Cloning, characterization and in vitro and in planta expression of a glucanase inhibitor protein (GIP) of Phytophthora cinnamomi.

Oomycetes from the genus Phytophthora are fungus-like plant pathogens that are devastating for agriculture and natural ecosystems. They are able to secrete a glucanase inhibitor protein (GIP) that inhibits the activity of endoglucanases (EGases) involved in defense responses against infection. One of the most widely distributed and aggressive Phytophthora species, with more than 1,000 host plants is P. cinnamomi. In this work we report the sequencing and characterization of a class of GIPs secreted by Phytophthora cinnamomi. The gip gene from P. cinnamomi has a 937 bp ORF encoding a putative peptide of 312 deduced amino acids. The expression of this gene was studied during growth in different carbon sources (glucose, cellulose and sawdust), by RT-qPCR and its level of expression was evaluated at five time points. The highest expression of gip gene occurred in sawdust at 8 h of induction. In vivo infection of C. sativa revealed an increase in gip expression from 12 to 24 h. At 36 h its expression decreased suggesting that a compensatory mechanism must occur in plant.

Answering the Cell Stress Call: Satellite Non-Coding Transcription as a Response Mechanism.

Organisms are often subjected to conditions that promote cellular stress. Cell responses to stress include the activation of pathways to defend against and recover from the stress, or the initiation of programmed cell death to eliminate the damaged cells. One of the processes that can be triggered under stress is the transcription and variation in the number of copies of satellite DNA sequences (satDNA), which are involved in response mechanisms. Satellite DNAs are highly repetitive tandem sequences, mainly located in the centromeric and pericentromeric regions of eukaryotic chromosomes, where they form the constitutive heterochromatin. Satellite non-coding RNAs (satncRNAs) are important regulators of cell processes, and their deregulation has been associated with disease. Also, these transcripts have been associated with stress-response mechanisms in varied eukaryotic species. This review intends to explore the role of satncRNAs when cells are subjected to adverse conditions. Studying satDNA transcription under various stress conditions and deepening our understanding of where and how these sequences are involved could be a key factor in uncovering important facts about the functions of these sequences.

From Policies to Practices: Factors Related to the Use of Inclusive Practices in Portugal.

Inclusion is considered a foundation for quality education, and teachers' inclusive practices are essential for success in mainstream classrooms. Portugal has been making progressive improvements in its policies for inclusive education, although there is little consistency in school practices within or between schools. Moreover, data identifying the personal and career variables relevant to teachers' inclusive practices in Portugal are scarce. Therefore, the purpose of this study was to determine the relationship between teachers' inclusive practices and personal and career-based characteristics, including gender, level of teaching, years of experience, roles performed at school, and perception of inclusive resources. The participants were 924 teachers who worked in private and public schools in Portugal. Regression analysis showed that perceived inclusive resources, level of teaching, and gender predicted variance in inclusive practices. Mean difference analyses revealed that teachers at the lower levels of teaching, females, and teachers reporting more inclusive resources had the highest scores for inclusive practices. These findings are discussed in terms of their practical relevance for inclusive school systems.

Neonatal Glycogen Storage Disease Type IA: A Rare Presentation.

Glucose homeostasis is essential for energy production and the central nervous system function, depending on glycogen metabolism. Glycogen storage diseases (GSD) are caused by enzymatic defects of the glycogen degradation and mainly involve the liver since the inhibition of hepatic glycogen breakdown results in its excessive storage and hepatomegaly. Other findings are hypoglycemia and hyperlactatemia and consequent neurological symptoms. GSD Type Ia is a severe disease with clinical manifestations usually occurring in the first months. Morbidity and mortality are high, when not treated. The patient was a male newborn, with nonconsanguineous couple, born by eutocic delivery and weight 3760 g. On Day 2, weight loss >10% and jaundice were noticed, and physical examination was as normal. The investigation showed low glucose that only respond to iv glucose, metabolic acidosis, hyperlactatemia and elevated liver enzymes. Considering his inherited metabolic disease, he was transferred to the Reference Center. Complementary tests showed hypertriglyceridemia and absence of ketone bodies. Abdominal US revealed a liver in the upper limit of normal. Most likely clinical diagnosis was GSD type Ia, confirmed by genetic test. He needed iv glucose, but then stabilized with formula without galactose, supplemented with dextrin every 2 hours. He is now 7 months old, has flash glucose self-monitoring system, maintaining frequent feedings, with sporadic hypoglycemia with normal physical development and no hepatomegaly. Hypoglycemia and early weight loss in newborns are red flags for metabolic diseases or other conditions. When accompanied by other metabolic findings, such as hyperlactatemia and metabolic acidosis, associated with short fasting periods, glycogen metabolism disorders must be considered. Patients with GSD Type Ia generally appear normal at birth and an early presentation is not frequent within the first hours after birth. Moreover, avoiding fasting and hypoglycemia are of vital importance for better cognitive outcome, global prognosis, and prevention of other metabolic abnormalities.

Leptospira spp. in Free-Ranging Capybaras (Hydrochoerus hydrochaeris) from Midwestern Brazil.

Background: Leptospirosis is a contagious disease that affects domestic and wild animals as well as humans. It is caused by infection with some pathogenic species of the genus Leptospira. In Brazil, studies on leptospirosis in capybaras are scarce or nonexistent in some regions, such as the Federal District. The objective of this study was to analyze the presence of DNA of the agent and/or anti-Leptospira spp. antibodies in capybaras. Materials and Methods: Blood samples were collected from 56 free-living capybaras captured in two different sites in the study region. The samples were submitted to hematology and clinical chemistry tests. To identify Leptospira positive samples, a conventional PCR (cPCR) and analysis of anti-Leptospira spp. antibodies by microscopic agglutination test (MAT) were used. Results: No animal showed cPCR amplification of the Lip32 gene, but 41.1% (23/56) of the animals had anti-Leptospira spp. antibodies on MAT. The serovars present were icterohaemorrhagiae (82.61%), copenhageni (65.22%), grippotyphosa (4.35%), and hardjo (4.35%). In the laboratorial tests, differences (p < 0.05) were observed in the biochemical assays of alkaline phosphatase, creatinine, albumin, and globulin. Although these values differed significantly between groups, they all remained within reference range (excluding albumin), and thus there is not enough to infer that this alteration could be caused by Leptospira infection. Conclusions: cPCR using whole blood samples to evaluate Leptospira spp. infection of free-living capybaras was not an efficient tool. The presence of Leptospira seroreactive capybaras shows that the bacteria are circulating in the urban environment of the Federal District.

Successful application of antimicrobial photodynamic and photobiomodulation therapies for controlling osteoradionecrosis and xerostomia after laryngeal carcinoma treatment: A case report of full oral rehabilitation.

We present a clinical case where a conservative treatment based on photonics [antimicrobial Photodynamic Therapy (aPDT) associated to Photobiomodulation therapy (PBMT)] of a patient with osteoradionecrosis (ORN) due to radiotherapy treatment of a laryngeal cancer. As a result of this combined treatment the ORN was controlled (e.g. the necrosis, infection and suppuration disappeared). Moreover, the symptoms reported by the patient (pain and xerostomia) also diminished along with the repair of oral mucosa. In future cases this combined therapy (e.g. PBM therapy and the aPDT) will be further examined.

[Evaluation of sensitization to Der p 1 and Der p 2 in a pediatric population of the North of Portugal]. / Evaluación de la sensibilización a Der p 1 y Der p 2 en una población pediátrica del Norte de Portugal.

INTRODUCTION: In Portugal, data on the role of Der p 1 and Der p 2 in patients with house dust mite (HDM) allergy are scarce. Allergen-specific immunotherapy (sIT) is the only treatment that improves symptoms, reduces the need for pharmacological therapy and modifies the natural history of the disease. With this study, the authors aim to understand the local epidemiology and to clarify if the molecular assay of major allergens is advantageous in deciding and/or modifying the decision to initiate sIT in children with clinical indication which are sensitized to Dermatophagoides pteronyssinus. METHODS: Retrospective study with analysis of patients with asthma and/or rhinitis. STUDY PERIOD: January/2013-December/2016. INCLUSION CRITERIA: 1) positive prick-test to Dermatophagoides pteronyssinus; and 2) clinically relevant disease under treatment. Assay Der p 1 and Der p 2 values ≥0.35 kUA/L were considered positive. Statistical significance was set at P<.05. RESULTS: The clinical files of 279 patients. Mean ages 9.55 years (min.4-max.17). Asthma was present in 199 children (71.3%) and rhinitis in 245 (87.8%). Der p 1 and Der p 2 was <0.35kUA/L in 29 (10,4%) patients. The value of Der p 1/Der p 2 correlated with the size of the prick-test papule, the value of the eosinophils and the total IgE. CONCLUSIONS: Der p 1 and Der p 2 are dominant allergens in our population and there may be benefits in determining these molecular allergen levels in patients with a positive prick-test and a clinical indication for sIT prior to a decision of initiating sIT or not.

[Burkitt's lymphoma]. / Linfoma de Burkitt.

BACKGROUND: Burkitt's lymphoma (BL) is a highly aggressive B-cell neoplasm characterized by the translocation and deregulation of the c-myc gene on chromosome 8. Three distinct clinical forms of BL are recognized: endemic, sporadic, and human immunodeficiency-associated. BL is a rapidly growing neoplasm requiring immediate diagnosis and treatment. AIM: We described and analyzed our experience with Burkitt's lymphoma (BL) diagnosis, treatment and outcome, during ten years. MATERIALS AND METHODS: Retrospective study; clinical records of all children admitted with BL between 1st January 1998 and 31st December 2008 were analyzed. The following data were collected: age at admission, gender, clinical presentation, and time elapsed from initial complaints until diagnosis, disease localization, treatment and evolution. RESULTS: During the time period 21 children were admitted (19 boys), seven (33.3%) of which were diagnosed in 2008. The median age at diagnosis was seven years with a mean delay to diagnosis of 20,8 days (range 2-125 days). The most frequent site of primitive tumour was the abdomen (13), followed by tonsils (three), orbit (one), central nervous system CNS (two), tongue (one) and nasopharynx (one). The majority of patients in our study were presenting with a painfull abdominal mass. Diagnosis was established through tumour biopsy in 17 children, three by paracentesis or toracocentesis and one case was diagnosed only by genetic tests to the bone marrow. Genetic tests were positive in 11 patients. According to the Murphy classification, there were three stage II, 12 stage III and six stage IV tumours; 29% and 19% had bone marrow and central nervous system involvement, respectively. One child relapsed and was successfully treated with Rituximab® and autologous stem cell transplantation. The overall survival rate was 100%.

A implementação de decisões vocacionais: Revisão da literatura / Implementation of career decisions: Literature review / La implementación de decisiones vocacionales: Revisión de la bibliografía

A decisão ou escolha vocacional constitui um tópico central da Psicologia Vocacional. Trabalhos recentes apontam para a necessidade de aprofundamento da execução ou implementação de objetivos e planos vocacionais pelos clientes, tendo em conta as suas consequências em termos de satisfação, sucesso e adaptabilidade nas escolhas realizadas. Contudo, este aspeto é muitas vezes negligenciado na investigação e nas intervenções de carreira. Ao longo deste artigo, chamamos a atenção para a importância da fase de implementação das escolhas, nos processos de tomada de decisão vocacional, revendo a teoria e os estudos mais dedicados a este tópico. Finalmente apontam-se algumas implicações para a prática e futura investigação neste âmbito.

Career decision making or career choice is a central topic in Vocational Psychology. Recent work has acknowleged the need to deepen career goals and plan execution or implementation by the subjects, taking into account its consequences for adaptability to the career choice, and satisfaction and success with the career. Nevertheless, this aspect is often neglected in research and career interventions. Reviewing the theory and studies more focused on this topic, we draw attention to the importance of the implementation phase in career decision-making processes. Finally, some implications for practice and future research in this realm are pointed out.

La decisión o la elección vocacional constituyen un tema central de la Psicología Vocacional. Trabajos recientes apuntan a la necesidad de profundización de la ejecución o implementación de objetivos y planes vocacionales por los clientes, teniendo en cuenta sus consecuencias en términos de satisfacción, éxito y adaptabilidad en las elecciones realizadas. Sin embargo, este aspecto es muchas veces descuidado en la investigación y en las intervenciones de carrera. A lo largo de este artículo llamamos la atención sobre la importancia de la fase de implementación de las elecciones, en los procesos de toma de decisión vocacional, reviendo la teoría y los estudios más dedicados a este tema. Finalmente, se señalan algunas implicaciones para la práctica y futura investigación en este ámbito.

Temporalidade de amostras biológicas e de produtos no Instituto Adolfo Lutz / Temporality of biological samples and products at the Instituto Adolfo Lutz

O Instituto Adolfo Lutz (IAL), instituição centenária na prestação de serviços, pesquisa e ensino para a solução de agravos em saúde, tem constituído um valioso repositório de materiais biológicos empregado sem projetos científicos e de inovação tecnológica, bem como lhe cabe a guarda de produtos de análise fiscal ou pericial. Por iniciativa da administração central, criou-se um grupo técnico para elaborar critérios de temporalidade das amostras biológicas e dos produtos armazenados frente à legislação e às necessidades deste repositório institucional. Foram definidos os diversos tipos de amostras e, para cada modalidade, foram relacionados o estado físico, a finalidade – rotina ou pesquisa –, e as condições de armazenamento. Formulários específicos referentes às amostras ou produtos foram preenchidos pelos profissionais das diferentes áreas dos Laboratórios Central e Regionais. Os critérios de temporalidade das amostras biológicas e produtos foram propostos e apresentados ao conselho técnico e administrativo da instituição, o que resultou em publicação oficial em forma de Portaria da Diretoria Geral do IAL.

Isolation and characterization by asymmetric PCR of the ENDO1 gene for glucan endo-1, 3-β-D-glucosidase in Phytophthora cinnamomi associated with the ink disease of Castanea sativa Mill

Ink disease is one of the most destructive diseases in Castanea sativa. The most common symptoms are root necrosies and a reduction in root growth, which invariably lead to the death of the trees. Phytophthora cinnamomi is an oomycete associated with this disease whose life cycle develops integrally in the soil. In the present work, was a fragment with 1231bp of the glucan endo-1,3-β-D-glucosidase gene obtained by amplification, using conserved primers and the full-length gene sequence by flanking this known sequence by asymmetric PCR. This fragment was obtained from genomic DNA of Phytophthora cinnamomi isolated in the European Regions of Castilla-Leon (Spain) and Trás-os-Montes (Portugal) and associated with the ink disease of Castanea sativa Mill.

Doença da tinta é um das doenças mais destrutivas em Castanea sativa. Os sintomas mais comuns são necroses e uma redução em crescimento da raiz que invariavelmente leva à morte das plantas. Phytophthora cinnamomi é o oomycete associado a esta doença cujo ciclo de vida acontece integralmente no solo. Foi obtido um fragmento com 1231pb do gene glucan endo-1,3-β-D-glucosidase por amplificação usando oligonucleotidos conservados e a sequência completa do gene foi obtido flanqueando esta sequência conhecida por PCR assimétrico. Este fragmento foi obtido de ADN genómico de Phytophthora cinnamomi isolado por nós nas Regiões Europeias de Castilla-Léon (Espanha) e Trás-os-Montes (Portugal) e associado à doença da tinta da Castanea sativa Mill.

From suspicion to action: the chemical conjunctivitis and silver nitrate connexion example in Brazilian hospitals.

BACKGROUND: During the 20th century, silver nitrate (SN) eye drops instillation to newborns had been the best prophylaxis against ophthalmia neonatorum (ON) caused by Neisseria gonorrheae, the most frequent cause of ocular infections leading to blindness. At present, this treatment has been questioned because there is a growing prevalence of other pathogens such as Chlamydia trachomatis, and SN is associated with chemical conjunctivitis (ChC). In addition, SN could present some conservation problems in tropical climates. Among other alternative drugs, 2.5% povidone-iodine has a proven efficacy, not only against Neisseria, but also against Chlamydia, has no conservation problems, has not been associated with ChC and is cheap. METHODS: The recently created Setor de Farmacovigilãncia (SF) of the São Paulo State in Brazil has created a pharmacovigilance network of 11 big public hospitals. During a periodical signal searching process, the SF found a cluster of 33 ChC reports from one of the network hospitals. RESULTS: The problem was discussed with the remaining participant hospitals and this signal was used as a way to strengthen the network. Thirteen months later, 622 ChC reports were received from six hospitals. DISCUSSION: Thus, this well-known side-effect in the literature was highlighted as a 'real' problem in Brazil, and some participant hospitals began a discussion period together with the delivery and newborn care professionals in order to switch SN by povidone-iodine. This is an example of both, how a simple pharmacovigilance exercise could improve the implication of health professionals with their own therapeutic problems and how a pharmacovigilance network could be strengthened.

Influência de pais nas escolhas de carreira dos filhos: visão de diferentes atores / Parental influence on their children’s career choice: a view of different actors / Influencia de padres en las elecciones de carrera de los hijos: visión de diferentes actores

Este estudo tem como objectivo analisar as perspectivas de pais, estudantes, professores e profissionais de orientação acerca do papel dos pais na implementação de escolhas de carreira dos seus filhos, à entrada no ensino secundário. Através do método de grounded theory foram investigadas as perspectivas de um total de 119 participantes (16 pais, 46 alunos, 34 professores e 23 profissionais de orientação) com recurso a um questionário de respostas abertas. Foram identificados os processos através dos quais os pais influenciam as escolhas de carreira assim como os efeitos desejáveis dessa mesma influência. Estes dados apontam a necessidade de expandir a intervenção vocacional, contemplando os diversos contextos de vida e o seu papel nas decisões de carreira.

This study aimed at analyzing the views of parents, students, teachers and vocational counsellors about the parents’ role in the implementation of their children’s career choice when starting high school. Based on the “grounded theory” method, the perspectives of a total of 119 participants (16 parents, 46 students, 34 teachers and 23 career counsellors) were investigated by means of an open question questionnaire. The processes of parental influence as well as the consequences of that influence were identified. The data indicated the need for expanding vocational interventions, taking into consideration the contexts of life and their role in decision making.

Este estudio tiene como objetivo analizar las perspectivas de padres, estudiantes, profesores y profesionales de orientación acerca del papel de los padres en la implementación de elección de carrera de sus hijos, al entrar en la enseñanza secundaria. Mediante el método de grounded theory se investigaron las perspectivas de un total de 119 participantes (16 padres, 46 alumnos, 34 profesores y 23 profesionales de orientación) con el recurso de un cuestionario de respuestas abiertas. Se identificaron los procesos por medio de los cuales los padres influencian las elecciones de carrera así como los efectos deseables de esa misma influencia. Estos datos apuntan la necesidad de expandir la intervención vocacional, contemplando los diversos contextos de vida y su papel en las decisiones de carrera.

Parâmetros para seleção de pessoal através de concurso público: o caso INCA / Parameters for personnel selection through open competition: the case INCA

Na administração pública brasileira a regulamentação em vigor para a realização do processo de ingresso de pessoal no serviço público prioriza os níveis de conhecimentos e habilidades dos candidatos, tradicionalmente avaliados através de provas escritas e prova de títulos, reforçando a dimensão acadêmica e cognitiva do processo.A avaliação dos aspectos relacionados às atitudes, a conduta pessoal e interpessoal dos futuros servidores não são considerados neste processo, que se baseia no modelo clássico weberiano, privilegiando os princípios da impessoalidade e da competência técnica. Especialmente, na perspectiva da gestão do trabalho na área de saúde, o resultado destes processos seletivos tende agregar a instituição, profissionais com dificuldades de adaptação às rotinas laborativas, produtividade aquém do desejado e com elevados índices de doenças profissionais que acabam por comprometer a qualidade da atenção prestada ao paciente. O objetivo deste trabalho foi, a partir da análise dos processos de seleção utilizados pelo INCA e instituições congêneres, identificar, procedimentos que pudessem contribuir para o aperfeiçoamento e para a melhoria da qualidade da seleção dos profissionais que ingressam nas instituições públicas de saúde, particularmente, nas de alta complexidade, através da incorporação no processo avaliativo de procedimentos que permitirão a análise de outras competências além das competências técnicas e de formação acadêmica...

Parâmetros para seleção de pessoal através de concurso público: o caso INCA

Na administração pública brasileira a regulamentação em vigor para a realização doprocesso de ingresso de pessoal no serviço público prioriza os níveis de conhecimentos e habilidades dos candidatos, tradicionalmente avaliados através de provas escritas e prova de títulos, reforçando a dimensão acadêmica e cognitiva do processo.A avaliação dos aspectos relacionados às atitudes, a conduta pessoal e interpessoal dos futuros servidores não são considerados neste processo, que se baseia no modelo clássico weberiano, privilegiando os princípios da impessoalidade e da competência técnica. Especialmente, na perspectiva da gestão do trabalho na área de saúde, o resultado destes processos seletivos tende agregar a instituição, profissionais com dificuldades de adaptação às rotinas laborativas, produtividade aquém do desejado e com elevados índices de doenças profissionais que acabam por comprometer a qualidade da atenção prestada ao paciente. O objetivo deste trabalho foi, a partir da análise dos processos de seleção utilizados pelo INCA e instituições congêneres, identificar, procedimentos que pudessem contribuir para o aperfeiçoamento e para a melhoria da qualidade da seleção dos profissionais que ingressam nas instituições públicas de saúde, particularmente, nas de alta mplexidade,através da incorporação no processo avaliativo de procedimentos que permitirão a análise de outras competências além das competências técnicas e de formação acadêmica. Tendo como base teórica a discussão do modelo burocrático da administração pública e o modelo de competências como uma referência para a construção dos perfis profissionais, optou-se por um estudo de caso exploratório que envolveu gestores de enfermagem do INCA/Hospital do Câncer I e de um Hospital privado de referência na áreaoncológica. Como resultado desse estudo, podemos comprovar a relevância da avaliação dos aspectos comportamentais nos processos seletivos em geral como uma forma de melhorar a qualidade da assistência e a adaptação dos servidores às suas funções, bem como demonstrar a necessidade de se buscar alternativas legais e metodológicas para viabilizar um processo seletivo adequado às necessidades dos serviços

In the Brazilian public administration with the rules for carrying out the process of joining the public service staff in priority levels of knowledge and skills of candidates traditionally assessed through written tests and proof of title, increasing the size of the academic and cognitive process. The evaluation of aspects related to attitudes, interpersonal and personal conduct of future servers are not considered in this process, which is based on the classic Weberian model, emphasizing the principles of impartiality and technical competence. Especially in view of work management in health care, the result of this selection process tends to add professional institution with difficulties in adapting to the routines to work, with lower than expected productivity and high rates of diseases that ultimately compromise the quality of attention to the patient. This study was based on the analysis of the selection process used by INCA and similar institutions, identify procedures that could contribute to the improvement and to improve the quality of the selection of the professionals who join the public health institutions, particularly the highly complex through incorporation into the assessment process for procedures that allow the analysis of other skills besides the technical skills and academic training. Based on the theoretical discussion of the bureaucratic model of public administration and the competency model as a reference for the construction of professional profiles, we chose an exploratory case study involving nursing managers INCA / Hospital do Cancer I and a Private hospital reference in oncology. As a result of this study, we confirmed the relevance of the assessment of behavioral aspects in the selection processes in general as a way to improve the quality of care and the response of servers to their functions, as well as demonstrating the need to seek alternatives to enable legal and methodological an appropriate selection process service needs

Perfil da automedicaçäo no Brasil / Aspects of self-medication in Brazil

Os dados apresentados fazem parte de um estudo multicêntrico sobre automedicaçäo na América Latina realizado pela Organizaçäo Mundial de Saúde (OMS). Objetivou-se traçar um perfil da automedicaçäo através da análise da procura de medicamentos em farmácias sem prescriçäo médica ou aconselhamento do farmacêutico/balconista. As especialidades farmacêuticas foram classificadas pelo código "Anatomical Therapeutical Classification" e analisadas sob quatro aspectos qualitativos: valor intrínseco, essencialidade (lista da OMS e Relaçäo Nacional de Medicamentos Essenciais (RENAME), combinaçäo em dose fixa e necessidade de prescriçäo médica. Foram solicitadas 5.332 especialidades farmacêuticas (785 diferentes princípios ativos), sendo 49,5 por cento combinaçöes em doses fixas, 53,o por cento de valor intrínseco näo elevado, 44,1 por cento sujeitos a prescriçäo médica, 71,0 por cento näo essenciais e 40,0 por cento baseados em prescrições médicas anteriores. Os medicamentos mais solicitados foram analgésicos (17,3 por cento), descongestionantes nasais (7,0 por cento), antiinflamatório/antireumático e antiinfecciosos de uso sistêmico, ambos com 5,6 por cento. Os dados sugerem que a automedicaçäo no Brasil reflete as carências e hábitos da populaçäo, é consideravelmente influenciada pela prescriçäo médica e tem a sua qualidade prejudicada pela baixa seletividade do mercado farmacêutico.