BACKGROUND: The ability to recognize and respond appropriately to threat is critical to survival, and the neural substrates subserving attention to threat may be probed using depictions of media violence. Whether neural responses to potential threat differ in Down syndrome is not known. METHODS: We performed functional MRI scans of 15 adolescent and adult Down syndrome and 14 typically developing individuals, group matched by age and gender, during 50 min of passive cartoon viewing. Brain activation to auditory and visual features, violence, and presence of the protagonist and antagonist were compared across cartoon segments. fMRI signal from the brain's dorsal attention network was compared to thematic and violent events within the cartoons between Down syndrome and control samples. RESULTS: We found that in typical development, the brain's dorsal attention network was most active during violent scenes in the cartoons and that this was significantly and specifically reduced in Down syndrome. When the antagonist was on screen, there was significantly less activation in the left medial temporal lobe of individuals with Down syndrome. As scenes represented greater relative threat, the disparity between attentional brain activation in Down syndrome and control individuals increased. There was a reduction in the temporal autocorrelation of the dorsal attention network, consistent with a shortened attention span in Down syndrome. Individuals with Down syndrome exhibited significantly reduced activation in primary sensory cortices, and such perceptual impairments may constrain their ability to respond to more complex social cues such as violence. CONCLUSIONS: These findings may indicate a relative deficit in emotive perception of violence in Down syndrome, possibly mediated by impaired sensory perception and hypoactivation of medial temporal structures in response to threats, with relative preservation of activity in pro-social brain regions. These findings indicate that specific genetic differences associated with Down syndrome can modulate the brain's response to violence and other complex emotive ideas.

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El síndrome de Down es una alteración cromosómica que se asocia con un aumento de la incidencia de una serie de enfermedades autoinmunes. Dentro de estas destacan las de origen endocrino como la patología tiroidea, siendo el hipotiroidismo el más común. Los casos de hipertiroidismo son raros y más aún asociados a diabetes mellitus, siendo la edad de presentación tardía. Reportamos el caso de un niño de 2 años de edad con antecedente de síndrome de Down que es diagnosticado de diabetes mellitus tipo I e hipertiroidismo subclínico

Representations of people with a developmental disability are virtually not covered in the media. Although there is little coverage of people with developmental disabilities in the media, there are a few entertainment television characters who have Down syndrome and are represented in the media. This study will take a look at the history of how people with disabilities were represented in the media and examine how two television characters with Down syndrome were portrayed on the shows by examining their self-esteem. This study seeks to focus on portrayal of people with Down Syndrome because the physical features that people with Down Syndrome possess are easy to identify. Specifically, the study examines the portrayal of self-esteem in two television characters, Corky Thatcher (Life Goes On) and Becky Faye Jackson (Glee). The researcher will also examine how the portrayal of self-esteem in the two characters is similar or different in people who have Down Syndrome. In the study the researcher found that the representation of the character Corky was different from the character Becky. But both characters tackled issues that affected the Down Syndrome community and it affected their self-esteem. Corky and Becky were different from the interviewees in the way they realized their competencies. Although the interviewees who have Down Syndrome and the television characters used self-evaluation differently to evaluate one's own self-esteem, they all seem to exhibit a positive level of self-esteem.

Trisomies 18 and 13 are rare genetic conditions (occurring around 1 in 6,000 and 10,000 newborns respectively) which are caused by an extra copy of either chromosome 18 or 13, similar to trisomy 21 (Down syndrome). The only known risk factor for these syndromes is maternal age, however previous cluster analyses have linked trisomy risk to a number of alternate factors, including radiation exposure and infection. Cases of trisomies 18 and 13 from the National Down Syndrome Cytogenetic Register (NDSCR) were scanned for temporal and spatial clusters throughout England and Wales between 2004 and 2010. No temporal clusters were detected, however there were multiple significant spatial clusters detected for both trisomies in London. These clusters were likely caused by advanced maternal age in the region, and it is also possible that regional differences in gestational age at the time of prenatal screening could have contributed to these clusters. In order to account for maternal age and gestational age at diagnosis, a novel method was developed in R to directly weight cases based on these factors. Applying weights to cases directly allowed both factors to be simultaneously accounted for by multiplying weights together. This method was evaluated using synthetic data and compared with an alternate method in the widely used program SaTScan. Both programs returned similar results when the weighting method was mild, but when extreme weights were applied at random significant clusters were observed in SaTScan but not in R. The NDSCR data was weighted and then rescanned for spatial clusters in both programs. No evidence of clustering was detected using the novel method, while SaTScan returned multiple highly significant clusters. These findings, combined with those obtained using the synthetic data, indicate that the novel method produces more reliable results than SaTScan when extreme adjustment is applied.

Patients with trisomy of chromosome 21, known as Down’s syndrome (DS), have a lower incidence of solid tumours than unaffected age-matched individuals. However, the cellular and molecular basis for this observation is not well understood. We hypothesised that a direct link between Down’s syndrome and angiogenesis exists, whereby the overexpression of human chromosome 21 (Hsa21) genes causes the repression of angiogenesis (gene dosage effects) resulting in the inhibition of solid tumour growth. In this project we investigated the angiogenic phenotype of an animal model of Down’s syndrome, the Tc1 mouse, which contains a large freely segregating fragment of Hsa21 containing over 200 human genes. We found that the growth of both B16F0 melanoma and Lewis Lung Carcinoma cells was impaired in Tc1 mice. Tumour vascularity also was reduced. This is supportive of the epidemiological data from the human DS population and supports the hypothesis that Hsa21 contains anti-angiogenic genes. Candidate genes were selected due to their endothelial specificity or likelihood to function in angiogenesis based on functional data or similarity to other proteins. Ex vivo RNAi assays were used to examine their roles in angiogenesis. We have found that reducing the expression of human Adamts1, Erg, Jamb or Pttg1ip in Tc1 tissue can restore its angiogenic potential, suggesting that the dosage of these genes (i.e. 3 copies instead of 2) can inhibit angiogenesis. Following from this study we also examined the role of selected adhesion related genes found on chromosome 21 in angiogenesis. Cldn14 encodes the tight junction molecule Claudin14 but its role in angiogenesis was unknown. We found that partial, but not complete, depletion of Cldn14 can increase the proportion of non-lumenated tumour blood vessels; decrease supporting cell association with tumour vessels; and increase endothelial cell proliferation in vivo, ex vivo and in vitro. Taken together this series of experiments has identified novel regulators of angiogenesis and has demonstrated the gene dosage effects of a subset of Hsa21 genes on angiogenic processes.

Down's syndrome (DS) is a congenital disorder caused by trisomy of chromosome 21, giving rise to symptoms including intellectual disability, poor muscle tone and characteristic facial features. Located on chromosome 21 is a gene encoding ubiquitin specific protease 25 (USP25), a member of the deubiquitinating family of enzymes. Studies of partial trisomies have revealed that although the USP25 gene is situated outside the critical region of chromosome 21 required to be triplicated to induce full DS symptoms, it is in a region linked to mild mental retardation and muscle hypotonia. Previous data has shown that, when overexpressed, USP25 forms novel rod shaped structures approximately 3-5 μm in length and 0.3-0.6 μm wide, and with a copy number, on average, of no more than 1-2 per cell. These structures do not associate with any known cellular organelle or with any component of the cytoskeleton. In this work, endogenous USP25 rods were detected in cultures of primary human foetal astrocytes, and a comparison of healthy and DS human primary foetal astrocytes revealed that in the DS culture a higher percentage of astrocytes contain rods. The domains of USP25 required for rod formation were identified using a series of GFP-tagged deletion constructs. USP25 rods could be purified from HEK293 cells using subcellular fractionation techniques and were assayed for deubiquitinating activity; however, none was detected suggesting that rods may be catalytically inactive. Interacting partners of USP25 were identified using mass spectrometry, but none were found to localise in rods. Additionally, a USP25 null human embryonic stem cell line was generated in order to interrogate the function of USP25 in astrocytes, and was found to be deficient in maintaining the integrity of an epithelial cell layer in an in vitro model of the blood brain barrier.

Introducción: La obesidad se ha convertido en un problema importante de salud y es más frecuente en las personas con Síndrome de Down que en el resto de la población. Se ha reportado que adolescentes con Síndrome de Down tienen mayor porcentaje de grasa corporal a comparación de la población sin Síndrome de Down. Objetivo: Determinar el componente endomórfico y el porcentaje de masa grasa de los adolescentes con Síndrome de Down y su relación con la ingesta de energía según el nivel de actividad física. Diseño: descriptivo de asociación cruzada, observacional y transversal. Lugar: Sociedad Peruana de Síndrome de Down. Participantes: 48 adolescentes (71% varones) con Síndrome de Down integrantes de la Sociedad Peruana de Síndrome de Down cuyos padres aceptaron participar. Intervenciones: Se realizaron las mediciones antropométricas para evaluar el componente endomórfico y porcentaje de masa grasa, para calcular la ingesta de energía se aplicó una frecuencia semicuantitativa de consumo de alimentos y para estimar el nivel de actividad física se aplicó el Cuestionario Internacional de Actividad Física (International Physical Activity Questionnaire)-IPAQ. Principales medidas de resultados: componente endomórfico, porcentaje de masa grasa, ingesta de energía y nivel de actividad física. Resultados: Se encontró que la mayoría de adolescentes (n=32) presentaban actividad física intensa, en comparación con los de actividad física moderada (n= 13) y los de actividad física leve (n= 3) Los adolescentes que tuvieron un nivel de actividad física leve tuvieron un mayor componente endomórfico (6.1±1.34) y mayor porcentaje de masa grasa (19.0±7.9) que quienes tuvieron actividad física moderada o intensa. Sin embargo estas diferencias no fueron significativas, el nivel de ingesta energética fue similar entre los tres grupos. Conclusiones: No se ha encontrado relación entre el componente endomórfico; el porcentaje de masa grasa y la ingesta de energía según el nivel de actividad física en los adolescentes con Síndrome de Down. Palabras clave: componente endomórfico, porcentaje de masa grasa, ingesta de energía, actividad física. / Background: Obesity has become a major health problem and is more common in people with Down syndrome than in the rest. It is reported that adolescents with Down syndrome have a higher percentage of body fat compared to people without DS. Objective: To determine the endomorphic component and the percentage of fat mass in adolescents with Down syndrome and their relation to energy intake by level of physical activity. Design: Cross-sectional. Location: Peruvian Society Down Syndrome. Participants: 48 adolescents (71% males) with Down syndrome that are involved in the Peruvian Society for Down syndrome. Interventions: Anthropometric measurements were performed to evaluate the endomorphic component and percentage of fat mass to calculate energy intake was applied semi quantitative frequency of food consumption and to estimate the level of physical activity was applied International Physical Activity Questionnaire (International Physical activity Questionnaire)-IPAQ. Main outcome measures: endomorphic component, percentage of body fat, energy intake and physical activity level. Results: We found that most adolescents (n = 32) showed intense physical activity, compared with the moderate physical activity (n = 13) and the mild physical activity (n = 3). Adolescents who had a mild level of physical activity had greater endomorphic component (6.1 ± 1.34), greater percentage of fat mass (19.0 ± 7.9) than those who had moderate or intense physical activity. However, these differences were not significant; the level of energy intake was similar among the three groups. Conclusions: No relationship was found between the endomorphic component, the percentage of fat mass and energy intake by level of physical activity in adolescents with Down syndrome. Keywords: endomorphic component, percentage of body fat, energy intake, physical activity. / Tesis

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