Hybrid coatings for orthopaedic implants formed by physical vapour deposition and microarc oxidation

This study is focused on the preparation of new hybrid layers intended for surface modification of Ti-6Al-4V alloys for potential orthopaedic and dental applications. Combination of the technology of physical vapour deposition (PVD) and subsequent micro-arc oxidation (MAO) was utilized for the deposition of Ti and ZrTi to form hybrid oxide layers. The oxide layers were prepared using an alkaline electrolyte with glycerol as an additive under micro-arc discharge conditions with different Si content on their surfaces. The hybrid ZrTi coatings with a Zr/Si structure achieved the best tribological properties described by a low friction coefficient of 0.3 and high abrasion resistance. There was also an increase in corrosion potential and polarization resistance of hybrid ZrTi coatings. Although the proliferation of human bone marrow mesenchymal stem cells was slower on these hydrophilic Ti and ZrTi coatings than both on uncoated Ti-6Al-4V and the reference tissue culture polystyrene dishes, both types of hybrid coating promoted greater osteogenic differentiation of these cells, indicated by approx. twice as high activity of alkaline phosphatase. The hybrid oxide layers newly developed in this study - especially the layers with Zr - are therefore promising for coating metallic bone implants.Web of Science219art. no. 11081

Ablation of single-crystalline cesium iodide by extreme ultraviolet capillary-discharge laser

Extreme ultraviolet (XUV) capillary-discharge lasers (CDLs) are a suitable source for the efficient, clean ablation of ionic crystals, which are obviously difficult to ablate with conventional, long-wavelength lasers. In the present study, a single crystal of cesium iodide (CsI) was irradiated by multiple, focused 1.5-ns pulses of 46.9-nm radiation delivered from a compact XUV-CDL device operated at either 2-Hz or 3-Hz repetition rates. The ablation rates were determined from the depth of the craters produced by the accumulation of laser pulses. Langmuir probes were used to diagnose the plasma plume produced by the focused XUV-CDL beam. Both the electron density and electron temperature were sufficiently high to confirm that ablation was the key process in the observed CsI removal. Moreover, a CsI thin film on MgO substrate was prepared by XUV pulsed laser deposition; a fraction of the film was detected by X-ray photoelectron spectroscopy.Web of Science65421020

Low Frequency of Cancer-Predisposition Gene Mutations in Liver Transplant Candidates with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) mainly stems from liver cirrhosis and its genetic predisposition is believed to be rare. However, two recent studies describe pathogenic/likely pathogenic germline variants (PV) in cancer-predisposition genes (CPG). As the risk of de novo tumors might be increased in PV carriers, especially in immunosuppressed patients after a liver transplantation, we analyzed the prevalence of germline CPG variants in HCC patients considered for liver transplantation. Using the panel NGS targeting 226 CPGs, we analyzed germline DNA from 334 Czech HCC patients and 1662 population-matched controls. We identified 48 PVs in 35 genes in 47/334 patients (14.1%). However, only 7/334 (2.1%) patients carried a PV in an established CPG (PMS2, 4×NBN, FH or RET). Only the PV carriers in two MRN complex genes (NBN and RAD50) were significantly more frequent among patients over controls. We found no differences in clinicopathological characteristics between carriers and non-carriers. Our study indicated that the genetic component of HCC is rare. The HCC diagnosis itself does not meet criteria for routine germline CPG genetic testing. However, a low proportion of PV carriers may benefit from a tailored follow-up or targeted therapy and germline testing could be considered in liver transplant recipients

ENIGMA CHEK2gether Project : a comprehensive study identifies functionally impaired CHEK2 germline missense variants associated with increased breast cancer risk

Purpose: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT). Experimental Design: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1–CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case–control datasets, including 73,048 female patients with breast cancer and 88,658 ethnicity-matched controls. Results: A total of 430/460 VUS were successfully analyzed, of which 340 (79.1%) were concordant in both functional assays and categorized as functionally impaired (N = 102), functionally intermediate (N = 12), or functionally wild-type (WT)–like (N = 226). We then examined their association with breast cancer risk in the case–control analysis. The OR and 95% CI (confidence intervals) for carriers of functionally impaired, intermediate, and WT-like variants were 2.83 (95% CI, 2.35–3.41), 1.57 (95% CI, 1.41–1.75), and 1.19 (95% CI, 1.08–1.31), respectively. The meta-analysis of population-specific datasets showed similar results. Conclusions: We determined the functional consequences for the majority of CHEK2 missense VUS found in patients with breast cancer (3,660/4,436; 82.5%). Carriers of functionally impaired missense variants accounted for 0.5% of patients with breast cancer and were associated with a moderate risk similar to that of truncating CHEK2 variants. In contrast, 2.2% of all patients with breast cancer carried functionally wild-type/intermediate missense variants with no clinically relevant breast cancer risk in heterozygous carriers