Characterization of an Additive Manufactured TiAl Alloy-Steel Joint Produced by Electron Beam Welding

In this work, the characterization of the assembly of a steel shaft into a γ-TiAl part for turbocharger application, obtained using Electron Beam Welding (EBW) technology with a Ni-based filler, was carried out. The Ti-48Al-2Nb-0.7Cr-0.3Si (at %) alloy part was produced by Electron Beam Melting (EBM). This additive manufacturing technology allows the production of a lightweight part with complex shapes. The replacement of Nickel-based superalloys with TiAl alloys in turbocharger automotive applications will lead to an improvement of the engine performance and a substantial reduction in fuel consumption and emission. The welding process allows a promising joint to be obtained, not affecting the TiAl microstructure. Nevertheless, it causes the formation of diffusive layers between the Ni-based filler and both steel and TiAl, with the latter side being characterized by a very complex microstructure, which was fully characterized in this paper by means of Scanning Electron Microscopy, Energy Dispersive X-ray Spectroscopy, and nanoindentation. The diffusive interface has a thickness of about 6 µm, and it is composed of several layers. Specifically, from the TiAl alloy side, we find a layer of Ti₃Al followed by Al₃NiTi₂ and AlNi₂Ti. Subsequently Ni becomes more predominant, with a first layer characterized by abundant carbide/boride precipitation, and a second layer characterized by Si-enrichment. Then, the chemical composition of the Ni-based filler is gradually reached

Long-term assessment of plasma lipids in transplant recipients treated with tacrolimus in relation to fatty liver.

Immunosuppression has improved graft and recipient survival in transplantation but is associated with possible adverse effects including cardiovascular diseases. The impact of tacrolimus on the lipidic profile has been debated for several years. Twenty-nine kidney transplant recipients on tacrolimus treatment were monitored for six years, and multiple laboratory parameters investigating the lipid asset, as well as glucose profile, were carried out. Tacrolimus has been responsible for significant changes in plasma lipid concentrations only for the first six months, but not for the remaining time of observation. Similarly, in the same periods, glycemic imbalance was highlighted. The liver enzyme activity showed a modest derangement during the tacrolimus treatment, suggesting the presence of lipid accumulation in the liver. Fatty liver reversed in the long term follow-up. Tacrolimus, although it is not a completely safe option in the first months of the immunosuppressive protocols in organ transplanted recipients, still retains a certain role in the long-term post-transplantation immunosuppressive approach with high cardiovascular risk

Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer

Bladder cancer is one of the leading cancer of the urinary tract. It is often diagnosed at advanced stage of the disease. To date, no specific and effective early detection biomarkers are available. Cancer development and progression are associated with the involvement of both epithelial-mesenchymal transition (EMT) and tumor microenvironment of which NGAL/MMP-9 complex represents the main player in bladder cancer. It is known that change in microRNAs (miRNAs) expression may result in gene modulation. Therefore, the identification of specific miRNAs associated with EMT pathway and NGAL/MMP-9 complex may be useful to detect the development of bladder cancer at early stages. On this ground, the expression levels of miRNAs in public available datasets of bladder cancer containing data of non-coding RNA profiling was evaluated. This analysis revealed a group of 16 miRNAs differentially expressed between bladder cancer patients and related healthy controls. By miRNA prediction tool (mirDIP), the relationship between the identified miRNAs and the EMT genes was established. Using the DIANA-mirPath (v.2) software, miRNAs, able to modulate the expression of NGAL and MMP-9 genes, were recognized. The results of this study provide evidence that the downregulated hsa-miR-145-5p and hsa-miR-214-3p may modulate the expression of both EMT and NGAL/MMP-9 pathways. Therefore, further validation analyses may confirm the usefulness of these selected miRNAs for predicting the development of bladder cancer at the early stage of the disease

Identification of novel chemotherapeutic strategies for metastatic uveal melanoma

Melanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease. We have first carried out a meta-analysis of publicly available whole-genome datasets, that included data from 132 patients, comparing metastatic vs. non metastatic uveal melanomas, in order to identify the most relevant genes characterizing the spreading of tumor to the liver. Subsequently, the L1000CDS(2) web-based utility was used to predict small molecules and drugs targeting the metastatic uveal melanoma gene signature. The most promising drugs were found to be Cinnarizine, an anti-histaminic drug used for motion sickness, Digitoxigenin, a precursor of cardiac glycosides, and Clofazimine, a fat-soluble iminophenazine used in leprosy. In vitro and in vivo validation studies will be needed to confirm the efficacy of these molecules for the prevention and treatment of metastatic uveal melanoma

Effects of mitotane on the hypothalamic-pituitary-adrenal axis in patients with adrenocortical carcinoma

Objective: Mitotane, a drug used to treat adrenocortical cancer (ACC), inhibits multiple enzymatic steps of adrenocortical steroid biosynthesis, potentially causing adrenal insufficiency. Recent studies in vitro have also documented a direct inhibitory effect of mitotane at the pituitary level. The present study was aimed to assess the hypothalamic-pituitary-adrenal axis in patients with ACC receiving mitotane. Design and methods: We prospectively enrolled 16 patients on adjuvant treatment with mitotane after radical surgical resection of ACC, who underwent standard hormone evaluation and h-CRH stimulation. A group of 10 patients with primary adrenal insufficiency (PAI) served as controls for the CRH test. Results: We demonstrated a close correlation between cortisol-binding globulin (CBG) and plasma mitotane levels, and a non-significant trend between mitotane dose and either serum or salivary cortisol in ACC patients. We did not find any correlation between the dose of cortisone acetate and either ACTH or cortisol levels. ACTH levels were significantly higher in patients with PAI than that in patients with ACC, both in baseline conditions (88.99 (11.04-275.00) vs 24.53 (6.16-121.88) pmol/L, P = 0.031) and following CRH (158.40 (34.32-275.00) vs 67.43 (8.8-179.52) pmol/L P = 0.016). Conclusions: The observation of lower ACTH levels in patients with ACC than that in patients with PAI, both in basal conditions and after CRH stimulation, suggests that mitotane may play an inhibitory effect on ACTH secretion at the pituitary levels. In conclusion, the present study shows that mitotane affects the HPA axis at multiple levels and no single biomarker may be used for the assessment of adrenal insufficiency