Modulation of Toll-like receptors in psoriatic patients during therapy with adalimumab

Toll-like receptors (TLRs) are a key part of the innate immune system that detect pathogen-associated molecular patterns (PAMPs) of microorganisms and their stimulation results in the activation of signaling pathways leading to the modulation of inflammatory and immune responses. Since psoriasis is a complex, inflammatory and immune skin disease, characterized by an abnormal immune response and increased proliferation of keratinocytes, with an increased production of proinflammatory cytokines, TLRs could play an important role in the pathogenesis of the disease. We propose to assess the modulation of TLR expression on psoriatic skin of patients treated with Adalimumab and systemic conventional therapies. We therefore recruited fifteen patients: ten were treated with adalimumab and five with systemic conventional therapies; their clinical conditions were analyzed by PASI index and skin biopsies were evaluated for TLR1 and TLR2 expression by immunohistochemistry assays. Our data suggest adalimumab is not only able to improve the clinical condition of psoriatic patients, but also to modulate TLR1 and TLR2 expression involved in psoriasis, as in healthy skin. Adalimumab is a most promising biological drug able to orchestrate immune and inflammatory responses in psoriatic lesions, recovering TLR expression on basal keratinocytes and improving clinical conditions of psoriatic patients, with no evident side effects

Polyethylene Glycol Epirubicin-Loaded Transcatheter Arterial Chemoembolization Procedures Utilizing a Combined Approach with 100 and 200 μm Microspheres: A Promising Alternative to Current Standards

PURPOSE:To report clinical effectiveness, toxicity profile, and prognostic factors of combined 100 μm ± 25 and 200 μm ± 50 epirubicin-loaded polyethylene glycol (PEG) microsphere drug-eluting embolic transcatheter arterial chemoembolization protocol in patients with hepatocellular carcinoma. MATERIALS AND METHODS: In this prospective, single-center, single-arm study with 18 months of follow-up, 36 consecutive patients (mean age 69.9 y ± 10.8; 26 men, 10 women; 54 naïve lesions) were treated. Embolization was initiated with 100 μm ± 25 microspheres, and if stasis (10 heart beats) was not achieved, 200 μm ± 50 microspheres were administered. Each syringe (2 mL) of PEG microsphere was loaded with 50 mg of epirubicin. Results were evaluated using Modified Response Evaluation Criteria In Solid Tumors with multidetector computed tomography/magnetic resonance imaging at 1, 3-6, 9-12, and 15-18 months. Toxicity profile was assessed by laboratory testing before and after the procedure. Complications were recorded. Postembolization syndrome (PES) was defined as onset of fever/nausea/pain after the procedure. Patient/lesion characteristics and treatment results were correlated with predicted outcome using regression analysis. Child-Pugh score was A in 86.1% of patients (31/36) and B in 13.9% (5/36). RESULTS: In 10 of 21 lesions, < 2 cm in diameter (47.5%) stasis was achieved with 100 μm ± 25 microspheres only, whereas all other lesions required adjunctive treatment with 200 μm ± 50 microspheres. Reported adverse events were grade 1 acute liver bile duct injury (3/39 cases, 7.7%) and PES (grade 2; 3/39 cases, 7.7%). Complete response (CR) at 1, 3-6, 9-12, and 15-18 months was 61.1%, 65.5%, 63.63%, and 62.5%. Objective response (CR + partial response) at 1, 3-6, 9-12, and 15-18 months was 83.3%, 65.85%, 63.63%, and 62.5%. No single factor (laboratory testing, etiology, patient status, hepatic status, tumor characteristics, administration protocol) predicted outcomes except for albumin level at baseline for CR (P < .05, odds ratio = 1.09). CONCLUSIONS: The combined microsphere sizing strategy was technically feasible and yielded promising results in terms of effectiveness and toxicity

Basin-scale interaction between post-LGM faulting and morpho-sedimentary processes in the S. Eufemia Gulf (Southern Tyrrhenian Sea)

The integrated interpretation of high-resolution multibeam bathymetry, seismic profiles and backscatter data in the S. Eufemia Gulf (SEG; Calabro-Tyrrhenian continental margin, south-eastern Tyrrhenian Sea) documents the relationship between postglacial fault activity and morpho-sedimentary processes. Three systems of active normal faults that affect the seafloor or the shallow subsurface, have been identified: 1) the S. Eufemia fault system located on the continental shelf with fault planes mainly oriented N26E-N40E; 2) the offshore fault system that lies on the continental slope off Capo Suvero with fault planes mainly oriented N28E-N60E; 3) the Angitola Canyon fault system located on the seafloor adjacent to the canyon having fault planes oriented N60EN85E. The faults produce a belt of linear escarpments with vertical displacement varying from a few decimeters to about 12 m. One of the most prominent active structures is the fault F1 with the highest fault length (about 9.5 km). Two main segments of this fault are identified: a segment characterised by seafloor deformation with metric slip affecting Holocene deposits; a segment characterised by folding of the seafloor. A combined tectonostratigraphic model of an extensional fault propagation fold is proposed here to explain such different deformation.In addition to the seabed escarpments produced by fault deformation, in the SEG, a strong control of fault activity on recent sedimentary processes is clearly observed. For example, canyons and channels frequently change their course in response to their interaction with main tectonic structures. Moreover, the upper branch of the Angitola Canyon shows straight flanks determined by fault scarps. Tectonics also determined different sediment accumulation rates and types of sedimentation (e.g., the accumulation of hanging wall turbidite deposits and the development of contourite deposits around the Maida Ridge). Furthermore, the distribution of landslides is often connected to main fault scarps and fluids are locally confined in the hanging wall side of faults and can escape at the seabed, generating pockmarks aligned along their footwall

Positioning by multicell fingerprinting in urban NB-IoT networks

Narrowband Internet of Things (NB-IoT) has quickly become a leading technology in the deployment of IoT systems and services, owing to its appealing features in terms of coverage and energy efficiency, as well as compatibility with existing mobile networks. Increasingly, IoT services and applications require location information to be paired with data collected by devices; NB-IoT still lacks, however, reliable positioning methods. Time-based techniques inherited from long-term evolution (LTE) are not yet widely available in existing networks and are expected to perform poorly on NB-IoT signals due to their narrow bandwidth. This investigation proposes a set of strategies for NB-IoT positioning based on fingerprinting that use coverage and radio information from multiple cells. The proposed strategies were evaluated on two large-scale datasets made available under an open-source license that include experimental data from multiple NB-IoT operators in two large cities: Oslo, Norway, and Rome, Italy. Results showed that the proposed strategies, using a combination of coverage and radio information from multiple cells, outperform current state-of-the-art approaches based on single cell fingerprinting, with a minimum average positioning error of about 20 m when using data for a single operator that was consistent across the two datasets vs. about 70 m for the current state-of-the-art approaches. The combination of data from multiple operators and data smoothing further improved positioning accuracy, leading to a minimum average positioning error below 15 m in both urban environments

Gli atteggiamenti degli insegnanti di scuola elementare nelle scienze biologico-naturalistiche

This paper stresses the need of coherence between the science teachers training and the emergent constructivist model of science learning

A Multi-Disciplinary Approach to the Study of Large Rock Avalanches Combining Remote Sensing, GIS and Field Surveys: The Case of the Scanno Landslide, Italy

This is the final version. Available from MDPI via the DOI in this record.This research aims to highlight the importance of adopting a multi-disciplinary approach to understanding the factors controlling large rock avalanches using the Scanno landslide, Italy, as a case study. The study area is the Mount Genzana, Abruzzi Central Apennines, characterized by the regional Difesa-Mount Genzana-Vallone delle Masserie fault zone. The Scanno landslide is famous for its role in the formation of the Scanno Lake. The landslide is characterized by a wide exposed scar, which was interpreted in previous studies as the intersection of high-angle joints and an outcropping bedding plane on which the landslide failed sometime between the Upper Pleistocene and the Holocene. In this study, the Scanno landslide was investigated through the integration of geological, geomechanical and geomorphological surveys. Remote sensing techniques were used to enrich the conventionally gathered datasets, while Geographic Information Systems (GIS) were used to integrate, manage and investigate the data. The results of the authors investigation show that the outcropping landslide scar can be interpreted as a low-angle fault, associated with the Difesa-Mount Genzana-Vallone delle Masserie fault zone, which di ers from previous investigations and interpretations of the area. The low-angle fault provides the basal failure surface of the landslide, with two systematic high-angle joint sets acting as lateral release and back scarp surfaces, respectively. In light of these new findings, pre- and post-failure models of the area have been created. The models were generated in GIS by combining LiDAR (Light Detection and Ranging) and geophysics data acquired on the landslide body and through bathymetric survey data of the Scanno Lake. Using the pre- and post-failure models it was possible to estimate the approximate volume of the landslide. Finally, back-analyses using static and dynamic limit equilibrium methods is also used to show the possible influence of medium-to-high magnitude seismic events in triggering the Scanno landslide

Macromolecular and electrical coupling between inner hair cells in the rodent cochlea

Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other. We report that, upon developmental maturation, in mice 30% of the IHCs are electrochemically coupled in ‘mini-syncytia’. This coupling permits transfer of fluorescently-labeled metabolites and macromolecular tracers. The membrane capacitance, Ca2+-current, and resting current increase with the number of dye-coupled IHCs. Dual voltage-clamp experiments substantiate low resistance electrical coupling. Pharmacology and tracer permeability rule out coupling by gap junctions and purinoceptors. 3D electron microscopy indicates instead that IHCs are coupled by membrane fusion sites. Consequently, depolarization of one IHC triggers presynaptic Ca2+-influx at active zones in the entire mini-syncytium. Based on our findings and modeling, we propose that IHC-mini-syncytia enhance sensitivity and reliability of cochlear sound encoding