Reduced transferrin binding in Down syndrome:a route to senile plaque formation and dementia

Plasma transferrin binding in Down syndrome and Alzheimer's disease is significantly reduced compared with age matched controls and it was thought this may help elucidate a pathological time sequence for the onset of dementia in Down syndrome. In Down syndrome, there was a reduction in gallium and aluminium transferrin binding both with age and the onset of dementia. Non-transferrin bound gallium species were identified as non-transportable phosphate or silicate. Thus, the route of entry of metals into the brain must be via a transferrin mediated complex only. A clear sequence of pathological events has been demonstrated in Down syndrome which shows the pathway to development of plaques and dementia and this is believed to have an immunological origin.

Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia

Children with Down syndrome (DS) have a greatly increased risk of acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia (ALL). Both DS-AMKL and the related transient myeloproliferative disorder (TMD) have GATA1 mutations as obligatory, early events. To identify mutations contributing to leukemogenesis in DS-ALL, we undertook sequencing of candidate genes, including FLT3, RAS, PTPN11, BRAF, and JAK2. Sequencing of the JAK2 pseudokinase domain identified a specific, acquired mutation, JAK2R683, in 12 (28%) of 42 DS-ALL cases. Functional studies of the common JAK2R683G mutation in murine Ba/F3 cells showed growth factor independence and constitutive activation of the JAK/STAT signaling pathway. High-resolution SNP array analysis of 9 DS-ALL cases identified additional submicroscopic deletions in key genes, including ETV6, CDKN2A, and PAX5. These results infer a complex molecular pathogenesis for DS-ALL leukemogenesis, with trisomy 21 as an initiating or first hit and with chromosome aneuploidy, gene deletions, and activating JAK2 mutations as complementary genetic events. (Blood. 2009; 113: 646-648)

Prevalence and risk of Down syndrome in monozygotic and dizygotic multiple pregnancies in Europe: implications for prenatal screening

OBJECTIVE: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome.

DESIGN: Population-based prevalence study based on EUROCAT congenital anomaly registries.

SETTING: Eight European countries.

POPULATION: 14.8 million births 1990-2009; 2.89% multiple births.

METHODS: DS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases.

MAIN OUTCOME MEASURES: Relative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome.

STATISTICAL ANALYSIS: Poisson and logistic regression stratified for maternal age, country and time.

RESULTS: Overall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59]).

CONCLUSIONS: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening.

Erythrocyte Phospholipid Molecular Species and Fatty Acids of Down Syndrome Children Compared with Non-affected Siblings

The majority of children with Down syndrome (DS) develop Alzheimer's disease (AD) at an early age. Although long-chain n-3 fatty acids (FA) are protective of neurodegeneration, little is known about the FA status in DS. In the present study, we aimed to investigate whether children with DS presented altered plasma and erythrocyte membrane phospholipids (PL) FA composition, when compared with their non-affected siblings. Venous blood samples were analysed for plasma and erythrocyte membrane FA composition by TLC followed by GC techniques. Lipid molecular species were determined by electrospray ionisation/tandem MS (ESI-MS/MS). FA analysis measured by standard GC showed an increased concentration of MUFA and a decreased concentration of plasmalogens in major PL fractions, but there were no differences in the concentrations of arachidonic acid or DHA. However, as identified by ESI-MS/MS, children with DS had increased levels of the following erythrocyte PL molecular species: 16 : 0–16 : 0, 16 : 0–18 : 1 and 16 : 0–18 : 2n-6, with reduced levels of 16 : 0–20 : 4n-6 species. Children with DS presented significantly higher levels of MUFA in both plasma and erythrocyte membrane, as well as higher levels of saturated and monounsaturated molecular species. Of interest was the almost double proportion of 16 : 0–18 : 2n-6 and nearly half the proportion of 16 : 0–20 : 4n-6 of choline phosphoacylglycerol species in children with DS compared with their non-affected siblings. These significant differences were only revealed by ESI-MS/MS and were not observed in the GC analysis. Further investigations are needed to explore molecular mechanisms and to test the association between the pathophysiology of DS and the risk of AD.

Dentists’ actions about oral health of individuals with Down Syndrome

Aim: To investigate the knowledge and actions of dentists for treatment of individuals with Down syndrome. Methods: A questionnaire was applied to all the dentists (n=90) working at the FHS (Family Health Strategy) modules in the urban limits of Parnaíba, PI, Brazil. Four of the questions in the questionnaire were written according to the Theory of Planned Behavior Table and Likert scale (questions 6,7,9 and 15), in order to analyze the professionals’ intentions. Sixteen objective questions were elaborated with the purpose of collecting information about the degree of the dentists’ knowledge as regards the intention of attending courses in the patients with special needs area including DS, and interaction with other professionals and families. The option was to use a questionnaire applied to the dentists of the region, from August to November 2014. Results: It was found that most professionals were women and they considered themselves able to identify these patients. Among the professionals, 70% showed they had no difficulty in identifying the patient with DS, and 5.2% had no opinion about the subject. Only 6.6% of the professionals showed to be certain about their aptitude to attend to these patients; 70% were partially apt, that is, they were not absolutely sure about their aptness. There was a statistical relationship between the variables understanding and difficulty in the treatment. There was no statistical relationship between the variable capacity to identify, understanding of the needs and fitness variable in attendance. Conclusions: Patients with Down syndrome need more attention and care of dentists, they must also be involved in a multidisciplinary approach. Most of the professionals do not follow the procedures laid down by the Ministry of Health, but showed interest in attending a course in this area and there is a low number of SD patients being cared in Parnaíba, PI.

The effectiveness of outcome measures for Malaysian children with Down Syndrome

Study found that the assessments used were reliable and acceptable culturally for Malaysian children with Down Syndrome, with some changes on Parent Strengths and Difficulties Questionnaire. To identify specific difficulties with motor movement, level of involvement in the learning process, and socio-emotional wellbeing, the use of accurate assessment tools were crucial among health care teams, especially Occupational Therapist in Malaysia.

Early hearing loss and language abilities in children with Down syndrome

BACKGROUND: Although many children with Down syndrome experience hearing loss, there has been little research to investigate its impact on speech and language development. Studies that have investigated the association give inconsistent results. These have often been based on samples where children with the most severe hearing impairments have been excluded and so results do not generalize to the wider population with Down syndrome. Also, measuring children's hearing at the time of a language assessment does not take into account the fluctuating nature of hearing loss in children with Down syndrome or possible effects of losses in their early years. AIMS: To investigate the impact of early hearing loss on language outcomes for children with Down syndrome. METHODS & PROCEDURES: Retrospective audiology clinic records and parent report for 41 children were used to categorize them as either having had hearing difficulties from 2 to 4 years or more normal hearing. Differences between the groups on measures of language expression and comprehension, receptive vocabulary, a narrative task and speech accuracy were investigated. OUTCOMES & RESULTS: After accounting for the contributions of chronological age and nonverbal mental age to children's scores, there were significant differences between the groups on all measures. CONCLUSIONS & IMPLICATIONS: Early hearing loss has a significant impact on the speech and language development of children with Down syndrome. Results suggest that speech and language therapy should be provided when children are found to have ongoing hearing difficulties and that joint audiology and speech and language therapy clinics could be considered for preschool children.

Functional activity of neutrophils and systemic inflammatory response of Down's syndrome patients with periodontal disease

Periodontal disease (PD) is characterized as an inflammatory process that compromises the support and protection of the periodontium. Patients with Down's syndrome (DS) are prone to develop PD. Neutrophils (NE) are the first line of defense against infection and their absence sets the stage for disease. Aim: To compare the activity and function of NE in the peripheral blood from DS patients with and without PD, assisted at the Center for Dental Assistance to Patients with Special Needs affiliated with the School of Dentistry of Araçatuba, Brazil. Methods: Purified NE were collected from peripheral blood of 22 DS patients. NE were used to detect the 5-lypoxigenase (5-LO) expression by RT-PCR. Plasma from peripheral blood was collected to measure tumor necrosis factor-a (TNF-α) and interleukin-8 (IL-8) by ELISA and nitrite (NO 3) using a Griess assay. Results: Data analysis demonstrated that DS patients with PD present high levels of TNF-a and IL-8 when compared with DS patients without PD. However, there was no statistically significant difference in the levels of NO 3 production between the groups. The levels of the inflammatory mediator 5-LO expression increased in DS patients with PD. Conclusions: According with these results, it was concluded that TNF-α and IL-8 are produced by DS patients with PD. Furthermore, DS patients with PD presented high levels of 5-LO expression, suggesting the presence of leukotriene B 4 (LTB 4) in PD, thus demonstrating that the changes in NE function due to the elevation of inflammatory mediators contribute to PD.

Crenças e conhecimento de pais e profissionais de saúde sobre desenvolvimento de crianças com síndrome de Down até dois anos de idade

Este estudo apoia-se na abordagem sociocultural, em uma perspectiva interacionista da relação biologia cultura, beneficiando-se também do olhar da psicologia evolucionista para os fenômenos humanos. Estas abordagens, a partir de uma visão do homem como biologicamente cultural fazem-se relevantes para o estudo de crenças e conhecimento sobre o desenvolvimento de crianças com síndrome de Down (SD). Esta síndrome tem prevalência de um a cada 700 nascimentos, não importando classe social, racial ou local de nascimento dos pais, ou seja, é universal. A revisão da literatura revelou uma carência de estudos psicológicos sobre o contexto de desenvolvimento dessas crianças, inclusive as crenças de seus cuidadores e de profissionais de saúde. Sendo assim, o objetivo desse trabalho foi investigar crenças e conhecimento de dois grupos (pais e profissionais de saúde) sobre o desenvolvimento de crianças com síndrome de Down até dois anos de idade no Estado do Rio de Janeiro. Participaram da pesquisa 101 pessoas sendo 60 pais com filhos de até oito anos com síndrome de Down e 41 profissionais de saúde, médicos ou residentes do Instituto Fernandes Figueira, IFF/Fiocruz. Foram utilizados os seguintes instrumentos: Questionário com duas perguntas abertas sobre crenças sobre síndrome de Down que foram respondidas livremente pelos participantes; inventário sobre concepção de desenvolvimento infantil (ICDI); inventário sobre conhecimento de desenvolvimento infantil (KIDI) modificado, adaptado para crianças com síndrome de Down. Os dados foram analisados em aspectos qualitativos e quantitativos. A aplicação dos instrumentos foi realizada individualmente, em local conveniente para o participante ou no IFF/Fiocruz e após a assinatura do termo de consentimento. Os dados dos três instrumentos foram tratados e reduzidos. As respostas ao instrumento de crenças foram organizadas em categorias e comparadas. Escores nas diferentes subescalas do ICDI foram calculados e, em cada grupo (pais e profissionais) analisaram-se as concepções sobre desenvolvimento predominantes, estabelecendo-se comparações entre eles. Escores nas diferentes partes do KIDI foram ainda calculados (porcentagem de acertos). Foram feitas comparações intra e entre grupos. Os resultados foram tratados em cada um dos aspectos: crenças sobre SD, concepções e conhecimento sobre desenvolvimento. Os resultados obtidos mostram que as crenças dos pais estão distribuídas em oito categorias com três focos distintos (na criança, nos pais ou nos dois) e a dos profissionais em nove categorias, também, com três focos distintos (na SD, no médico e na criança e família). O resultado obtido no ICDI indica que os participantes valorizam mais as concepções de aprendizagem e interacionismo do que de maturação e que não há diferença significativa entre os grupos. Para o KIDI observou-se diferença significativa entre os grupos tanto no resultado geral de percentual de acertos como nos resultados em cada subescala. Espera-se que os resultados obtidos possam contribuir para a literatura sobre psicologia do desenvolvimento e síndrome de Down.

Down sindromea duen kolektiboaren agilidadean, koordinazioan eta orekan taekwondo-a duen eragina

[EUS] Proiektu honen bitartez, Down sindromea pairatzen duten, >14 urteko 8 parte hartzaileen agilidadea, koordinazioa eta oreka ebaluatu izan da, taekwondo-ko ordu bateko lau saio eginez. Aipaturiko faktoreak neurtzeko, ECOMI eskala egokitua erabili da. Hau, lehenengo eta azkenengo saioetan erabili izan da, datuak hartzeko eta konparaketak egin ahal izateko, eboluzioa ikusiz. Neurketak behin eginda, ikusi egin da bai koordinazioan eta orekan hobekuntzak izan dituztela orokorrean, aldiz, agilitatean ez da hobekuntza aipagarririk egon, eta aldi berean, parte hartzaileen arteko aldea nahiko nabarmena izan da. Hobekuntza ezak edo txikiak izateak, denbora eskasagatik izan dela esan daiteke. Beste autore batzuen esanetan, 20 saiotan hobekuntza nabarmenak lortu daitezke.