Gravity “steps” at Mt. Etna volcano (Italy). Instrumental effects or evidences of earthquake-triggered magma density changes?

On two occasions, sudden gravity changes occurred simultaneously at two summit Etna’s stations, during local low-magnitude earthquakes. A systematic coupling between earthquakes inducing comparable maximum acceleration and displacement at the observation points and gravity steps is missing, implying (a) the non-instrumental nature of the steps and (b) the need for particular underlying conditions for the triggering mechanism(s) to activate. We review some of the volcanological processes that could induce fast underground mass redistributions, resulting in gravity changes at the surface. These processes involve bubbles and crystals present in the magma and require particular conditions in order to be effective as mass-redistributing processes. The gravity steps could be a geophysical evidence of the dynamical stress transfer between tectonic and magmatic systems at a local scale. Given the implications that these transfers may have on the volcanic activity, routine volcano monitoring should include the observation of fast gravity changes

Disentangling the Structure-Activity Relationships of Naphthalene Diimides as Anticancer G-Quadruplex-Targeting Drugs

In the context of developing efficient anticancer therapies aimed at eradicating any sort of tumors, G-quadruplexes represent excellent targets. Small molecules able to interact with G-quadruplexes can interfere with cell pathways specific of tumors and common to all cancers. Naphthalene diimides (NDIs) are among the most promising, putative anticancer G-quadruplextargeting drugs, due to their ability to simultaneously target multiple G-quadruplexes and their strong, selective in vitro and in vivo anticancer activity. Here, all the available biophysical, biological, and structural data concerning NDIs targeting Gquadruplexes were systematically analyzed. Structure−activity correlations were obtained by analyzing biophysical data of their interactions with G-quadruplex targets and control duplex structures, in parallel to biological data concerning the antiproliferative activity of NDIs on cancer and normal cells. In addition, NDI binding modes to G-quadruplexes were discussed in consideration of the structures and properties of NDIs by in-depth analysis of the available structural models of G-quadruplex/NDI complexes

Anti-VEGF DNA-based aptamers in cancer therapeutics and diagnostics

The vascular endothelial growth factor (VEGF) family and its receptors play fundamental roles not only in physiological but also in pathological angiogenesis, characteristic of cancer progression. Aiming at finding putative treatments for several malignancies, various small molecules, antibodies, or protein-based drugs have been evaluated in vitro and in vivo as VEGF inhibitors, providing efficient agents approved for clinical use. Due to the high clinical importance of VEGF, also a great number of anti-VEGF nucleic acid-based aptamers-that is, oligonucleotides able to bind with high affinity and specificity a selected biological target-have been developed as promising agents in anticancer strategies. Notable research efforts have been made in optimization processes of the identified aptamers, searching for increased target affinity and/or bioactivity by exploring structural analogues of the lead compounds. This review is focused on recent studies devoted to the development of DNA-based aptamers designed to target VEGF. Their therapeutic potential as well as their significance in the construction of highly selective biosensors is here discussed

Tuning the polymorphism of the anti-VEGF G-rich V7t1 aptamer by covalent dimeric constructs

In the optimization process of nucleic acid aptamers, increased affinity and/or activity are generally searched by exploring structural analogues of the lead compound. In many cases, promising results have been obtained by dimerization of the starting aptamer. Here we studied a focused set of covalent dimers of the G-quadruplex (G4) forming anti-Vascular Endothelial Growth Factor (VEGF) V7t1 aptamer with the aim of identifying derivatives with improved properties. In the design of these covalent dimers, connecting linkers of different chemical nature, maintaining the same polarity along the strand or inverting it, have been introduced. These dimeric aptamers have been investigated using several biophysical techniques to disclose the conformational behavior, molecularity and thermal stability of the structures formed in different buffers. This in-depth biophysical characterization revealed the formation of stable G4 structures, however in some cases accompanied by alternative tridimensional arrangements. When tested for their VEGF165 binding and antiproliferative activity in comparison with V7t1, these covalent dimers showed slightly lower binding ability to the target protein but similar if not slightly higher antiproliferative activity on human breast adenocarcinoma MCF-7 cells. These results provide useful information for the design of improved dimeric aptamers based on further optimization of the linker joining the two consecutive V7t1 sequences

Insights into the G-rich VEGF-binding aptamer V7t1: when two G-quadruplexes are better than one!

The G-quadruplex-forming VEGF-binding aptamer V7t1 was previously found to be highly polymorphic in a K+-containing solution and, to restrict its conformational preferences to a unique, well-defined form, modified nucleotides (LNA and/or UNA) were inserted in its sequence. We here report an in-depth biophysical characterization of V7t1 in a Na+-rich medium, mimicking the extracellular environment in which VEGF targeting should occur, carried out combining several techniques to analyse the conformational behaviour of the aptamer and its binding to the protein. Our results demonstrate that, in the presence of high Na+ concentrations, V7t1 behaves in a very different way if subjected or not to annealing procedures, as evidenced by native gel electrophoresis, size exclusion chromatography and dynamic light scattering analysis. Indeed, not-annealed V7t1 forms both monomeric and dimeric G-quadruplexes, while the annealed oligonucleotide is a monomeric species. Remarkably, only the dimeric aptamer efficiently binds VEGF, showing higher affinity for the protein compared to the monomeric species. These findings provide new precious information for the development of improved V7t1 analogues, allowing more efficient binding to the cancer-related protein and the design of effective biosensors or theranostic devices based on VEGF targeting

Expanded Endoscopic Approach for Anterior Skull Base Tumors: Experience of a Multidisciplinary Skull Base Team

Abstract: The aim of this study is to describe the experience of a multidisciplinary skull base team with transnasal endoscopic surgery for anterior cranial base tumors. A retrospective chart review was conducted on patients who underwent an exclusive expanded transnasal approach to the anterior skull base in the period from December 2014 to November 2015. Data on patient demographics, tumor characteristics, surgical information, imaging, and postoperative complications were collected and analyzed. From a total of 120 patients with skull base diseases managed by the skull base team, 36 were admitted to this study. The overall complication rate in this series was 16.7%, gross total resection was achieved in 32 cases (88.9%) and postoperative CSF leakage occurred in 5 cases (13.9%). Our preliminary results confirm that an exclusive endoscopic transnasal approach to the anterior cranial base

High Flow Nasal Cannulae in preterm infants

Despite of improved survival of premature infants, the incidence of long term pulmonary complications, mostly associated with ventilation-induced lung injury, remains high. Non invasive ventilation (NIV) is able to reduce the adverse effects of mechanical ventilation. Although nasal continuous positive airway pressure (NCPAP) is an effective mode of NIV, traumatic nasal complications and intolerance of the nasal interface are common. Recently high flow nasal cannula (HFNC) is emerging as an efficient, better tolerated form of NIV, allowing better access to the baby's face, which may improve nursing, feeding and bonding. The aim of this review is to discuss the available evidence of effectiveness and safety of HFNC in preterm newborns with respiratory distress syndrome (RDS). It is known that distending pressure generated by HFNC increases with increasing flow rate and decreasing infant size and varies according to the amount of leaks by nose and mouth. The effects of HFNC on lung mechanics, its clinical efficacy and safety are still insufficiently investigated. In conclusion, there is a growing evidence of the feasibility of HFNC as an alternative mode of NIV. However, further larger randomized trials are required, before being able to recommend HFNC in the treatment of moderate respiratory distress of preterm infants