Browsing by Issue Date, starting with "2020-06-05"
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- Natural compounds with the capacity to reactivate the gene of gamma-globin and induction of fetal hemoglobin - In vitro testPublication . Matos, Elisabete Cristina Conceição de; Brito, Miguel; Ribeiro, Edna Soraia Gregórioβ-hemoglobinopathies are the most common recessive genetic diseases worldwide. Currently available treatments for these disorders are expensive and associated with severe side effects. Pharmacological reactivation of Fetal Hemoglobin (HbF) is seen as a promising therapeutic strategy. Hydroxyurea (HU), a potent ribonucleotide reductase inhibitor, is the only Food and Drug Administration (FDA) approved HbF inducing agent. However, its cytotoxicity, potential carcinogenicity and variable clinical effects limit severely its use. Identification of novel agents, with higher HbF inducing activity, lower cytotoxicity and available in low-income countries, such as natural compounds, has become a great challenge today. Here, we performed an assessment of potential transcriptional effects induced by two natural bioactive compounds, namely Genistein (GN) a naturally occurring flavonoid found in soybean and soy derivates and Epigallocatechin-3-gallate (EGCG) the major polyphenol component of green tea, in globin and HbF regulators/silencer genes. K562 cell line was exposed for 72 and 96 hours to three different concentrations of GN and EGCG that mimic cellular exposure in vivo after supplementation (100 ƞg/ml, 250 ƞg/ml and 500 ƞg/ml), and 25 μg/ml HU was used as a positive control. Cell viability and proliferation were measured and the transcriptional effects of GN and EGCG on α, β and γ-globin genes, as well as the HbF regulators genes BCL11A and KLF1, were evaluated by qRT-PCR using specific primers. Our results demonstrated that both compounds impact cellular metabolism and proliferation with no cytotoxic effects and have a potential specific molecular target for BCL11A with associated downregulation, without altering KLF1 levels. GN and EGCG also affected globin expression levels in a dose and time-dependent manner. Interestingly, transcriptional analysis of both compounds revealed non-monotonic dose-responses (NMDRs). Overall, our preliminary study sustains the potential of these compounds for γ-globin reactivation and consequently HbF induction, which indicates that GN and EGCG may be potential candidates for new therapeutic strategies. Further research must be performed in order to assess the effectiveness of HbF induction and the underlying molecular mechanisms.
- En pointe: dancers report their pain less variably than do controlsPublication . Canaipa, Rita; Mendonça, Diogo; Agostinho, Mariana; Nascimento, Vanda; Honigman, Liat; Treister, RoiThe subjective nature of pain and the lack of a gold standard for objective measurement hinders effective assessment, diagnosis, and treatment. Some individuals, such as professional dancers, are better in assessing and reporting bodily sensations. This observational study aimed to assess whether dancers report their pain less variably, than other people do. After consenting, subjects completed the Focused Analgesia Selection Task (FAST), which assesses subjects' variability of pain reports. FAST outcomes, ICC and R2 reflect the magnitude of variability of pain reports observed. In addition, subjects underwent a taste task, which similarly assesses variability of tastes (salty and sweet) intensity reports and completed the Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire. Thirty-three professional dancers and thirty-three healthy aged-matched controls were recruited. The dancers exhibited less variability of pain reports then controls (P=0.013), but not in case of tastes-reports. Years of practice was positively correlated with pain reporting variability (r=0.447, P=0.009, and r=0.380, P=0.029; for FAST ICC and R2, respectively). MAIA sub-scores correlated with pain reporting variability: R2 and ICC with emotional awareness (r=0.260, P=0.040, and r=0.274, P=0.030, respectively), and R2 with trusting [r=0.254, P=0.044]). Perspective The difference between dancers and controls in the magnitude of variability of pain reports is probably due to the dancers' extensive training, which focuses on attention to body signals. Our results suggest that training can improve subjective pain reports, which are essential for quality clinical care.
- O contributo das histórias para o desenvolvimento da compreensão oral em Jardim de InfânciaPublication . Coelho, Eglantina Beatriz Rodrigues; Rosa, JoãoO presente relatório resulta da análise, reflexão crítica e avaliação do percurso de intervenção da Prática Profissional Supervisionada II e evidencia o processo de uma investigação em sala de atividades no mesmo âmbito, junto de um grupo de crianças em contexto de Jardim de Infância, com idades compreendidas entre os 4 e os 6 anos. A partir de um momento de leitura – prática recorrente neste contexto –, é detetada a dificuldade deste grupo de crianças em inferir acerca da história ouvida. Como consequência desta situação desencadeadora, emerge como problemática da investigação a compreensão oral em crianças desta faixa etária. O objeto de estudo tornou-se o de saber se o questionamento das histórias para a infância contribui para o desenvolvimento da compreensão inferencial das crianças. Para uma intervenção pertinente, utilizou-se a investigação-ação, em que, através do desenho de um plano de ação com a leitura de histórias e suas questões, se pretendeu demonstrar quais eram os contributos desta prática para a compreensão oral das crianças. A análise, comparação e apresentação dos resultados foram possíveis através da observação, notas de campo e testes de compreensão aplicados. É possível trabalhar ao nível da compreensão inferencial com crianças desta idade, assumindo-se as histórias como uma estratégia privilegiada por não formalizarem a apreensão desta capacidade. As crianças demonstraram que passaram a saber inferir, com explicações complexas e próprias, acerca do conteúdo das histórias lidas, de acordo com o que ouviam, observavam das ilustrações e mobilizavam de conhecimentos prévios. Desta forma, o Jardim de Infância com mediadores preocupados em enriquecer os momentos da leitura de contos oferece um ambiente de excelência para o desenvolvimento desde tipo de capacidades que são tão importantes para a vida escolar (e geral) das crianças.