The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio

Synergic deposition route for the functionalisation of biomedical devices

Abstract: Titanium has been widely used for dental implants due to its biocompatibility, corrosion resistance, and mechanical properties. In order to improve osseointegration, the Ti surface is generally functionalized. A typical methodology for surface modification is the coating of Ti substrates with bioactive layers of calcium phosphate ceramics (CPCs) [1]. However, CPC coatings on metal implants usually suffer from poor adhesion. With the aim of improving the adhesion strength, the insertion of dense and compact ceramic interlayers is reported to be useful[1]. Among various ceramics, crystalline TiO2 has been extensively used thanks to its well-known biocompatibility and bioactivity [2]. In this work, a multi-step solvent free process is proposed, with the aim of obtaining a final composite material made up of a dense, compact and crystalline titania inter-layer (obtained via Metal Organic Chemical Vapour Deposition technique) and of a homogeneously spread discontinuous CPC toplayer, with particular chemical composition, crystallinity and morphology (obtained by means of water-based spray pyrolysis technique). Finally, a thermal treatment is carried out. These synthesis approaches are relatively simple and economic, eco-compatible and consequently suitable for an easy industrial scale-up of the process. The morphology, crystalline structures and wettability of the coated surfaces is here presented. Moreover, ions release and in vitro acellular bioactivity have also been evaluated