A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia

Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad

Analysis of a probabilistic approach for modelling and assessment of the water quality of rivers

Monitoring the ecological status of water bodies is crucial to guarantee human health and economic development. However, monitoring is often deficient in developing regions due to high installation and maintenance costs, thus it is frequently supported by water quality models, whose results are themselves affected by the lack of detailed input data. A possible solution is to use probabilistic models that consider the inherent uncertainty of the different inputs. In this research, we extended a simple water quality model (QUAL-UFMG, based on Qual2E) through Monte Carlo simulations to generate probabilistic results and applied it to a representative case study in Brazil. Results showed that, depending on the distribution of probabilities and variability of parameters adopted, the outcome of a non-deterministic modelling approach may differ significantly from a deterministic one regarding compliance with water quality standards. Moreover, the probabilistic strategy is more scientifically transparent and robust, as it explicitly communicates the uncertainty in both the measured data and modelling results. We conclude that a probabilistic approach is particularly useful in regions with a low data availability such as developing countries, as uncertainties are high due to insufficient monitoring, and the risk to human health is elevated due to a low prevalence of sanitation

Os paradigmas atuais da formação docente: olhares sobre o PIBID

Dissertação apresentada como requisito parcial para obtenção do título de Mestre ao Programa de PósGraduação em Educação da Universidade Federal de Rondônia.Nesta pesquisa investigamos os atuais paradigmas da formação docente e a proposta de formação do PIBID de Química da UNIR. O objetivo central deste estudo buscou investigar em quais aspectos o PIBID contribuiu para a formação inicial dos ex-bolsistas de iniciação à docência do período de 2009 a 2013. O estudo tem uma abordagem qualitativa/exploratória e utilizamos os seguintes instrumentos de coleta de dados: questionários, entrevistas e análise documental. Os sujeitos da pesquisa foram oito egressas do curso de Química e expibidianas; dois coordenadores de área e; duas supervisoras do PIBID/Química da UNIR. Ao analisarmos os dados coletados, identificamos uma proposta de formação pautada no paradigma da prática-reflexiva diferentemente do modelo apresentado pelo currículo do curso de Química. Assim, o programa é um norteador para o desenraizamento da racionalidade técnica presente no curso de Licenciatura em Química da UNIR. Os principais resultados encontrados foram: maior articulação entre a teoria e prática; mobilização dos saberes da experiência aos licenciandos por meio do contato com a realidade escolar e com os coordenadores e supervisores; o ensino da Química pauta-se em fundamentos atuais, nos quais são priorizados uma função social dos conteúdos relacionando a disciplina com o contexto social e com uma aprendizagem significativa para a formação do cidadão; desenvolvimento de trabalhos em equipe e; metodologia baseada em ensino prático reflexivo. Embora haja alguns limitantes no programa, como: 1) não haver um prazo para a continuidade do programa, ou seja, pode ser encerrado a qualquer momento e; 2) não dar acesso a todos os estudantes de licenciatura, os aspectos positivos promovidos pelo programa em um curto espaço de tempo são singulares para a (re)construção da carreira docente e do ensino de Química

Neural crest E-cadherin loss drives cleft lip/palate by epigenetic modulation via pro-inflammatory gene-environment interaction

Gene-environment interactions are believed to play a role in multifactorial phenotypes, although poorly described mechanistically. Cleft lip/palate (CLP), the most common craniofacial malformation, has been associated with both genetic and environmental factors, with little gene-environment interaction experimentally demonstrated. Here, we study CLP families harbouring CDH1/E-Cadherin variants with incomplete penetrance and we explore the association of pro-inflammatory conditions to CLP. By studying neural crest (NC) from mouse, Xenopus and humans, we show that CLP can be explained by a 2-hit model, where NC migration is impaired by a combination of genetic (CDH1 loss-of-function) and environmental (pro-inflammatory activation) factors, leading to CLP. Finally, using in vivo targeted methylation assays, we demonstrate that CDH1 hypermethylation is the major target of the pro-inflammatory response, and a direct regulator of E-cadherin levels and NC migration. These results unveil a gene-environment interaction during craniofacial development and provide a 2-hit mechanism to explain cleft lip/palate aetiology

A Novel Autosomal Recessive GJA1 Missense Mutation Linked to Craniometaphyseal Dysplasia

Craniometaphyseal dysplasia (CMD) is a rare sclerosing skeletal disorder with progressive hyperostosis of craniofacial bones. CMD can be inherited in an autosomal dominant (AD) trait or occur after de novo mutations in the pyrophosphate transporter ANKH. Although the autosomal recessive (AR)form of CMD had been mapped to 6q21-22 the mutation has been elusive. In this study, we performed whole-exome sequencing for one subject with AR CMD and identified a novel missense mutation (c.716G>A, p.Arg239Gln) in the C-terminus of the gap junction protein alpha-1 (GJA1) coding for connexin 43 (Cx43). We confirmed this mutation in 6 individuals from 3 additional families. The homozygous mutation cosegregated only with affected family members. Connexin 43 is a major component of gap junctions in osteoblasts, osteocytes, osteoclasts and chondrocytes. Gap junctions are responsible for the diffusion of low molecular weight molecules between cells. Mutations in Cx43 cause several dominant and recessive disorders involving developmental abnormalities of bone such as dominant and recessive oculodentodigital dysplasia (ODDD; MIM #164200, 257850) and isolated syndactyly type III (MIM #186100), the characteristic digital anomaly in ODDD. However, characteristic ocular and dental features of ODDD as well as syndactyly are absent in patients with the recessive Arg239Gln Cx43 mutation. Bone remodeling mechanisms disrupted by this novel Cx43 mutation remain to be elucidated

NOVAS TECNOLOGIAS: ABRIDOR DE AMPOLAS

Trata-se do relato da construção do projeto e execução de um abridor de ampolas. A peça confeccionada, classifica-se como uma tecnologia dura e, tem o objetivo de reduzir os riscos de acidentes no dia a dia do trabalho dos profissionais da área da saúde, especialmente os que lidam com a aplicação de medicamentos que tenham a sua apresentação em forma de ampolas. Para o desenvolvimento da peça (abridor de ampolas) inicialmente, utilizamos madeira, após, cano PVC e por fim encontramos o melhor material, por ser passível de esterilização que foi o aço inox. A peça não foi inserida no mercado de trabalho, mais fizemos experiências com ampolas de diversos tamanhos e modelos, obtendo um ótimo resultado, uma vez que os estilhaços de vidro ficam todos no interior do abridor diminuindo o risco de acidente por material perfuro cortante entre os profissionais. Esperamos que este peça se torne um instrumento de trabalho dos profissionais da saúde.Palavras-chaves: Inovação. Assistência de Enfermagem. Segurança no Trabalho

Anthropometric self-reported measures: relationship to body image perception and satisfaction among adolescents

OBJECTIVE: To assess the reliability of the classification for nutritional status and height-for-age when using self-reported weight and height and its relationships with self-reported data of body image perception and satisfaction among adolescents. METHODS: In this retrospective study, 304 adolescents before they had measured their height and weight, they self-reported these measures, they were asked about their body shape perception and body image classification was obtained by using a body silhouette scale. It was also used specific tests to assess body satisfaction and food behavior. RESULTS: It was found full agreement between height-for-age classification using self-reported and measured height (k = 1.00) and an intermediate level of agreement between body mass index calculated with self-reported and measured data (k < 0.75). However, adolescents who perceived themselves as skinny underestimated their self-reported body mass index whereas those who perceived themselves as fat overestimated it. Those who perceived themselves as fat in the silhouette scale underestimated their body mass index. Gender was also a factor for unreliable answers, as females tended to underestimate their self-reported body mass index and males to overestimate it. CONCLUSION: The adolescents adequately self-reported weight and height information. However, body shape perception and body image classification were factors affecting answer reliability.OBJETIVO: Verificar a validade da classificação do estado nutricional e da estatura para idade quando utilizadas massa corporal e estatura autorreferidas por adolescentes, bem como relacionar essa validade com percepção e com satisfação corporal. MÉTODOS: 304 adolescentes antes de terem suas medidas de massa e estatura aferidas autorreferiram essas medidas, foram questionados sobre a percepção de seu corpo e a classificação da imagem corporal foi obtida com o uso de uma escala de silhuetas corporais. Também foram aplicados testes específicos para avaliar a satisfação corporal e o comportamento alimentar. RESULTADOS: As classificações feitas com base nos dados autorreferidos e aferidos tiveram concordância alta (K = 1,00) para a classificação da estatura por idade e moderada (K < 0,75) para a classificação de índice de massa corporal. No entanto, adolescentes que se consideravam abaixo do peso subestimaram o índice de massa corporal autorrelatado e, os que se percebiam como gordos, o superestimaram. As meninas e os que se classificaram como obesos tenderam a subestimar o índice de massa corporal, e os meninos, a superestimá-lo. CONCLUSÃO: Os adolescentes autorrelataram suas medidas de massa e estatura de maneira adequada. No entanto, o sexo, a percepção e a classificação da imagem corporal foram variáveis que influenciaram na obtenção de respostas não válidas.Universidade Federal de São Paulo (UNIFESP) Centro de Atendimento e Apoio ao Adolescente Departamento de PediatriaUniversidade Estadual de Campinas Faculdade de Ciências MédicasUNIFESP, Centro de Atendimento e Apoio ao Adolescente Depto. de PediatriaSciEL

Association of polymorphisms at the ADIPOR1 regulatory region with type 2 diabetes and body mass index in a Brazilian population with European or African ancestry

Association studies between ADIPOR1 genetic variants and predisposition to type 2 diabetes (DM2) have provided contradictory results. We determined if two single nucleotide polymorphisms (SNP c.-8503G>A and SNP c.10225C>G) in regulatory regions of ADIPOR1 in 567 Brazilian individuals of European (EA; N = 443) or African (AfA; N = 124) ancestry from rural (quilombo remnants; N = 439) and urban (N = 567) areas. We detected a significant effect of ethnicity on the distribution of the allelic frequencies of both SNPs in these populations (EA: -8503A = 0.27; AfA: -8503A = 0.16; P = 0.001 and EA: 10225G = 0.35; AfA: 10225G = 0.51; P < 0.001). Neither of the polymorphisms were associated with DM2 in the case-control study in EA (SNP c.-8503G>A: DM2 group -8503A = 0.26; control group -8503A = 0.30; P = 0.14/SNP 10225C>G: DM2 group 10225G = 0.37; control group 10225G = 0.32; P = 0.40) and AfA populations (SNP c.-8503G>A: DM2 group -8503A = 0.16; control group -8503A = 0.15; P = 0.34/SNP 10225C>G: DM2 group 10225G = 0.51; control group 10225G = 0.52; P = 0.50). Similarly, none of the polymorphisms were associated with metabolic/anthropometric risk factors for DM2 in any of the three populations, except for HDL cholesterol, which was significantly higher in AfA heterozygotes (GC = 53.75 ± 17.26 mg/dL) than in homozygotes. We conclude that ADIPOR1 polymorphisms are unlikely to be major risk factors for DM2 or for metabolic/anthropometric measurements that represent risk factors for DM2 in populations of European and African ancestries.FAPESP 04/0185-5CEPIDHospital de Clínicas de Porto Alegr

Abridor de ampolas: ferramenta para a enfermagem / Ampoule opener: tool for nursing

Trata-se do relato da construção do projeto e execução de um abridor de ampolas. A peça confeccionada, classifica-se como uma tecnologia dura e, tem o objetivo de reduzir os riscos de acidentes no dia a dia do trabalho dos profissionais da área da saúde, especialmente os que lidam com a aplicação de medicamentos que tenham a sua apresentação em forma de ampolas. Para o desenvolvimento da peça (abridor de ampolas) inicialmente, utilizamos madeira, após, cano PVC e por fim encontramos o melhor material, por ser passível de esterilização que foi o aço inox. A peça não foi inserida no mercado de trabalho, mais fizemos experiências com ampolas de diversos tamanhos e modelos, obtendo um ótimo resultado, uma vez que os estilhaços de vidro ficam todos no interior do abridor diminuindo o risco de acidente por material perfuro cortante entre os profissionais. Esperamos que este peça se torne um instrumento de trabalho dos profissionais da saúde

mir152 hypomethylation as a mechanism for non-syndromic cleft lip and palate

Non-syndromic cleft lip with or without cleft palate (NSCLP), the most common human craniofacial malformation, is a complex disorder given its genetic heterogeneity and multifactorial component revealed by genetic, epidemiological, and epigenetic findings. Epigenetic variations associated with NSCLP have been identified; however, functional investigation has been limited. Here, we combined a reanalysis of NSCLP methylome data with genetic analysis and used both in vitro and in vivo approaches to dissect the functional effects of epigenetic changes. We found a region in mir152 that is frequently hypomethylated in NSCLP cohorts (21–26%), leading to mir152 overexpression. mir152 overexpression in human neural crest cells led to downregulation of spliceosomal, ribosomal, and adherens junction genes. In vivo analysis using zebrafish embryos revealed that mir152 upregulation leads to craniofacial cartilage impairment. Also, we suggest that zebrafish embryonic hypoxia leads to mir152 upregulation combined with mir152 hypomethylation and also analogous palatal alterations. We therefore propose that mir152 hypomethylation, potentially induced by hypoxia in early development, is a novel and frequent predisposing factor to NSCLP