Genes, Crianças e Pediatras

info:eu-repo/semantics/publishedVersio

Defeitos congénitos da glicosilação

Congenital disorders of glycosylation are a highly variable, rapidly expanding family of genetic diseases that result from defects in the synthesis of glycans. The vast majority of these monogenic diseases are inherited in an autosomal recessive way, but some types follow an autosomal dominant or X-linked inheritance. The present work aimed to review the state of the art of congenital disorders of glycosylation, including available therapeutic options, and present a simplified diagnostic approach to this group of diseases. Congenital disorders of glycosylation can be classified into four categories: N-linked glycosylation defects, O-linked glycosylation defects, combined glycosylation defects, and glycosphingolipid and glycosylphosphatidylinositol anchor synthesis defects. The phenotype may range from mild to severe, depending on disease severity. Clinical features include dysmorphic features, neurologic, dermatologic, cardiac, endocrine, immunologic, hematologic, gastrointestinal and liver involvement, and skeletal muscle abnormalities. As there is no universal or pathognomonic sign or symptom and no sensitive diagnostic test, it is of foremost importance to keep a high index of suspicion of these diseases. When a congenital disorder of glycosylation is suspected, the first step in screening is to perform serum transferrin isoelectric focusing. Molecular genetic testing is the most specific diagnostic test. Treatment is usually symptomatic, with specific treatment only available for some of these disorders. Since congenital defects of glycosylation may affect any organ at any age and have variable clinical presentation, they should be considered in the differential diagnosis of any patient with multiorgan involvement.info:eu-repo/semantics/publishedVersio

Iron-sulfur Cluster ISD11 Deficiency (LYRM4 Gene) Presenting as Cardiorespiratory Arrest and 3-methylglutaconic Aciduria

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31497476/In the era of genomics, the number of genes linked to mitochondrial disease has been quickly growing, producing massive knowledge on mitochondrial biochemistry. LYRM4 gene codifies for ISD11, a small protein (11 kDa) acting as an iron-sulfur cluster, that has been recently confirmed as a disease-causing gene for mitochondrial disorders. We present a 4-year-old girl patient, born from non-consanguineous healthy parents, with two episodes of cardiorespiratory arrest after respiratory viral illness with progressive decreased activity and lethargy, at the age of 2 and 3 years. She was asymptomatic between crisis with regular growth and normal development. During acute events of illness, she had hyperlactacidemia (maximum lactate 5.2 mmol/L) and urinary excretion of ketone bodies and 3-methylglutaconic acid, which are normalized after recovery. A Next Generation Sequence approach with a broad gene panel designed for mitochondrial disorders revealed a novel probably pathogenic variant in homozygosity in the LYRM4 gene [p.Tyr31Cys (c.92A>G)] with Mendelian segregation. Functional studies in the skeletal muscle confirmed a combined deficiency of the mitochondrial respiratory chain (I, II, and IV complexes). To our knowledge, this is the third case of LYRM4 deficiency worldwide and the first with 3-methylglutaconic aciduria, not reported in any Fe-S cluster deficiency. Remarkably, it appears to be no neurological involvement so far, only with life-threating acute crisis triggered by expectably benign autolimited illnesses. Respiratory chain cofactors and chaperones are a new field of knowledge and can play a remarkable effect in system homeostasis.Fundação para a Ciência e a Tecnologia, Grant/Award Number: PTDC/DTP‐PIC/2220/2014; NORTE2020, Grant/Award Number: NORTE‐01‐0246‐FEDER‐000014info:eu-repo/semantics/publishedVersio

Seguindo as Linhas de Blaschko

.

Desenvolvimento da competência cultural na formação dos estudantes de enfermagem

The aim was to identify and map the strategies for the development of cultural competence during the training of students in nursing education institutions. For the elaboration of this Integrative Literature Review, the PCC method was used to develop the research question: What are the strategies used by Nursing Education Institutions to develop cultural competence during the training of students? To answer the question asked, a search was carried out, using the EBSCO-host and PubMed search engines, and the respective databases Cumulative Index to Nursing and Allied Health Literature and MedLine. No time horizon limits were applied. The established languages ​​were Portuguese, English and Spanish. For the assessment of methodological quality, we used a critical assessment instrument, specific for each type of study (qualitative and quantitative). Seven studies were included in the selection, which after being analyzed showed that there are strategies through which students can develop CC, but the most used are: Mobility Programs and Cultural Competence Courses. These results provide evidence of the potential use of educational strategies for the development of CC in nursing students.Objetivou-se identificar e mapear as estratégias de desenvolvimento da competência cultural durante a formação dos estudantes nas instituições de ensino de enfermagem. Para a elaboração da presente Revisão Integrativa da Literatura, recorreu-se ao método PCC, de forma a desenvolver a questão de investigação: Quais são as estratégias utilizadas pelas Instituições de Ensino de Enfermagem para Desenvolvimento da competência cultural durante a formação dos estudantes? De modo a dar resposta à questão formulada, realizou-se uma pesquisa, com recurso aos motores de busca EBSCO-host e PubMed, e às respectivas bases de dados Cumulative Index to Nursing and Allied Health Literature e MedLine. Não foram aplicados limites de horizonte temporal. Os idiomas estabelecidos foram, português, inglês e espanhol. Para a avaliação da qualidade metodológica, utilizamos um instrumento de avaliação crítica, específico para cada tipo de estudo (qualitativo e quantitativo). Sete estudos foram incluídos na seleção, que após analisados demonstraram que há estratégias através das quais os estudantes podem desenvolver CC, porém as mais utilizadas são: os Programas de Mobilidade e os Cursos de Competência Cultural. Estes resultados fornecem evidências do potencial da utilização das estratégias educativas relativamente ao desenvolvimento da CC nos estudantes de Enfermagem

Desenvolvimento da competência cultural na formação dos estudantes de enfermagem

The aim was to identify and map the strategies for the development of cultural competence during the training of students in nursing education institutions. For the elaboration of this Integrative Literature Review, the PCC method was used to develop the research question: What are the strategies used by Nursing Education Institutions to develop cultural competence during the training of students? To answer the question asked, a search was carried out, using the EBSCO-host and PubMed search engines, and the respective databases Cumulative Index to Nursing and Allied Health Literature and MedLine. No time horizon limits were applied. The established languages ​​were Portuguese, English and Spanish. For the assessment of methodological quality, we used a critical assessment instrument, specific for each type of study (qualitative and quantitative). Seven studies were included in the selection, which after being analyzed showed that there are strategies through which students can develop CC, but the most used are: Mobility Programs and Cultural Competence Courses. These results provide evidence of the potential use of educational strategies for the development of CC in nursing students.Objetivou-se identificar e mapear as estratégias de desenvolvimento da competência cultural durante a formação dos estudantes nas instituições de ensino de enfermagem. Para a elaboração da presente Revisão Integrativa da Literatura, recorreu-se ao método PCC, de forma a desenvolver a questão de investigação: Quais são as estratégias utilizadas pelas Instituições de Ensino de Enfermagem para Desenvolvimento da competência cultural durante a formação dos estudantes? De modo a dar resposta à questão formulada, realizou-se uma pesquisa, com recurso aos motores de busca EBSCO-host e PubMed, e às respectivas bases de dados Cumulative Index to Nursing and Allied Health Literature e MedLine. Não foram aplicados limites de horizonte temporal. Os idiomas estabelecidos foram, português, inglês e espanhol. Para a avaliação da qualidade metodológica, utilizamos um instrumento de avaliação crítica, específico para cada tipo de estudo (qualitativo e quantitativo). Sete estudos foram incluídos na seleção, que após analisados demonstraram que há estratégias através das quais os estudantes podem desenvolver CC, porém as mais utilizadas são: os Programas de Mobilidade e os Cursos de Competência Cultural. Estes resultados fornecem evidências do potencial da utilização das estratégias educativas relativamente ao desenvolvimento da CC nos estudantes de Enfermagem

A comprehensive assessment of the transcriptome of cork oak (Quercus suber) through EST sequencing

Background: Cork oak (Quercus suber) is one of the rare trees with the ability to produce cork, a material widely used to make wine bottle stoppers, flooring and insulation materials, among many other uses. The molecular mechanisms of cork formation are still poorly understood, in great part due to the difficulty in studying a species with a long life-cycle and for which there is scarce molecular/genomic information. Cork oak forests are of great ecological importance and represent a major economic and social resource in Southern Europe and Northern Africa. However, global warming is threatening the cork oak forests by imposing thermal, hydric and many types of novel biotic stresses. Despite the economic and social value of the Q. suber species, few genomic resources have been developed, useful for biotechnological applications and improved forest management. Results: We generated in excess of 7 million sequence reads, by pyrosequencing 21 normalized cDNA libraries derived from multiple Q. suber tissues and organs, developmental stages and physiological conditions. We deployed a stringent sequence processing and assembly pipeline that resulted in the identification of ~159,000 unigenes. These were annotated according to their similarity to known plant genes, to known Interpro domains, GO classes and E.C. numbers. The phylogenetic extent of this ESTs set was investigated, and we found that cork oak revealed a significant new gene space that is not covered by other model species or EST sequencing projects. The raw data, as well as the full annotated assembly, are now available to the community in a dedicated web portal at http://www.corkoakdb.org. Conclusions: This genomic resource represents the first trancriptome study in a cork producing species. It can be explored to develop new tools and approaches to understand stress responses and developmental processes in forest trees, as well as the molecular cascades underlying cork differentiation and disease response.Peer Reviewe

Diagnosis, management, and follow-up of mitochondrial disorders in childhood: a personalized medicine in the new era of genome sequence

Primary mitochondrial disorders are highly variable in clinical presentation, biochemistry, and molecular etiology. Mitochondrial disorders can be caused by genetic defects in the mitochondrial, in nuclear genome, or in the interplay between the two genomes. Biochemical screening tests may be inconclusive or misleading since patients, with confirmed mitochondrial disorders specially in pediatric age, may exhibit normal routine biochemistry, muscle histology, or enzymatic analysis of the mitochondrial respiratory chain. Diagnosis is often challenging even with combination of multiple criteria (clinical, biochemical, histological, and functional), as innumerous conditions cause secondary mitochondrial dysfunction. Nowadays, a definite diagnosis is only possible by genetic confirmation since no single score system is satisfactorily accurate, being sensitive but not specific.Conclusion: Awareness between physicians is of major importance considering that clinical suspicion may not be obvious regarding the heterogenicity in presentation and biochemical features of mitochondrial disorders. In this review, we provide information on diagnosis approach to patients suspected for mitochondrial disorders as well as management on chronic and acute settings. Follow-up should provide comprehensive information on patient's status, since intervention on these diseases is mostly supportive and prognosis is variable and sometimes unpredictable. What is Known: • Mitochondrial disorders are heterogenous and may present at any age, with any symptoms and any type of inheritance. • Mitochondrial disorders may be due to pathogenic variants in mitochondrial DNA (mtDNA) or nuclear genes (nDNA). What is New: • Since no single score system is satisfactorily accurate, a definite diagnosis is only possible with genetic studies with gene panels proving to be a cost-effective approach. • Clinical and biochemical features of patients without a confirmed diagnosis must be reviewed and other diagnosis must be considered. A wider genetic approach may be applied (WES or WGS).The customized gene panel referred in this paper was supported by FCT (PTDC/DTP-PIC/2220/2014) and NORTE2020 (NORTE-01-0246-FEDER-000014)info:eu-repo/semantics/publishedVersio