O timo é o órgão linfóide primário responsável pelo estabelecimento inicial de um repertório funcional de células T. A via de sinalização Notch é essencial para o desenvolvimento de células T a partir de células-tronco hematopoiéticas, e a distribuição de seus receptores e ligantes no timo humano ainda é desconhecida. A expressão de AIRE é crucial para a seleção de um repertório de receptores de linfócitos T (TCR) sem autorreatividade. Neste estudo, analisamos o padrão de expressão de AIRE e a distribuição de Notch em timos pacientes com cardiopatias congênitas, parte dos quais com síndrome de Down. Descrevemos a localização intratímica e os tipos celulares capazes de expressar os diferentes receptores e ligantes Notch. A expressão de AIRE em células epiteliais medulares foi significantemente reduzida em timos de crianças com síndrome de Down, deficiência esta que pode explicar a alta incidência de doenças autoimunes nesta cromossomopatia. / The thymus is a primary lymphoid organ which is essential for the initial establishment of a functional repertoire of T cells. Notch signaling is crucial for T-cell lineage development from hematopoietic stem cells; however, distribution of Notch ligands and receptors in human thymus is still unknown. AIRE is crucial for the selection of a T-cell-receptor (TCR) repertoire purged of self-reactive specificities. In this study, we analyzed the expression patterns of AIRE and Notch in human thymuses from children with congenital cardiopathies that undergo heart surgery, part of whom with Down syndrome. We described the intra-thymic localization and the cell types that express Notch receptors and ligands. AIRE expression in medullary epithelial cells is significantly decreased in Down syndrome patients. This deficiency could explain higher incidence of autoimmune disease in Down syndrome.

This work deals with displaying and measuring ultrasonic markers of congenital defects of the fetus in first trimester of pregnancy. Background research of ultrasonic markers was based on the studies of prof. Kypros Nicolaides (Great Britain), the president of the Fetal Medicine Foundation. This work contains a brief description of diagnosing of congenital defects during all three trimesters, and lists in detail defects that can be diagnosed properly during first trimester, as well as methods of calculating the risk of chromosomal abnormalities. In the next parts of this work, there are descriptions of methods used to improve results while measuring nuchal translucence (NT) strongest marker of Down syndrome in first trimester. The imaging capabilities of ultrasound devices were tested. Using scanned images, the influence of different display parameters on the resolution could be determined. Furthermore, using recommendations of the FMF, algorithms for adjusting correct slice of fetus and automatic measurement NT were designed and tested. A program application was designed that enabled testing of those algorithms on real images and calculating risks of chromosomal abnormalities from CRL and NT value. Designed algorithms were tested on real images. The program application, in witch the algorithms for measuring NT (NT detection algorithms) are included, was created.

Das Ziel dieser Arbeit ist es, ein für die besonderen Lernbedingungen von Kindern und Jugendlichen mit Down Syndrom geeignetes Training zu entwickeln, das es PädagogInnen ermöglicht, einen geplanten Förderwortschatz in strukturierter Weise zu vermitteln. Das Projekt folgt mit seinem Ansatz des syndromspezifischen Förderns dem probabilistischen Interventionsmodell (Fidler et al., 2009). Dafür liegt der Entwicklung des Wortschatztrainings eine Analyse der Spezifika der lexikalischen Entwicklung und des Wortlernens bei Kindern mit Down Syndrom (Darmer, 2018) sowie eine Befragung von Praktiker*innen aus Schule und Therapie zugrunde. Entsprechend der syndromspezifischen Bedingungen des Wortlernens bei Kindern mit Down Syndrom findet die Förderung schwerpunktmäßig auf der Ebene der Wortform statt und wird durch verschiedene Visualisierungen unterstützt. Besonders innovativ ist dabei der Einsatz von Lautgebärden, die PädagogInnen bislang vor allem im Kontext des Schriftspracherwerbs bekannt sind. Zielgruppe des so entstandenen lexikalischen Trainings „Worte lernen mit Lautgebärden (WoLLen) “ sind Schüler*innen mit Down Syndrom, die einen produktiven Wortschatz von mindestens 50 Wörtern erreicht haben und Mehrwortäußerungen produzieren. Daher ist nicht das Alter, sondern das Sprachentwicklungsniveau entscheidendes Kriterium. Im Rahmen der Konzeptentwicklung wurde eine kontrollierte Einzelfalluntersuchung mit drei Schülerinnen mit Down Syndrom im Alter von elf bis vierzehn Jahren des oben beschriebenen Sprachentwicklungsstandes im Multiple-Probe-Design durchgeführt. Die Trainingssitzungen wurden über einen Zeitraum von drei Monaten an vier Tagen in der Woche in jeweils zwanzigminütigen Sitzungen im Einzelsetting durchgeführt. Die Einzelfalluntersuchung erfolgte entsprechend des Versuchsplanes des Multiple-Probe-Designs mit drei Sets an Trainingswörtern. Die Produktion der vorab individuell festgelegten Trainingswörter war dabei die abhängige Variable und wurde im Rahmen einer Bildbenennung mit Frageimpuls und Abrufhilfen für alle Trainingswörter eines Sets in jeder Sitzung erhoben. Videoaufzeichnungen der Testungen ermöglichten die Berechnung einer Interrater-Reliabilität. Bei diesem Versuchsplan mit drei Kindern und jeweils drei Datensets konnte ein großer Wirksamkeitseffekt neun Mal nachgewiesen werden, womit die Studie einen Beitrag zur Entwicklung spezifischer Förderangebote für Kinder mit Down Syndrom leistet. Dennoch diskutiert die Arbeit das Konzept des syndromspezifischen Förderns im Abschluss kritisch und überträgt die Erfahrungen schließlich auf ein Modell zur Entwicklung von Förderkonzepten im Spiegel der evidenzbasierten Praxis. / This thesis aims to develop a lexical training program for teachers and teaching assistants that is adopted to the learning conditions of children and teenagers with Down Syndrome. This project is based on the idea of syndrome-specific interventions and the probabilistic intervention model (Fidler et al., 2009). The intervention builds on a structured review of the specific lexical development in children with Down Syndrome (Darmer, 2018) and a survey of practical experiences from speech and language therapists and special education teachers. According to the specific conditions of word learning in children with Down Syndrome, the intervention focuses on the morpho-phonological codes stored in the mental lexicon and uses a variety of visualization methods. The use of phonological gestures—signs that are known in German elementary schools to facilitate the association of sounds and letters—is considered especially innovative in a lexical training. The lexical training is hence called “learning words with phonological gestures.” It targets children with Down Syndrome with a productive mental lexicon of at least 50 words and the ability to produce multiple word utterances. Thus, it is not the chronological age of a child that is considered as criteria, but the level of language development. As an important step in the development of the intervention, three children with Down Syndrome, ages 11 to 14 years, participated in a single case design experiment. In the experiment, their response to the individual lexical training in 20-minute sessions four times a week was documented over a period of nearly three months. The study used a multiple-probe design with three sets of training words. Each set of words was chosen by testing the items in advance in order to assure they were not produced by the participant prior to the study. Hence, the production of the words was the dependent variable in this single case research. This was tested by having the participants label pictures belonging to the set of words. Cues were presented in the form of the phonological gesture of the first sound of the word or as a second step naming the first sound. Video recording allowed the analysis of interrater-reliability. As a result, the lexical training was found to have a strong effect in three participants in all three sets of training words. This initial evidence, which proves the efficacy of the training, is an important step in the development of specific interventions for children with Down Syndrome. Nevertheless, the research project concludes by discussing the approach of syndrome-specific interventions in a very critical way and transfers this discussion to a paradigm of how to develop pedagogical interventions by following the idea of evidence-based practice.

The purpose of this study was twofold: 1) To analyze the similarities and differences between parent responses to the birth and rearing of a child with Down syndrome and; 2) To document the characteristics of grieving described in Engel's 3-stage model of grieving. A questionnaire was used to assess responses from randomly chosen parent members of the Dallas Down Syndrome Guild. Qualitative data analysis was conducted, using the methodology of triangulation.

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No description available.

<p>  </p> <p>Down syndrome (DS) is caused by the partial or complete trisomy of human chromosome 21 (Hsa21) and can result in skeletal deficits, including lower bone mineral density (BMD) and increased risk of fracture and osteoporosis or osteopenia earlier than the general population. Mouse models of DS have been developed to understand the genetic mechanisms resulting in these phenotypes, but models differ due to the complex genetic nature of DS and differing genome structures between humans and mice. Ts65Dn mice have been a popular model of DS as they contain ~50% of Hsa21 orthologous genes on a freely segregating minichromosome, but there is speculation that the phenotypes are exaggerated by non-Hsa21 orthologous trisomic genes also present. To address this issue, the Ts66Yah mouse model was developed to remove the non-Hsa21 orthologous trisomic genes. In this study, male and female Ts66Yah mouse femurs were evaluated during bone accrual and peak bone mass to investigate structural differences using micro-computed tomography. Additionally, the role of trisomic <em>Dyrk1a</em>, a Hsa21 gene previously linked to bone deficits in Ts65Dn mice, was evaluated through genetic and pharmacological means in Ts66Yah femurs at postnatal day 36. Ts66Yah mice were found to have little or no trabecular deficits at any age evaluated, but sex-dependent cortical deficits were present at all ages investigated. Reducing <em>Dyrk1a</em> copy number in Ts66Yah mice significantly improved cortical deficits but did not return cortical bone to euploid levels. Pharmacological treatment with DYRK1A inhibitor L21 was confounded by multiple variables, making it difficult to draw conclusions about DYRK1A inhibition in this manner. Overall, these results indicate trabecular deficits associated with Ts65Dn mice may be due to the non-Hsa21 orthologous trisomic genes, and more Hsa21 orthologous trisomic genes are necessary to produce trabecular deficits in DS model mice. As more mouse models of DS are developed, multiple models need to be assessed to accurately define DS-associated phenotypes and test potential treatments.</p>

The intent of this thesis is to discover teaching strategies for students who have exceptionalities with a focus on students who have Autism, Down syndrome, or Visual Impairment and how these teaching strategies can be used to teach students in a mainstreamed secondary art classroom. Since the mainstreaming of the public school system has increased, students with exceptionalities have caused uncertainty among teachers about which teaching strategies to use in the classroom to meet all of their students needs. New teaching strategies need to be brought into the classroom to change the way students are learning. This thesis will include: the general facts, characteristics, accommodations, and modifications of Autism, Down syndrome, and Visual Impairment. An understanding of how students with Autism, Down syndrome, or Visual Impairment learn and what teaching strategies can be used in a secondary art classroom to provide the least restrictive learning environment to the students will be addressed. Suggested teaching strategies for students with Autism include the use of visualizations, change in pace, adaptive tools, and choosing materials wisely. For students with Down syndrome include simplification, repetition, breaking the lesson down into parts, and pacing. Students with Visual Impairment will need tactile materials, clear wording, descriptive visuals, and labeling, light, and intense color.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in an array of phenotypes including intellectual disability. Ts65Dn mice, the most extensively studied DS model, have three copies of ~50% of the genes on Hsa21 and display many phenotypes associated with DS, including cognitive deficits. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including CNS development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have shown that a three-week EGCG treatment (~10mg/kg/day) during adolescence normalizes skeletal abnormalities in Ts65Dn mice, yet the same dose did not rescue deficits in the Morris water maze spatial learning task (MWM) or novel object recognition (NOR). Others have reported that An EGCG dose of 2-3 mg per day (90mg/ml) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated deficits in a radial arm maze pattern separation task in Ts65Dn mice. Pattern separation requires differentiation between similar memories acquired during learning episodes; distinguishing between these similar memories is thought to depend on distinctive encoding in the hippocampus. Pattern separation has been linked to functional activity of newly generated granule cells in the dentate gyrus. Recent studies in Ts65Dn mice have reported significant reductions in adult hippocampal neurogenesis, and after EGCG treatment, enhanced hippocampal neurogenesis. Thus, it was hypothesized that Ts65Dn mice would be impaired in the pattern separation task, and that EGCG would alleviate the pattern separation deficits seen in trisomic mice, in association with increased adult hippocampal neurogenesis. At weaning, Ts65Dn mice and euploid littermates were randomly assigned to the water control, or EGCG [0.4 mg/mL], with both treatments yielding average daily intakes of ~50 mg/kg/day. Beginning on postnatal day 75, all mice were trained on a radial arm maze-delayed non-matching-to-place pattern separation task. Euploid mice performed significantly better over training than Ts65Dn mice, including better performance at each of the three separations. EGCG did not significantly alleviate the pattern separation deficits in Ts65Dn mice. After the behavioral testing commenced, animals were given ad libitum food access for five days, received a 100mg/kg injection of BrdU, and were perfused two hours later. Coronal sections through the dorsal hippocampus were processed for BrdU labeling, and cells were manually counted throughout the subgranular zone of the dentate gyrus. The euploid controls had significantly more BrdU labeled cells than Ts65Dn mice, however, EGCG does not appear to increase proliferation of the hippocampal neuroprogenitor cells. This is the first report of deficits in Ts65Dn mice on a pattern separation task. To the extent that pattern separation depends on the functional involvement of newly generated neurons in an adult dentate gyrus, this approach in Ts65Dn mice may help identify more targeted pharmacotherapies for cognitive deficits in individuals with DS.