Introdução: A síndrome de Down (SD) é uma alteração genética caracterizada pela presença de um cromossomo extra, suas principais dificuldades são causadas pelas alterações motoras e cognitivas que interferem na capacidade de realizar atividades diárias. Para propiciar funcionalidade às pessoas com SD, uma opção é utilizar tarefas em ambiente de realidade virtual para possibilitar o ganho de habilidades motoras. Objetivo: Avaliar o desempenho de pessoas com SD em tarefa virtual em telefone móvel. Método: Foi utilizado o jogo Marble Maze Classic®, onde os participantes moviam o telefone móvel para conduzir uma bola virtual por um desenho de labirinto. Foram avaliadas 100 pessoas separadas em dois grupos, sendo o grupo 1 (controle) formado por 25 participantes com Desenvolvimento Típico e grupo 2 (experimental) formado por 25 pessoas com SD, sendo o desenho do labirinto do grupo 2 totalmente oposto ao do grupo 1. Como variável dependente utilizou-se o tempo em segundos e foram submetidas a ANOVA. As comparações post-hoc foram realizadas por meio do teste Tukey-HSD (p < 0,05). Resultados: O grupo controle manteve o desempenho na fase de retenção e conseguiram transferir tanto no labirinto 1 como no 2. Já o grupo SD conseguiu transferir a tarefa apenas no labirinto 2. No labirinto 1 não conseguiu transferir quando invertemos o início e o fim do trajeto. Conclusão: Pessoas com SD conseguiram se adaptar a tarefa proposta, porém com desempenho sempre inferior às pessoas com DT. Assim como, demonstraram dificuldade em manter o desempenho com o aumento do grau de dificuldade da tarefa, o que sugere que novas tecnologias devem ser adaptáveis às dificuldades de pessoas com SD, permitindo assim maior funcionalidade / Introduction: Down syndrome (DS) is a genetic disorder characterized by the presence of an extra chromosome, which is typically associated with motor and cognitive changes that interfere with the ability to perform daily activities. To provide functionality to individuals with DS, one option is to use tasks in a virtual reality environment to enable gains in motor skills. Objective: To evaluate the performance of individuals with DS in a virtual task on a mobile phone. Method: The game Marble Maze Classic® was used, in which the participants moved the mobile phone to conduct a virtual marble through a maze design. We evaluated 100 individuals divided into group 1 and 2, where each group consisted of 25 participants in the control group (typical development) and 25 in the experimental group (DS), with group 2 using a maze design totally opposite to group 1. The dependent variable used was time in seconds and was subjected to ANOVA. Post-hoc comparisons were performed using Tukey\'s Honest Significant Difference test (p <0.05). Results: The control group maintained performance in the retention phase and was able to transfer both in maze 1 and 2. The DS group managed transfer to the task only in maze 2. In maze1, the DS group failed to transfer when we inverted the start and end of the path. Conclusion: People with DS have managed to adapt the proposed task, but with always underperform people with DT. As demonstrated difficulty in maintaining performance with increased task difficulty, suggesting that new technologies must be adaptable to the difficulties people with DS, thereby enabling increased functionality

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-07-19T17:12:32Z No. of bitstreams: 1 Jamile Benite Palma Lopes.pdf: 2604798 bytes, checksum: 02648b7db4e837bd186b6ad03db7b39b (MD5) / Made available in DSpace on 2018-07-19T17:12:32Z (GMT). No. of bitstreams: 1 Jamile Benite Palma Lopes.pdf: 2604798 bytes, checksum: 02648b7db4e837bd186b6ad03db7b39b (MD5) Previous issue date: 2017-10-26 / Objective: To perform a comparative analysis of the effects of manual reach training through virtual reality in the upper limb, with and without the association of transcranial stimulation by direct current of children with Down's Syndrome. Materials and methods: Study I: A systematic review was conducted with a search in four databases, according to: randomized controlled study; virtual reality, cerebral palsy; Down Syndrome published between 2010 and 2016. Study II: A systematic review was conducted with a search in four databases according to: randomized controlled study; cross-sectional study; evaluation; motion analysis; Dowm syndrome; Member published between 2010 and 2016. Study III: Detailed description of the protocol of a virtual reality intervention study associated with transcriana stimulation by direct current. Study IV: Comparative study between children with Down Syndrome and with typical Development, making a relation between the parameters of motor function of the upper limbs to the assessments constituted by single evaluation of three-dimensional analysis of the movement. Study V: ETCC anodic was performed with an intensity of 1 mA in bilateral M1 in a sample of 24 children with Down Syndrome, allocated in two groups (active and sham). The pacing protocol was performed with three training sessions per week, and the evaluations took place in three moments: pre, post-protocol and 1-month follow-up, consisting of three-dimensional analysis of manual upper limb movement, quality of manual skills and brain activity in the C3 and Cz regions of the cortex. Materials and methods: Study I: A systematic review was conducted with a search in four databases, according to: randomized controlled study; virtual reality, cerebral palsy; Down Syndrome published between 2010 and 2016. Study II: A systematic review was conducted with a search in four databases according to: randomized controlled study; cross-sectional study; evaluation; motion analysis; Dowm syndrome; Member published between 2010 and 2016. Study III: Detailed description of the protocol of a virtual reality intervention study associated with transcriana stimulation by direct current. Study IV: Comparative study among children with Down Syndrome and with typical Development, making a relation between the parameters of motor function of the upper limbs to the assessments constituted by single evaluation of three-dimensional analysis of the movement. Study V: ETCC was performed with an intensity of 1 mA in bilateral M1 in a sample of 24 children with Down Syndrome, allocated in two groups (active and sham). The pacing protocol was performed with three training sessions per week, and the evaluations took place in three moments: pre, post-protocol and 1-month follow-up, consisting of three-dimensional analysis of manual upper limb movement, quality of manual skills and brain activity in the C3 and Cz regions of the cortex. / Objetivo: Realizar uma análise comparativa dos efeitos do treino de alcance manual por meio da realidade virtual em membro superior, com e sem a associação da estimulação transcraniana por corrente contínua de crianças com Síndrome de Down. Materiais e método: Estudo I: Foi realizada uma revisão sistemática com uma busca em quatro bases de dados, de acordo com: estudo controlado randomizado; realidade virtual, paralisia cerebral; Síndrome de Down publicados entre 2010 e 2016. Estudo II: Foi realizada uma revisão sistemática com uma busca em quatro bases de dados de acordo com: estudo controlado randomizado; estudo transversal; avaliação; análise de movimento; Síndrome de Dowm; membro superior publicados entre 2010 e 2016. Estudo III: Descrição detalhada do protocolo de um estudo de intervenção de realidade virtual associada a estimulação transcriana por corrente contínua. Estudo IV: Estudo comparativo entre crianças com Síndrome de Down e com desenvolvimento típico, fazendo uma relação entre os parâmentros de função motora dos membros superiores às avaliações constituídas por única avaliação de análise tridimensional do movimento. Estudo V: ETCC anódica realizada com uma intensidade de 1 mA em M1 bilateral numa amostra de 24 crianças com Síndrome de Down, alocadas em dois grupos (ativo e sham) - RESULTADOS PRELIMARES. O protocolo de estimulação foi realizado com três sessões de treino por semana, sendo que as avaliações ocorreram em três momentos: pré, pós-protocolo e follow-up de 1 mês, sendo constituída por análise tridimensional do movimento de alcance manual dos membros superiores, qualidade das habilidades manuais e atividade cerebral nas regiões C3 e Cz do córtex. Resultados: Estudo I: cinco ensaios clínicos foram selecionados com uma qualidade metodológica de 4 pontos ou mais na escala PEDro, sendo aceito para publicação no periódico Journal of bodywork and Movement Therapies. Estudo II: cinco ensaios clínicos foram selecionados com uma qualidade metodológica avaliados pelo instrumento de Avaliação Crítica Crowe, sendo submetido ao Journal Infant Behavior. Estudo III: artigo de protocolo de estudo com metodologia de intervenção com estimulação transcraniana por corrente continua associada a treino motor de realidade virtual, publicado no periódico BMJOPEN. Estudo VI: Os resultados da análise da cinemática do movimento de alcance manual entre crianças com desenvolvimento típico e Sindrome de Down apresentaram diferenças no aspecto da velocidade, tempo e acurácia do movimento. Estudo V: Os resultados deste estudo demonstraram que o grupo de crianças com SD que recebeu o treinamento com o protocolo de 10 sessões de 20 minutos de ETCC anódica sobre o córtex motor primário (C3 e C4) com montagem extracefalica bilateral apresentou respostas positivas a esta intervenção nos aspectos funcionais e do movimento dos MMSS nas avaliações realizadas logo após o término do protocolo, bem como ao follow-up de um mês pós intervenção em comparação com o grupo que recebeu ETCC Sham durante o mesmo tipo de treino motor. Conclusão: A combinação de treinamento funcional do alcance manual e ETCC anódica sobre o córtex motor primário bilateral em crianças com SD demonstrou resultados encorajadores, tanto a curto quanto a longo prazo no que diz respeito à melhora do movimento do MS, como não houve resultado significativo quando analisados dados prelimares de parâmetros da cinemática do movimento e aumento da melhora da qualidade das habilidades e de MMSS.

INTRODUÇÃO: A prevalência dos fatores de risco clássicos para a doença cardiovascular (DCV), maior causa de morbimortalidade no Brasil e no mundo, encontra-se razoavelmente estabelecida na população geral. Entretanto, pouco se conhece sobre sua incidência em populações especiais, entre elas, a com síndrome de Down. O objetivo do presente estudo foi avaliar a incidência de fatores de risco para a DCV em indivíduos jovens com trissomia do cromossomo 21. MÉTODOS: Estudo transversal que inclui 45 crianças e 44 adultos jovens com síndrome de Down, matriculados em uma instituição de ensino não governamental. Parâmetros antropométricos, como peso, altura e circunferência abdominal (CA), foram avaliados em conjunto com parâmetros clínicos, como pressões sistólica (PAS) e diastólica (PAD). Também foram obtidas de todos os indivíduos, amostras de sangue para dosagens de glicemia, índice HOMA-ir, proteína C reativa de alta sensibilidade (PCRas) e perfil lipídico. Todas as variáveis foram consideradas como fatores de risco cardiovascular. RESULTADOS: As alterações encontradas com maior frequência no grupo pediátrico foram o índice de massa corpórea (IMC): 60,0% e as alterações nos níveis de PCRas: 69,4%. Para o grupo adulto, as taxas foram ainda mais elevadas, IMC: 65,9% e PCRas 77,2%. Valores de IMC elevados correlacionaram-se com uma maior prevalência de obesidade central, representada pela CA ( < 0,001), PAS (p < 0,02), PAD (p=0,007), e níveis elevados de insulina basal (p=0,003) e de HOMA-ir (p=0.01). O achado mais relevante foi uma forte associação com níveis de PCRas alterados, presentes em três quartos (76,8%) dos indivíduos com excesso de peso. CONCLUSÃO: Obesidade central e a alta prevalência de fatores de risco para a doença cardiovascular sugerem a necessidade de um maior monitoramento desses parâmetros, em conjunto com alterações de estilo de vida / BACKGROUND: Down syndrome patients are subject to highly deleterious conditions such as obesity and sedentarism. DESIGN: Transverse study including 45 children and 44 young adults with Down syndrome from a healthcare center. METHODS: Weight, height, waist (WC) and blood pressure [systolic (SBP) and diastolic (DBP)] were recorded according to the international criteria. Blood samples for fasting glucose, insulin, HOMA-ir, high-sensitivity C-reactive protein (hsCRP), and lipid profile were obtained of all individuals. RESULTS: The most frequently found alterations in the pediatric group were BMI (60.0%,) and hsCRP (69.4%). For the adult group, BMI (65.9%) and hsCRP (77.2%) rates were even higher. Body mass index (BMI) elevations from individuals correlated with a higher prevalence of central obesity, represented by WC ( < 0.001), SBP (p < 0.02), DBP (p=0.007), basal insulin (p=0.003) and HOMA-ir (p=0.01). The major characteristic was the hsCRP elevation, present in three quarters (76.8%) of the individuals with excess weight. CONCLUSION: Central obesity and a high frequency of cardiovascular risk markers in individuals with Down syndrome urge to a careful monitoring and better lifestyle habits

<p>Down syndrome (DS) is a genetic disorder that results from triplication of human chromosome 21 (Hsa21) and occurs in around 1 in 1000 live births. All individuals with DS present with skeletal abnormalities typified by craniofacial features, short stature and low bone mineral density (BMD). Differences between males and females with DS suggest a sexual dimorphism in how trisomy affects skeletal deficits associated with trisomy 21 (Ts21). Previous investigations of skeletal abnormalities in DS have varied methodology, sample sizes and ages making the underlying causes of deficits uncertain. Mouse models of DS were used to characterize skeletal abnormalities, but the genetic and developmental origin remain unidentified. Over-expression <i>Dyrk1a</i>, found on Hsa21 and mouse chromosome 16 (Mmu16) has been linked to cognitive deficits and skeletal deficiencies. Dp1Tyb mice contain three copies of all of the genes on Mmu16 that are homologous to Hsa21, males and females are fertile, and therefore are an excellent model to test the hypothesis that gene dosage influences the sexual dimorphism of bone abnormalities in DS. Dp1Tyb at 6 weeks 16 weeks showed distinctive abnormalities in BMD, trabecular architecture, and reduced bone strength over time that occur generally through an interaction between sex and genotype. Increased gene dosage and sexual dimorphism in Dp1Tyb mice revealed distinct phenotypes in bone formation and resorption. To assess how <i>Dyrk1a</i> influences the activity and function of osteoblasts Ts65Dn female trisomic mice, female mice with a floxed <i>Dyrk1a</i> gene (Ts65Dn, <i>Dyrk1a</i>^fl/+) were be bred to <i>Osx1</i>-GFP::Cre+ mice to generate Ts65Dn animals with a reduced copy of <i>Dyrk1a </i>in mature osteoblast cells. Female Ts65Dn,<i>Dyrk1a^+/+/+</i>and Ts65Dn,<i>Dyrk1a^+/+/-</i>displayed significant defects in both trabecular architecture and cortical geometry. Ultimate force was reduced in trisomic animals, suggesting whole bone and tissue level properties are not adversely affected by trisomy. Reduction of <i>Dyrk1a</i> functional copy number in female mice did not improve skeletal deficits in an otherwise trisomic animal. <i>Dyrk1a </i>may not alter osteoblast cellular activity in an autonomous manner in trisomic female mice. These data establish sex, gene dosage, skeletal site and age as important factors in skeletal development of the skeleton in DS mice, potentially paving the way for identification of the causal dosage-sensitive genes in both male and female animals. </p>

Cellular senescence is thought to play an essential role in many biological functions including tumor suppression and organismal aging. Senescent cells, which are permanently removed from the cell cycle, can be found both in vivo in many different tissue types and in vitro within cultures of non-immortalized cells. Despite their inability to proliferate, these cells persist and remain metabolically active for indefinite periods of time. This physiologic process occurs in response to a variety of cellular insults including oxidative stress, shortened telomeres, constitutive oncogene expression, and DNA damage, and can be initiated by upregulation of one of the two known senescent pathways, involving p16/Rb or p53/p21. The senescent cell phenotype is also characterized by changes to cell and nuclear morphology and to the secretory profile of the cell. Related to changes in nuclear morphology, epigenetic modifications to the packaging of DNA are thought to be key to the initiation and maintenance of the senescence program. While a large number of earlier studies focused on the findings that senescent cells gain regions of condensed heterochromatin, often in the form of Senescent Associated Heterochromatin Foci (SAHF), this thesis work shows that there is a marked loss of heterochromatin in the peri/centromeric regions of the genome. In fact, both α-satellite and satellite II sequences across the genome distend in a striking and unanticipated fashion; this can be readily visualized by fluorescence in situ hybridization (FISH) as their structure changes from a condensed spot to highly elongated and fine thread-like signals. We have termed this exceptional decondensation of constitutive heterochromatin Senescence Associated Distension of Satellites (SADS). Importantly, a series of experiments shows that SADS is both a consistent and an early event in the cell senescence process, which occurs as a result of every senescence induction method examined. We also observed that this distension was characteristic of both human and murine cells and in vivo in human benign Prostatic Intraepithelial Neoplasia (PIN) tissue. Furthermore, unlike SAHF formation, SADS can occur due to the activation of either of the two senescence pathways, p16/Rb or p53/p21. Additionally, the cytological dimensions of the thread-like satellite signals indicates that SADS represents “unraveling” of DNA on an unprecedented scale. Thus, it was surprising that this event was not facilitated by changes to several canonical histone modifications associated with condensed heterochromatin, namely H3K9Me3, H3K27Me3, or H3K4Me3, nor is it caused by loss of DNA methylation. Consequently, we believe that this marked distension of satellite DNA is due to changes in higher-order folding of the chromatin fiber. This is important for understanding fundamental events in the cell senescence process, but also provides a unique system for study of chromatin packaging that may provide new insights into the organization of DNA well beyond nucleosome packaging and the ten nanometer fiber. In fact, initial super resolution images of SADS suggest that the satellite sequences may be organized into domains or “globules”. Hence, we suggest that the changes to satellite sequence packaging may be facilitated by changes to higher-order nuclear structural proteins, such as LaminB1, which is reduced in senescent cells. Finally, this work provides analysis of the literature and preliminary experiments to consider the possibility that there are increased levels of cell senescence in Down syndrome (trisomy 21) cells. As individuals with Down syndrome (DS) experience many manifestations of premature aging (including early-onset Alzheimer’s Disease), have a resistance to solid tumor formation, are more susceptible to oxidative stress, and are trisomic for several genes implicated in causing senescence, our analysis provides plausibility for the hypothesis that accelerated rates of senescence may play a significant role in DS physiology. We also provide results of preliminary studies and outline the next steps for experimentation, using DS fibroblasts and a unique genetically engineered DS iPS cell system. As a final note, the quantification of cell senescence in trisomic versus disomic cells for these experiments relies substantially on the new single-cell marker of senescence discovered and established by this theses work, the Senescence-Associated Distension of Satellites.

No description available.

Contexte. En France, les Troubles du Spectre de l'Autisme (TSA) sont encore rarement identifiés chez des enfants présentant une Trisomie 21 (T21), malgré la disponibilité d'outils de dépistage et de diagnostic. La T21 est une maladie génétique associée à une déficience intellectuelle ainsi qu'à des difficultés sociales, communicatives et comportementales qui rendent le diagnostic additionnel de TSA délicat à poser. Pourtant de nombreux enfants avec T21 présentent aussi un autisme. L'errance diagnostique prive les jeunes enfants d'une prise en charge comportementale et développementale précoce et adaptée. Objectif. Le but de l'étude est (1) de mieux comprendre les caractéristiques du développement cognitif et socio-émotionnel et du fonctionnement de la régulation des activités de ces enfants au double diagnostic et (2) d'en identifier les spécificités comparativement à des enfants atteints de trisomie 21 d'une part et des enfants avec autisme d'autre part. Cette recherche a aussi pour objectif finalisé de sensibiliser les professionnels et les institutions à la reconnaissance de cette psychopathologie du développement (double diagnostic) afin notamment d'encourager un meilleur repérage de l'autisme dès le plus jeune âge chez les enfants atteints de T21 et pour déterminer le plus tôt possible les prises en charge répondant à leurs besoins spécifiques, centrées sur le développement cognitif et socio-émotionnel et la régulation des activités. Méthode. Participants : Les participants sont des volontaires recrutés dans des institutions d'accueil et des associations de familles. Trois groupes d'enfants, appariés en âge de développement, sont comparés : (1) 18 enfants au double diagnostic T21 et TSA, (2) 25 enfants porteurs de T21 et (3) 21 enfants avec TSA. Leur niveau de développement se situe dans la période d'âge de 4 à 24 mois. Matériel : Le diagnostic d'autisme est réalisé à l'aide du Manuel Diagnostique et Statistique des troubles mentaux -5ème édition- (DSM-5, APA, 2013) et la Childhood Autism Rating Scale (CARS, Schopler, Reichler & Daly, 1980). Le développement cognitif et socio-émotionnel est évalué à l'aide de La Batterie d'Évaluation Cognitive et Socio-émotionnelle (BECS, Adrien, ECPA, 2007) et la régulation des activités cognitives et émotionnelles à l'aide de la Grille Régulation Adaptation Modulation (GRAM, Adrien,1996), de la Grille d'analyse des stratégies autorégulatrices et hétérorégulatrices en situation d'apprentissage ou de résolution de problème (Nader-Grosbois, 2000) et de Emotion Regulation Checklist (Shields & Cicchetti,1997). Procédure : Un formulaire d'information et de consentement a été proposé aux familles avant de participer à une évaluation unique du développement et du comportement de l'enfant. Résultats. On note l'existence de profils développementaux spécifiques chez les enfants atteints conjointement de trisomie 21 et d'autisme, et de grandes variabilités inter et intra-individuelles dans le développement et la régulation émotionnelle des enfants atteints de troubles du développement : trisomie 21 avec autisme / trisomie 21 sans autisme / autisme. Conclusion : La meilleure connaissance des caractéristiques du développement et du fonctionnement régulateur des enfants au double diagnostic de T21 et de TSA permet d'envisager des interventions personnalisées et une plus grande sensibilisation des professionnels et des institutions à l'importance de la reconnaissance précoce de ce double diagnostic. Diagnostiquer les TSA chez de jeunes enfants avec T21 et les considérer comme trouble primaire semble justifié, afin de leur proposer une intervention plus adaptée. / Context. In France, Autism Spectrum Disorder (ASD) is still rarely identified in children with Down's syndrome (DS). However, specific autism diagnostic instruments have shown good sensitivity for detecting ASD in this population. DS is a genetic disease associated with mental retardation and with social, communicative and behavioural impairment making difficult the dual diagnosis. However, a lot of children with DS also present TSA. The lack of diagnosis deprives young children of an early and appropriate behavioural and developmental support. Objective. This study aimed (1) to provide evidence of specific features in the cognitive and socio-emotional development and activity regulation functioning of young children with a dual diagnosis and (2) to identify specificities compared to children with DS and children with TSA. This research also aimed to sensitize professionals to the recognition of this developmental psychopathology (dual diagnosis). This included encourage better identification of autism at an early age in children with DS, and to determine an appropriate support to their specific needs, focusing on cognitive and social development and activity regulation. Method. Participants: They were volunteers recruited in institutions and family associations. Three groups of children, matched in their developmental age, were compared: (i) 18 children with a dual diagnosis, (ii) 25 children with DS and (iii) 21 children with ASD. Their developmental level is included in the 4 to 24 months' age period. Tools: To diagnose autism, we used Dianostic and Statiscal Manual of mental disorders -fifth edition- (DSM-5, APA, 2013) and Childhood Autism Rating Scale (CARS, Schopler, Reichler & Daly, 1980). Cognitive and socio-emotional development assessed by means of the Socio-emotional and Cognitive Evaluation Battery (SCEB). Cognitive and emotional activities regulation assessed by Regulation Disorders Evaluation Grid (RDEG, Adrien,1996), the Coding and scoring grid for other-regulation and self-regulation (Nader-Grosbois, 2000) and the Emotion Regulation Checklist (Shields & Cicchetti,1997). Procedure: Parents were signed informed consent forms before the developmental and behavioural assessment of children. Results. We revealed the existence of specific developmental profiles among children with dual diagnosis of DS and ASD, and large variability inter- and intra-individual in the development and emotional regulation of children with developmental disorders: DS with TSA / DS without TSA / TSA. Conclusion. A better knowledge of the developmental and regulation functioning characteristics of children with dual diagnosis of DS and ASD allows to propose personalized support and to increase awareness among professionals to to the importance of early recognition this dual diagnosis. It seems justified to diagnose ASD in young children with DS and consider it a primary disorder, in order to offer them a more adapted intervention.

Indiana University-Purdue University Indianapolis (IUPUI) / Down syndrome (DS) is the result of trisomy of human chromosome 21 (Hsa 21) and occurs in approximately 1/700 live births. Mouse models of DS have been crucial in understanding the gene-phenotype relationships that underlie many DS anomalies. The Ts65Dn mouse model, trisomic for half of the Hsa 21 orthologs replicates many DS phenotypes including craniofacial alterations such as a small, dysmorphic mandible, midface, and maxilla. Other mouse models, such as the Ts1Rhr which contains a triplication of 33 Hsa 21 orthologs, have been used to better understand the genes responsible for craniofacial alterations. Our laboratory has demonstrated that the postnatal mandibular phenotype found in Ts65Dn mice can be traced back to an original neural crest cell (NCc) deficit in the developing first pharyngeal arch (PA1) at embryonic day 9.5 (E9.5). Furthermore, evidence suggested that both a proliferation deficit in the PA1 and a migration deficit in the NCC from the neural tube (NT) could be the mechanism behind this deficit. However, the molecular mechanisms behind these deficits remain to be elucidated. Due to the involvement of the Hsa 21 genes DYRK1A and RCAN1 in regulation of signaling pathways including NFATc (NFAT2), a transcription factor known to influence cellular proliferation and, later, bone development, we hypothesized that dysregulation of these genes could underlie the cellular deficit in the PA1. Furthermore, we hypothesized that targeting Dyrk1a by decreasing activity or available protein could ameliorate the established deficits. Through the use of RNA isolation techniques and cell culture systems of cell from the PA1 and NT of E9.5 Ts65Dn, Ts1Rhr, and control embryos, we established that trisomic genes Dyrk1a and Rcan1 ara dysregulated in both structures and that these two genes may interact. Furthermore, we established that a proliferation deficit in the Ts65Dn PA1 and a migration deficit in the Ts65Dn PA1 and NT exists at E9.5 and can be rescued to euploid levels in vitro with the addition of the Dyrk1a inhibitor, EGCG, a green tea polyphenol. We also confirmed that harmine, a more highly studied and specific Dyrk1a inhibitor, is capable of similar effects on proliferation of PA1 cell from E9.5 Ts65Dn embryos. Furthermore, when Ts65Dn pregnant mothers were treated with EGCG in vivo, the cellular deficit found in the developing E9.5 embryonic PA1 was rescued to near euploid volume and NCC number. Treatment with EGCG did not adversely impact litter size or embryonic development. Interestingly, euploid embryonic volume increased with EGCG treatment. Expression analysis of the E9.5 PA1 of EGCG treated Ts65Dn and control embryos revealed dysregulation of several genes involved in craniofacial and developmental pathways including Dyrk1a, Rcan1, Ets2 and members of the sonic hedgehog pathways. Our novel results provide a foundation for better understanding the molecular mechanisms of craniofacial development and may provide evidence-based therapeutic options to improve the quality of life for individuals with DS.

No description available.

Syfte: Syfte med denna litteraturstudie var att undersöka oral hälsa hos barn och ungdomar med Downs syndrom    Metod: Studien är en allmän litteraturstudie där sökningarna genomfördes i databaserna CINAHL, MEDLINE och Dentistry &amp; oral sciences source (DOSS). Vetenskapliga artiklar som svarade på studiens syfte valdes utifrån inklusions- och exklusionskriterier samt relevanta sökord. Resultat: Totalt granskades 22 kvantitativa studier som visade att barn och ungdomar med Downs syndrom hade sämre munhygien, fler orala sjukdomar och bettavvikelser jämfört med barn och ungdomar utan Downs syndrom. De redovisade orala sjukdomarna/ tillstånden var karies, gingivit, parodontit, oral candidos, bettavvikelser, attrition, agenesi och dental erosion. Riskfaktorer som kan påverka utveckling av orala sjukdomar och bettutvecklings störningar var exempelvis munhygienvanor och oralmotoriska faktorer. Slutsats: Barn och ungdomar med Downs syndrom har en ökad risk att drabbas av orala sjukdomar och bettavvikelser. Genom ökad kunskap om den orala hälsan hos barn och ungdomar med Downs syndrom kan tandhygienister arbeta förebyggande och motivera till stöd och omhändertagande för denna riskgrupp. / Aim: The aim of this literature study was to investigate oral health in children and adolescents with Down syndrome. Method: The study is a general literature study where the searches were carried out in the databases CINAHL, MEDLINE and Dentistry &amp; oral sciences source (DOSS). Scientific articles that responded to the purpose of the study were selected based on inclusion and exclusion criteria and relevant keywords. Results: A total of 22 quantitative studies were reviewed which showed that children and adolescents with Down syndrome had poorer oral hygiene, more oral diseases and malocclusions compared to children and adolescents without Down syndrome. The reported oral diseases/conditions were caries, gingivitis, periodontitis, oral candidosis, malocclusions, attrition, agenesis and dental erosion. Risk factors that can influence the development of oral diseases and malocclusions, for example, oral hygiene habits and oral motor factors. Conclusion: Children and young people with Down syndrome have an increased risk of suffering from oral diseases and malocclusions. Through increased knowledge about the oral health of children and young people with Down syndrome, dental hygienists can work preventively and motivate support and care for this risk group.