Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges

Dry electrode Bio-potential Recordings

As wireless bio-medical long term monitoring moves towards personal monitoring it demands very high input impedance systems capable to extend the reading of bio-signal during the daily activities offering a kind of “stress free”, convenient connection, with no need for skin preparation. In particular we highlight the development and broad applications of our own circuits for wearable bio-potential sensor systems enabled by the use of an FET based amplifier circuit with sufficiently high impedance to allow the use of passive dry electrodes which overcome the significant barrier of gel based contacts. In this paper we present the ability of dry electrodes in long term monitoring of ECG, EEG and fetal ECG

Innovative Scaffold Solution for Bone Regeneration Made of Beta-Tricalcium Phosphate Granules, Autologous Fibrin Fold, and Peripheral Blood Stem Cells

The drawbacks of traditional bone defect treatments have prompted the exploration of bone tissue engineering. The use of porous biomaterial scaffolds from calcium, bio-ceramic, and other different polymers to induce and increase bone cell and tissue growth is a present hot topic. In bone transplantation, the use of biomaterials may be a solution to avoid the lack of donor sites for autografts and the risk of rejection with allograft procedures. Challenges and efforts involve the use of engineered biomaterials that can mimic both the mechanical and biological properties of real bone tissue, supporting the vascularization of the implanted site. β-Tricalcium phosphate (β-TCP) has been used by dentists and clinicians for a decade in clinical applications on over a thousand patients with different bone pathologies including mandibular and maxillary reconstruction. This study aimed to explore suitable combination of β-TCP granules, autologous fibrin from human peripheral blood (hPB), and autologous peripheral blood stem cells (PB-SCs) for the realization of a bioscaffold (Compact Bio-BoneR) for bone regeneration and identify an efficient method to establish it as effective osteo-regenerators. It has been assessed that human PB is an exceptional source of multiple type of stem cells including mesenchymal (MSCs), neural (NSCs), hematopoietic (HSCs), and embryonic like (ESCs) which may differentiate into different cell phenotypes such as osteoblasts, chondrocytes, adipocytes, myocytes, cardiomyocytes, and neurons. Isolated PB-SCs were induced into osteoblasts using β-TCP granules. Cultured PB-SCs were directly transferred and seeded into the scaffolds and induced to differentiate into osteoblasts. β-TCP granules with diameters of 1 mm and 1–2.5 mm were embedded in a fibrin gel matrix and PB-SCs were added successively. The bioscaffold was poured in culture with serum-free medium (SFM) for a period of 7–10 days. Improved proliferation of PBSCs was assessed by the expression of multipotent and pluripotent stem cell biomarkers performed by flow cytometry analysis as CD34, CD45, CD90, CD105, and SSEA3; osteoblasts were assessed by the positive expression of immune stain as alizarin red (AR), von Kossa (VK), and alkaline phosphatase (ALP). This study provides an alternative to biofunctionalized scaffold that exhibits improved osteogenesis that can be extremely beneficial in dentistry and orthopedics