CARATkids questionnaire development process

Introdução: A asma e a rinite alérgica (ARA) são doenças inflamatórias crónicas das vias aéreas que frequentemente coexistem. O questionário para avaliação do controlo da asma e da rinite alérgica (CARAT) encontra‑se validado para o adulto. O objectivo foi desenvolver o questionário CARATkids para crianças entre os 4 e os 12 anos de idade, com o diagnóstico médico de ARA. Este trabalho pretende descrever o processo do desenvolvimento do questionário. Métodos: O desenvolvimento do questionário foi estruturado em três fases: 1) revisão da literatura sobre questionários pediátricos existentes; 2) realização de reuniões de consenso que permitiu a criação de uma versão preliminar do CARATkids, com duas versões (crianças e pais), composto por 17 itens. Para as crianças, as perguntas foram acompanhadas por ilustrações para cada questão, com formato de resposta dicotómica (sim / não). Para os pais o questionário manteve o formato de CARAT17, com questões com 4 pontos de Likert e outras questões com opção de resposta com escala dicotómica; 3) realização de um estudo transversal através de entrevistas cognitivas efectuadas a 29 crianças e respectivos pais. Resultados: Foram incluídas 29 crianças (11 do sexo feminino) e respectivos pais. A mediana de idades (P25‑P75) foi de 8 (6‑10) anos. As crianças com 4 a 5 anos não sabiam ler o questionário; com 6‑8 eram capazes de ler / compreender as perguntas, embora referindo dificuldades para algumas expressões. As crianças com mais de 9 anos consideraram o questionário muito simples e claro. O grau de concordância entre as crianças e seus pais foi de 61%, tendo ambos considerado as ilustrações muito claras e esclarecedoras quanto aos conceitos subjacentes. Os pais concordaram que a versão destinada aos pais estava muito completa, considerando a versão da criança muito clara e adequada. Consideraram ainda a escala dicotómica como mais apropriada para crianças, em comparação com a escala de Likert do questionário aplicado aos pais. As expressões identificadas como de difícil entendimento foram alteradas. Conclusão: O questionário CARATkids é o primeiro que avalia o controlo da asma e da rinite na criança. Os testes cognitivos demonstraram a sua aplicabilidade dos 6 aos 12 anos de idade.info:eu-repo/semantics/publishedVersio

Development Process and Cognitive Testing of CARATkids - Control of Allergic Rhinitis and Asthma Test for Children

Background: Allergic rhinitis and asthma (ARA) are chronic inflammatory diseases of the airways that often coexist in children. The only tool to assess the ARA control, the Control of Allergic Rhinitis and Asthma Test (CARAT) is to be used by adults. We aimed to develop the Pediatric version of Control of Allergic Rhinitis and Asthma Test (CARATkids) and to test its comprehensibility in children with 4 to 12 years of age. Methods: The questionnaire development included a literature review of pediatric questionnaires on asthma and/or rhinitis control and two consensus meetings of a multidisciplinary group. Cognitive testing was carried out in a cross-sectional qualitative study using cognitive interviews. Results: Four questionnaires to assess asthma and none to assess rhinitis control in children were identified. The multidisciplinary group produced a questionnaire version for children with 17 questions with illustrations and dichotomous (yes/no) response format. The version for caregivers had 4-points and dichotomous scales. Twenty-nine children, 4 to 12 years old, and their caregivers were interviewed. Only children over 6 years old could adequately answer the questionnaire. A few words/expressions were not fully understood by children of 6 to 8 years old. The drawings illustrating the questions were considered helpful by children and caregivers. Caregivers considered the questionnaire complete and clear and preferred dichotomous over the 4-points scales. The proportion of agreement between children and their caregivers was 61%. The words/expressions that were difficult to understand were amended. Conclusion: CARATkids, the first questionnaire to assess a child’s asthma and rhinitis control was developed and its content validity was assured. Cognitive testing showed that CARATKids is well-understood by children 6 to 12 years old. The questionnaire’s measurement properties can now be assessed in a validation study

Activity of the antiarrhythmic drug amiodarone against Leishmania (L.) infantum: an in vitro and in vivo approach

<div><p>Abstract Background: Considering the high toxicity and limited therapies available for treating visceral leishmaniasis (VL), the drug repositioning approach represents a faster way to deliver new therapies to the market. Methods: In this study, we described for the first time the activity of a potent antiarrhythmic, amiodarone (AMD), against L. (L.)infantum and its in vitro and in vivo activity. Results: The evaluation against promastigotes has shown that amiodarone presents leishmanicidal effect against the extracellular form, with an IC50 value of 10 μM. The activity was even greater against amastigotes in comparison with promastigotes with an IC50 value of 0.5 μM. The selectivity index in relation to the intracellular form demonstrated that the antiparasitic activity was approximately 56 times higher than its toxicity to mammalian cells. Investigation of the in vivo AMD activity in the L. infantum-infected hamster model showed that 51 days after the initial infection, amiodarone was unable to reduce the parasite burden in the spleen and liver when treated for 10 consecutive days, intraperitoneally, at 50 mg/kg/day, as determined by qPCR. Although not statistically significant, AMD was able to reduce the parasite burden by 20% in the liver when treated for 10 consecutive days, orally, at 100 mg/kg/day; no reduction in the spleen was found by qPCR. Conclusions: Our findings may help further drug design studies seeking new AMD derivatives that may provide new candidates with an in vitro selectivity close to or even greater than that observed in the prototype delivering effectiveness in the experimental model of VL.</p></div

Patterns of sediment dispersion coastwise the State of Bahia - Brazil

Using the average directions of the main wave-fronts which approach the coast of Bahia State - coinciding with that of the main wind occurring in the area - and of their periods, we define a wave climate model based on the construction of refraction diagrams. The resulting model of sediment transport was able to reproduce, in a general way, the sediment dispersion patterns furnished by geomorphic indicators of the littoral drift. These dispersion patterns control the generation of different types of sediment accumulations and of coastal stretches under erosion. We demonstrate that the presence of the Abrolhos and Corumbaú Point coral reefs is an important factor controlling the sediment dispersion patterns, since them act as a large protection against the waves action

Phosphorylation Modulates Clearance of Alpha-Synuclein Inclusions in a Yeast Model of Parkinson's Disease

Alpha-synuclein (aSyn) is the main component of proteinaceous inclusions known as Lewy bodies (LBs), the typical pathological hallmark of Parkinson’s disease (PD) and other synucleinopathies. Although aSyn is phosphorylated at low levels under physiological conditions, it is estimated that ,90% of aSyn in LBs is phosphorylated at S129 (pS129). Nevertheless, the significance of pS129 in the biology of aSyn and in PD pathogenesis is still controversial. Here, we harnessed the power of budding yeast in order to assess the implications of phosphorylation on aSyn cytotoxicity, aggregation and sub-cellular distribution. We found that aSyn is phosphorylated on S129 by endogenous kinases. Interestingly, phosphorylation reduced aSyn toxicity and the percentage of cells with cytosolic inclusions, in comparison to cells expressing mutant forms of aSyn (S129A or S129G) that mimic the unphosphorylated form of aSyn. Using highresolution 4D imaging and fluorescence recovery after photobleaching (FRAP) in live cells, we compared the dynamics of WT and S129A mutant aSyn. While WT aSyn inclusions were very homogeneous, inclusions formed by S129A aSyn were larger and showed FRAP heterogeneity. Upon blockade of aSyn expression, cells were able to clear the inclusions formed by WT aSyn. However, this process was much slower for the inclusions formed by S129A aSyn. Interestingly, whereas the accumulation of WT aSyn led to a marked induction of autophagy, cells expressing the S129A mutant failed to activate this protein quality control pathway. The finding that the phosphorylation state of aSyn on S129 can alter the ability of cells to clear aSyn inclusions provides important insight into the role that this posttranslational modification may have in the pathogenesis of PD and other synucleinopathies, opening novel avenues for investigating the molecular basis of these disorders and for the development of therapeutic strategies.peerReviewe