Geophysical Methods as Support to Aquifer Recharge

AbstractIn the framework of WAter Re-BOrn Project a large pond in Mereto (upper Friuli plain) was chosen as artificial recharge test site. Several geophysical investigations (GPR, Electrical Resistivity Tomography and High Resolution Seismic) were carried out to study and to characterize the vadose zone of this large infiltration basin. These geophysical integrated methods supplied us many information to characterize the vadose zone and the unconfined aquifer in the study area. The geophysical information greatly reduces the hydrogeological knowledge gaps and was used to improve the three-dimensional Finite Element numerical model to predict the effect of the artificial recharge

Case Report: Circulating Myeloid-Derived Suppressive-Like Cells and Exhausted Immune Cells in Non-Small Cell Lung Cancer Patients Treated With Three Immune Checkpoint Inhibitors

none12noImmune checkpoint inhibition induced a great step forward in the treatment of non-small cell lung cancer patients. In cancer immune microenvironment many checkpoints were studied and their involvement could represent a mechanism of resistance to cancer immunotherapy. For this reason, the inhibition of multiple immune checkpoints is under development. However, myeloid-derived suppressor cells (MDSC) and exhausted immune cells could limit the efficacy of cancer immunotherapy. We analyzed the variation of circulating immune suppressive-like cell subsets and exhausted immune cells in three non-small cell lung cancer patients treated with the combination of anti-CTLA-4 plus anti-PD-1 plus anti-LAG-3 at T0 (baseline), T1 (after 2 months) and T2 (after 4 months). We also describe the clinical and radiological course of the disease during this treatment in all three patients. We observed both clinical differences and changes in the composition of immune suppressive-like cell subsets and exhausted immune cells between the patients receiving the same schedule of treatment with immune checkpoint inhibitors. The study on a wider patient population and experimental model design could help to clarify the kinetics of these cell subpopulations with the perspective to find new targets for treatment or new biomarkers for resistance to cancer immunotherapy.openBronte G.; Verlicchi A.; De Matteis S.; Rossi A.; Affatato A.; Sullo F.G.; Gianni C.; Canale M.; Burgio M.A.; Delmonte A.; Milella M.; Crino L.Bronte, G.; Verlicchi, A.; De Matteis, S.; Rossi, A.; Affatato, A.; Sullo, F. G.; Gianni, C.; Canale, M.; Burgio, M. A.; Delmonte, A.; Milella, M.; Crino, L

Perturbation of cytochrome P450, generation of oxidative stress and induction of DNA damage in Cyprinus carpio exposed in situ to potable surface water

Epidemiological evidence suggests a link between consumption of chlorinated drinking water and various cancers. Chlorination of water rich in organic chemicals produces carcinogenic organochlorine by-products (OBPs) such as trihalomethanes and haloacetic acids. Since the discovery of the first OBP in the 1970s, there have been several investigations designed to determine the biological effects of single chemicals or small artificial OBP combinations. However, there is still insufficient information regarding the general biological response to these compounds, and further studies are still needed to evaluate their potential genotoxic effects. In the current study, we evaluated the effect of three drinking water disinfectants on the activity of cytochrome P450 (CYP)-linked metabolizing enzymes and on the generation of oxidative stress in the livers of male and female Cyprinus carpio fish (carp). The fish were exposed in situ for up 20 days to surface water obtained from the Trasmene lake in Italy. The water was treated with 1-2 mg/L of either sodium hypochlorite (NaClO) or chlorine dioxide (ClO2) as traditional disinfectants or with a relatively new disinfectant product, peracetic acid (PAA). Micronucleus (MN) frequencies in circulating erythrocytes from the fish were also analysed as a biomarker of genotoxic effect. In the CYP-linked enzyme assays, a significant induction (up to a 57-fold increase in the deethylation of ethoxyresorufin with PAA treatment) and a notable inactivation (up to almost a 90% loss in hydroxylation of p-nitrophenol with all disinfectants, and of testosterome 2 beta-hydroxylation with NaClO) was observed in subcellular liver preparations from exposed fish. Using the electron paramagnetic resonance (EPR) spectroscopy radical-probe technique, we also observed that CYP-modulation was associated with the production of reactive oxygen species (ROS). In addition, we found a significant increase in MN frequency in circulating erythrocytes after 10 days of exposure of fish to water treated with ClO2, while a non-significant six-fold increase in MN frequency was observed with NaClO, but not with PAA. Our data suggest that the use of ClO2 and NaClO to disinfect drinking water could generate harmful OBP mixtures that are able to perturb CYP-mediated reactions, generate oxidative stress and induce genetic damage. These data may provide a mechanistic explanation for epidemiological studies linking consumption of chlorinated drinking water to increased risk of urinary, gastrointestinal and bladder cancers. (c) 2006 Elsevier B.V. All rights reserved

Burst strength of BIOLOX\uaedelta femoral heads and its dependence on low-temperature environmental degradation

Zirconia-toughened alumina (ZTA) currently represents the bioceramic gold standard for load-bearing components in artificial hip joints. ZTA is long known for its high flexural strength and fracture toughness, both properties arising from a microscopic crack-tip shielding mechanism due to the stress-induced tetragonal-to-monoclinic (t\u2192m) polymorphic transformation of zirconia. However, there have been concerns over the years regarding the long-term structural performance of ZTA since the t\u2192m transformation also spontaneously occurs at the material's surface under low-temperature environmental conditions with a concomitant degradation of mechanical properties. Spontaneous surface degradation has been extensively studied in vitro, but predictive algorithms have underestimated the extent of in vivo degradation observed in retrievals. The present research focused on burst-strength assessments of 828 mm ZTA femoral before and after long-term in vitro hydrothermal ageing according to ISO 7206-10. An average burst strength of 52 kN was measured for pristine femoral heads. This value was 3c36% lower than results obtained under the same standard conditions by other authors. A further loss of burst strength 3c13% in ultimate load) was observed after hydrothermal ageing, with increased surface monoclinic content ranging from 3c6% to >50%. Nevertheless, the repetitively stressed and hydrothermally treated ZTA heads exceeded the minimum burst strength stipulated by the US Food and Drug Administration (FDA) despite severe test conditions. Lastly, Raman spectroscopic assessments of phase transformation and residual stresses on the fracture surface of the femoral heads were used to clarify burst-strength fluctuations and the effect of hydrothermal ageing on the material's overall strength degradation

Isolation and characterization of two newly established thymoma PDXs from two relapses of the same patient: a new tool to investigate thymic malignancies

BackgroundThymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies.Main bodyStarting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin.Short conclusionThe newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer

The influence of simulator input conditions on the wear of total knee replacements: an experimental and computational study

Advancements in knee replacement design, material and sterilisation processes have provided improved clinical results. However, surface wear of the polyethylene leading to osteolysis is still considered the longer-term risk factor. Experimental wear simulation is an established method for evaluating the wear performance of total joint replacements. The aim of this study was to investigate the influence of simulation input conditions, specifically input kinematic magnitudes, waveforms and directions of motion and position of the femoral centre of rotation, on the wear performance of a fixed-bearing total knee replacement through a combined experimental and computational approach. Studies were completed using conventional and moderately cross-linked polyethylene to determine whether the influence of these simulation input conditions varied with material. The position of the femoral centre of rotation and the input kinematics were shown to have a significant influence on the wear rates. Similar trends were shown for both the conventional and moderately cross-linked polyethylene materials, although lower wear rates were found for the moderately cross-linked polyethylene due to the higher level of cross-linking. The most important factor influencing the wear was the position of the relative contact point at the femoral component and tibial insert interface. This was dependent on the combination of input displacement magnitudes, waveforms, direction of motion and femoral centre of rotation. This study provides further evidence that in order to study variables such as design and material in total knee replacement, it is important to carefully control knee simulation conditions. This can be more effectively achieved through the use of displacement control simulation

Un approccio innovativo per una migliore comprensione dell’interazione sismica tra suolo e strutture: il test site di Ferrara

Abstract assent

Intravitreal Brolucizumab for Pachychoroid Neovasculopathy Associated With Chronic Central Serous Chorioretinopathy

Purpose: To evaluate the anatomical and functional outcomes of intravitreal brolucizumab in eyes with chronic central serous chorioretinopathy complicated by pachychoroid neovasculopathy. Methods: Retrospective analysis of 34 eyes treated with intravitreal brolucizumab. Twenty-five eyes (73.5%) had been treated with other anti-vascular endothelial growth factor agents before switching to brolucizumab, whereas nine eyes were naïve. Outcome measures included the change of central foveal thickness and subfoveal choroidal thickness, evaluation of sub/intraretinal fluid on optical coherence tomography, and change in best-corrected visual acuity. Results: Before starting brolucizumab, 23 eyes showed subretinal fluid, 8 both subretinal and intraretinal fluid, and 3 intraretinal fluid only. At the last visit, 22 eyes (64.7%) showed complete reabsorption of both intraretinal and subretinal fluid, whereas subretinal fluid was still present in 8 eyes (23.5%), and both intraretinal and subretinal fluid in 4 eyes (11.8%). The mean number of brolucizumab injections required to achieve complete fluid reabsorption was 2.8 ± 1.8. central foveal thickness decreased from 317.8 ± 109.3 μm to 239.8 ± 74.8 μm (P = 0.0005) and subfoveal choroidal thickness decreased from 399.3 ± 86.2 μm to 355.5 ± 92.7 μm at the end of the follow-up period (P = 0.0008). The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.4 ± 0.2 to 0.3 ± 0.2 at 1 month after the first injection and remained stable at the same values at the end of the follow-up period (P = 0.04). Conclusions: Intravitreal brolucizumab is effective for the treatment of naïve and recalcitrant pachychoroid neovasculopathy. Translational relevance: Intravitreal brolucizumab may represent an option in patients with pachychoroid neovasculopathy complicating chronic central serous chorioretinopathy