N-methyl-D-aspartate (NMDA) receptors mediate excitatory neurotransmission in the mammalian brain. Two glycine-binding NR1 subunits and two glutamate-binding NR2 subunits each form highly ...Ca2+-permeable cation channels which are blocked by extracellular Mg2+ in a voltage-dependent manner. Either GRIN2B or GRIN2A, encoding the NMDA receptor subunits NR2B and NR2A, was found to be disrupted by chromosome translocation breakpoints in individuals with mental retardation and/or epilepsy. Sequencing of GRIN2B in 468 individuals with mental retardation revealed four de novo mutations: a frameshift, a missense and two splice-site mutations. In another cohort of 127 individuals with idiopathic epilepsy and/or mental retardation, we discovered a GRIN2A nonsense mutation in a three-generation family. In a girl with early-onset epileptic encephalopathy, we identified the de novo GRIN2A mutation c.1845C>A predicting the amino acid substitution p.N615K. Analysis of NR1-NR2AN615K (NR2A subunit with the p.N615K alteration) receptor currents revealed a loss of the Mg2+ block and a decrease in Ca2+ permeability. Our findings suggest that disturbances in the neuronal electrophysiological balance during development result in variable neurological phenotypes depending on which NR2 subunit of NMDA receptors is affected.
Purpose: to investigate the effectiveness of an early identification screening based on the Dynamic Indicators of Basic Early Literacy Skills (DIBELS) test, 6th edition, to early identify first ...graders at risk of dyslexia. Methods: the sample comprised 34 children assessed at two moments--the screening was conducted while they were in the first grade, while a word dictation was used when they were in the second grade. The data were analyzed with Pearson's correlation test, linear regression analysis, and ANOVA, with a p-value < 0.05. Results: the results provide evidence that agrees with other studies in that children with signs of risk of dyslexia differ from children with typical development in terms of less phonological skills and that these differences are already present at the beginning of the literacy process. Conclusion: the early screening allows for the identification of the risk factors for dyslexia, making it possible to implement preventive and personalized phonological skills training to make the literacy process easier. Keywords: Dyslexia; Reading; Handwriting; Academic Failure
OBJETIVO: verificar como os pais percebem e descrevem seus filhos com relação à voz e às características de comportamento e personalidade. MÉTODOS: participaram do estudo 66 pais de crianças entre 6 ...e 9 anos, de ambos os sexos, os quais responderam a um questionário com 28 questões que investigavam características de voz, comportamento e personalidade de seus filhos. RESULTADOS: os resultados indicaram que a maioria dos pais (90,9%) se mostra satisfeita com o som da voz de seu filho(a). Somente 9,1% dos pais caracterizaram a voz de seu filho como sendo pior que a das demais crianças e 31,8% achou que seu filho(a) fala muito mais se comparado aos colegas. Aproximadamente um quarto (22,7%) dos pais observou que o volume de voz utilizado por seus filhos é aumentado. Os pais que caracterizaram seus filhos como sendo mais falantes também perceberam a voz deles como sendo mais aguda (p=0,013). O volume de voz aumentado mostrou correlação positiva com agitação (p=0,044), inquietação (p=0,005), sociabilidade (p=0,021), menos quantidade de horas dormidas (p=0,013) e extroversão (p=0,014). Crianças caracterizadas como sendo mais calmas (p=0,011) e menos argumentativas (p=0,044) são também menos falantes na comparação com outras crianças. CONCLUSÃO: em geral, os pais parecem perceber características vocais em seus filhos, têm forte tendência a considerar seus filhos sensíveis, observadores e exigentes quanto a si mesmos, além de perceberem relação entre volume de voz e características de comportamento e personalidade.
OBJETIVO: verificar como os pais percebem e descrevem seus filhos com relação à voz e às características de comportamento e personalidade. MÉTODOS: participaram do estudo 66 pais de crianças entre 6 ...e 9 anos, de ambos os sexos, os quais responderam a um questionário com 28 questões que investigavam características de voz, comportamento e personalidade de seus filhos. RESULTADOS: os resultados indicaram que a maioria dos pais (90,9%) se mostra satisfeita com o som da voz de seu filho(a). Somente 9,1% dos pais caracterizaram a voz de seu filho como sendo pior que a das demais crianças e 31,8% achou que seu filho(a) fala muito mais se comparado aos colegas. Aproximadamente um quarto (22,7%) dos pais observou que o volume de voz utilizado por seus filhos é aumentado. Os pais que caracterizaram seus filhos como sendo mais falantes também perceberam a voz deles como sendo mais aguda (p=0,013). O volume de voz aumentado mostrou correlação positiva com agitação (p=0,044), inquietação (p=0,005), sociabilidade (p=0,021), menos quantidade de horas dormidas (p=0,013) e extroversão (p=0,014). Crianças caracterizadas como sendo mais calmas (p=0,011) e menos argumentativas (p=0,044) são também menos falantes na comparação com outras crianças. CONCLUSÃO: em geral, os pais parecem perceber características vocais em seus filhos, têm forte tendência a considerar seus filhos sensíveis, observadores e exigentes quanto a si mesmos, além de perceberem relação entre volume de voz e características de comportamento e personalidade.
PURPOSE: to check how parents perceive and describe their children with 'regard to their voice and behavior and personality traits. METHODS: the study involved the participation of 66 parents of children between 6 and 9 year old, from both genders, who answered a questionnaire with 28 questions addressing voice, behavior and personality traits of their children. RESULTS: results indicated that the majority of the parents (90.9%) perceived themselves satisfied with the sound of their child's voice. Only 9.1% of the parents characterized the voice of their child as being worse than other children and 31.8% felt that their child speaks more compared to his/her friends. Approximately a quarter (22.7%) of the parents observed that the voice volume used by their children is higher. The parents that characterized their children as being more talkative also perceived their voices as having a higher pitch (p=0.013). The increased voice volume showed a positive correlation with agitation (0.044), restlessness (0.005), sociability (0.021), less hours of sleep (0.013) and extroversion (0.014). Children characterized as being calmer (p=0.011) and less argumentative (p=0.044) were also seen as less talkative compared to other children. CONCLUSION: in general, the parents seem to notice vocal traits in their children, they have a strong trend to consider their children as sensitive, observant and demanding in relation to themselves, in addition to noting a relationship among voice volume and behavior and personality traits.
OBJETIVO: verificar como os pais percebem e descrevem seus filhos com relação à voz e às características de comportamento e personalidade. MÉTODOS: participaram do estudo 66 pais de crianças entre 6 ...e 9 anos, de ambos os sexos, os quais responderam a um questionário com 28 questões que investigavam características de voz, comportamento e personalidade de seus filhos. RESULTADOS: os resultados indicaram que a maioria dos pais (90,9%) se mostra satisfeita com o som da voz de seu filho(a). Somente 9,1% dos pais caracterizaram a voz de seu filho como sendo pior que a das demais crianças e 31,8% achou que seu filho(a) fala muito mais se comparado aos colegas. Aproximadamente um quarto (22,7%) dos pais observou que o volume de voz utilizado por seus filhos é aumentado. Os pais que caracterizaram seus filhos como sendo mais falantes também perceberam a voz deles como sendo mais aguda (p=0,013). O volume de voz aumentado mostrou correlação positiva com agitação (p=0,044), inquietação (p=0,005), sociabilidade (p=0,021), menos quantidade de horas dormidas (p=0,013) e extroversão (p=0,014). Crianças caracterizadas como sendo mais calmas (p=0,011) e menos argumentativas (p=0,044) são também menos falantes na comparação com outras crianças. CONCLUSÃO: em geral, os pais parecem perceber características vocais em seus filhos, têm forte tendência a considerar seus filhos sensíveis, observadores e exigentes quanto a si mesmos, além de perceberem relação entre volume de voz e características de comportamento e personalidade.PURPOSE: to check how parents perceive and describe their children with 'regard to their voice and behavior and personality traits. METHODS: the study involved the participation of 66 parents of children between 6 and 9 year old, from both genders, who answered a questionnaire with 28 questions addressing voice, behavior and personality traits of their children. RESULTS: results indicated that the majority of the parents (90.9%) perceived themselves satisfied with the sound of their child's voice. Only 9.1% of the parents characterized the voice of their child as being worse than other children and 31.8% felt that their child speaks more compared to his/her friends. Approximately a quarter (22.7%) of the parents observed that the voice volume used by their children is higher. The parents that characterized their children as being more talkative also perceived their voices as having a higher pitch (p=0.013). The increased voice volume showed a positive correlation with agitation (0.044), restlessness (0.005), sociability (0.021), less hours of sleep (0.013) and extroversion (0.014). Children characterized as being calmer (p=0.011) and less argumentative (p=0.044) were also seen as less talkative compared to other children. CONCLUSION: in general, the parents seem to notice vocal traits in their children, they have a strong trend to consider their children as sensitive, observant and demanding in relation to themselves, in addition to noting a relationship among voice volume and behavior and personality traits.
ObjectivesTreat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. ...Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE.MethodsAn international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%.ResultsThe task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life.ConclusionsThe work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.
The combination of autologous mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) synergistically reduces scar size and improves cardiac function in ischemic cardiomyopathy. Whereas ...allogeneic (allo-)MSCs are immunoevasive, the capacity of CSCs to similarly elude the immune system remains controversial, potentially limiting the success of allogeneic cell combination therapy (ACCT).
This study sought to test the hypothesis that ACCT synergistically promotes cardiac regeneration without provoking immunologic reactions.
Göttingen swine with experimental ischemic cardiomyopathy were randomized to receive transendocardial injections of allo-MSCs + allo-CSCs (ACCT: 200 million MSCs/1 million CSCs, n = 7), 200 million allo-MSCs (n = 8), 1 million allo-CSCs (n = 4), or placebo (Plasma-Lyte A, n = 6). Swine were assessed by cardiac magnetic resonance imaging and pressure volume catheterization. Immune response was tested by histologic analyses.
Both ACCT and allo-MSCs reduced scar size by −11.1 ± 4.8% (p = 0.012) and −9.5 ± 4.8% (p = 0.047), respectively. Only ACCT, but not MSCs or CSCs, prevented ongoing negative remodeling by offsetting increases in chamber volumes. Importantly, ACCT exerted the greatest effect on systolic function, improving the end-systolic pressure-volume relation (+0.98 ± 0.41 mm Hg/ml; p = 0.016). The ACCT group had more phospho-histone H3+ (a marker of mitosis) cardiomyocytes (p = 0.04), and noncardiomyocytes (p = 0.0002) than did the placebo group in some regions of the heart. Inflammatory sites in ACCT and MSC-treated swine contained immunotolerant CD3+/CD25+/FoxP3+ regulatory T cells (p < 0.0001). Histologic analysis showed absent to low-grade inflammatory infiltrates without cardiomyocyte necrosis.
ACCT demonstrates synergistic effects to enhance cardiac regeneration and left ventricular functional recovery in a swine model of chronic ischemic cardiomyopathy without adverse immunologic reaction. Clinical translation to humans is warranted.
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