Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation.

The TNF family ligand ectodysplasin A (EDA) regulates the induction, morphogenesis and/or maintenance of skin-derived structures such as teeth, hair, sweat glands and several other glands. Deficiencies in the EDA - EDA receptor (EDAR) signalling pathway cause hypohidrotic ectodermal dysplasia (HED). This syndrome is characterized by the absence or malformation of several skin-derived appendages resulting in hypotrychosis, hypodontia, heat-intolerance, dry skin and dry eyes, susceptibility to airways infections and crusting of various secretions. The EDA-EDAR system is an important effector of canonical Wnt signalling in developing skin appendages. It functions by stimulating NF-κB-mediated transcription of effectors or inhibitors of the Wnt, Sonic hedgehog (SHH), fibroblast growth factor (FGF) and transforming growth factor beta (TGFβ) pathways that regulate interactions within or between epithelial and mesenchymal cells and tissues. In animal models of Eda-deficiency, soluble EDAR agonists can precisely correct clinically relevant symptoms with low side effects even at high agonist doses, indicating that efficient negative feedback signals occur in treated tissues. Hijacking of the placental antibody transport system can help deliver active molecules to developing foetuses in a timely manner. EDAR agonists may serve to treat certain forms of ectodermal dysplasia

Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells

Chronic myeloid leukaemia (CML) is maintained by a rare population of tyrosine kinase inhibitor (TKI)-insensitive malignant stem cells. Our long-term aim is to find a BcrAbl-independent drug that can be combined with a TKI to improve overall disease response in chronic-phase CML. Omacetaxine mepesuccinate, a first in class cetaxine, has been evaluated by clinical trials in TKI-insensitive/resistant CML. Omacetaxine inhibits synthesis of anti-apoptotic proteins of the Bcl-2 family, including (myeloid cell leukaemia) Mcl-1, leading to cell death. Omacetaxine effectively induced apoptosis in primary CML stem cells (CD34<sup>+</sup>38<sup>lo</sup>) by downregulation of Mcl-1 protein. In contrast to our previous findings with TKIs, omacetaxine did not accumulate undivided cells <i>in vitro</i>. Furthermore, the functionality of surviving stem cells following omacetaxine exposure was significantly reduced in a dose-dependant manner, as determined by colony forming cell and the more stringent long-term culture initiating cell colony assays. This stem cell-directed activity was not limited to CML stem cells as both normal and non-CML CD34<sup>+</sup> cells were sensitive to inhibition. Thus, although omacetaxine is not leukaemia stem cell specific, its ability to induce apoptosis of leukaemic stem cells distinguishes it from TKIs and creates the potential for a curative strategy for persistent disease

Psychological effects of gamified didactics with exergames in Physical Education at primary schools: Results from a natural experiment

The physical effects of exergaming have been proven, but less is known about the psychological effects in elementary schools that make exergames an effective educational tool. The application of gamification to education is still an emerging practice that has been barely studied. The aim of this study was to analyse the effects of a gamified exergaming intervention in Physical Education classes in primary schools on psychological variables like motivation, flow, basic psychological needs and academic performance. A natural experiment with a non-randomised controlled design was run. The participants were recruited from four schools (n = 417), and received traditional didactic intervention or a gamified exergaming intervention. Both lasted 1 month. The results showed better positive gamified exergaming effects on basic psychological needs, academic performance and some flow dimensions. No interaction effects were found in intrinsic motivation, external regulation and amotivation, although specific improvements in the gamified exergaming group are discussed. The Mechanics-Dynamics-Aesthetics gamification model and the Just Dance Now exergame may be resources capable of producing positive psychological effects on school-based Physical Education

Corioamnionite e Morbilidade Neonatal

CHORIOAMNIONITIS AND NEONATAL MORBIDITY Introduction - Several studies highlight the association between perinatal infection/ inflammation and neonatal morbidity, mainly bronchopulmonary dysplasia and periventricular leukomalacia. Aim – To evaluate the role of histological chorioamnionitis on the overall morbidity of preterm newborns. Methods – A retrospective study on preterm newborns less than 34 weeks gestational age at birth, and respective mothers, at three tertiary medical centers (Hospital de São João, Maternidade Júlio Dinis and Centro Hospitalar de Vila Nova de Gaia) in the north of Portugal, between January 2001 and December 2002. We evaluated the association between histological chorioamnionitis and the overall neonatal morbidity. The association between histological chorioamnionitis and acute (respiratory distress syndrome) and chronic (bronchopulmonary dysplasia) lung damage was also evaluated in the subgroup of less than 1000 g birthweight preterm neonates. Results – 452 [ M 253 / F 217; birthweight 1440 (515 – 2620) g; gestational age 31 (23 – 33) weeks] preterm newborns were included. The association between histological chorioamnionitis and the overall neonatal morbidity was: respiratory distress syndrome OR 1,5 (95% CI 0,94 – 2,31); bronchopulmonary dysplasia OR 2,6 (95% CI 1,16 – 6,03); patent ductus arteriosus OR 2,5 (95% CI 1,17 – 5,44); sepsis OR 1,2 (95% CI 0,9 – 2,13); necrotizing enterocolitis OR 1,4 (95% CI 0,9 – 1,76); intraventricular hemorrhage grades III-IV OR 2,5 (1,20 – 5,11); cystic periventricular leukomalacia OR 3,0 (1,5 – 6,07); retinopathy of prematurity OR 1,4 (95% CI 0,8 – 1,35). The association adjusted to birthweight and gestational age was: bronchopulmonary dysplasia OR 1,2 (95% CI 0,51 – 2,95); patent ductus arteriosus OR 0,9 (95% CI 0,4 – 2,35); intraventricular hemorrhage grades III-IV OR 0,9 (95% CI 0,39 – 2,28); cystic periventricular leukomalacia OR 2,2 (95% CI 1,03 – 4,61). The association between histological chorioamnionitis and lung damage in the subgroup of less than 1000 g birthweight preterm neonates was: respiratory distress syndrome OR 0,23 (95% CI 0,01 – 2,51); bronchopulmonary dysplasia OR 1,61 (95% CI 0,38 – 6,97). Conclusion – This study confirms the association between histological chorioamnionitis and cystic periventricular leukomalacia of the preterm newborn

Transport mechanism of macromolecules on hydrophilic bio-polymeric matrices : diffusion of protein-based compounds from chitosan films

The transport mechanism of protein-based bioactive compounds (a peptide fraction from whey protein concentrate, glycomacropeptide and lactoferrin), from chitosan films to liquid medium, was studied. Mathematical models were used to discuss the transport mechanism. Data from release experiments was successfully described by a model which accounts for both Fick and Case II transport – the linear superimposition model. Results show that the mechanism of transport and the effect of temperature and peptide type could be related with physical properties of chitosan films where the tested bioactive compounds were incorporated. The approach presented here allows interpretation of the phenomena involved in mass transport in the systems studied and, once extended to other systems, may contribute to an understanding of transport in hydrophilic bio-polymeric matrices.This work was supported by Fundacao para a Ciencia e a Tecnologia through project PTDC/AGR/ALI/67194/2006. Authors Ana C. Pinheiro, Ana I. Bourbon and Mafalda A.C. Quintas gratefully acknowledge their Grants SFRH/BD/48120/2008, SFRH/BD/73178/2010 and SFRH/BPD/41715/2007, respectively

Inhibition of Membrane-Bound BAFF by the Anti-BAFF Antibody Belimumab.

B cell activating factor of the TNF family (BAFF, also known as BLyS), a cytokine that regulates homeostasis of peripheral B cells, is elevated in the circulation of patients with autoimmune diseases such as systemic lupus erythematosus (SLE). BAFF is synthetized as a membrane-bound protein that can be processed to a soluble form after cleavage at a furin consensus sequence, a site that in principle can be recognized by any of the several proteases of the pro-protein convertase family. Belimumab is a human antibody approved for the treatment of SLE, often cited as specific for the soluble form of BAFF. Here we show in different experimental systems, including in a monocytic cell line (U937) that naturally expresses BAFF, that belimumab binds to membrane-bound BAFF with similar EC50 as the positive control atacicept, which is a decoy receptor for both BAFF and the related cytokine APRIL (a proliferation inducing ligand). In U937 cells, binding of both reagents was only detectable in furin-deficient U937 cells, showing that furin is the main BAFF processing protease in these cells. In CHO cells expressing membrane-bound BAFF lacking the stalk region, belimumab inhibited the activity of membrane-bound BAFF less efficiently than atacicept, while in furin-deficient U937 cells, belimumab inhibited membrane-bound BAFF and residual soluble BAFF as efficiently as atacicept. These reagents did not activate complement or antibody-dependent cell cytotoxicity upon binding to membrane-bound BAFF in vitro. In conclusion, our data show that belimumab can inhibit membrane-bound BAFF, and that BAFF in U937 cells is processed by furin

Positive attitudes towards racquet sport of primary school teachers

The aim of this study was to know the attitudes towards racquet sports in Spanish primary school teachers. Eighty one teachers from Zaragoza participated in this study, filling out the scale Positive attitudes towards racquet sport of the validated Table Tennis Attitudes Questionnaire. The internal consistency of this scale was measured with the Cronbach alpha coefficient. The results indicate Md=2.19 (SD=0.38) in this scale. The 27.2% of the teachers have never done one training course of this kind of sports, being the badminton the most studied sport. However, the teachers have mainly badminton teaching material. This study shows which is the prevalence of the racquet sports in the teacher programs. Statistically significant relationships were found between the studies of the teachers or the kind of the school, and the attitudes towards racquet sport. The results of this study suggest us that there have to be more educative programs to implementation racquet sports