Resistance to thyroid hormone and down syndrome: coincidental association or genetic linkage?

We report the first case of RTH and DS. Although this congruence could be coincidental, we cannot exclude a possible linkage between both syndromes.

Intervenció del psicòleg d'educació en l'assessorament a una alumna amb Síndrome de Down de 1r de primària en l'àrea de lectoescriptura

Davant la diversitat d'alumnat que es troba a les aules de les escoles ordinàries i, sobretot, per la creixent orientació inclusiva dels alumnes amb necessitats educatives especials en aquestes, a continuació es presenta un cas d'una alumna amb síndrome de Down i dictamen de reconeixement de necessitats educatives especials, que està escolaritzada en un centre d'educació infantil primària de Barcelona ciutat. A l'actualitat, ha iniciat 1r de primària i s'ha vist la necessitat d'elaborar un Pla Individualitzat per adequar els objectius i continguts per el curs escolar 2011-2012. Es mostren una sèrie d'actuacions, enfocades a conèixer quines són les àrees curriculars que cal adaptar, quines habilitats té a nivell de manipulació fina i saber quines són les competències en aquestes per poder elaborar uns objectius reals en el Pla Individualitzat. Els materials utilitzats han estat una sèrie de fitxes de treball, el programari Click facilitat pel Departament d'Ensenyament, el web www.edu365.cat i un test específic de valoració de la motricitat fina. Les activitats realitzades han inclòs el passar aquest test, observacions a l'aula del grup classe en diferents moments, a logopèdia i al pati, i entrevistes amb la tutora, la logopeda, la monitora de reforç, la família de l'alumna, així com una coordinació de tots els professionals que intervenen amb la nena. Els resultats obtinguts han permès facilitar l'elaboració del Pla Individualitzat.

A constitutively active mutant of the alpha 1B-adrenergic receptor can cause greater agonist-dependent down-regulation of the G-proteins G9 alpha and G11 alpha than the wild-type receptor.

Rat 1 fibroblasts transfected to express either the wild-type hamster alpha 1B-adrenergic receptor or a constitutively active mutant (CAM) form of this receptor resulting from the alteration of amino acid residues 288-294 to encode the equivalent region of the human beta 2-adrenergic receptor were examined. The basal level of inositol phosphate generation in cells expressing the CAM alpha 1B-adrenergic receptor was greater than for the wild-type receptor, The addition of maximally effective concentrations of phenylephrine or noradrenaline resulted in substantially greater levels of inositol phosphate generation by the CAM alpha 1B-adrenergic receptor, although this receptor was expressed at lower steady-state levels than the wild-type receptor. The potency of both phenylephrine and noradrenaline to stimulate inositol phosphate production was approx. 200-fold greater at the CAM alpha 1B-adrenergic receptor than at the wild-type receptor. In contrast, endothelin 1, acting at the endogenously expressed endothelin ETA, receptor, displayed similar potency and maximal effects in the two cell lines. The sustained presence of phenylephrine resulted in down-regulation of the alpha subunits of the phosphoinositidase C-linked, pertussis toxin-insensitive, G-proteins G9 and G11 in cells expressing either the wild-type or the CAM alpha 1B-adrenergic receptor. The degree of down-regulation achieved was substantially greater in cells expressing the CAM alpha 1B-adrenergic receptor at all concentrations of the agonist. However, in this assay phenylephrine displayed only a slightly greater potency at the CAM alpha 1B-adrenergic receptor than at the wild-type receptor. There were no detectable differences in the basal rate of G9 alpha/G11 alpha degradation between cells expressing the wild-type or the CAMalpha 1B-adrenergic receptor. In both cell lines the addition of phenylephrine substantially increased the rate of degradation of these G-proteins, with a greater effect at the CAM alpha 1B-adrenergic receptor. The enhanced capacity of agonist both to stimulate second-messenger production at the CAM alpha 1B-adrenergic receptor and to regulate cellular levels of its associated G-proteins by stimulating their rate of degradation is indicative of an enhanced stoichiometry of coupling of this form of the receptor to G9 and G11.

CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD). Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS) phagocytosis by the retinal pigment epithelium (RPE) in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR) and CD36-/- mice). Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF) expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

CB1 blockade potentiates down-regulation of lipogenic gene expression in perirenal adipose tissue in high carbohydrate diet-induced obesity.

De novo lipogenesis and hypercaloric diets are thought to contribute to increased fat mass, particularly in abdominal fat depots. CB1 is highly expressed in adipose tissue, and CB1-mediated signalling is associated with stimulation of lipogenesis and diet-induced obesity, though its contribution to increasing fat deposition in adipose tissue is controversial. Lipogenesis is regulated by transcription factors such as liver X receptor (LXR), sterol-response element binding protein (SREBP) and carbohydrate-responsive-element-binding protein (ChREBP). We evaluated the role of CB1 in the gene expression of these factors and their target genes in relation to lipogenesis in the perirenal adipose tissue (PrAT) of rats fed a high-carbohydrate diet (HCHD) or a high-fat diet (HFD). Both obesity models showed an up-regulated gene expression of CB1 and Lxrα in this adipose pad. The Srebf-1 and ChREBP gene expressions were down-regulated in HFD but not in HCHD. The expression of their target genes encoding for lipogenic enzymes showed a decrease in diet-induced obesity and was particularly dramatic in HFD. In HCHD, CB1 blockade by AM251 reduced the Srebf-1 and ChREBP expression and totally abrogated the remnant gene expression of their target lipogenic enzymes. The phosphorylated form of the extracellular signal-regulated kinase (ERK-p), which participates in the CB1-mediated signalling pathway, was markedly present in the PrAT of obese rats. ERK-p was drastically repressed by AM251 indicating that CB1 is actually functional in PrAT of obese animals, though its activation loses the ability to stimulate lipogenesis in PrAT of obese rats. Even so, the remnant expression levels of lipogenic transcription factors found in HCHD-fed rats are still dependent on CB1 activity. Hence, in HCHD-induced obesity, CB1 blockade may help to further potentiate the reduction of lipogenesis in PrAT by means of inducing down-regulation of the ChREBP and Srebf-1 gene expression, and consequently in the expression of lipogenic enzymes.

A representação social da mãe acerca da criança com síndrome de down

Desenvolvido à luz da Teoria das Representações Sociais, o estudo buscou compreender a representação social da mãe acerca da criança com Síndrome de Down. Participaram nove mães, cujos filhos tinham idade escolar e frequentavam um serviço especializado no município de São Paulo. Os dados, obtidos por entrevista semi-estruturada e individual, foram analisados por meio do método de análise de conteúdo, especificamente a análise temática. Os resultados apontaram para urna representação da criança na qual predominaram elementos negativos, levando a mãe a experimentar sentimentos ambivalentes em relação ao filho e comportar-se de modo superprotetor.

15-hydroxyprostaglandin dehydrogenase is down-regulated in gastric cancer.

PURPOSE: We have investigated the expression and regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in gastric cancer. EXPERIMENTAL DESIGN: Clinical gastric adenocarcinoma samples were analyzed by immunohistochemistry and quantitative real-time PCR for protein and mRNA expression of 15-PGDH and for methylation status of 15-PGDH promoter. The effects of interleukin-1beta (IL-1beta) and epigenetic mechanisms on 15-PGDH regulation were assessed in gastric cancer cell lines. RESULTS: In a gastric cancer cell line with a very low 15-PGDH expression (TMK-1), the 15-PGDH promoter was methylated and treatment with a demethylating agent 5-aza-2'-deoxycytidine restored 15-PGDH expression. In a cell line with a relatively high basal level of 15-PGDH (MKN-28), IL-1beta repressed expression of 15-PGDH mRNA and protein. This effect of IL-1beta was at least in part attributed to inhibition of 15-PGDH promoter activity. SiRNA-mediated knockdown of 15-PGDH resulted in strong increase of prostaglandin E(2) production in MKN-28 cells and increased cell growth of these cells by 31% in anchorage-independent conditions. In clinical gastric adenocarcinoma specimens, 15-PGDH mRNA levels were 5-fold lower in gastric cancer samples when compared with paired nonneoplastic tissues (n = 26) and 15-PGDH protein was lost in 65% of gastric adenocarcinomas (n = 210). CONCLUSIONS: 15-PGDH is down-regulated in gastric cancer, which could potentially lead to accelerated tumor progression. Importantly, our data indicate that a proinflammatory cytokine linked to gastric carcinogenesis, IL-1beta, suppresses 15-PGDH expression at least partially by inhibiting promoter activity of the 15-PGDH gene.

Estudi de xarxes socials interactives amb gent de Síndrome de Down i disseny d'un primer prototip

En aquest PFC s’ha investigat si les xarxes socials poden ser una eina útil i enriquidora per persones amb Síndrome de Down. S’han estudiat els diferents tipus i objectius que tenen les xarxes socials més comunes, i a partir de les característiques de les persones amb SD, s’ha definit un nou tipus de xarxa social que compleix les necessitats dels usuaris. Els usuarisinvolucrats en aquest PFC no sempre saben exterioritzar els seus sentiments i opinions així que s’han buscat altres formes d’arribar a comprendre les seves necessitats. En una primera fase dedisseny centrat en l’usuari s’han trobat solucions a característiques especials del perfil dels usuaris. Més tard en una segona fase de disseny contextual s’ha comprès l’entorn dels usuaris a través, entre d’altres, d’una entrevista amb els pares dels usuaris. En tercer lloc, en la fase dedisseny centrat en l’ús s’han definit millor els diferent rols, tasques, continguts i navegació de la xarxa social. El nou model de xarxa social utilitzarà avanços tecnològics per facilitar l’accessibilitat com un pendrive d’identificació digital o un tutor virtual, a més a més decomptar amb la participació activa a la xarxa social dels familiars dels usuaris per motivar-los.Finalment amb el software Macromedia Fireworks 8 s’ha creat un primer prototip simulant les diferents característiques, directrius i solucions tractades anteriorment en les etapes de disseny.

NF-kappaB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth.

A novel function of NF-kappaB in the development of most ectodermal appendages, including two types of murine pelage hair follicles, was detected in a mouse model with suppressed NF-kappaB activity (c(IkappaBalphaDeltaN)). However, the developmental processes regulated by NF-kappaB in hair follicles has remained unknown. Furthermore, the similarity between the phenotypes of c(IkappaBADeltaN) mice and mice deficient in Eda A1 (tabby) or its receptor EdaR (downless) raised the issue of whether in vivo NF-kappaB regulates or is regulated by these novel TNF family members. We now demonstrate that epidermal NF-kappaB activity is first observed in placodes of primary guard hair follicles at day E14.5, and that in vivo NF-kappaB signalling is activated downstream of Eda A1 and EdaR. Importantly, ectopic signals which activate NF-kappaB can also stimulate guard hair placode formation, suggesting a crucial role for NF-kappaB in placode development. In downless and c(IkappaBalphaDeltaN) mice, placodes start to develop, but rapidly abort in the absence of EdaR/NF-kappaB signalling. We show that NF-kappaB activation is essential for induction of Shh and cyclin D1 expression and subsequent placode down growth. However, cyclin D1 induction appears to be indirectly regulated by NF-kappaB, probably via Shh and Wnt. The strongly decreased number of hair follicles observed in c(IkappaBalphaDeltaN) mice compared with tabby mice, indicates that additional signals, such as TROY, must regulate NF-kappaB activity in specific hair follicle subtypes.

Disfagia orofaringea sindrome geriatrico en el paciente anciano

El present treball es basa per una banda en una revisió bibliogràfica de la disfàgia orofaríngia en el pacient ancià amb especial èmfasi en el pacient ancià fràgil. Aquest document ha estat dissenyat per a la publicació pròxima com capítol Nº29 del primer tractat de Geriatria en espanyol de l'editorial ELSEVIER organitzat pel Dr Pedro Abizanda Soler. El segon document és un protocol de recerca del meu primer disseny de projecte de tesi doctoral. El projecte ha estat aprovat recentment pel Comitè d´Ètica del nostre centre i ha estat presentat a l'oposició de beques hospitalàries de l'Acadèmia de Ciències Mèdiques de la Filial del Maresme

Actividade Física e Síndrome de Down Prática de Actividade Física para as Crianças com Síndrome de Down no E.B.I. na Praia Urbana

O presente trabalho subordinado ao tema “Actividade Física e Síndrome de Down – A Prática de Actividade Física para as Crianças com Síndrome de Down no E.B.I. na Praia Urbana” visou recolher informações e opiniões dos professores do E.B.I. acerca da participação das Crianças com Síndrome de Down nas Actividades Físicas ou mesmo nas aulas de Educação Física. O objectivo principal deste estudo é determinar e revelar a forma mais adequada de trabalhar em harmonia o físico e a mente das Crianças Down. Para a recolha de dados foi aplicado um questionário dirigido a 120 professores em várias escolas da Praia Urbana, assim como inúmeras consultas de variadas bibliografias específicas e especializadas neste campo, nomeadamente, Actividades Físicas para pessoas com Necessidades Educativas Especiais (NEE) e observação de vídeos na área de actividade físicas com crianças com Síndrome de Down. Segundo os dados analisados, a maioria dos professores questionados não está preparada para enfrentar o dilema das crianças com NEE principalmente as com Síndrome de Down (SD). Ainda conforme o mesmo estudo ficou bem explícito que a falta de preparação dos professores influencia directamente a participação dessas crianças nas aulas de Educação Física (EF). A maior parte dos professores manifestou o desejo e a vontade de ter uma formação ou um instrumento de guia que possa facilitar e ajudar no trabalho com tais crianças. É bastante vincada a consciência de integração e importância da inserção dessas crianças/alunos nas aulas de Educação Física ou em qualquer outra Actividade Física, justificando que tal atitude contribui para que a criança/aluno possa cuidar de si. Tornando-se mais independente no seu quotidiano, elas já poderão participar na vida familiar da escola obtendo assim mais rendimento nos estudos e no trabalho, podendo assumir um papel de liberdade profissional e emocional. Depois da análise destas reflexões, ficou bastante claro que é necessário uma preparação mais profunda dos professores assim como um documento que possa servir de suporte de pesquisa para todos aqueles que pretendem trabalhar com das crianças/aluno com Síndrome de Down.