Buccal tablets containing cysteine and chlorhexidine for the reduction of acetaldehyde levels in the oral cavity

There is growing evidence that a large proportion of upper digestive tract tumors are ascribable to heavy alcohol drinking and tobacco consumption. The cancer-promoting action of ethanol is mediated by acetaldehyde, its first metabolite, also derived from the bacterial oxidation of alcohol by the oral microflora, classified by the International Agency for the Research on Cancer as a carcinogen. Acetaldehyde is also one of the major components of tobacco smoke. These findings suggest two different strategies to decrease the risk of alcohol-related oral cancers: the reduction of the levels of alcohol-derived acetaldehyde in saliva and the reduction of oral bacterial flora. Therefore, the aim of our study was to develop and characterize some buccal tablet formulations containing both 20 mg L-cysteine hydrochloride (able to chemically neutralize acetaldehyde) and 10 mg chlorhexidine diacetate (well-known antiseptic compound active against a large spectrum of oral microbes). One of these formulations, chosen on the basis of its favourable delivery kinetics of the active principles, was demonstrated to be able to reduce acetaldehyde concentration in an in vitro system and to lower its salivary levels in volunteers after ethanol contact. Our findings support the hypothesis that the application of buccal devices containing cysteine and chlorhexidine could reduce salivary acetaldehyde levels and thus the incidence of upper gastrointestinal cancer in drinkers and smokers.     

Self‐Assembled Conjugated Thiophene‐Based Rotaxane Architectures: Structural,Computational, and Spectroscopic Insights into Molecular Aggregation

A comparative study of the self‐assembly at a variety of surfaces of a dithiophene rotaxane 1 ?β‐CD and its corresponding dumbbell, 1, by means of atomic force microscopy (AFM) imaging and scanning tunneling microscopy (STM) imaging on the micrometer and nanometer scale, respectively. The dumbbell is found to have a greater propensity to form ordered supramolecular assemblies, as a result of π–π interactions between dithiophenes belonging to adjacent molecules, which are hindered in the rotaxane. The fine molecular structure determined by STM was compared to that obtained by molecular modelling. The optical properties of both rotaxane and dumbbell in the solid state were investigated by steady‐state and time‐resolved photoluminescence (PL) experiments on spin‐cast films and diluted solutions. The comparison between the optical features of the threaded and unthreaded systems reveals an effective role of encapsulation in reducing aggregation and exciton migration for the rotaxanes with respect to the dumbbells, thus leading to higher PL quantum efficiency and preserved single‐molecule photophysics for longer times after excitation in the threaded oligomers.     

Simulator evaluation of drivers' speed, deceleration and lateral position at rural intersections in relation to different perceptual cues

Aim of the study was to investigate, by means of a driving simulator experiment, drivers’ behaviour in terms of speed, deceleration, and lateral position on major approaches of rural intersections in relation to different perceptual cues.In the experiment, ten different design conditions with and without speed-reducing treatments along the approach to the intersection were tested. Twenty-three drivers drove a test route two times and data from the second drive were used for comparison. The order of the ten design conditions was counterbalanced for all the drivers to minimize the presentation order effect. Three different data analysis techniques were used: (a) cluster analysis of speed and lateral position data, (b) statistical tests of speed and lateral position data, and (c) categorical analysis of deceleration behaviour patterns.The most effective treatments were the dragon teeth markings (based on the principle of optical road narrowing), the colored intersection area (based on the principle of intersection highlighting), and the raised median island (based on the principle of physical road narrowing). These measures, in comparison to the base intersection, produced: (1) a significant speed reduction starting from 250 m before the intersection in the range between 13 and 23 km/h, (2) a significant change in the deceleration behaviour with a reduction in the proportion of drivers which did not decelerate, and (3) a shift away from the intersection of the deceleration beginning. Given the significant effects on drivers’ behaviour, the dragon teeth markings, the colored intersection area, and the raised median island are strongly recommended for real world implementation.     

Microwave-assisted photochemical reactor for the online oxidative decomposition and determination of p-hydroxymercurybenzoate and its thiolic complexes by cold vapor generation atomic fluorescence detection

We developed a photochemical method for the online oxidation of p-hydroxymercurybenzoate (PHMB), an organic mercury species widely used for mercaptan and thiolic compound labeling. The method is based on a fully integrated online UV/microwave (MW) photochemical reactor for the digestion of PHMB, followed by cold vapor generation atomic fluorescence spectrometry (CVG-AFS) detection. The MW/UV process led to the quantitative conversion of PHMB and thiol-PHMB complexes to Hg(II), with a yield between 91% and 98%, without using chemical oxidizing reagents and avoiding the use of toxic carcinogenic compounds. This reaction was followed by the reduction of Hg(II) to Hg(0), performed in a knitted reaction coil with NaBH(4) solution, and AFS detection in an Ar/H(2) miniaturized flame. The low MW power applied (18 W) allowed us to keep constant the temperature of the photochemical reactor (21 ± 1 °C), using a flowing water bath. This avoided peak widening due to diffusion processes generally occurring at high temperatures and in the additional cooling coil. This method has been applied to the determination of thiols in human plasma, blood, and wine.     

Moisture-induced stresses perpendicular to grain in cross-sections of timber members exposed to different climates

In variable humidity conditions, wood absorbs or desorbs moisture from the air. Unless the change in humidity is very slow, this will develop moisture gradients in the wood sections. These gradients will develop stresses due to constrained swelling or shrinkage strains. These stresses are named moisture-induced stresses. The present paper investigates the main parameters affecting such moisture-induced stresses, including the type of climate, the size of the timber cross-section, and the type of protective coating. A first attempt to identify moisture-induced stresses in different European climatic regions was made. For each climatic region, relative humidity and temperature histories were identified, and characteristic and mean values of yearly and daily variations were calculated. Using a finite element model implemented in Abaqus, the moisture content and stress distribution were computed on different timber cross-sections exposed to the climatic regions and protected with different types of coating. A Fickian moisture transfer model was used to compute the moisture distribution, and a mechanical model for time-dependent behaviour of wood was implemented to calculate the corresponding stress distribution. The variation of moisture was found to result in stresses of magnitudes that would probably cause cracking of wood in the perimeter of any uncoated cross-section size. The use of a protective coating, however, reduced considerably the moisture-induced stresses, and can be regarded as an effective protective measure to avoid cracking due to humidity variations. Considering European climates, Northern climates were found to result in higher surface tensile stresses than Southern climates.     

Provisioning of dynamic traffic in mixed-line-rate optical networks with launch power determination

In mixed-line-rate (MLR) networks, different line rates on different wavelengths can coexist on the same fiber. MLR architectures can be built over transparent optical networks, where the transmitted signals remain in the optical domain along the entire path. Along the transparent optical path, a signal experiences various physical layer impairments (PLIs), and its quality degrades as it travels through each optical component. One of the major factors that affect the transmission quality is the launch power of the optical signal. The power must be large enough to ensure noise resiliency at the receiver, but it must be below the limit where fiber nonlinearities distort the signal. Moreover, high launch power is disruptive not only for the actual lightpath itself but also for neighboring lightpaths, and this effect is particularly critical in MLR networks since advanced modulation techniques used for high line rates are highly susceptible to PLIs. In this study, we investigate the problem of determining the appropriate launch power for provisioning of dynamic connection requests in MLR networks. By setting the appropriate launch power for each connection, we aim to maximize the number of established connections. We propose two different heuristics to determine the appropriate launch power of a lightpath. Worst-case best-case average (WBA) is based on optical reach of signal in a transparent optical network. In impairment-aware launch power determination (I-ALPD), current state of the network and impairments are evaluated to determine the launch power. The proposed approaches are practical and can adapt to the needs of network operators. Simulation results show that the performances of the proposed approaches show better results than the existing schemes in terms of blocking probability and bandwidth blocking ratio.     

Disaster-aware service provisioning with manycasting in cloud networks

Cloud services delivered by high-capacity optical datacenter networks are subject to disasters which may cause large-area failures, leading to huge data loss. Survivable service provisioning is crucial to minimize the effects of network/datacenter failures and maintain critical services in case of a disaster. We propose a novel disaster-aware service-provisioning scheme that multiplexes service over multiple paths destined to multiple servers/datacenters with manycasting. Our scheme maintains some bandwidth (i.e., degraded service) after a disaster failure vs. no service at all. We formulate this problem into a mathematical model which turns out to be an Integer Linear Program (ILP), and we provide heuristic optimization approaches as ILP is intractable for large problem instances. Numerical examples show that exploiting manycasting by intelligently selecting destinations in a risk-aware manner for service provisioning offers high level of survivability against link and node failures that may be caused by disasters and post-disaster failures at no extra cost compared to the other survivable schemes.     

TRPML2 Mucolipin Channels Drive the Response of Glioma Stem Cells to Temozolomide and Affect the Overall Survival in Glioblastoma Patients

The survival of patients with glioblastoma (GBM) is poor. The main cause is the presence of glioma stem cells (GSCs), exceptionally resistant to temozolomide (TMZ) treatment. This last may be related to the heterogeneous expression of ion channels, among them TRPML2. Its mRNA expression was evaluated in two different neural stem cell (NS/PC) lines and sixteen GBM stem-like cells by qRT-PCR. The response to TMZ was evaluated in undifferentiated or differentiated GSCs, and in TRPML2-induced or silenced GSCs. The relationship between TRPML2 expression and responsiveness to TMZ treatment was evaluated by MTT assay showing that increased TRPML2 mRNA levels are associated with resistance to TMZ. This research was deepened by qRT-PCR and western blot analysis. PI3K/AKT and JAK/STAT pathways as well as ABC and SLC drug transporters were involved. Finally, the relationship between TRPML2 expression and overall survival (OS) and progression-free survival (PFS) in patient-derived GSCs was evaluated by Kaplan–Meier analysis. The expression of TRPML2 mRNA correlates with worse OS and PFS in GBM patients. Thus, the expression of TRPML2 in GSCs influences the responsiveness to TMZ in vitro and affects OS and PFS in GBM patients.     

Polymer Encapsulated Liposomes for Oral Co-Delivery of Curcumin and Hydroxytyrosol

Curcumin (Cur) is a hydrophobic polyphenol from the rhizome of Curcuma spp., while hydroxytyrosol (HT) is a water-soluble polyphenol from Olea europaea. Both show outstanding antioxidant properties but suffer from scarce bioavailability and low stability in biological fluids. In this work, the co-encapsulation of Cur and HT into liposomes was realized, and the liposomal formulation was improved using polymers to increase their survival in the gastrointestinal tract. Liposomes with different compositions were formulated: Type 1, composed of phospholipids and cholesterol; Type 2, also with a PEG coating; and Type 3 providing an additional shell of Eudragit^® S100, a gastro-resistant polymer. Samples were characterized in terms of size, morphology, ζ-potential, encapsulation efficiency, and loading capacity. All samples were subjected to a simulated in vitro digestion and their stability was investigated. The Eudragit^®S100 coating demonstrated prevention of early releases of HT in the mouth and gastric phases, while the PEG shell reduced bile salts and pancreatin effects during the intestinal digestion. In vitro antioxidant activity showed a cumulative effect for Cur and HT loaded in vesicles. Finally, liposomes with HT concentrations up to 40 μM and Cur up to 4.7 μM, alone or in combination, did not show cytotoxicity against Caco-2 cells.