Efficiency of CFRP NSM strips and EBR laminates for flexural strengthening of RC beams

The efficiency of Fiber Reinforced Polymer (FRP) materials for strengthening existing Reinforced Concrete (RC) structures according to the Near Surface Mounted (NSM) technique can be greater than the External Bonded Reinforcement (EBR) technique since the tensile strength of the FRP materials is in general better exploited. Firstly, this paper deals with analyzing the effect of the loading pattern on RC beams strengthened with both types of strengthening technique; in particular, two loading patterns have been used for the experimental tests on simple supported beams: 1) a four points bending scheme, and 2) a scheme with distributed loads, in order to check the sensitivity of failure modes and ultimate loads to different distributions of bending moment and shear along the beam. Then, a comparison between the results of flexural tests on RC beams strengthened with both NSM and EBR techniques is dealt with

Reduced expression of THRβ in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression

Purpose Down-regulation of thyroid hormone receptor beta (THRβ) gene has been described in several human malignancies, including thyroid cancer. In this study, we analyzed THRβ mRNA expression in surgical specimens from a series of human papillary thyroid carcinomas (PTCs), characterized by their genotypic and clinical–biological features. Methods Thirty-six PTCs were divided into two groups according to the 2009 American Thyroid Association risk classification (17 low, 19 intermediate), and each group was divided into subgroups based on the presence or absence of the BRAFV600E mutation (21 BRAF mutated, 15 BRAF wild type). Gene expression was analyzed using fluidic cards containing probes and primers specific for the THRβ gene, as well as for genes of thyroperoxidase (TPO), sodium/iodide symporter (NIS), thyroglobulin (Tg) and thyroid stimulating hormone receptor (TSH-R) and for some miRNAs involved in thyroid neoplasia and targeting THRβ. The mRNA levels of each tumor tissue were compared with their correspondent normal counterpart. Results THRβ transcript was down-regulated in all PTCs examined. No significant differences were found between intermediate- vs low-risk PTCs patients, and BRAF-mutated vs BRAF wild-type groups. THRβ expression was directly correlated with NIS, TPO, Tg and TSH-R, and inversely correlated to miR-21, -146a, -181a and -221 expression. Conclusions Our results demonstrate that down-regulation of THRβ is a common feature of PTCs. While it is not associated with a more aggressive phenotype of PTC, it correlates with the reduction of all the markers of differentiation and is associated with overexpression of some miRNAs supposed to play a role in thyroid tumorigenesis

Experimental characterization of tensile strength of steel and fibre rovings also under environmental conditioning

The efficiency of the strengthening techniques by externally applied materials can be improved enhancing the debonding strength of the reinforcement from the support by the use of connectors (anchor spikes) consisting of unidirectional bundles of fibres embedded in concrete or masonry by means of organic or inorganic matrices. The use of connectors is suggested in various codes and guidelines of strengthening techniques by composite materials and provisions for their application are given, but currently there are no details for the qualification of the material. In order to investigate anchor spikes made of glass, basalt, aramid, carbon, PBO and steel, a large experimental campaign was carried out at the Materials and Structures Laboratory of the University of Sannio. The tests allowed to evaluate the mechanical characteristics (tensile strength, modulus of elasticity, deformation at the maximum load) of the anchor spikes constituted by only dry fibres, not impregnated, also as a result of environmental conditioning such as freezing and thawing, controlled humidity, alkaline and saline environment

Targeted metabolomic profiling in rat tissues reveals sex differences

Sex differences affect several diseases and are organ-and parameter-specific. In humans and animals, sex differences also influence the metabolism and homeostasis of amino acids and fatty acids, which are linked to the onset of diseases. Thus, the use of targeted metabolite profiles in tissues represents a powerful approach to examine the intermediary metabolism and evidence for any sex differences. To clarify the sex-specific activities of liver, heart and kidney tissues, we used targeted metabolomics, linear discriminant analysis (LDA), principal component analysis (PCA), cluster analysis and linear correlation models to evaluate sex and organ-specific differences in amino acids, free carnitine and acylcarnitine levels in male and female Sprague-Dawley rats. Several intra-sex differences affect tissues, indicating that metabolite profiles in rat hearts, livers and kidneys are organ-dependent. Amino acids and carnitine levels in rat hearts, livers and kidneys are affected by sex: male and female hearts show the greatest sexual dimorphism, both qualitatively and quantitatively. Finally, multivariate analysis confirmed the influence of sex on the metabolomics profiling. Our data demonstrate that the metabolomics approach together with a multivariate approach can capture the dynamics of physiological and pathological states, which are essential for explaining the basis of the sex differences observed in physiological and pathological conditions

Precision oncology for RET-related tumors

Aberrant activation of the RET proto-oncogene is implicated in a plethora of cancers. RET gain-of-function point mutations are driver events in multiple endocrine neoplasia 2 (MEN2) syndrome and in sporadic medullary thyroid cancer, while RET rearrangements are driver events in several non-medullary thyroid cancers. Drugs able to inhibit RET have been used to treat RET-mutated cancers. Multikinase inhibitors were initially used, though they showed modest efficacy and significant toxicity. However, new RET selective inhibitors, such as selpercatinib and pralsetinib, have recently been tested and have shown good efficacy and tolerability, even if no direct comparison is yet available between multikinase and selective inhibitors. The advent of high-throughput technology has identified cancers with rare RET alterations beyond point mutations and fusions, including RET deletions, raising questions about whether these alterations have a functional effect and can be targeted by RET inhibitors. In this mini review, we focus on tumors with RET deletions, including deletions/insertions (indels), and their response to RET inhibitors

The legacy of the COVID-19 pandemics for thyroid cancer patients: towards the application of clinical practice recommendations

The outbreak of COVID-19 pandemic has acted as a significant stress test for healthcare systems worldwide, due to the need for hospitalization of an increasing number of infected patients. The shift of massive resources to the acute needs of the pandemic led to an upheaval of the usual diagnostic and therapeutic pathways of chronic diseases, including thyroid cancer disease. The motto was to reduce crowding at clinics and to maintain essential health services. However, thyroid cancer clinical practice recommendations already encouraged physicians to reduce “low-value” care: in particular, to avoid screening of general population, to reduce the number of unnecessary biopsies, and to adopt a conservative approach to indeterminate thyroid nodules and low-risk thyroid cancer

Prediction of response to vemurafenib in BRAF V600E mutant cancers based on a network approach

Lung adenocarcinoma is the tumor with the highest number of switch genes (298) compared to its normal tissue, followed by thyroid (227) and colorectal (183) cancers. Switch genes codifying for kinases were 14,7 and 3 respectively.We looked for three homology sequences identified across vemurafenib targets and we found that thyroid cancer and lung adenocarcinoma have a similar number of putative targetable switch genes kinase (5-6); on the contrary, colorectal cancer has just one,with minor homology sequence

Circulating miR-26b-5p and miR-451a as diagnostic biomarkers in medullary thyroid carcinoma patients

Purpose/methodsThe determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis is still challenging. The aim of this study was to identify non-invasive circulating biomarkers in MTC. To achieve this goal, paired MTC tissue and plasma extracellular vesicle samples were collected from multiple centres and microRNA (miRNA) expression levels were evaluated.ResultsThe samples from a discovery cohort of 23 MTC patients were analysed using miRNA arrays. Lasso logistic regression analysis resulted in the identification of a set of circulating miRNAs as diagnostic biomarkers. Among them, miR-26b-5p and miR-451a, were highly expressed and their expression decreased during follow-up in disease-free patients in the discovery cohort. Circulating miR-26b-5p and miR-451a were validated using droplet digital PCR in a second independent cohort of 12 MTC patients.ConclusionThis study allowed the identification and validation of a signature of two circulating miRNAs, miR-26b-5p and miR-451a, in two independent cohorts reporting a significant diagnostic performance for MTC. The results of this study offer advancements in molecular diagnosis of MTC proposing a novel non-invasive tool to use in precision medicine