Genetic study of atypical femoral fractures using exome sequencing in three affected sisters and three unrelated patients

Objectives: Atypical femoral fractures (AFF) are rare, often related to long-term bisphosphonate (BPs) tre- atment. Their pathogenic mechanisms are not precisely known and there is no evidence to identify patients with a high risk of AFF. The aim of this work is to study the genetic bases of AFFs. Material and methods: Whole-exome sequencing was carried out on 3 sisters and 3 unrelated additional patients, all treated with BPs for more than 5 years. Low frequency, potentially pathogenic variants sha- red by the 3 sisters, were selected, were selected and a network of gene and protein interactions was constructed with the data found. Results: We identified 37 rare variants (in 34 genes) shared by the 3 sisters, some not previously descri- bed. The most striking variant was the p.Asp188Tyr mutation in the enzyme geranylgeranyl pyrophos- phate synthase (encoded by the GGPS1 gene), from the mevalonate pathway and essential for osteoclast function. Another noteworthy finding was two mutations (one in the 3 sisters and one in an unrelated patient) in the CYP1A1 gene, involved in the metabolism of steroids. We identified other variants that could also be involved in the susceptibility to AFFs or in the underlying osteoporotic phenotype, such as those present in the SYDE2, NGEF, COG4 and FN1 genes. Conclusions: Our data are compatible with a model where the accumulation of susceptibility variants could participate in the genetic basis of AFFs

GGPS1 Mutation and Atypical Femoral Fractures with Bisphosphonates

Atypical femoral fractures have been associated with long-term bisphosphonate treatment.1,2 However, the underlying mechanisms remain obscure. We studied three sisters who had atypical femoral fractures after receiving various oral bisphosphonates for 6 years. Two of the sisters had a single fracture (at the ages of 64 and 73 years), and one had bilateral fractures (one at the age of 60 years and the other at the age of 61 years). Given the low incidence of atypical femoral fractures in the general population (5.9 per 10,000 person-years),3 we hypothesized that these sisters might have an underlying genetic background that contributed to these fractures

Titanium carbide and carbonitride electrocatalyst supports: Modifying Pt-Ti interface properties by electrochemical potential cycling

Titanium carbide and carbonitride are expected to be good materials to replace carbon as electrocatalyst supports, since they are chemically stable in acidic media and possess high electrical conductivity. However, they eventually can be transformed to titanium oxide, which is a thermodynamically stable compound, at potentials higher than 0.9 V (vs. RHE) in acidic media. In this communication, we report an enhanced catalytic activity towards CO and methanol electrooxidation on TiC and TiCN materials induced by surface oxides at the Pt/support interface. In particular, the current density obtained for Pt/TiC, activated up to 1.0 V, is 2-fold higher than that achieved with the commercial PtRu/C catalyst, which is accepted to be one of the best catalysts for methanol oxidation reaction.This work was supported by the Spanish Science and Innovation Ministry under project CTQ2011-28913-CO2-O2. MR acknowledges the FPU-2012 program for nancial support.Peer Reviewe

Titanium‐based materials as new supports for Pt electrocatalysts for CO and methanol oxidation in acidic and alkaline media

Trabajo presentado en Hyceltec 2013 - IV Iberian symposium on hydrogen, fuel cells and advanced batteries, celebrado en Estoril (Portugal) del 26 al 28 de junio de 2013.Peer Reviewe

TiC, TiCN, and TiN supported Pt electrocatalysts for CO and methanol oxidation in acidic and alkaline media

TiC, TiCN, and TiN supported Pt nanoparticles have been investigated as anode electrocatalytic materials for direct methanol fuel cells. The catalysts were studied in acidic and alkaline media and compared with platinum supported on carbon black. CO and methanol oxidation were studied by voltammetry and chronoamperometry techniques. Transmission electron microscopy, X-ray photoelectron spectroscopy and X-ray diffraction analysis were employed to characterize the novel catalysts. Results show that a carbon-supported Pt catalyst is mainly formed by nanoparticles with long (111) domains, and those catalysts with a titanium-based support present a huge amount of defect sites with diverse symmetries. Additionally to geometric factors, an electronic effect by the Ti-based support leads to considerably enhanced CO electrooxidation with respect to carbon-supported catalysts, which is of special relevance in alkaline media. However, no such improvement is observed during the methanol oxidation reaction on Ti-based catalysts at high pH. © 2013 American Chemical Society.This work has been supported by the Spanish Science and Innovation Ministry under projects ENE2010-15381 and CTQ2011-28913-CO2-O2. M.R. and G.G. acknowledge to the FPU-2012 program and the European Social Fund and JAE Program (CSIC) for financial support.Peer Reviewe

Catalytic electro-activation of the Pt-Ti interphase for CO and metanol oxidation

Trabajo presentado en la European Hydrogen Energy Conference - EHEC, celebrada en Sevilla (España) del 12 al 14 de mayo de 2014.Peer Reviewe

Electrocatalytic stability of Ti based-supported Pt3Ir nanoparticles for unitized regenerative fuel cells

Trabajo presentado en Hyceltec 2013 - IV Iberian symposium on hydrogen, fuel cells and advanced batteries, celebrado en Estoril (Portugal) del 26 al 28 de junio de 2013.Peer Reviewe

The role of Sn, Ru and Ir on the ethanol electrooxidation on Pt3M/TiCN electrocatalysts

In the present work, titanium carbonitride (TiCN) that possesses good electrical conductivity and high corrosion resistance has been used to anchor Pt3M (M: Ir, Sn, Ru) nanoparticles to study the ethanol electrooxidation reaction. Electrocatalysts were prepared by the polyol method and physicochemical characterized by TEM, FEM, ICP-OES, XRD and XPS analysis. Noble metal deposition onto the catalyst support produced metallic particle sizes between 3 and 6 nm and an increment of surface TiO2. The electrochemical characterization was performed by cyclic voltammetry and chronoamperometry techniques. Results revealed that, besides the beneficial effect provided by the catalysts support, the activity toward ethanol electrooxidation was highly dependent on the second metal and directly related to CO tolerance. The performance toward ethanol oxidation reaction was found to increase in the following way: Pt3Ir/TiCN << Pt3Ru/TiCN << Pt3Sn/TiCN.This work has been supported by the Spanish MINECO under project CTQ2011-28913-C02-01 and the European Union Seventh Framework Programme support via the EU project DECORE (project 309741) under contract no. FP7-NMP-2012-SMALL-6 for Research and Technological Development. MR acknowledges to the FPU-2012 program.Peer Reviewe

Ti based-supports for unitized regenerative fuel cells

Trabajo presentado en la European Hydrogen Energy Conference - EHEC, celebrada en Sevilla (España) del 12 al 14 de mayo de 2014.Peer Reviewe