Relation Between the North-Atlantic Oscillation and Hydroclimatic Conditions in Mediterranean Areas

Mediterranean basins are known for their susceptibility to water stress conditions resulting from a reduction in winter-season precipitation. This region is also prone to the effects of the North Atlantic Oscillation (NAO), a large-scale climatic pattern associated with a displacement of air mass between the arctic and the subtropical Atlantic. Even though previous studies have demonstrated the impact of the NAO on winter climate conditions in Europe and Northern Africa, it is still unclear to what extent the NAO is related to hydroclimatic patterns in Mediterranean areas and whether it can explain its recent drought history. To this end, this study investigates the interdependence between the NAO and winter precipitation, river flow and temperature in two Mediterranean regions: Southern Italy and Nile Delta (Egypt). The outcomes show the presence of significant connections between the NAO, winter rainfall and river discharge.     

The Antimicrobial Peptide Temporin G: Anti-Biofilm,Anti-Persister Activities,and Potentiator Effect of Tobramycin Efficacy Against Staphylococcus aureus

Bacterial biofilms are a serious threat for human health, and the Gram-positive bacterium Staphylococcus aureus is one of the microorganisms that can easily switch from a planktonic to a sessile lifestyle, providing protection from a large variety of adverse environmental conditions. Dormant non-dividing cells with low metabolic activity, named persisters, are tolerant to antibiotic treatment and are the principal cause of recalcitrant and resistant infections, including skin infections. Antimicrobial peptides (AMPs) hold promise as new anti-infective agents to treat such infections. Here for the first time, we investigated the activity of the frog-skin AMP temporin G (TG) against preformed S. aureus biofilm including persisters, as well as its efficacy in combination with tobramycin, in inhibiting S. aureus growth. TG was found to provoke ~50 to 100% reduction of biofilm viability in the concentration range from 12.5 to 100 µM vs ATCC and clinical isolates and to be active against persister cells (about 70–80% killing at 50–100 µM). Notably, sub-inhibitory concentrations of TG in combination with tobramycin were able to significantly reduce S. aureus growth, potentiating the antibiotic power. No critical cytotoxicity was detected when TG was tested in vitro up to 100 µM against human keratinocytes, confirming its safety profile for the development of a new potential anti-infective drug, especially for treatment of bacterial skin infections.     

Development and characterization of a mucoadhesive sublingual formulation for pain control: extemporaneous oxycodone films in personalized therapy

Objective: The aim of this work was the development of mucoadhesive sublingual films, prepared using a casting method, for the administration of oxycodone.

Materials and methods: A solvent casting method was employed to prepare the mucoadhesive films. A calibrated pipette was used to deposit single aliquots of different polymeric solutions on a polystyrene plate lid. Among the various tested polymers, hydroxypropylcellulose at low and medium molecular weight (HPC) and pectin at two different degrees of esterification (PC) were chosen for preparing solutions with good casting properties, capable of producing films suitable for mucosal application.

Results and discussion: The obtained films showed excellent drug content uniformity and stability and rapid drug release, which, at 8?min, ranged from 60% to 80%. All films presented satisfactory mucoadhesive and mechanical properties, also confirmed by a test on healthy volunteers, who did not experience irritation or mucosa damages. Pectin films based on pectin at lower degrees of esterification have been further evaluated to study the influence of two different amounts of drug on the physicochemical properties of the formulation. A slight reduction in elasticity has been observed in films containing a higher drug dose; nevertheless, the formulation maintained satisfactory flexibility and resistance to elongation.

Conclusions: HPC and PC sublingual films, obtained by a simple casting method, could be proposed to realize personalized hospital pharmacy preparations on a small scale.     

Reinforcement of acrylic resins for provisional fixed restorations. Part II: Changes in mechanical properties as a function of time and physical properties

In Part I, it was found that (i) 2 vol.% admixture of reinforcing elements in PMMA (Jet) resin matrix had a significant beneficial effects on the mechanical properties, and (ii) among these, zirconia exhibited the greatest improvements in modulus of elasticity, transverse strength, toughness, and hardness number. Using the best combination (i.e., PMMA resin matrix and 2 vol.% ZrO2), exothermic temperature raise and polymerization shrinkage were further investigated. Deterioration in mechanical properties due to prolonged water sorption were also studied for 5 weeks. The following can be concluded: (1) By increasing liquid/powder ratio for PMMA control samples, the peak temperature occurrence was retarded by 3 min and raised by 8 degrees C. (2) The effect of admixed oxide particles to PMMA resin matrix or the heat generated during polymerization was not significant. (3) The polymerization volumetric shrinkage was influenced by the a mixture of particles, with increases as large as 0.9% (or 0.3% in linear shrinkage). (4) PMMA resin admixed with 2 vol.% of zirconia particles showed a continuous weight gain due to water sorption, mechanical properties appears to be increasing up to 1-week sorption, followed by rapid drop of all properties. (5) Autopolymerizing acrylic resins are a resin-resin composite material of pre-polymerized beads embedded in a newly formed acrylic matrix. The main fracture modality appears to occur through the matrix and at the interface, although some trans-beads fractures were identified. (6) It was suggested that incorporating certain type of oxide particles into the pre-polymerized beads would provide stronger resin matrix.     

A cluster analysis study based on profitability and financial indicators in the Italian gas retail market

In the European Union, the natural gas market is increasingly being liberalized. The liberalization process is aimed at leading to lower prices and higher volumes, and hence higher consumer welfare.     

Somatostatin,a Presynaptic Modulator of Glutamatergic Signal in the Central Nervous System

Somatostatin is widely diffused in the central nervous system, where it participates to control the efficiency of synaptic transmission. This peptide mainly colocalizes with GABA, in inhibitory, GABA-containing interneurons from which it is actively released in a Ca²⁺ dependent manner upon application of depolarizing stimuli. Once released in the synaptic cleft, somatostatin acts locally, or it diffuses in the extracellular space through “volume diffusion”, a mechanism(s) of distribution which mainly operates in the cerebrospinal fluid and that assures the progression of neuronal signalling from signal-secreting sender structures towards receptor-expressing targeted neurons located extrasynaptically, in a non-synaptic, inter-neuronal form of communication. Somatostatin controls the efficiency of central glutamate transmission by either modulating presynaptically the glutamate exocytosis or by metamodulating the activity of glutamate receptors colocalized and functionally coupled with somatostatin receptors in selected subpopulations of nerve terminals. Deciphering the role of somatostatin in the mechanisms of “volume diffusion” and in the “receptor-receptor interaction” unveils new perspectives in the central role of this fine tuner of synaptic strength, paving the road to new therapeutic approaches for the cure of central disorders.     

Broad-Spectrum Bactericidal Activity of a Synthetic Random Copolymer Based on 2-Methoxy-6-(4-Vinylbenzyloxy)-Benzylammonium Hydrochloride

Low-molecular-weight organic ammonium salts exert excellent antimicrobial effects by interacting lethally with bacterial membranes. Unfortunately, short-term functionality and high toxicity limit their clinical application. On the contrary, the equivalent macromolecular ammonium salts, derived from the polymerization of monomeric ammonium salts, have demonstrated improved antibacterial potency, a lower tendency to develop resistance, higher stability, long-term activity, and reduced toxicity. A water-soluble non-quaternary copolymeric ammonium salt (P7) was herein synthetized by copolymerizing 2-methoxy-6-(4-vinylbenzyloxy)-benzylammonium hydrochloride monomer with N, N-di-methyl-acrylamide. The antibacterial activity of P7 was assessed against several multidrug-resistant (MDR) clinical isolates of both Gram-positive and Gram-negative species. Except for colistin-resistant Pseudomonas aeruginosa, most isolates were susceptible to P7, also including some Gram-negative bacteria with a modified charge in the external membrane. P7 showed remarkable antibacterial activity against isolates of Enterococcus, Staphylococcus, Acinetobacter, and Pseudomonas, and on different strains of Escherichia coli and Stenotrophomonas maltophylia, regardless of their antibiotic resistance. The lowest minimal inhibitory concentrations (MICs) observed were 0.6–1.2 µM and the minimal bactericidal concentrations (MBC) were frequently overlapping with the MICs. In 24-h time–kill and turbidimetric studies, P7 displayed a rapid non-lytic bactericidal activity. P7 could therefore represent a novel and potent tool capable of counteracting infections sustained by several bacteria that are resistant to the presently available antibiotics.     

Reinforcement of acrylic resins for provisional fixed restorations. Part I: Mechanical properties

Acrylic resins are commonly used in many dental applications; especially in the fabrication of provisional fixed partial dentures. Among noticed technical drawbacks associated with this material are unsatisfactory mechanical properties. Moreover, if acrylic resins are exposed to moist environment, water sorption results in further mechanical deterioration. In order to improve the mechanical properties, aluminum, magnesium, and zirconium oxide powders and pulverized E-glass particles were separately admixed with pre-polymerized acrylic resin beads prior to mixing with monomer liquid. Particle loading ratios were 1, 2 and 3 vol.% with respect to pre-polymerized beads. Poly(methyl methacrylate), poly(ethyl methacrylate) and poly(isobutyl methacrylate) were used as resin matrices. Furthermore, a metal primer agent was employed in order to form a strong interphase between admixed particles and polymer matrix phase. Samples were subjected to three-point transverse bending tests at a crosshead speed of 10 mm/min. It was concluded that (1) addition of particles generally increases the water sorbed by the composite resins systems, (2) however, two vol.% admixtures in a PMMA resin matrix showed significant improvements in the mechanical properties (p < 0.05), (3) among the oxide particles, zirconia exhibited the greatest improvements in modulus of elasticity, transverse strength, toughness and hardness, and (4) mechanical properties (transverse strength, 0.2% offset yield strength and modulus of elasticity) were linearly correlated to hardness numbers.     

Generation of a Retargeted Oncolytic Herpes Virus Encoding Adenosine Deaminase for Tumor Adenosine Clearance

Background: Oncolytic viruses are immunotherapeutic agents that can be engineered to encode payloads of interest within the tumor microenvironment to enhance therapeutic efficacy. Their therapeutic potential could be limited by many avenues for immune evasion exerted by the tumor. One such is mediated by adenosine, which induces pleiotropic immunosuppression by inhibiting antitumor immune populations as well as activating tolerogenic stimuli. Adenosine is produced starting from the highly immunostimulatory ATP, which is progressively hydrolyzed to ADP and adenosine by CD39 and CD73. Cancer cells express high levels of CD39 and CD73 ectoenzymes, thus converting immunostimulatory purinergic signal of ATP into an immunosuppressive signal. For this reason, CD39, CD73 and adenosine receptors are currently investigated in clinical trials as targets for metabolic cancer immunotherapy. This is of particular relevance in the context of oncovirotherapy, as immunogenic cell death induced by oncolytic viruses causes the secretion of a high amount of ATP which is available to be quickly converted into adenosine. Methods: Here, we took advantage of adenosine deaminase enzyme that naturally converts adenosine into the corresponding inosine derivative, devoid of immunoregulatory function. We encoded ADA into an oncolytic targeted herpes virus redirected to human HER2. An engineered ADA with an ectopic signal peptide was also generated to improve enzyme secretion (ADA-SP). Results: Insertion of the expression cassette was not detrimental for viral yield and cancer cell cytotoxicity. The THV_ADA and THV_ADA-SP successfully mediated the secretion of functional ADA enzyme. In in vitro model of human monocytes THP1, this ability of THV_ADA and THV_ADA-SP resulted in the retrieval of eADO-exposed monocytes replication rate, suggesting the proficiency of the viruses in rescuing the immune function. Conclusions: Encoding ADA into oncolytic viruses revealed promising properties for preclinical exploitation.