Characterization of insect bite hypersensitivity in a population of Lusitano horses : contribution for future implementation of skin prick tests (SPT) in IBH diagnosis

Tese especialmente elaborada para obtenção do grau de Doutor em Ciências Veterinárias na especialidade ClínicaInsect Bite Hypersensitivity (IBH) is a recurrent seasonal pruritic dermatitis affecting many horses worldwide. It is mainly a type I hypersensitivity, but type IV may also occur, to allergens present in the saliva of Culicoides spp. It is a multifactorial disease affecting different breeds, with a variable prevalence. Treatment options are very limited, but being an allergic disease IgE-mediated, there is the possibility of developing specific immunotherapy. This study aimed to characterize IBH in Lusitano horses living in Portugal mainland, through a case control study involving 30 IBH-affected animals and 30 healthy controls. Questionnaires were performed for all the horses involved in the study in order to characterize the studied population. In vivo allergen testing was evaluated by performing skin tests, both skin prick tests (SPT) and intradermal tests (IDT), using 14 specific allergens, including 13 different recombinant (r-) proteins from Culicoides nubeculosus (Cul n) or Culicoides obsoletus (Cul o) salivary glands (termed Cul n 1 to Cul n 11, Cul o 1P and Cul o 2P) as well as Cul n whole body extract (WBE). Moreover, a cluster of 12 of these horses, 6 IBH-affected and 6 from the control group, were also tested with allergens produced in insect cells (Cul n 3Bac, Cul n 4Bac) and barley (Cul n 3 Bar, Cul n 4Bar) as well as Cul o 3 and Cul o whole body extract (WBE). Furthermore, in vitro diagnostic tests have been performed, namely, serum IgEs that were measured by ELISA for the allergens Cul n 3, 4, 9, 10 and Cul o 2, 3, as well as Cul o1P and Cul o2P and in vitro sulfidoleukotriene (sLT) release assay which were carried out with Cul n WBE and Cul o WBE. In our study SPTs presented a higher discriminatory diagnostic potential than IDTs, and should be preferred, being a potential breakthrough in the establishment of more suitable allergen avoidance measures in IBH diagnosis. Regarding the in vitro tests, even though serology measurement of specific IgEs showed that IBH-affected horses had higher serum IgE levels for the significant allergens, sLT release assay performed best. It was also possible to study and identify Culicoides spp found in the stud farms, which may be related to IBH in the studied horses. The most frequently found were Obsoletus group species, C. nubeculosus and C. imicola. This study contributed to improve IBH diagnosis, representing a step forward for the future implementation of locally relevant diagnostic allergen panels and eventually for the establishment of patient tailored, component resolved specific immunotherapyRESUMO - Hipersensibilidade à picada de insetos (HPI) em equinos Puro-Sangue Lusitano: contribuição para o desenvolvimento de testes cutâneos por picada (TCP) no diagnóstico da HPI - A Hipersensibilidade à Picada de Insetos (HPI) é uma dermatite pruriginosa sazonal, que afeta um elevado número de cavalos a nível mundial. É uma reação de hipersensibilidade tipo I e IV a alergénios presentes na saliva Culicoides spp. É uma doença multifatorial, que afeta diferentes raças com uma prevalência variável. O tratamento é limitado, mas sendo uma doença alérgica imunomediada por IgEs, há a possibilidade de se desenvolver imunoterapia específica. O trabalho apresentado visou a caracterização da HPI em cavalos Lusitanos em Portugal continental, através de um estudo de caso controlo envolvendo 30 animais com HPI e 30 animais saudáveis. A população de cavalos estudados foi caracterizada pela avaliação de questionários individuais. Testes intradérmicos (TID) e cutâneos por picada (TCP) foram efetuados, sendo testados 14 alergénios específicos, 13 proteínas recombinantes de Culicoides nubeculosus (Cul n) e Culicoides obsoletus (Cul o) designadas de Cul n 1 a Cul n 11, Cul o 1P and Cul o 2P, e extrato de Cul n (WBE). Adicionalmente 12 destes 30 cavalos, 6 teste e 6 controlo, foram testados com alergénios produzidos em células de insetos (Cul n 3Bac, Cul n 4Bac) e cevada (Cul n 3 Bar, Cul n 4Bar) bem como Cul o 3 e Cul o WBE. Foram ainda realizados testes in vitro, nomeadamente determinação sorológica de IgEs específicas por ELISA, para os alergénios Cul n 3, 4, 9, 10, Cul o 2, 3, Cul o1P e Cul o2P, e determinação de sulfitoleucotrienos (sLT) produzidos por leucócitos do sangue periférico (CAST), quando estimulados por Cul n WBE e Cul o WBE. O nosso estudo indicou que os TCP apresentam uma matriz de discriminação superior aos TID, sendo por isso recomendados, podendo ser um potencial avanço no estabelecimento de testes de diagnóstico mais adequados. Relativamente aos testes in vitro, embora a determinação sorológica de IgEs específicas demonstrasse que os cavalos afetados tinham níveis séricos de IgEs mais elevados para os alergénios significativos, o teste de libertação de sulfidoleucotrienos (sLT) teve melhor desempenho. Além disso foi possível estudar e identificar as espécies de culicóides encontradas em coudelarias, que podem estar relacionadas com a HPI nos equinos estudados, sendo as espécies do grupo Obsoletus, C. nubeculosus e C. imicola as mais prevalentes. Este estudo visa contribuir para a melhoria de métodos de diagnóstico da HPI, representando um avanço para a futura implementação de painéis de diagnóstico de alergénios específicos e, eventualmente, para a futura implementação de imunoterapia específicaN/

Comparison of Skin Prick Tests (SPT), Intradermal Tests (IDT) and In Vitro Tests in the Characterization of Insect Bite Hypersensitivity (IBH) in a Population of Lusitano Horses: Contribution for Future Implementation of SPT in IBH Diagnosis.

Thirty controls (C) and 30 IBH-affected (T) Lusitano horses were evaluated. T horses were included based on anamnesis and physical examination, supported by questionnaires. All horses were submitted to skin tests, Intrademal (IDT) and Skin Prick Tests (SPT), on the neck with 14 specific allergens, 13 recombinant proteins (r-proteins) from Culicoides nubeculosus (Cul n) and Culicoides obsoletus (Cul o) salivary glands and Culicoides nubeculosus Whole Body Extract (Cul n WBE). Addicionally, a cluster of six T and six C horses were also tested with Cul n 3 and Cul n 4 produced in insect cells and barley, as well as E. coli produced Cul o 3 and Cul o WBE. Allergen concentrations were 10 µg/mL for IDT and 100 µg/mL for SPT, and wheal diameters assessed at 20 min, 6 and 48 h. IDTs were considered positive when wheal diameter was ≥50% of the histamine wheal and SPT's ≥ 0.9 cm. In vitro tests, allergen-specific serum IgE and sulfidoleukotriene (sLT) release assay were also carried out. Results showed that Cul n WBE, Cul n 7, 8, 9, Cul o1P and Cul o 2P were the best performing allergens for SPTs (p ≤ 0.0001) for the 1st allergen panel and Cul o WBE, Cul n 3 Bar and Cul n 4 Bac (p ≤ 0.05) for the 2nd, presenting a higher discriminatory diagnostic potential than IDTs, at a concentration of 100 µg/mL, with readings assessed at 20 min. Regarding in vitro tests overall, the sLT release assay performed best

Analysis of the particularities of Lusophone participation in a Nursing Knowledge Network

Objetivo Descrever o exercício conceitual de reflexão sobre as possibilidades e particularidades da participação das Escolas de Enfermagem e Faculdades de Enfermagem lusófonas na Rede de Conhecimentos em Enfermagem. Método Análise das informações obtidas em um levantamento de recursos institucionais de acordo com o marco conceitual proposto por Prug e Prusak sobre rede de conhecimentos. A ponderação de aspectos positivos e negativos - analisando o aprendizado com as informações - levou em consideração as possíveis soluções para um plano de ação. Resultados Tanto nas ações institucionais para suportar a pesquisa em Enfermagem como nos benefícios almejados com a participação na Rede existe o interesse na internacionalização da pesquisa e no trabalho colaborativo. Com a ampliação dos horizontes da ciência da Enfermagem lusófona, este trabalho visa aumentar o impacto da pesquisa e agilizar a divulgação e a utilização dos resultados, tanto na educação como na clínica. Conclusão e Implicações para a prática A participação das referidas instituições oferece inúmeras possibilidades de demonstrar originalidade, criatividade e perícia de sua prática docente e de pesquisa, favorecendo o compartilhamento de ideias e práticas. A prática de produção científica, por docentes e discentes, pode ser aprimorada pelo refinamento de modos de pensar, criar, produzir e disseminar.Objective To describe the conceptual exercise of reflecting on the possibilities and particularities of the participation of Lusophone schools of nursing in the Nursing Knowledge Network. Method An analysis was conducted using information obtained from an environmental scan of institutional resources following the conceptual framework by Prug and Prusak on the knowledge networks. The learnings reported in the analysis are based on the collected information and reflections on the positive and negative aspects of participation, while proposing possible solutions for an action plan. Results There is interest in the internationalization of research and collaborative work both as institutional actions to support nursing research and potential benefits due to participation in the Network. The collaborative work has potential to increase the impact of research, expedite dissemination and use of results both in education and in clinical practice, broadening the horizons of Lusophone nursing science. Conclusion and Implications for practice Participation of these institutions in the Network offers numerous possibilities to demonstrate the originality, creativity and expertise of their teaching and research practice, encouraging the sharing of ideas and practices. The practice of scientific production in all its scenarios by educators and students can be improved through refined ways of thinking, creating, producing, and disseminating knowledge.info:eu-repo/semantics/publishedVersio

Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazili an centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome83289298CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO GRANDE DO SUL - FAPERGSSem informaçãoSem informação2006/60402-1; 2010/51547-1; 2013/01476-9; 2014/06570-6; 2009/50575-4; 2010/51546-5; 2012/21942-116/2551-0000482-

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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