QUI/50006/2013-POCI/01/0145/FEDER/007265 (LAQV/REQUIMTE) and Programa Operacional Regional do Norte (ON. 2), under the Quadro de Referencia Estrategico Nacional (QREN) and funded by Fundo Europeu de Desenvolvimento Regional (Feder) NORTE-01-0145-FEDER-000011. A Araujo was funded by the Portuguese Science Foundation (FCT-MCTES) through grant SFRH/BD/85587/2012. M Almeida was funded by the Portuguese Science Foundation (FCT-MCTES) through grant SFRH/BD/95983/2013 in program POCH. The authors thank the Conservation and Restoration Department, FCT/UNL and LAQV, REQUIMTE for the use of the Raman spectrometer.For analytical applications in portable sensors to be used in the point-of-need, low-cost SERS substrates using paper as a base, are an alternative. In this work, SERS substrates were produced on two different types of paper: A high porosity paper (Whatman no. 1); and a low porosity paper (commercially available office paper, Portucel Soporcel). Solutions containing spherical silver nanoparticles (AgNPs) and silver nanostars (AgNSs) were separately drop-casted on hydrophilic wells patterned on the papers. The porosity of the paper was found to play a determinant role on the AgNP and AgNS distribution along the paper fibres, with most of the nanoparticles being retained at the illuminated surface of the office paper substrate. The highest SERS enhancements were obtained for the office paper substrate, with deposited AgNSs. A limit of detection for rhodamine-6G as low as 11.4 ± 0.2 pg could be achieved, with an analytical enhancement factor of â ‰107 for this specific analyte. The well patterning technique allowed good signal uniformity (RSD of 1.7%). Besides, these SERS substrates remained stable after 5 weeks of storage (RSD of 7.3%). Paper-induced aggregation of AgNPs was found to be a viable alternative to the classical salt-induced aggregation, to obtain a highly sensitive SERS substrates.publishersversionpublishe

Physiological and proteomic analyses of Saccharum spp. grown under salt stress

Sugarcane (Saccharum spp.) is the world most productive sugar producing crop, making an understanding of its stress physiology key to increasing both sugar and ethanol production. To understand the behavior and salt tolerance mechanisms of sugarcane, two cultivars commonly used in Brazilian agriculture, RB867515 and RB855536, were submitted to salt stress for 48 days. Physiological parameters including net photosynthesis, water potential, dry root and shoot mass and malondialdehyde (MDA) content of leaves were determined. Control plants of the two cultivars showed similar values for most traits apart from higher root dry mass in RB867515. Both cultivars behaved similarly during salt stress, except for MDA levels for which there was a delay in the response for cultivar RB867515. Analysis of leaf macro- and micronutrients concentrations was performed and the concentration of Mn2+ increased on day 48 for both cultivars. In parallel, to observe the effects of salt stress on protein levels in leaves of the RB867515 cultivar, two-dimensional gel electrophoresis followed by MS analysis was performed. Four proteins were differentially expressed between control and salt-treated plants. Fructose 1,6-bisphosphate aldolase was down-regulated, a germin-like protein and glyceraldehyde 3 phosphate dehydrogenase showed increased expression levels under salt stress, and heat-shock protein 70 was expressed only in salt-treated plants. These proteins are involved in energy metabolism and defense-related responses and we suggest that they may be involved in protection mechanisms against salt stress in sugarcane

Effect of transcranial direct current stimulation combined with gait and mobility training on functionality in children with cerebral palsy: study protocol for a double-blind randomized controlled clinical trial

Background: The project proposes three innovative intervention techniques (treadmill training, mobility training with virtual reality and transcranial direct current stimulation that can be safely administered to children with cerebral palsy. The combination of transcranial stimulation and physical therapy resources will provide the training of a specific task with multiple rhythmic repetitions of the phases of the gait cycle, providing rich sensory stimuli with a modified excitability threshold of the primary motor cortex to enhance local synaptic efficacy and potentiate motor learning. Methods/design A prospective, double-blind, randomized, controlled, analytical, clinical trial will be carried out.Eligible participants will be children with cerebral palsy classified on levels I, II and III of the Gross Motor Function Classification System between four and ten years of age. The participants will be randomly allocated to four groups: 1) gait training on a treadmill with placebo transcranial stimulation; 2) gait training on a treadmill with active transcranial stimulation; 3) mobility training with virtual reality and placebo transcranial stimulation; 4) mobility training with virtual reality and active transcranial stimulation. Transcranial direct current stimulation will be applied with the anodal electrode positioned in the region of the dominant hemisphere over C3, corresponding to the primary motor cortex, and the cathode positioned in the supraorbital region contralateral to the anode. A 1 mA current will be applied for 20 minutes. Treadmill training and mobility training with virtual reality will be performed in 30-minute sessions five times a week for two weeks (total of 10 sessions). Evaluations will be performed on four occasions: one week prior to the intervention; one week following the intervention; one month after the end of the intervention;and 3 months after the end of the intervention. The evaluations will involve three-dimensional gait analysis, analysis of cortex excitability (motor threshold and motor evoked potential), Six-Minute Walk Test, Timed Up-and-Go Test, Pediatric Evaluation Disability Inventory, Gross Motor Function Measure, Berg Balance Scale, stabilometry, maximum respiratory pressure and an effort test. Discussion This paper offers a detailed description of a prospective, double-blind, randomized, controlled, analytical, clinical trial aimed at demonstrating the effect combining transcranial stimulation with treadmill and mobility training on functionality and primary cortex excitability in children with Cerebral Palsy classified on Gross Motor Function Classification System levels I, II and III. The results will be published and will contribute to evidence regarding the use of treadmill training on this population. Trial registration ReBEC RBR-9B5DH

Reusable and highly sensitive SERS immunoassay utilizing gold nanostars and a cellulose hydrogel-based platform

This work was funded by FEDER funds through the COMPETE 2020 Programme and National Funds through the FCT---Fun-dação para a Ciência e a Tecnologia, I. P., under the scope of the project. This work also received funding from the European Community’s H2020 program under grant agreement No. 716510 (ERC-2016-STG TREND), 640598 (ERC-StG-2014, NEWFUN), and 685758 (1D-Neon). This work was supported by the Applied Molecular Biosciences Unit – UCIBIO and Associate Laboratory for Green Chemistry – LAQV which are financed by Portugal national funds from /2016 and SFRH/BD/132057/2017 from the FCT/MCTES and MIT Portugal PhD Program (to I. C. and M. J. O., respectively). Professor César Laia (LAQV-REQUIMTE, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Portugal) is acknowledged for permitting the use of DLS equipment. Professor Ludwig Krippahl (NOVA LINCS, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Portugal) is acknowledged for developing the gel analysis application eReuss. M. J. O. acknowledges Rocío Palomares Jurado PhD for visualisation/data presentation support and continued interest in the project. M. J. O. acknowledges David Peitinho MSc for help and advice in Python script. Diego Wiechers de Carvalho BSc is acknowledged for purifying the recombinant Plasmodium falciparum histidine-rich protein 2 sample and Daniela Gomes PhD for providing SEM images. Publisher Copyright: © The Royal Society of Chemistry 2021.The development of robust and sensitive point-of-care testing platforms is necessary to improve patient care and outcomes. Surface-enhanced Raman scattering (SERS)-based immunosensors are especially suited for this purpose. Here, we present a highly sensitive and selective SERS immunoassay, demonstrating for example the detection of horseradish peroxidase (HRP), in a sandwich format. The strength of our biosensor lies in merging: (i) SERS-immunotags based on gold nanostars, allowing exceptional intense SERS from attached Raman probes, covalent attachment of anti-HRP antibodies by a simple chemical method providing exceptional antigen binding activity; (ii) the ease of preparation of the capture platform from a regenerated cellulose-based hydrogel, a transparent material, ideal for microfluidics applications, with low background fluorescence and Raman signal, particularly suited for preserving high activity of the covalently bound anti-HRP antibodies. The sandwich complexes formed were characterised by atomic force microscopy, and by scanning electron microscopy coupled with electron diffraction spectroscopy; and (iii) the robustness of the simple Classical Least Squares method for SERS data analysis, resulting in superior discrimination of SERS signals from the background and much better data fitting, compared to the commonly used peak integral method. Our SERS immunoassay greatly improves the detection limits of traditional enzyme-linked immunosorbent assay approaches, and its performance is better or comparable to those of existing SERS-based immunosensors. Our approach successfully overcomes the main challenges of application at point-of-care, including increasing reproducibility, sensitivity, and specificity, associated with an environmentally friendly and robust design. Also, the proposed design withstands several cycles of regeneration, a feature absent in paper-SERS immunoassays and this opens the way for sensitive multiplexing applications on a microfluidic platform.preprintpublishe

ACALABRUTINIBE NO TRATAMENTO DE LEUCEMIA LINFOCÍTICA CRÔNICA

Introduction: Chronic lymphocytic leukemia is the most common adult leukemia. It is characterized by clonal expansion of mature CD5+ B cells into blood, bone marrow, and lymphoid tissues. Objectives: To evaluate the efficacy and adverse events of the use of acalabrutinib in the treatment of chronic lymphocytic leukemia. Materials and methods: This is an integrative review, in which the guiding question was “Is acalabrutinib effective in the treatment of chronic lymphocytic leukemia?”. The search for articles was carried out in the main databases (PubMed and Scielo) using the terms “acalabrutinib” and “chronic lymphocytic leukemia”, combined using Boolean operators. Results and Discussion: Compared to ibrutinib, acalabrutinib is highly selective and characterized by a lack of inhibition towards other kinases. Overall survival comparisons favored acalabrutinib alone and in combination with obinutuzumab over all comparators. Acalabrutinib monotherapy was also associated with statistically improved progression-free survival over obinutuzumab-chlorambucil. Conclusion: Acalabrutinib is an effective and safe treatment of chronic lymphocytic leukemia. Acalabrutinib plus obinutuzumab or acalabrutinib monotherapy were associated with improved efficacy over standard immunochemotherapy.Introducción: La leucemia linfocítica crónica es la leucemia más frecuente en adultos. Se caracteriza por la expansión clonal de células B CD5+ maduras en la sangre, la médula ósea y los tejidos linfoides. Objetivos: Evaluar la eficacia y los eventos adversos del uso de acalabrutinib en el tratamiento de la leucemia linfocítica crónica. Materiales y métodos: Se trata de una revisión integradora, en la que la pregunta orientadora fue “¿Es efectivo el acalabrutinib en el tratamiento de la leucemia linfocítica crónica?”. La búsqueda de artículos se realizó en las principales bases de datos (PubMed y Scielo) utilizando los términos “acalabrutinib” y “crónica linfocítica leucemia”, combinados mediante operadores booleanos. Resultados y Discusión: Comparado con ibrutinib, acalabrutinib es altamente selectivo y se caracteriza por una falta de inhibición hacia otras quinasas. Las comparaciones de supervivencia general favorecieron a acalabrutinib solo y en combinación con obinutuzumab sobre todos los comparadores. La monoterapia con acalabrutinib también se asoció con una supervivencia libre de progresión estadísticamente superior a la de obinutuzumab-clorambucilo. Conclusión: Acalabrutinib es un tratamiento eficaz y seguro de la leucemia linfocítica crónica. Acalabrutinib más obinutuzumab o la monoterapia con acalabrutinib se asociaron con una mayor eficacia en comparación con la inmunoquimioterapia estándar.A leucemia linfocítica crônica é a leucemia adulta mais comum. É caracterizada pela expansão clonal de células B maduras CD5 + no sangue, medula óssea e tecidos linfóides. Objetivos: Avaliar a eficácia e os eventos adversos ao uso do Acalabrutinibe no tratamento de leucemia linfocítica crônica. Materiais e métodos: Trata-se de uma revisão integrativa, em que a questão norteadora foi “O acalabrutinibe é eficaz no tratamento de leucemia linfocítica crônica?”. A busca pelos artigos ocorreu nas principais bases de dados (PubMed e Scielo) a partir dos termos “acalabrutinib” e “chronic lymphocytic leukemia”, combinados entre si por operadores booleanos. Resultados e discussão: Em comparação com o ibrutinibe, o acalabrutinibe é altamente seletivo e caracterizado pela falta de inibição em relação a outras quinases. As comparações de sobrevida global favoreceram a monoterapia com acalabrutinibe e em combinação com obinutuzumabe sobre todos os comparadores. A monoterapia com acalabrutinibe também foi associada a sobrevida livre de progressão estatisticamente melhorada em relação a obinutuzumabe-clorambucil. Conclusão: O acalabrutinib é um tratamento eficaz e seguro da leucemia linfocítica crônica. O acalabrutinibe mais obinutuzumabe ou a monoterapia com acalabrutinibe foram associados a uma eficácia melhorada em relação à imunoquimioterapia padrão. A leucemia linfocítica crônica é a leucemia adulta mais comum. É caracterizada pela expansão clonal de células B maduras CD5 + no sangue, medula óssea e tecidos linfóides. Objetivos: Avaliar a eficácia e os eventos adversos ao uso do Acalabrutinibe no tratamento de leucemia linfocítica crônica. Materiais e métodos: Trata-se de uma revisão integrativa, em que a questão norteadora foi “O acalabrutinibe é eficaz no tratamento de leucemia linfocítica crônica?”. A busca pelos artigos ocorreu nas principais bases de dados (PubMed e Scielo) a partir dos termos “acalabrutinib” e “chronic lymphocytic leukemia”, combinados entre si por operadores booleanos. Resultados e discussão: Em comparação com o ibrutinibe, o acalabrutinibe é altamente seletivo e caracterizado pela falta de inibição em relação a outras quinases. As comparações de sobrevida global favoreceram a monoterapia com acalabrutinibe e em combinação com obinutuzumabe sobre todos os comparadores. A monoterapia com acalabrutinibe também foi associada a sobrevida livre de progressão estatisticamente melhorada em relação a obinutuzumabe-clorambucil. Conclusão: O acalabrutinib é um tratamento eficaz e seguro da leucemia linfocítica crônica. O acalabrutinibe mais obinutuzumabe ou a monoterapia com acalabrutinibe foram associados a uma eficácia melhorada em relação à imunoquimioterapia padrão.

AVALIAÇÃO DA DISPONIBILIDADE DE MEDICAMENTOS PARA TRATAMENTO DA ENDOMETRIOSE NO SUS EM COMPARAÇÃO COM AS RECOMEDAÇÕES DO MINISTÉRIO DA SAÚDE

Endometriosis affects 7 million women in Brazil, mainly between 25 and 29 years old. This disease occurs when there are parts of the endometrial tissue in extrauterine locations. Its pathophysiological mechanism can be explained by three theories, with retrograde menstruation being the main cause of ectopic implantation of endometrial tissue, which produces local irritation and a series of symptoms. Goals. This article aims to evaluate the treatment for endometriosis available in the National Network of Essential Medicines (RENAME) in comparison with the Clinical Protocol and Therapeutic Guidelines of the Ministry of Health. Methods. This article's methodology is bibliographic research, in which the bibliographic material was based on the use of the Clinical Protocol and Therapeutic Guidelines of the Ministry of Health and the National List of Essential Medicines (RENAME). Results. The 2022 National List of Essential Medicines (RENAME) provides four medicines for the treatment of endometriosis, which are analogues of GnRH and Danazol. While the Clinical Protocol and Therapeutic Guidelines of the Ministry of Health describes six medications as treatment possibilities, being GnRH analogues, progestins, oral contraceptives and Danazol. Conclusion. Given the information collected and the comparisons made, it was possible to identify that the Clinical Protocol and Therapeutic Guidelines of the Ministry of Health on Endometriosis covers a more complete treatment given the many specificities of endometriosis, encompassing treatment for mild and moderate cases with milder adverse effects.A endometriose acomete 7 milhões de mulheres no Brasil, principalmente entre 25 e 29 anos. Essa doença ocorre quando há partes do tecido endometrial em locais extraútero. Seu mecanismo fisiopatológico pode ser explicado por três teorias, sendo a menstruação retrógada a principal causa da implantação do tecido endometrial de maneira ectópica, o que produz irritação local e uma série de sintomas. Objetivos. Esse artigo tem como objetivo avaliar o tratamento para endometriose disponível na Rede Nacional de Medicamentos Essenciais (RENAME) em comparação com o Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde. Métodos. Esse artigo tem como metodologia a pesquisa bibliográfica, em que o material bibliográfico teve como base a utilização do Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde e a Relação Nacional de Medicamentos Essenciais (RENAME). Resultados. A Relação Nacional de Medicamentos Essenciais (RENAME) de 2022 disponibiliza quatro medicamentos para o tratamento da endometriose, que são análogos do GnRH e o Danazol. Enquanto que o Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde descreve seis medicamentos como possibilidades de tratamento, sendo análogos do GnRH, progestágenos, anticoncepcionais orais e o Danazol. Conclusão. Diante das informações coletadas e das comparações realizadas, foi possível identificar que o Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde sobre Endometriose abrange um tratamento mais completo diante de tantas especificidades da endometriose, englobando tratamento para casos leves e moderados com efeitos adversos mais leves

Incidence and characteristics of cesarean deliveries in a public hospital in Paraguay

Objetivo: Verificar la incidencia de cesáreas y parto vaginal en mujeres tratadas en un hospital público en la ciudad de Pedro Juan Caballero (Paraguay) y conocer las indicaciones más frecuentes de operaciones cesáreas. Metodología: El estudio fue descriptivo, retrospectivo y documental, a partir de las informaciones de prontuarios. El lugar de recolección de los datos fue el Hospital Regional de Pedro Juan Caballero, Paraguay. La población escogida para el estudio se constituyó de gestantes a partir de 14 años, en el periodo de junio de 2018 a junio de 2019, totalizando 2.087 prontuarios. Fueron analizados 2087 prontuarios, de los cuales se seleccionaron 200 partos por cesárea 200 prontuarios de partos por cesáreas realizados en este periodo (26,28% del total). Resultados: Fueron registrados 761 cesáreas, que corresponden al 36,28% de los partos y 1326 partos vaginales. La operación cesárea fue más prevalente entre mujeres entre 24-27 años de edad, representando el 24% del total. Entre las indicaciones de la operación cesárea, se observó que 16,5% fueron por una cesárea anterior, 11% por preeclampsia, 10,5% desprendimiento de placenta, 10% por bradicardia fetal y 8,5% por presentación podálica, todas estas indicaciones representaron 56% del total de los partos por cesárea evaluados.  Conclusión: El índice de partos por cesárea fue elevado en el Hospital investigado (36,28%), cuando la OMS establece un índice deseado de hasta 15%. Las indicaciones más frecuentes encontradas en este estudio fueran Cesárea anterior, preeclampsia , desprendimiento de placenta y bradicardia fetal.Objective: To verify the incidence of caesarean and vaginal delivery in women treated in a public hospital in the city of Pedro Juan Caballero - Paraguay and to know the most frequent indications for caesarean operations. Material and methods: The study was descriptive, retrospective, and documentary, based on information from medical records. The data collection place was the Pedro Juan Caballero Regional Hospital, Paraguay. The population chosen for the study consisted of pregnant women from 14 years of age, in the period from June 2018 to June 2019, totaling 2,087 records. 2087 records were analyzed, of which 200 deliveries by caesarean section were selected 200 records of deliveries by caesarean section performed in this period (26.28% of the total). Results: 761 cesarean sections were registered, corresponding to 36.28% of deliveries and 1,326 vaginal deliveries. Cesarean section was more prevalent among women between 24-27 years of age, representing 24% of the total. Among the indications for caesarean section, it was observed that 16.5% were for a previous caesarean section, 11% for preeclampsia, 10.5% placental abruption, 10% for fetal bradycardia, and 8.5% for breech presentation, all These indications represented 56% of the total number of cesarean deliveries evaluated. Conclusion: The cesarean delivery rate was high in the investigated Hospital (36.28%), when the WHO established a desired rate of up to 15%. The most frequent indications found in this study were Cesarean section, Preeclampsia, Placental abruption, and Fetal bradycardia

Os aspectos atuais epidemiológicos e clínicos da Monkeypox: uma revisão de literatura

Neste artigo propomos um estudo que visa entender a fisiopatologia da Varíola dos Macacos, bem como seu quadro clínico e sua epidemiologia atual. Revisão de literatura de caráter exploratório, com uma avaliação de pesquisas e casos da prática clínica, em que se fez uma análise da epidemiologia da Varíola dos Macacos e seu quadro clínico. Foram selecionados 31 estudos para compor essa revisão de literatura. Entre as bases de dados selecionadas estão: PubMed, BVS, Google Scholar e SciELO. A análise das pesquisas mostrou uma ascensão da Monkeypox por todo o mundo após o ano de 2022.  A sintomatologia tem sido muito diversa, tendo como principais sinais e sintomas lesões cutâneas, febre e linfadenopatias. A maioria dos casos não precisou de hospitalização. Contudo, em pacientes imunossuprimidos, crianças e gestantes a infecção se mostrou mais perigosa. A Monkeypox deixou de ser endêmica da África Ocidental no ano de 2022 e vem tomando proporções globais desde então. É de suma importância pesquisas epidemiológicas de rotina para que a doença seja controlada de perto e para que os profissionais da saúde tenham consciência de seu quadro clínico para a adequada notificação da doença