The growing interest on the therapeutic potential against neurodegeneration of Cannabis sativa extracts, and of phytocannabinoids in particular, is paralleled by a limited understanding of the ...undergoing biochemical pathways in which these natural compounds may be involved. Computational tools are nowadays commonly enrolled in the drug discovery workflow and can guide the investigation of macromolecular targets for such molecules. In this contribution, in silico techniques have been applied to the study of C. sativa constituents at various extents, and a total of seven phytocannabinoids and four terpenes were considered. On the side of ligand‐based virtual screening, physico‐chemical descriptors were computed and evaluated, highlighting the phytocannabinoids possessing suitable drug‐like properties to potentially target the central nervous system. Our previous findings and literature data prompted us to investigate the interaction of these molecules with phosphodiesterases (PDEs), a family of enzymes being studied for the development of therapeutic agents against neurodegeneration. Among the compounds, structure‐based techniques such as docking and molecular dynamics (MD), highlighted cannabidiol (CBD) as a potential and selective PDE9 ligand, since a promising calculated binding energy value (−9.1 kcal/mol) and a stable interaction in the MD simulation timeframe were predicted.
Additionally, PDE9 inhibition assay confirmed the computational results, and showed that CBD inhibits the enzyme in the nanomolar range in vitro, paving the way for further development of this phytocannabinoid as a therapeutic option against neurodegeneration.
A multi‐level computational study, including ligand‐based and structure‐based screenings, together with in vitro tests, highlighted cannabidiol (CBD) as a central nervous system (CNS)‐targeting PDE9 inhibitor.
Airborne particulate (PM) components from fossil fuel combustion can induce oxidative stress initiated by reactive oxygen species (ROS) that are strongly correlated with airway inflammation and ...asthma. A valid biomarker of airway inflammation is fractionated exhaled nitric oxide (FENO). The oxidative potential of PM2.5 can be evaluated with the dithiothreitol (DTT) dosage, which represents both ROS chemically produced and intracellular ROS of macrophages. This correlates with quality indicators of the internal environment and ventilation strategies such as dilution and removal of airborne contaminants.
No large study to date has ever evaluated the effectiveness, safety and tolerability of imipenem/clavulanate versus meropenem/clavulanate to treat multidrug- and extensively drug-resistant ...tuberculosis (MDR- and XDR-TB). The aim of this observational study was to compare the therapeutic contribution of imipenem/clavulanate versus meropenem/clavulanate added to background regimens to treat MDR- and XDR-TB cases.84 patients treated with imipenem/clavulanate-containing regimens showed a similar median number of antibiotic resistances (8 versus 8) but more fluoroquinolone resistance (79.0% versus 48.9%, p<0.0001) and higher XDR-TB prevalence (67.9% versus 49.0%, p=0.01) in comparison with 96 patients exposed to meropenem/clavulanate-containing regimens. Patients were treated with imipenem/clavulanate- and meropenem/clavulanate-containing regimens for a median (interquartile range) of 187 (60-428) versus 85 (49-156) days, respectively.Statistically significant differences were observed on sputum smear and culture conversion rates (79.7% versus 94.8%, p=0.02 and 71.9% versus 94.8%, p<0.0001, respectively) and on success rates (59.7% versus 77.5%, p=0.03). Adverse events to imipenem/clavulanate and meropenem/clavulanate were reported in 5.4% and 6.5% of cases only.Our study suggests that meropenem/clavulanate is more effective than imipenem/clavulanate in treating MDR/XDR-TB patients.
Premotor neurons play a fundamental role in transforming physical properties of observed objects, such as size and shape, into motor plans for grasping them, hence contributing to "pragmatic" ...affordance processing. Premotor neurons can also contribute to "semantic" affordance processing, as they can discharge differently even to pragmatically identical objects depending on their behavioural relevance for the observer (i.e. edible or inedible objects). Here, we compared the response of monkey ventral premotor area F5 neurons tested during pragmatic (PT) or semantic (ST) visuomotor tasks. Object presentation responses in ST showed shorter latency and lower object selectivity than in PT. Furthermore, we found a difference between a transient representation of semantic affordances and a sustained representation of pragmatic affordances at both the single neuron and population level. Indeed, responses in ST returned to baseline within 0.5 s whereas in PT they showed the typical sustained visual-to-motor activity during Go trials. In contrast, during No-go trials, the time course of pragmatic and semantic information processing was similar. These findings suggest that premotor cortex generates different dynamics depending on pragmatic and semantic information provided by the context in which the to-be-grasped object is presented.
BACKGROUNDDuring the COVID-19 pandemic, the implementation of telemedicine has represented a new potential option for outpatient care. The aim of our study was to evaluate digital literacy among ...cardiology outpatients. METHODSFrom March to June 2020, a survey on telehealth among cardiology outpatients was performed. Digital literacy was investigated through six main domains: age; sex; educational level; internet access; availability of internet sources; knowledge and use of teleconference software programs. RESULTSThe study included 1067 patients, median age 70 years, 41.3% females. The majority of the patients (58.0%) had a secondary school degree, but among patients aged ≥ 75 years old the most represented educational level was primary school or none. Overall, for internet access, there was a splitting between "never" (42.1%) and "every day" (41.0%), while only 2.7% answered "at least 1/month" and 14.2% "at least 1/week". In the total population, the most used devices for internet access were smartphones (59.0%), and WhatsApp represented the most used app (57.3%). Internet users were younger compared to non-internet users (63 vs. 78 years old, respectively) and with a higher educational level. Age and educational level were associated with non-use of internet (age-per 10-year increase odds ratio (OR) = 3.07, 95% CI: 2.54-3.71, secondary school OR = 0.18, 95% CI: 0.12-0.26, university OR = 0.05, 95% CI: 0.02-0.10). CONCLUSIONSTelemedicine represents an appealing option to implement medical practice, and for its development it is important to address the gaps in patients' digital skills, with age and educational level being key factors in this setting.
New data on the distribution of the Annex I Habitats 3120, 3260, 6310, 9180* and 92A0 are reported in this contribution. In detail, 3 new occurrences in Natura 2000 Sites are presented and 5 new ...cells in the EEA 10 km x 10 km Reference grid are added. The new data refer to Italy and in particular to the Administrative Regions of Liguria, Sardinia, Sicily and Umbria. This issue of the section “Habitat records” includes an
Errata corrige
referring to the last released issue.
The two-dimensional electron system (2DES) located at the surface of strontium titanate (STO) and at several other STO-based interfaces has been an established platform for the study of novel ...physical phenomena since its discovery. Here we report how the interfacing of STO and tetracyanoquinodimethane (TCNQ) results in a charge transfer that depletes the number of free carriers at the STO surface, with a strong impact on its electronic structure. Our study paves the way for efficient tuning of the electronic properties, which promises novel applications in the framework of oxide/organic-based electronics.
Tunnel Boring Machine (TBM) tunnelling in weak rock associated with high overburden is very demanding due to the difficulties in predicting the complex interactions between the rock mass, the tunnel ...machine, its system components, and the tunnel support during excavation/construction. These factors affect the performance and even the feasibility of a TBM drive (sticking of the cutterhead and jamming of the shield may occur). In this respect, several computational models such as the Convergence–Confinement Method (CCM), axially symmetric model and three-dimensional (3D) simulation have been developed in the literature. Among these models, this paper presents three modelling techniques (i.e., a 3D simulator using the Finite Element Method (FEM), an axisymmetric model using the Finite Difference Method (FDM) and an LDP (Longitudinal Displacement Profile) approach based on the CCM), and applies them to the Headrace Tunnel from the Kishanganga Hydroelectric Project in India. The three approaches are not considered to be alternatives but rather complementary to each other, depending on the real situation. The LDP approach is a simplified analytical method but is still efficient to provide a conceptual framework for evaluating the ground-shield interplay during mechanised excavation. The FDM axisymmetric model represents a powerful tool (i.e., with a large deformation scheme available) for the simulation of ground behaviour and its interaction with the machine components, especially in the case of weak rocks with high deformability. However, when the conditions violate the important assumptions underlying these two approaches, true 3D numerical analyses are necessary, which consider all the TBM components. Finally, the paper highlights the potentials of the 3D simulator to model the basic features (i.e., stepwise conicity of the shield, backfilling layer and anisotropic in-situ stress state) of a shield-driven deep tunnel, which determine the tunnel’s behaviour and its response to TBM advancement. The obtained results show that the 3D nature of the complex interactions and the in-situ state of stress, including the nonlinear behaviour can be better reproduced in a 3D simulation than in the other two methods.
New Italian data on the distribution of the Annex I Habitats are reported in this contribution. Specifically, 8 new occurrences in Natura 2000 sites are presented and 49 new cells are added in the ...EEA 10 km × 10 km reference grid. The new data refer to the Italian administrative regions of Campania, Calabria, Marche, Piedmont, Sardinia, Sicily, Tuscany and Umbria. Relevés and figures are provided as Supplementary material respectively 1 and 2.
New Italian data on the distribution of the Annex I Habitats 3170*, 6110*, 91E0*, 9320, 9330 are reported in this contribution. Specifically, one new occurrence in Natura 2000 sites is presented and ...six new cells are added in the European Environment Agency 10 km × 10 km reference grid. The new data refer to the Italian administrative regions of Sardinia, Sicily and Umbria.
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