A novel DMD intronic alteration: a potentially disease-causing variant of an intermediate muscular dystrophy phenotype.

Pathogenic germline variants in DMD gene, which encodes the well-known cytoskeletal protein named dystrophin, are associated with a wide range of dystrophinopathies disorders, such as Duchenne muscular dystrophy (DMD, severe form), Becker muscular dystrophy (BMD, mild form) and intermediate muscular dystrophy (IMD). Muscle biopsy, immunohistochemistry, molecular (multiplex ligation-dependent probe amplification (MLPA)/next-generation sequencing (NGS) and Sanger methods) and in silico analyses were performed in order to identify alterations in DMD gene and protein in a patient with a clinical manifestation and with high creatine kinase levels. Herein, we described a previously unreported intronic variant in DMD and reduced dystrophin staining in the muscle biopsy. This novel DMD variant allele, c.9649+4A>T that was located in a splice donor site within intron 66. Sanger sequencing analysis from maternal DNA showed the presence of both variant c.9649+4A>T and wild-type (WT) DMD alleles. Different computational tools suggested that this nucleotide change might affect splicing through a WT donor site disruption, occurring in an evolutionarily conserved region. Indeed, we observed that this novel variant, could explain the reduced dystrophin protein levels and discontinuous sarcolemmal staining in muscle biopsy, which suggests that c.9649+4A>T allele may be re-classified as pathogenic in the future. Our data show that the c.9649+4A>T intronic sequence variant in the DMD gene may be associated with an IMD phenotype and our findings reinforce the importance of a more precise diagnosis combining muscle biopsy, molecular techniques and comprehensive in silico approaches in the clinical cases with negative results for conventional genetic analysis.

Preparation, structural, microstructural, mechanical and cytotoxic characterization of as-cast Ti-25Ta-Zr alloys.

Titanium alloys have been widely used as biomaterials, especially for orthopedic prostheses and dental implants, but these materials have Young's modulus almost three times greater than human cortical bones. Because of this, new alloys are being produced for the propose of decreasing Young's modulus to achieve a more balanced mechanical compatibility with the bone. In this paper, it is reported the development of Ti-25Ta alloys as a base material, in which was introduced zirconium, with concentration varying between 0 and 40 wt%, with the aim of biomedical applications. The alloys were prepared in an arc-melting furnace. The microstructural analysis was performed by x-ray diffraction as well as optical and scanning electron microscopy. Selected mechanical properties were analyzed by microhardness and Young's modulus measurements, and cytotoxicity analysis by indirect test. X-ray measurements revealed the presence of α″ phase in the alloy without zirconium; α″ + ß phases for alloys with 10, 20, and 30 wt% of zirconium, and ß phase only for the alloy with 40 wt% of zirconium. These results were corroborated by the microscopy results. The hardness of the alloy was higher than that of cp-Ti due to the actions of zirconium and tantalum as hardening agents. The Young's modulus decreases with high levels of zirconium due to the stabilization of the ß phase. The cytotoxicity test showed that the extracts of studied alloys are not cytotoxic for osteoblast cells in short periods of culture.

Effect of Thermomechanical Treatments on the Phases, Microstructure, Microhardness and Young's Modulus of Ti-25Ta-Zr Alloys.

Titanium and its alloys currently are used as implants, possessing excellent mechanical properties (more suited than stainless steel and Co-Cr alloys), good corrosion resistance and good biocompatibility. The titanium alloy used for most biomedical applications is Ti-6Al-4V, however, studies showed that vanadium and aluminum cause allergic reactions in human tissues and neurological disorders. New titanium alloys without the presence of these elements are being studied. The objective of this study was to analyze the influence of thermomechanical treatments, such as hot-rolling, annealing and solution treatment in the structure, microstructure and mechanical properties of the Ti-25Ta-Zr ternary alloy system. The structural and microstructural analyses were performed using X-ray diffraction, as well as optical, scanning and transmission electron microscopy. The mechanical properties were analyzed using microhardness and Young's modulus measurements. The results showed that the structure of the materials and the mechanical properties are influenced by the different thermal treatments: rapid cooling treatments (hot-rolling and solubilization) induced the formation of α" and ß phases, while the treatments with slow cooling (annealing) induced the formation of martensite phases. Alloys in the hot-rolled and solubilized conditions have better mechanical properties results, such as low elastic modulus, due to retention of the ß phase in these alloys.

[Analysis of infant mortality trends and risk factors in Porto Alegre, Rio Grande do Sul State, Brazil, 1996-2008]. / Análise de tendências das taxas de mortalidade infantil e de seus fatores de risco na cidade de Porto Alegre, Rio Grande do Sul, Brasil, no período de 1996 a 2008.

The aim of this article was to determine trends in infant mortality and related risk factors in Porto Alegre, Rio Grande do Sul State, Brazil. The study was based on data from a live birth and infant death registry for the years 1996 to 2008. Times trends were analyzed for overall and partial infant mortality rates according to maternal schooling, number of prenatal visits, maternal age, number of live and dead children, sex of the newborn, type of delivery, birth weight, and type of hospital. Poisson regression was used to estimate the influence of socioeconomic status and other risk factors. The infant mortality rate dropped among mothers with less than 11 years of schooling. There were no significant changes among newborns of mothers with 12 or more years of schooling. Maternal socioeconomic status was the factor most closely associated with the reduction in infant mortality. Still, the downward trend failed to achieve its full potential, due to the increase in low birth weight.

Análise de tendências das taxas de mortalidade infantil e de seus fatores de risco na cidade de Porto Alegre, Rio Grande do Sul, Brasil, no período de 1996 a 2008 / Analysis of infant mortality trends and risk factors in Porto Alegre, Rio Grande do Sul State, Brazil, 1996-2008

Objetiva-se determinar as tendências de mortalidade infantil e de seus fatores de risco em Porto Alegre. Este é um estudo baseado nas informações do registro de nascidos vivos e de óbitos infantis no período de 1996-2008. Foi analisada a tendência temporal das taxas de mortalidade infantil (TMI) e de seus componentes, de acordo com a escolaridade materna, o número de consultas de pré-natal, idade materna, número de filhos vivos e mortos, sexo do recém-nascido, o tipo de parto, a idade gestacional, o peso de nascimento e o tipo de hospital. Foi utilizada a regressão sequencial de Poisson para estimar a influência da condição socioeconômica e os demais fatores de risco. A TMI decaiu entre os nascidos de mães com escolaridade inferior a 11 anos. Entre os nascidos de mães com 12 ou mais anos de escolaridade, não houve alterações significativas. A condição socioeconômica materna foi o fator que mais se associou à redução da mortalidade infantil. Contudo, a tendência de redução não atingiu todo o potencial devido ao aumento do baixo peso ao nascer.

The aim of this article was to determine trends in infant mortality and related risk factors in Porto Alegre, Rio Grande do Sul State, Brazil. The study was based on data from a live birth and infant death registry for the years 1996 to 2008. Times trends were analyzed for overall and partial infant mortality rates according to maternal schooling, number of prenatal visits, maternal age, number of live and dead children, sex of the newborn, type of delivery, birth weight, and type of hospital. Poisson regression was used to estimate the influence of socioeconomic status and other risk factors. The infant mortality rate dropped among mothers with less than 11 years of schooling. There were no significant changes among newborns of mothers with 12 or more years of schooling. Maternal socioeconomic status was the factor most closely associated with the reduction in infant mortality. Still, the downward trend failed to achieve its full potential, due to the increase in low birth weight.

Colangite aguda / Cholangitis acute

A colangite é uma afecção do trato biliar com significativa morbi-mortalidade associada. Muitos pacientes com colangite aguda respondem à antibioticoterapia. Entretanto, aqueles com a forma severa ou tóxica da doença usualmente não respondem, necessitando de drenagem biliar de emergência

Colostomias: atualização e análise crítica / Colostomies: update and critical analyse

Os autores se propõem a realizar atualização e análise crítica das colostomias, enfatizando noções sobre conceito, indicações, classificação, cuidados pré-operatórios, complicações e fechamento das mesmas