To determine the long-term (10-year) survival of patients with colorectal liver metastases treated with radiofrequency (RF) ablation and systemic chemotherapy with intention to treat. Institutional review board approval was obtained for this study. From 1997 to 2006, 99 consecutive patients with 202 small (0.8-4.0 cm; mean: 2.2 cm ± 1.1) metachronous colorectal liver metastases underwent ultrasonography-guided percutaneous RF ablation with internally-cooled electrodes in association with systemic chemotherapy. Patients ineligible for surgery (n = 80) or whose lesions were potentially resectable and who refused surgery (n = 19) were included. Patients were followed up with contrast agent-enhanced computed tomography and/or magnetic resonance imaging for a minimum of 3 years to more than 10 years after RF ablation (n = 99, 67, 49, and 25 for 3, 5, 7, and 10 or more years, respectively). Overall local response rates and long-term survival rates were assessed. For each of these primary endpoints, Kaplan-Meier curves were generated and log-rank tests were used to assess for statistically significant differences. Primary and secondary technical success rates were 93.1% (188 of 202) and 100% (14 of 14), respectively. Local tumor progression occurred in 11.9% (24 of 202) metastases, and 54.2% (13 of 24) of these were re-treated. Patient survival rates increased with re-treatment versus no re-treatment (P < .001). At follow-up, 125 new liver metastases were found, and of these 32.8% (41 of 125) were treated with RF ablation. Overall survival rates were 98.0%, 69.3%, 47.8%, 25.0%, and 18.0% (median: 53.2 months) at 1, 3, 5, 7, and 10 years, respectively. The major complication rate was 1.3% (two of 156), and there were no procedure-related deaths. At the time this article was written, 32.3% (32 of 99) of the patients were alive, and 67.7% (67 of 99) were deceased, with a median follow-up of 72 months. Adding RF ablation to systemic chemotherapy achieved local control in a large majority of metachronous colorectal liver metastases. The 3- to 10-year survival rates of this relatively large series of patients were essentially equivalent to those of most surgical series reported in the literature.

MiR-210 is a key player of cell response to hypoxia, modulating cell survival, VEGF-driven endothelial cell migration, and the ability of endothelial cells to form capillary-like structures. A crucial step in understanding microRNA (miRNA) function is the identification of their targets. However, only few miR-210 targets have been identified to date. Here, we describe an integrated strategy for large-scale identification of new miR-210 targets by combining transcriptomics and proteomics with bioinformatic approaches. To experimentally validate candidate targets, the RNA-induced silencing complex (RISC) loaded with miR-210 was purified by immunoprecipitation along with its mRNA targets. The complex was significantly enriched in mRNAs of 31 candidate targets, such as BDNF, GPD1L, ISCU, NCAM, and the non-coding RNA Xist. A subset of the newly identified targets was further confirmed by 3′-untranslated region (UTR) reporter assays, and hypoxia induced down-modulation of their expression was rescued blocking miR-210, providing support for the approach validity. In the case of 9 targets, such as PTPN1 and P4HB, miR-210 seed-pairing sequences localized in the coding sequence or in the 5′-UTR, in line with recent data extending miRNA targeting beyond the “classic” 3′-UTR recognition. Finally, Gene Ontology analysis of the targets highlights known miR-210 impact on cell cycle regulation and differentiation, and predicts a new role of this miRNA in RNA processing, DNA binding, development, membrane trafficking, and amino acid catabolism. Given the complexity of miRNA actions, we view such a multiprong approach as useful to adequately describe the multiple pathways regulated by miR-210 during physiopathological processes.

Significance: Atherosclerotic cardiovascular diseases (ACVDs) continue to be a primary cause of mortality worldwide in adults aged 35–70 years, occurring more often in countries with lower economic development, and they constitute an ever-growing global burden that has a considerable socioeconomic impact on society. The ACVDs encompass diverse pathologies such as coronary artery disease and heart failure (HF), among others. Recent Advances: It is known that oxidative stress plays a relevant role in ACVDs and some of its effects are mediated by lipid oxidation. In particular, lipid peroxidation (LPO) is a process under which oxidants such as reactive oxygen species attack unsaturated lipids, generating a wide array of oxidation products. These molecules can interact with circulating lipoproteins, to diffuse inside the cell and even to cross biological membranes, modifying target nucleophilic sites within biomolecules such as DNA, lipids, and proteins, and resulting in a plethora of biological effects. Critical Issues: This review summarizes the evidence of the effect of LPO in the development and progression of atherosclerosis-based diseases, HF, and other cardiovascular diseases, highlighting the role of protein adduct formation. Moreover, potential therapeutic strategies targeted at lipoxidation in ACVDs are also discussed. Future Directions: The identification of valid biomarkers for the detection of lipoxidation products and adducts may provide insights into the improvement of the cardiovascular risk stratification of patients and the development of therapeutic strategies against the oxidative effects that can then be applied within a clinical setting.

Lipids can go through lipid peroxidation, an endogenous chain reaction that consists in the oxidative degradation of lipids leading to the generation of a wide variety of highly reactive carbonyl species (RCS), such as short-chain carbonyl derivatives and oxidized truncated phospholipids. RCS exert a wide range of biological effects due to their ability to interact and covalently bind to nucleophilic groups on other macromolecules, such as nucleic acids, phospholipids, and proteins, forming reversible and/or irreversible modifications and generating the so-called advanced lipoxidation end-products (ALEs). Lipoxidation plays a relevant role in the onset of cardiovascular diseases (CVD), mainly in the atherosclerosis-based diseases in which oxidized lipids and their adducts have been extensively characterized and associated with several processes responsible for the onset and development of atherosclerosis, such as endothelial dysfunction and inflammation. Herein we will review the current knowledge on the sources of lipids that undergo oxidation in the context of cardiovascular diseases, both from the bloodstream and tissues, and the methods for detection, characterization, and quantitation of their oxidative products and protein adducts. Moreover, lipoxidation and ALEs have been associated with many oxidative-based diseases, including CVD, not only as potential biomarkers but also as therapeutic targets. Indeed, several therapeutic strategies, acting at different levels of the ALEs cascade, have been proposed, essentially blocking ALEs formation, but also their catabolism or the resulting biological responses they induce. However, a deeper understanding of the mechanisms of formation and targets of ALEs could expand the available therapeutic strategies.

The aim of the study was to identify and correlate myofascial trigger points (MTPs) in the masticatory muscles, using thermography and algometry. 26 female volunteers were recruited. The surface facial area over the masseter and anterior temporalis muscles was divided into 15 subareas on each side (n=780). This investigation consisted of three steps. The first step involved thermographic facial examination, using lateral views. The second step involved the pressure pain threshold (PPT), marking the MTP pattern areas for referred pain (n=131) and local pain (n=282) with a coloured pencil, and a photograph of the lateral face with the head in the same position as the infrared imaging. The last step was the fusion of these two images, using dedicated software (Reporter® 8.5-SP3 Professional Edition and QuickReport® 1.2, FLIR Systems, Wilsonville, OR); and the calculation of the temperature of each point. PPT levels measured at the points of referred pain in MTPs (1.28±0.45 kgf) were significantly lower than the points of local pain in MTPs (1.73±0.59 kgf; p<0.05). Infrared imaging indicated differences between referred and local pain in MTPs of 0.5 °C (p<0.05). Analysis of the correlation between the PPT and infrared imaging was done using the Spearman non-parametric method, in which the correlations were positive and moderate (0.4≤r<0.7). The sensitivity and specificity in MTPs were 62.5% and 71.3%, respectively, for referred pain, and 43.6% and 60.6%, respectively, for local pain. Infrared imaging measurements can provide a useful, non-invasive and non-ionizing examination for diagnosis of MTPs in masticatory muscles.