Sociodemographic factors and patient perceptions are associated with attitudes to kidney transplantation among haemodialysis patients

Background. Treatment decisions made by patients with chronic kidney disease are crucial in the renal transplantation process. These decisions are influenced, amongst other factors, by attitudes towards different treatment options, which are modulated by knowledge and perceptions about the disease and its treatment and many other subjective factors. Here we study the attitude of dialysis patients to renal transplantation and the association of sociodemographic characteristics, patient perceptions and experiences with this attitude. Methods. In a cross-sectional study, all patients from eight dialysis units in Budapest, Hungary, who were on haemodialysis for at least 3 months were approached to complete a self-administered questionnaire. Data collected from 459 patients younger than 70 years were analysed in this manuscript. Results. Mean age of the study population was 53 +/- 12 years, 54% were male and the prevalence of diabetes was 22%. Patients with positive attitude to renal transplantation were younger (51 +/- 11 versus 58 +/- 11 years), better educated, more likely to be employed (11% versus 4%) and had prior transplantation (15% versus 7%)(P < 0.05 for all). In a multivariate model, negative patient perceptions about transplantation, negative expectations about health outcomes after transplantation and the presence of fears about the transplant surgery were associated, in addition to incre- asing age, with unwillingness to consider transplantation. Conclusions. Negative attitudes to renal transplantation are associated with potentially modifiable factors. Based on this we suggest that it would be necessary to develop standardized, comprehensible patient information systems and personalized decision support to facilitate modality selection and to enable patients to make fully informed treatment decisions

A Three Dimensional Analysis of Au-Silica Core-Shell Nanoparticles Using Medium Energy Ion Scattering

The medium energy ion scattering (MEIS) facility at the IIAA Huddersfield has been used for the analysis of a monolayer of Au-silica core-shell nanoparticles deposited on Si substrate. Both spherical and rod shape particles were investigated and the spectra produced by 100 keV He+ ions scattered through angles of 90º and 125º were compared with the results of RBS-MAST [1] simulations performed on artificial 3D model cells containing the nanoparticles. The thickness of the silica shell, the diameter of the Au spheres, and the diameter and length of the Au nano-rods were determined from best fits of the measured set of MEIS spectra. In addition, the effect of ion irradiation on the silica shell and gold core was monitored by MEIS measurements in conjunction with RBS-MAST simulations. Ion bombardment was performed under largely different conditions, i.e., by 30 keV Ar+, 150 keV Fe+, or 2.8 MeV N+ ions in the dose range of 2×1015 - 2×1016 cm-2. Significant changes in the particle geometry can be observed due to ion beam-induced sputtering and recoil effects, the significance of which was estimated from full-cascade SRIM simulations. Rutherford backscattering spectrometry (RBS), Field emission scanning electron microscopy (FESEM), and Atomic Force Microscopy (AFM) techniques have been applied as complementary characterization tools to monitor the amount of gold and surface morphology on the un-irradiated and irradiated sample areas. We show that MEIS can yield spatial information on the geometrical changes of particulate systems at the nanometre scale

Crystal structures of the disease-causing D444V mutant and the relevant wild type human dihydrolipoamide dehydrogenase

We report the crystal structures of the human (dihydro)lipoamide dehydrogenase (hLADH, hE3) and its disease-causing homodimer interface mutant D444V-hE3 at 2.27 and 1.84 Å resolution, respectively. The wild type structure is a unique uncomplexed, unliganded hE3 structure with the true canonical sequence. Based on the structural information a novel molecular pathomechanism is proposed for the impaired catalytic activity and enhanced capacity for reactive oxygen species generation of the pathogenic mutant. The mechanistic model involves a previously much ignored solvent accessible channel leading to the active site that might be perturbed also by other disease-causing homodimer interface substitutions of this enzyme. © 2018 Elsevier Inc

Chromatin structure regulates cancer-specific alternative splicing events in primary HPV-related oropharyngeal squamous cell carcinoma

Human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) represents a unique disease entity within head and neck cancer with rising incidence. Previous work has shown that alternative splicing events (ASEs) are prevalent in HPV+ OPSCC, but further validation is needed to understand the regulation of this process and its role in these tumours. In this study, eleven ASEs (GIT2, CTNNB1, MKNK2, MRPL33, SIPA1L3, SNHG6, SYCP2, TPRG1, ZHX2, ZNF331, and ELOVL1) were selected for validation from 109 previously published candidate ASEs to elucidate the post-transcriptional mechanisms of oncogenesis in HPV+ disease. In vitro qRT-PCR confirmed differential expression of 9 of 11 ASE candidates, and in silico analysis within the TCGA cohort confirmed 8 of 11 candidates. Six ASEs (MRPL33, SIPA1L3, SNHG6, TPRG1, ZHX2, and ELOVL1) showed significant differential expression across both methods. Further evaluation of chromatin modification revealed that ASEs strongly correlated with cancer-specific distribution of acetylated lysine 27 of histone 3 (H3K27ac). Subsequent epigenetic treatment of HPV+ HNSCC cell lines (UM-SCC-047 and UPCI-SCC-090) with JQ1 not only induced downregulation of cancer-specific ASE isoforms, but also growth inhibition in both cell lines. The UPCI-SCC-090 cell line, with greater ASE expression, also showed more significant growth inhibition after JQ1 treatment. This study confirms several novel cancer-specific ASEs in HPV+OPSCC and provides evidence for the role of chromatin modifications in regulation of alternative splicing in HPV+OPSCC. This highlights the role of epigenetic changes in the oncogenesis of HPV+OPSCC, which represents a unique, unexplored target for therapeutics that can alter the global post-transcriptional landscape