Concomitant dehiscences of the temporal bone: a case-based study

Otic capsule dehiscences create a pathological third window in the inner ear that results in a dissipation of the acoustic energy consequent to the lowered impedance. Superior semicircular canal dehiscence (SSCD) was identified by Minor et al. in 1998 as a syndrome leading to vertigo and inner ear conductive hearing loss. The authors reported the relation between the dehiscence and pressure- or sound-induced vertigo (Tullio phenomenon). The pathophysiology of this entity still remains controversial. Prevalence rates of SSCD in anatomical studies range from 0.4 to 0.7 % with a majority of patients being asymptomatic. The observed association with other temporal bone dehiscences, as well as the propensity toward a bilateral or contralateral near-dehiscence, raises the question of whether a specific local bone demineralization or systemic mechanisms could be considered. The present report regards a case of a patient with a previous episode of meningitis, with a concomitant bilateral SSCD and tegmen tympani dehiscence from the side of meningitis. The patient was affected by dizziness, left moderate conductive hearing loss and pressure/sound-induced vertigo. Because of disabling vestibular symptoms, the patient underwent surgical treatment. A middle cranial fossa approach allowed to reach both dehiscences on the symptomatic side, where bone wax and fascia were used. At 6 months from the procedure, hearing was preserved and the vestibular symptoms disappeared

Epigallocatechin-3-gallate Delivered in Nanoparticles Increases Cytotoxicity in Three Breast Carcinoma Cell Lines

The anticancer act i v i t y of epigallocatechin-3-gallate (EGCG), orally administrated, is limited by poor bioavailabi l i t y , absorption, and unpredictable distribution in human tissues. EGCG charged nanoparticles may represent an opportunity to overcome these limitations. We assayed two different kinds of lipid nanoparticles (LNPs and LNPs functionalized with folic acid) charged with EGCG on three breast carcinoma cell lines (MCF-7, MDA-MB-231, and MCF-7TAM) and the human normal MCF10A mammary epithelial cells. Both LNPs loaded with EGCG, at low concentrations, induced a significant cytotoxicity in the three breast carcinoma cells but not in MCF10A cells. In view of a future application, both LNPs and LNPs-FA were found to be very suitable for in vitro studies and usef u l to improve EGCG administration in vivo. Since they are produced by inexpensive procedures using bioavailable, biocompatible, and biodegradable molecules, t h e y represent an applicable tool for a more rationale use of EGCG as an anti-cancer agent

Identification by Virtual Screening and In Vitro Testing of Human DOPA Decarboxylase Inhibitors

Dopa decarboxylase (DDC), a pyridoxal 5′-phosphate (PLP) enzyme responsible for the biosynthesis of dopamine and serotonin, is involved in Parkinson's disease (PD). PD is a neurodegenerative disease mainly due to a progressive loss of dopamine-producing cells in the midbrain. Co-administration of L-Dopa with peripheral DDC inhibitors (carbidopa or benserazide) is the most effective symptomatic treatment for PD. Although carbidopa and trihydroxybenzylhydrazine (the in vivo hydrolysis product of benserazide) are both powerful irreversible DDC inhibitors, they are not selective because they irreversibly bind to free PLP and PLP-enzymes, thus inducing diverse side effects. Therefore, the main goals of this study were (a) to use virtual screening to identify potential human DDC inhibitors and (b) to evaluate the reliability of our virtual-screening (VS) protocol by experimentally testing the “in vitro” activity of selected molecules. Starting from the crystal structure of the DDC-carbidopa complex, a new VS protocol, integrating pharmacophore searches and molecular docking, was developed. Analysis of 15 selected compounds, obtained by filtering the public ZINC database, yielded two molecules that bind to the active site of human DDC and behave as competitive inhibitors with Ki values ≥10 µM. By performing in silico similarity search on the latter compounds followed by a substructure search using the core of the most active compound we identified several competitive inhibitors of human DDC with Ki values in the low micromolar range, unable to bind free PLP, and predicted to not cross the blood-brain barrier. The most potent inhibitor with a Ki value of 500 nM represents a new lead compound, targeting human DDC, that may be the basis for lead optimization in the development of new DDC inhibitors. To our knowledge, a similar approach has not been reported yet in the field of DDC inhibitors discovery

The Tor Caldara CO2 Diffuse Degassing Structure (DDS): 222Rn/220Rn output before and after the August, 22, 2005 Anzio Earthquake (Mw=4.6).

Soon after a 222Rn and 220Rn survey in soil gases, performed (June 2005) in the frame of the Diffuse Degassing in Italy risk assessment project, a moderate earthquake (Mw=4.6) occurred in the Anzio offshore, on August, 22, 2005, only 5 miles from the Tor Caldara Diffuse Degassing Structure (DDS onward). Having available the pre-earthquake 222Rn and 220Rn grid-map on around 50 soil-gas points and being 222Rn both a stress-pathfinder and a discriminative component of activated-faults, a mirrorlike survey was repeated on the same 50 sites, soon after the close earthquake. Later, during a quiescent-aseismic period (December, 2005), a CO2 flux survey was performed for the same 50 sites, adding detailed measurements (more than 100 sites) for the highest flux sectors. The aim of this survey was both to have an overall picture of the background CO2 flux and to calculate the total budget of CO2 flux throughout the DDS, to better interpret the 222Rn and 220Rn areal surveys before and after the seismic event. Herewith, we distinguish the contribution of organic, diffusive and advective CO2 flux. Hints of convection and strong degassing linked to the fracture field, inside the DDS, have been envisaged on selected points, where continuous monitoring stations could be strategic, for seismic, volcanic and NGH surveillance. Despite we found higher 222Rn values in soils after the earthquake, suggesting an enhanced local degassing probably linked to a stress signal throughout the DDS as a whole, the results highlight an unmodified shape and location of the 222Rn anomalies before and after the earthquake. This evidence excludes both that the activated seismogenic segment has affected in some ways both the DDS degassing patterns and that fracture field changed. A similar result could be expected if the activated fault was oriented along the DDS itself and reached the surface. This evidence is well correlated with the reconstructed focal mechanism of the earthquake, pertaining to the transfer structure of the Ardea Graben , located along a peripheral sector of the degassing Alban Hills volcano and intersecting the DDS Tor Caldara itself. The shape and location of 222Rn anomalies inside the DDS for both the surveys are strictly inversely correlated with the areal CO2 flux data. The geometry of the degassing pathways is probably linked to the barrier action (sealing power) of the clays cropping out in the study area. These clays are generated by the strong leaching of the outcropping sedimentary Pleistocene rocks due to the huge flux of volcanic gas -rich fluids

Can Directional Resonances Be Used to Map Intensely Deformed Fault Zones of Mt. Etna Volcano ?

Mt. Etna is characterized by flank instability of the eastern to south-western portions of the volcanic edifice, producing down-slope movements with rates up to several decimeters in a month during eruptive events of the 2002-2003 activity. The unstable sector is bounded to the North by a E-W transtensive fault (the Pernicana fault system), extending from the NE Rift to the coastline of the Ionian Sea for a length of >18 km. The western portion of the Pernicana fault system (close to Piano Pernicana area) is characterized by the most intense deformation. In this area we have performed volcanic tremor measurements on a dense grid along and across the fault zone. Ambient vibration measurements are also performed along a second fault (Tremestieri fault) which confines the slip of the eastern flank to the south-east. The analysis using both microtremors and local earthquakes recorded in these faults shows persistent polarization of ground motion. Horizontal-to-vertical spectral ratios (HVSR) show large directional resonances of horizontal components within the damaged fault zones. The resonance occurs around 1Hz at Piano Pernicana, and around 4 Hz in the Tremestieri fault zone. The resonance amplitude in the HVSRs seems to be fairly well correlated to soil gas anomalous concentrations (in particular, radon and CO2 both considered tracer gases of major crustal discontinuity) in the two fault zones, suggesting that both the effects are linked to local fracturing conditions. According to previous results on velocity anisotropy in the shallow crust, we believe that a role on polarization could be played by stress-induced anisotropy and micro-fracture orientation in the near-surface lavas. The occurrence of directional resonances, if confirmed in other faults, can be a powerful tool to map buried damaged fault zones on the Mt. Etna volcano

Gene expression profile of human colon cancer cells treated with cross-reacting material 197, a diphtheria toxin non-toxic mutant

Cross-Reacting Material 197 (CRM197) is a diphtheria toxin non-toxic mutant that has shown anti-tumor activity in mice and humans. It is still unclear whether this anti-tumorigenic effect depends on its strong inflammatory- immunological property, its ability to inhibit heparin-binding epidermal growth factor (HB-EGF), or even its possible weak toxicity. CRM197 is utilized as a specific inhibitor of HB-EGF that competes for the epidermal growth factor receptor (EGFR), overexpressed in colorectal cancer and implicated in its progression. In this study we evaluate the effects of CRM197 on HT-29 human colon cancer cell line behaviour and, for CRM197 recognized ability to inhibit HB-EGF, its possible influence on EGFR activation. In particular, while HT-29 does not show any reduction of viability after CRM197 treatment (MTT modified assay), or changes in cell cycle distribution (flow cytometry), in EGFR localization, phospho-EGFR detected signals (immunohistochemistry) or in morphology (scanning electron microscopy, SEM) they show a change in the gene expression profile by microarray analysis (cDNA microarray SS-H19k8). The overexpression of genes like protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA), guanine nucleotide-binding protein G subunit alpha-1(GNAI1) and butyrophilin, subfamily 2, member A1 (BTN2A1) has been confirmed with real-time-qPCR. This is the first study where the CRM197 treatment on HT-29 shows a possible scarce implication of endogenous HB-EGF on EGFR expression and cancer cell development. At the same time, our results show the alteration of a specific and selected number of genes.Fil: Rivetti, S.. Universidad de Bologna; Italia. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; ItaliaFil: Lauriola, M.. Universidad de Bologna; Italia. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; ItaliaFil: Voltattorni, M.. Universidad de Bologna; ItaliaFil: Bianchini, Michele. Fundación para la Investigación, Docencia y Prevención del Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martini, D.. Universidad de Bologna; ItaliaFil: Ceccarelli, C.. Universidad de Bologna; ItaliaFil: Palmieri, A.. Università di Ferrara; ItaliaFil: Mattei, G.. Universidad de Bologna; Italia. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; ItaliaFil: Franchi, M.. Universidad de Bologna; ItaliaFil: Ugolini, G.. Universidad de Bologna; ItaliaFil: Rosati, G.. Universidad de Bologna; ItaliaFil: Montroni, I.. Universidad de Bologna; ItaliaFil: Taffurelli, M.. Universidad de Bologna; ItaliaFil: Solmi, Rosella. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; Italia. Universidad de Bologna; Itali

Geochemistry of hydrothermal fluids from the eastern sector of the Sabatini Volcanic District (central Italy).

This study reports a complete geochemical dataset of 215 water and 9 gas samples collected in 2015 from thermal and cold discharges located in the eastern sector of the Sabatini Volcanic District (SVD), Italy. Based on these data, two main aquifers were recognized, as follows: 1) a cold Ca-HCO3 to Ca(Na)-HCO3 aquifer related to a shallow circuit within Pliocene-Pleistocene volcanic and sedimentary formations and 2) a deep CO2-pressurized aquifer hosted in Mesozoic carbonate-evaporitic rocks characterized by a Ca- HCO3(SO4) to Na(Ca)-HCO3(Cl) composition. A thick sequence of low-permeability formations represents a physical barrier between the two reservoirs. Interaction of the CO2-rich gas phase with the shallow aquifer, locally producing high-TDS and low-pH cold waters, is controlled by fractures and faults related to buried horst-graben structures. The d18O-H2O and dD-H2O values indicate meteoric water as the main source for both the shallow and deep reservoirs. Carbon dioxide, which is characterized by d13C-CO2 values ranging from 4.7 to þ1.0‰ V-PDB, is mostly produced by thermo-metamorphic decarbonation involving Mesozoic rock formations, masking possible CO2 contribution from mantle degassing. The relatively low R/Ra values (0.07e1.04) indicate dominant crustal He, with a minor mantle He contribution. The CO2/3He ratios, up to 6 1012, support a dominant crustal source for these two gases. The d34SH2S values (from þ9.3 to þ11.3‰ V-CDT) suggests that H2S is mainly related to thermogenic reduction of Triassic anhydrites. The d13C-CH4 and dD-CH4 values (from 33.4 to 24.9‰ V-PDB and from 168 to 140‰ V-SMOW, respectively) and the relatively low C1/C2þ ratios (<100) are indicative of a prevailing CH4 production through thermogenic degradation of organic matter. The low N2/Ar and high N2/ He ratios, as well as the 40Ar/36Ar ratios (<305) close to atmospheric ratio, suggest that both N2 and Ar mostly derive from air. Notwithstanding, the positive d15N-N2 values (from þ0.91 to þ3.7‰ NBS air) point to a significant extra-atmospheric N2 contribution. Gas geothermometry in the CH4-CO2-H2 and H2S-CO2-H2 systems indicate equilibrium temperatures <200 C, i.e. lower than those measured in deep geothermal wells (~300 C), due to either an incomplete attainment of the chemical equilibria or secondary processes (dilution and/or scrubbing) affecting the chemistry of the uprising fluids. Although the highly saline Na-Cl fluids discharged from the explorative geothermal wells in the study area support the occurrence of a well-developed hydrothermal reservoir suitable for direct exploitation, the chemistry of the fluid discharges highlights that the uprising hydrothermal fluids are efficiently cooled and diluted by the meteoric water recharge from the nearby Apennine sedimentary belt. This explains the different chemical and isotopic features shown by the fluids from the eastern and western sectors of SVD, respectively, the latter being influenced by this process at a lesser extent. Direct uses may be considered a valid alternative for the exploitation of this resource.Published187-2016A. Geochimica per l'ambiente2IT. Laboratori sperimentali e analitici1VV. AltroJCR Journa

Feasibility study (I stage) of CO2 geological storage by ECBM tecniques in the Sulcis Coal Province (SW Sardinia).

An ECBM feasibility study started for the Sulcis Coal Province (SW Sardinia, Italy): available geochemical, structural-geology, stratigraphic and reservoir engineering considerations as well as the newly gathered experimental data are discussed, including: fluid geochemistry (major and minor elements, dissolved gases, C and He isotopic ratios) of different strata/reservoir, coal composition and experimental data on CO2/CH4 adsorption-desorption on coal. A MapInfo GIS structure was built up including stratigraphic, geo-structural, hydro-geochemical, coal-compositional and environmental-impact information as well as the CO2 sources location and typology. Despite preliminary, these data highlighted both the challenging positive and negative aspects of the Sulcis Coal Province versus the exploitation of the ECBM technique. The most important objective of this phase I of the project is the selection of the best Sulcis ECBM test-pilot site, which will be followed (Phase II-2007) by the choice of a scaled up site and possibly by a future network (Phase III-2008). CO2 geological storage and CH4 production potentials in Sulcis have been grossly evaluated as a whole, in the frame of the Sardinia region CO2 sources, including the coal-fired power plants, both existent and foreseen (hundreds of millions of tonnes of CO2 are possible to be stored underground in the next decades).UnpublishedTrondheim, Norway4.4. Scenari e mitigazione del rischio ambientaleope

Feasibility study (I stage) of CO2 geological storage by ECBM tecniques in the Sulcis Coal Province (SW Sardinia).

An ECBM feasibility study started for the Sulcis Coal Province (SW Sardinia, Italy): available geochemical, structural-geology, stratigraphic and reservoir engineering considerations as well as the newly gathered experimental data are discussed, including: fluid geochemistry (major and minor elements, dissolved gases, C and He isotopic ratios) of different strata/reservoir, coal composition and experimental data on CO2/CH4 adsorption-desorption on coal. A MapInfo GIS structure was built up including stratigraphic, geo-structural, hydro-geochemical, coal-compositional and environmental-impact information as well as the CO2 sources location and typology. Despite preliminary, these data highlighted both the challenging positive and negative aspects of the Sulcis Coal Province versus the exploitation of the ECBM technique. The most important objective of this phase I of the project is the selection of the best Sulcis ECBM test-pilot site, which will be followed (Phase II-2007) by the choice of a scaled up site and possibly by a future network (Phase III-2008). CO2 geological storage and CH4 production potentials in Sulcis have been grossly evaluated as a whole, in the frame of the Sardinia region CO2 sources, including the coal-fired power plants, both existent and foreseen (hundreds of millions of tonnes of CO2 are possible to be stored underground in the next decades)

Geodynamics, geophysical and geochemical observations, and the role of CO2 degassing in the Apennines

An accurate survey of old and new datasets allowed us to probe the nature and role of fluids in the seismogenic processes of the Apennines mountain range in Italy. New datasets include the 1985–2021 instrumented seismicity catalog, the computed seismogenic thickness, and geodetic velocities and strains, whereas data from the literature comprise focal mechanism solutions, CO2 release, Moho depth, tomographic seismic velocities, heat flow and Bouguer gravity anomalies. Most of the inspected datasets highlight differences between the western and eastern domains of the Apennines, while the transition zone is marked by high geodetic strain, prevailing uplift at the surface and high seismic release, and spatially corresponds with the overlapping Tyrrhenian and Adriatic Mohos. Published tomographic models suggest the presence of a large hot asthenospheric mantle wedge which intrudes beneath the western side of the Apennines and disappears at the southern tip of the southern Apennines. This wedge modulates the thermal structure and rheology of the overlying crust as well as the melting of carbonate-rich sediments of the subducting Adriatic lithosphere. As a result, CO2-rich fluids of mantle-origin have been recognized in association with the occurrence of destructive seismic sequences in the Apennines. The stretched western domain of the Apennines is characterized by a broad pattern of emissions from CO2-rich fluids that vanishes beneath the axial belt of the chain, where fluids are instead trapped within crustal overpressurized reservoirs, favoring their involvement in the evolution of destructive seismic sequences in that region. In the Apennines, areas with high mantle He are associated with different degrees of metasomatism of the mantle wedge from north to south. Beneath the chain, the thickness and permeability of the crust control the formation of overpressurized fluid zones at depth and the seismicity is favored by extensional faults that act as high permeability pathways. This multidisciplinary study aims to contribute to our understanding of the fluid-related mechanisms of earthquake preparation, nucleation and evolution encouraging a multiparametric monitoring system of different geophysical and geochemical observables that could lead the creation of a data-constrained and reliable conceptual model of the role of fluids in the preparatory phase of earthquakes in the Apennines