Analysis of Factor VIII polymorphic markers as a means for carrier detection in Brazilian families with haemophilia A

Haemophilia A is an X-linked, recessively inherited bleeding disorder of varying severity, which results from the deficiency of procoagulant factor VIII f(8). Linkage diagnosis using polymorphic markers in the f8 gene is widely used to detect carriers. The objective of this study was to verify the informativeness of three polymorphic markers in the Brazilian population, to evaluate the usefulness of such markers in carrier detection procedures. Sixty-three unrelated healthy volunteers and 10 haemophilic families were studied. Two microsatellite repeats and one HindIII RFLP markers were used. Carrier and non-carrier status could be determined in 80% of females investigated. Intron 13 markers presented the highest heterozygosity rate (79%) followed by intron 22 (68%) and intron 19 (57%). When all three markers were used together, linkage analysis informativeness increased significantly. We conclude that these markers are suitable for carrier detection in the Brazilian population and we recommend their use in combination to maximize diagnostic efficiency.

A memória de curto prazo e a síndrome de down: a relação entre contextos de desenvolvimento

Down syndrome (DS) is one of the most frequent causes of intellectual disability, affecting one in every 600 to 1000 live births. Studies have demonstrated that people with DS have a lower capacity for short-term memory (STM) and working memory (WM), which affects their capability to learn new words and to follow spoken instructions, specially when they involve multiple information or consecutive orders/orientations. It seems that the basis of the learning process, as it happens with language and mathematics comprehension and reasoning, relies in the STM and WM systems. Individuals with DS are increasingly included in mainstream education, and yet, very few researches have been conducted to investigate the influence of memory development and the type of enrollment (regular school and special school). This study investigated the relationship between the type of school enrollment with the performance on STM tests and also, the relationship of this performance with early stimulation (ES). The tests used in the first research were the digit span, free recall, word recognition and subtests of the Wechsler Intelligence Scale for Children Third Edition (WISC-III). Individuals enrolled in the regular schools group had higher scores on the digit span test and the subtests of the WISC-III. In the free recall and recognition tests, no differences were found. This study indicates that the type of enrollment might influence the memory development of individuals with DS and clearly points the need for future investigations. In the second research, the tests used were the digit span, free word recall and subtests of the WISC-III. The test results showed better performance by adults that received ES before six months of age. The studies showed improvement in STM both in people who attended or were attending regular school, as well as those who benefited from ES before six months of age. However, some issues still need to be better understood. What is the relation between this stimulation with the individual s education? Since ES may reflect a greater family involvement with the individual, what is the role of emotional components derived from this involvement in the cognitive improvement? These and other questions are part of the continuity of this study

Effect of Citrus aurantium l. essential oil on muscle regeneration in mdx mice

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disorder characterized by the progressive loss of muscular strength. Mdx mutant mice show a marked deficiency in dystrophin, which was related to muscle membrane stability. The aim of this study was to verify the possible protective anti-inflammatory effect of citrus oil on mdx muscle fibers. Thus, adult male and female mdx mice (014/06-CEEA) were divided into control and citrus-treated. After 60 days of treatment, one ml of blood was collected for creatine kinase (CK) test. Diaphragm, sternomastoideus, anterior tibial and gastrocnemius muscles were removed and processed according to histological routine methods. The observed alterations indicate a direct effect of citrus. Recent studies have improved the diagnosis of muscular diseases but with no definitions of efficient treatments. Intervention with several therapies is important to many patients presenting muscular dystrophy, which enables them to live longer and be more active, while there is no development of gene therapies.

Ectodermal dysplasia, ectrodactyly, clefting, anophthalmia microphthalmia, and genitourinary anomalies: nosology of goltz-gorlin syndrome versus eec syndrome

We report on two unrelated Brazilian girls born to normal and nonconsanguineous parents and presenting ectodermal dysplasia, ectrodactyly, clefting, tear duct anomalies, and micro/anophthalmia. The clinical picture presented by these patients suggests the diagnosis of Goltz-Gorlin (Focal dermal hypoplasia) syndrome and EEC syndrome.

Incontinentia pigmenti presenting as hypodontia in a 3-year-old girl: A case report

Introduction. Incontinentia pigmenti or Bloch-Sulzberger syndrome is a rare X-linked dominant disease that mainly affects the skin, eyes, hair, central nervous system and teeth. The disease is predominant among women. Although dermatologic manifestations are among the most important aspects for the diagnosis of the syndrome, they are less damaging to the patient and do not require treatment. However, oral involvement characterized by hypodontia of deciduous and permanent teeth is important for the diagnosis and treatment of the patient. Case presentation. We report the case of a 3-year-old girl with ophthalmologic and neurologic disturbances, cutaneous manifestations and hypodontia. Since the patient did not present more damaging manifestations such as neurologic and/or ophthalmologic problems, her most severe complications were related to dental anomalies. The importance of integrated dental treatment, which combines pediatric dentistry, orthodontics and conventional prosthesis, is emphasized. Conclusion. Hypodontia is a frequent finding in incontinentia pigmenti, and dentists should be aware of this condition in order to help with the diagnosis. © 2009 Kitakawa et al; licensee BioMed Central Ltd.

Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith-Magenis syndrome

Smith-Magenis syndrome (SMS) is a complex disorder whose clinical features include mild to severe intellectual disability with speech delay, growth failure, brachycephaly, flat midface, short broad hands, and behavioral problems. SMS is typically caused by a large deletion on 17p11.2 that encompasses multiple genes including the retinoic acid induced 1, RAI1, gene or a mutation in the RAI1 gene. Here we have evaluated 30 patients with suspected SMS and identified SMS-associated classical 17p11.2 deletions in six patients, an atypical deletion of ∼139 kb that partially deletes the RAI1 gene in one patient, and RAI1 gene nonsynonymous alterations of unknown significance in two unrelated patients. The RAI1 mutant proteins showed no significant alterations in molecular weight, subcellular localization and transcriptional activity. Clinical features of patients with or without 17p11.2 deletions and mutations involving the RAI1 gene were compared to identify phenotypes that may be useful in diagnosing patients with SMS. © 2012 Macmillan Publishers Limited All rights reserved.

HDAC inhibition decreases XIST expression on female IVP bovine blastocysts

During initial development, both X chromosomes are active in females, and one of them must be silenced at the appropriate time in order to dosage compensate their gene expression levels to male counterparts. Silencing involves epigenetic mechanisms, including histone deacetylation. Major X chromosome inactivation (XCI) in bovine occurs between hatching and implantation, although in vitro culture conditions might disrupt the silencing process, increasing or decreasing X-linked gene expression. In this study, we aimed to address the roles of histone deacetylase inhibition by trichostatin A (TSA) on female preimplantation development.We tested the hypothesis that by enhancing histone acetylation, TSA would increase the percentage of embryos achieving 16-cell stage, reducing percentage of embryos blocked at 8-cell stage, and interfere with XCI in IVF embryos. We noticed that after TSA treatment, acetylation levels in individual blastomeres of 8-16 cell embryos were increased twofold on treated embryos, and the samewas detected for blastocysts. Changes among blastomere levels within the same embryo were diminished on TSA group, as low-acetylated blastomeres were no longer detected. The percentage of embryos that reached the 5th cleavage cycle 118 h after IVF, analyzed by Hoechst staining, remained unaltered after TSA treatment. Then, we assessed XIST and G6PD expression in individual female bovine blastocysts by quantitative real-time PCR. Even though G6PD expression remained unaltered after TSA exposure, XIST expression was eightfold decreased, and we also detected a major decrease in the percentage of blastocysts expressing detectable XIST levels after TSA treatment. Based on these results, we conclude that HDAC is involved on XCI process in bovine embryos, and its inhibition might delay X chromosome silencing and attenuate aberrant XIST expression described for IVF embryos. © 2013 Society for Reproduction and Fertility.

Softwares educativos para alunos com deficiência intelectual: Estratégias utilizadas

The computer is present in everyday school life and using it with educational software must be mediated and planned in order for this resource to contribute to student learning, including those with intellectual disabilities (ID). Therefore, the aim was to propose specific computer activities for students with ID using educational software, and to quantify and analyze the technical and pedagogical strategies used. The participants were six students with ID enrolled in two public schools. To collect information we used observation protocols and a field journal. Data were analyzed quantitatively and qualitatively, based on the concepts of mediation and the zone of proximal development of cultural-historical theory. The results indicated that when the content developed in the computer classes were compatible with the proposed activities in the classroom, students with ID had opportunities to experience different activities that enable them to be successful. We noted that what enabled them to understand and correctly perform the proposed activities were the teaching strategies. Thus, we consider that technical knowledge about educational software and pedagogical knowledge about content that is being worked on, are insufficient to ensure that the proposed activity will contribute to the development of students with ID.

Enzyme replacement therapy for Anderson-Fabry disease.

Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers. To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease. We searched 'Clinical Trials' on The Cochrane Library, MEDLINE, EMBASE, LILACS and the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 11 September 2012). The original search was performed in September 2008.Date of the most recent search of the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register: 11 September 2012. Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease. Two authors selected relevant trials, assessed methodological quality and extracted data. Six trials comparing either agalsidase alfa or beta in 223 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One trial reported pain scores, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval (CI) -3.79 to -0.41); at up to five months, mean difference -1.90 (95% CI -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% CI -3.66 to -0.34). There was a significant difference in pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% CI -3.92 to -0.28) but not at other time-points. Neither trial reported deaths.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% CI -2.09 to -1.31); heart, mean difference -0.90 (95% CI -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% CI -5.45 to -4.15). There was no significant difference between groups for death; no trials reported on pain.Only one trial compared agalsidase alfa to agalsidase beta. There was no significant difference between the groups for any adverse events, risk ratio 0.36 (95% CI 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; 95% CI 0.03 to 2.57). Six small, poor quality randomised controlled trials provide no robust evidence for use of either agalsidase alfa and beta to treat Anderson-Fabry disease.

Escolarização de alunos com deficiência intelectual em classes comuns e em salas de recursos multifuncionais

Pós-graduação em Educação Escolar - FCLAR

A problematização das tarefas de casa no contexto da educação inclusiva: um estudo de caso

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Inclusão de alunos com deficiência intelectual: considerações sobre avaliação da aprendizagem escolar

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

O uso de objetos educacionais no ensino de Física e suas relações com o processo de inclusão

Pós-graduação em Educação - FCT

A inclusão das diferenças e as diferenças na inclusão: impasses na inclusão de alunos com necessidades especiais

Pós-graduação em Psicologia - FCLAS

Nas tramas da educação inclusiva: considerações sobre as políticas públicas educacionais para a inclusão

Pós-graduação em Serviço Social - FCHS