Fabrication, Characterization and Performance of Low Power Gas Sensors Based on (GaxIn1-x)2O3 Nanowires.

Active research in nanostructured materials aims to explore new paths for improving electronic device characteristics. In the field of gas sensors, those based on metal oxide single nanowires exhibit excellent sensitivity and can operate at extremely low power consumption, making them a highly promising candidate for a novel generation of portable devices. The mix of two different metal oxides on the same nanowire can further broaden the response of this kind of gas sensor, thus widening the range of detectable gases, without compromising the properties related to the active region miniaturization. In this paper, a first study on the synthesis, characterization and gas sensing performance of (GaxIn1-x)2O3 nanowires (NWs) is reported. Carbothermal metal-assisted chemical vapor deposition was carried out with different mixtures of Ga2O3, In2O3 and graphite powders. Structural characterization of the NWs revealed that they have a crystalline structure close to that of In2O3 nanowires, with a small amount of Ga incorporation, which highly depends on the mass ratio between the two precursors. Dedicated gas nanosensors based on single NWs were fabricated and tested for both ethanol and nitrogen dioxide, demonstrating an improved performance compared to similar devices based on pure In2O3 or Ga2O3 NWs.

Highly Sensitive Membrane-Based Pressure Sensors (MePS) for Real-Time Monitoring of Catalytic Reactions.

Functional, flexible, and integrated lab-on-chips, based on elastic membranes, are capable of fine response to external stimuli, so to pave the way for many applications as multiplexed sensors for a wide range of chemical, physical and biomedical processes. Here, we report on the use of elastic thin membranes (TMs), integrated with a reaction chamber, to fabricate a membrane-based pressure sensor (MePS) for reaction monitoring. In particular, the TM becomes the key-element in the design of a highly sensitive MePS capable to monitor gaseous species production in dynamic and temporally fast processes with high resolution and reproducibility. Indeed, we demonstrate the use of a functional MePS integrating a 2 µm thick polydimethylsiloxane TM by monitoring the dioxygen evolution resulting from catalytic hydrogen peroxide dismutation. The operation of the membrane, explained using a diffusion-dominated model, is demonstrated on two similar catalytic systems with catalase-like activity, assembled into polyelectrolyte multilayers capsules. The MePS, tested in a range between 2 and 50 Pa, allows detecting a dioxygen variation of the µmol L-1 s-1 order. Due to their structural features, flexibility of integration, and biocompatibility, the MePSs are amenable of future development within advanced lab-on-chips.

Morphomechanical and structural changes induced by ROCK inhibitor in breast cancer cells.

The EMT phenomenon is based on tumour progression. The cells lose their physiologic phenotype and assumed a mesenchymal phenotype characterized by an increased migratory capacity, invasiveness and high resistance to apoptosis. In this process, RHO family regulates the activation or suppression of ROCK (Rho-associated coiled-coil containing protein kinase) which in turn regulates the cytoskeleton dynamics. However, while the biochemical mechanisms are widely investigated, a comprehensive and careful estimation of biomechanical changes has not been extensively addressed. In this work, we used a strong ROCK inhibitor, Y-27632, to evaluate the effects of inhibition on living breast cancer epithelial cells by a biomechanical approach. Atomic Force Microscopy (AFM) was used to estimate changes of cellular elasticity, quantified by Young's modulus parameter. The morphometric alterations were analyzed by AFM topographies and Confocal Laser Scanning Microscopy (CLSM). Our study revealed a significant modification in the Young's modulus after treatment, especially as regards cytoskeletal region. Our evidences suggest that the use of Y-27632 enhanced the cell rigidity, preventing cell migration and arrested the metastasization process representing a potential powerful factor for cancer treatment.

Multipath interference characterization of bend-insensitive optical fibers and short jumpers.

Multipath interference (MPI) in bend-insensitive optical fibers is investigated by analyzing different aspects, ranging from a review of the theoretical background, through the analysis of measurement issues, to the characterization of short patch cords. Two setups for the characterization of MPI are analyzed, highlighting their advantages and limitations. Then, a number of commercial bend-insensitive fibers are compared, showing that they generally exhibit a level below -30 dB in the range of 1250-1350 nm. The investigation also includes short offset-spliced fiber segments, with lengths to 1 cm, to simulate the behavior of field-installable connectors and isolate their contribution to the MPI. The results show a step-like increment of MPI when two or more cm-long fiber segments are cascaded.

The emerging role of acid sphingomyelinase in autophagy.

Autophagy, the main intracellular process of cytoplasmic material degradation, is involved in cell survival and death. Autophagy is regulated at various levels and novel modulators of its function are being continuously identified. An intriguing recent observation is that among these modulators is the sphingolipid metabolising enzyme, Acid Sphingomyelinase (A-SMase), already known to play a fundamental role in apoptotic cell death participating in several pathophysiological conditions. In this review we analyse and discuss the relationship between autophagy and A-SMase describing how A-SMase may regulate it and defining, for the first time, the existence of an A-SMase-autophagy axis. The imbalance of this axis plays a role in cancer, nervous system, cardiovascular, and hepatic disorders.

Immunogenicity of meningococcal quadrivalent (serogroup A, C, W135 and Y) tetanus toxoid conjugate vaccine: systematic review and meta-analysis.

Meningococcal meningitis represents one of the leading cause of bacterial meningitis in developed countries. Among the thirteen described serogroups, only five are usually responsible of invasive infections making immunisation against multiple serogroups the best strategy to protect individuals from this disease. Herein we carried out a systematic review and meta-analysis, in accordance with the PRISMA statement, of the recently EU-licensed meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT). We included 15 randomised clinical trials, comparing MenACWY-TT and Men-PS (ten studies), MenACWY-TT and MenC-CRM197 (four studies) and MenACWY-TT and MenACWY-DT (one study). All studies included in the meta-analysis showed high immunogenicity for MenACWY-TT vaccines in all tested serogroups. Our results suggest that the MenACWY-TT vaccine is as immunogenic as the other commercial available meningococcal vaccines.

Can vaccines interact with drug metabolism?

Vaccines are safe and efficacious in reducing the burden of several serious infections affecting children and adults. Due to their efficacy, vaccines are often administered in patients with chronic diseases, likely to be under poly-therapy. Because of several case reports indicating changes in drug metabolism after vaccination, the hypothesis of an interaction between vaccines and specific drugs has been put forward. These interactions are conceivably of great concern, especially in patients treated with molecules characterised by a narrow therapeutic index. Herein, we review and systematise the available evidence on vaccine-drug interactions. The picture that emerges indicates that reduction in the activity of specific CYPs following vaccination may occur, most likely via interferon γ overproduction, and for specific drugs such as anticonvulsivant and theophylline may have significant clinical relevance. Clinical interaction between vaccines and drugs that are metabolised by cytochromes uninfluenced by INFγ levels, such as warfarin, are instead unlikely to happen. Further studies are however needed to gain a complete picture of vaccine-drug interactions and define their relevance in terms of possible negative clinical impact.

Modulation of Acid Sphingomyelinase in Melanoma Reprogrammes the Tumour Immune Microenvironment.

The inflammatory microenvironment induces tumours to acquire an aggressive and immunosuppressive behaviour. Since acid sphingomyelinase (A-SMase) downregulation in melanoma was shown to determine a malignant phenotype, we aimed here to elucidate the role of A-SMase in the regulation of tumour immunogenic microenvironment using in vivo melanoma models in which A-SMase was either downregulated or maintained at constitutively high levels. We found high levels of inflammatory factors in low A-SMase expressing tumours, which also displayed an immunosuppressive/protumoural microenvironment: high levels of myeloid-derived suppressor cells (MDSCs) and regulatory T lymphocytes (Tregs), as well as low levels of dendritic cells (DCs). In contrast, the restoration of A-SMase in melanoma cells not only reduced tumour growth and immunosuppression, but also induced a high recruitment at tumour site of effector immune cells with an antitumoural function. Indeed, we observed a poor homing of MDSCs and Tregs and the increased recruitment of CD8(+) and CD4(+) T lymphocytes as well as the infiltration of DCs and CD8(+)/CD44(high) T lymphocytes. This study demonstrates that change of A-SMase expression in cancer cells is sufficient per se to tune in vivo melanoma growth and that A-SMase levels modulate immune cells at tumour site. This may be taken into consideration in the setting of therapeutic strategies.

A Prospective Real-World Study of Bacillus clausii Evaluating Use, Treatment Habits and Patient Satisfaction in Italian Community Pharmacies: The PEGASO Study.

BACKGROUND: Ailments such as diarrhoea and antibiotic-associated gut symptoms are generally self-managed using probiotics. Real-world data on reasons behind self-medication with over-the-counter (OTC) products and patient-reported outcomes can be investigated strategically by the pharmacists. OBJECTIVE: This study evaluates the use of Bacillus clausii (Enterogermina®) at the Italian community pharmacies among self-medicating patients, their treatment habits and perceived benefits. DESIGN: This is a multicentre, prospective, non-interventional study which included two visits [at screening (T0) and end of the study (T1) when symptoms had subsided, ≤ 30 days from T0]. Patients who were already inclined to buy B. clausii were enrolled and instructed to complete a questionnaire at T0 and T1. The primary objective was to evaluate the reasons for taking B. clausii. Secondary objectives assessed treatment duration, perceived effectiveness, quality of life (QoL), treatment satisfaction and safety outcomes. RESULTS: Overall, 268 patients were enrolled; 99.6% of them were evaluated at T0 and 97.4% at T1, and safety was evaluated in 97.8% who had ≥ 1 dose of B. clausii. At T0, mean age was 50.7 years and majority were females (62.2%). In the interview, main reason stated for using B. clausii at T0 was diarrhoea (56.93%), followed by other gastrointestinal symptoms. Treatment duration was shorter in those with diarrhoea or abdominal pain versus those with constipation or abdominal tension. More than 90% perceived their symptoms to have improved or improved very much. Overall QoL improved in all the aspects measured. Treatment satisfaction was reported by nearly 90% of patients as satisfied, very satisfied or extremely satisfied. No adverse events were reported. CONCLUSION: This is the first pharmacy-based study in Italy that evaluated the real-world usage of an OTC probiotic containing B. clausii among self-medicating adults. Diarrhoea was the most common reason for use, with high-level of perceived effectiveness and patient satisfaction with B. clausii.

Green silver nanoparticles: Prospective nanotools against neurodegenerative cell line model.

Neurodegenerative diseases represent an increasingly burdensome challenge of the past decade, primarily driven by the global aging of the population. Ongoing efforts focus on implementing diverse strategies to mitigate the adverse effects of neurodegeneration, with the goal of decelerating the pathology progression. Notably, in recent years, it has emerged that the use of nanoparticles (NPs), particularly those obtained through green chemical processes, could constitute a promising therapeutic approach. Green NPs, exclusively sourced from phytochemicals, are deemed safer compared to NPs synthetized through conventional chemical route. In this study, the effects of green chemistry-derived silver NPs (AgNPs) were assessed in neuroblastoma cells, SHSY-5Y, which are considered a pivotal model for investigating neurodegenerative diseases. Specifically, we used two different concentrations (0.5 and 1 µM) of AgNPs and two time points (24 and 48 h) to evaluate the impact on neuroblastoma cells by observing viability reduction and intracellular calcium production, especially using 1 µM at 48 h. Furthermore, investigation using atomic force microscopy (AFM) unveiled an alteration in Young's modulus due to the reorganization of cortical actin following exposure to green AgNPs. This evidence was further corroborated by confocal microscopy acquisitions as well as coherency and density analyses on actin fibers. Our in vitro findings suggest the potential efficacy of green AgNPs against neurodegeneration; therefore, further in vivo studies are imperative to optimize possible therapeutic protocols.

Gold and silver nanoparticles in Alzheimer's and Parkinson's diagnostics and treatments.

Neurodegenerative diseases (NDs) impose substantial medical and public health burdens on people worldwide and represent one of the major threats to human health. The prevalence of these age-dependent disorders is dramatically increasing over time, a process intrinsically related to a constantly rising percentage of the elderly population in recent years. Among all the NDs, Alzheimer's and Parkinson's are considered the most debilitating as they cause memory and cognitive loss, as well as severely affecting basic physiological conditions such as the ability to move, speak, and breathe. There is an extreme need for new and more effective therapies to counteract these devastating diseases, as the available treatments are only able to slow down the pathogenic process without really stopping or resolving it. This review aims to elucidate the current nanotechnology-based tools representing a future hope for NDs treatment. Noble metal nano-systems, that is, gold and silver nanoparticles (NPs), have indeed unique physicochemical characteristics enabling them to deliver any pharmacological treatment in a more effective way within the central nervous system. This can potentially make NPs a new hope for reversing the actual therapeutic strategy based on slowing down an irreversible process into a more effective and permanent treatment.

Pulse-Atomic Force Lithography: A Powerful Nanofabrication Technique to Fabricate Constant and Varying-Depth Nanostructures.

The widespread use of nanotechnology in different application fields, resulting in the integration of nanostructures in a plethora of devices, has addressed the research toward novel and easy-to-setup nanofabrication techniques to realize nanostructures with high spatial resolution and reproducibility. Owing to countless applications in molecular electronics, data storage, nanoelectromechanical, and systems for the Internet of Things, in recent decades, the scientific community has focused on developing methods suitable for nanopattern polymers. To this purpose, Atomic Force Microscopy-based nanolithographic techniques are effective methods that are relatively less complex and inexpensive than equally resolute and accurate techniques, such as Electron Beam lithography and Focused Ion Beam lithography. In this work, we propose an evolution of nanoindentation, named Pulse-Atomic Force Microscopy, to obtain continuous structures with a controlled depth profile, either constant or variable, on a polymer layer. Due to the modulation of the characteristics of voltage pulses fed to the AFM piezo-scanner and distance between nanoindentations, it was possible to indent sample surface with high spatial control and fabricate highly resolved 2.5D nanogrooves. That is the real strength of the proposed technique, as no other technique can achieve similar results in tailor-made graded nanogrooves without the need for additional manufacturing steps.

Pile-Ups Formation in AFM-Based Nanolithography: Morpho-Mechanical Characterization and Removal Strategies.

In recent decades, great efforts have been made to develop innovative, effective, and accurate nanofabrication techniques stimulated by the growing demand for nanostructures. Nowadays, mechanical tip-based emerged as the most promising nanolithography technique, allowing the pattern of nanostructures with a sub-nanometer resolution, high reproducibility, and accuracy. Unfortunately, these nanostructures result in contoured pile-ups that could limit their use and future integration into high-tech devices. The removal of pile-ups is still an open challenge. In this perspective, two different AFM-based approaches, i.e., Force Modulation Mode imaging and force-distance curve analysis, were used to characterize the structure of pile-ups at the edges of nanogrooves patterned on PMMA substrate by means of Pulse-Atomic Force Lithography. Our experimental results showed that the material in pile-ups was less stiff than the pristine polymer. Based on this evidence, we have developed an effective strategy to easily remove pile-ups, preserving the shape and the morphology of nanostructures.

Investigation of the Effects of Pulse-Atomic Force Nanolithography Parameters on 2.5D Nanostructures' Morphology.

In recent years, Atomic Force Microscope (AFM)-based nanolithography techniques have emerged as a very powerful approach for the machining of countless types of nanostructures. However, the conventional AFM-based nanolithography methods suffer from low efficiency, low rate of patterning, and high complexity of execution. In this frame, we first developed an easy and effective nanopatterning technique, termed Pulse-Atomic Force Lithography (P-AFL), with which we were able to pattern 2.5D nanogrooves on a thin polymer layer. Indeed, for the first time, we patterned nanogrooves with either constant or varying depth profiles, with sub-nanometre resolution, high accuracy, and reproducibility. In this paper, we present the results on the investigation of the effects of P-AFL parameters on 2.5D nanostructures' morphology. We considered three main P-AFL parameters, i.e., the pulse's amplitude (setpoint), the pulses' width, and the distance between the following indentations (step), and we patterned arrays of grooves after a precise and well-established variation of the aforementioned parameters. Optimizing the nanolithography process, in terms of patterning time and nanostructures quality, we realized unconventional shape nanostructures with high accuracy and fidelity. Finally, a scanning electron microscope was used to confirm that P-AFL does not induce any damage on AFM tips used to pattern the nanostructures.

High Q light-emitting Si-rich Si3N4 microdisks.

We report on the optical properties of active silicon (Si)-rich Si3N4 microdisk cavities in the visible range. We have studied the correlation between the quality (Q) factor of the cavities and the active material deposition parameters. Microphotoluminescence measurements revealed subangstrom whispering galley modes resonances and a maximum Q of 104 around 760 nm. These values improve significantly the best results reported so far for Si-based light-emitting circular resonators in the visible range. In contrast to what is reported for Si-rich SiO2-based microcavities, we demonstrate the absence of a spectral widening at high pump fluxes associated to carrier absorption mechanisms, which allows high emitted power without degrading the Q of the cavity. These results open the route toward the monolithic integration of those structures into more complex circuits including Si photodetectors.

Herbal Remedies and Their Possible Effect on the GABAergic System and Sleep.

Sleep is an essential component of physical and emotional well-being, and lack, or disruption, of sleep due to insomnia is a highly prevalent problem. The interest in complementary and alternative medicines for treating or preventing insomnia has increased recently. Centuries-old herbal treatments, popular for their safety and effectiveness, include valerian, passionflower, lemon balm, lavender, and Californian poppy. These herbal medicines have been shown to reduce sleep latency and increase subjective and objective measures of sleep quality. Research into their molecular components revealed that their sedative and sleep-promoting properties rely on interactions with various neurotransmitter systems in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a major role in controlling different vigilance states. GABA receptors are the targets of many pharmacological treatments for insomnia, such as benzodiazepines. Here, we perform a systematic analysis of studies assessing the mechanisms of action of various herbal medicines on different subtypes of GABA receptors in the context of sleep control. Currently available evidence suggests that herbal extracts may exert some of their hypnotic and anxiolytic activity through interacting with GABA receptors and modulating GABAergic signaling in the brain, but their mechanism of action in the treatment of insomnia is not completely understood.

Improvement of PMMA Dental Matrix Performance by Addition of Titanium Dioxide Nanoparticles and Clay Nanotubes.

Over the last decades, several materials have been proposed for the fabrication of dental and mandibular prosthetic implants. Today, the poly(methyl-methacrylate) (PMMA) resin is the most spread material, due to its ease of processing, low cost, aesthetic properties, low weight, biocompatibility, and biostability in the oral cavity. However, the porous surface (which favors the adhesion of microorganisms) and the weak mechanical properties (which lead to wear or fracture) are the major concerns. The inclusion of engineered nanomaterials in the acrylic matrix could improve the performances of PMMA. In this study, we added two different kind of nanomaterials, namely titanium dioxide nanoparticles (TiO2NPs) and halloysite clay nanotubes (HNTs) at two concentrations (1% and 3% w/w) in PMMA. Then, we assessed the effect of nanomaterials inclusion by the evaluation of specific physical parameters: Young's modulus, roughness, and wettability. In addition, we investigated the potential beneficial effects regarding the Candida albicans (C. albicans) colonization reduction, the most common yeast responsible of several infections in oral cavity. Our experimental results showed an improvement of PMMA performance, following the addition of TiO2NPs and HNTs, in a dose dependent manner. In particular, the presence of TiO2NPs in the methacrylate matrix induced a greater increase in PMMA stiffness respect to HNTs addition. On the other hand, HNTs reduced the rate of C. albicans colonization more significantly than TiO2NPs. The results obtained are of great interest for the improvement of PMMA physico-chemical properties, in view of its possible application in clinical dentistry.

Kinetics of Intestinal Presence of Spores Following Oral Administration of Bacillus clausii Formulations: Three Single-Centre, Crossover, Randomised, Open-Label Studies.

BACKGROUND AND OBJECTIVE: Probiotics are live microorganisms that may provide benefits including the prevention of gastrointestinal disorders and other diseases. Enterogermina is a probiotic mix of spores from four strains of Bacillus clausii (O/C, T, N/R and SIN), available in several oral formulations. The objective of this analysis was to evaluate and compare the kinetic profiles of different formulations of Enterogermina-vial [E4 once daily (OD) and E2 twice daily (BID)], capsule [EC2 three times daily (TID)], oral powder for suspension (ES6 OD) and oral powder not requiring suspension (E6 OD) from two studies from 2012 (EUDRACT 2010-024497-19 and 2010-023187-41) and one study from 2016 (EUDRACT 2015-003330-27). METHODS: B. clausii spores were counted in homogenised faecal samples (results expressed as counts per gram) or after culture at 37 °C for 24-36 h (results expressed as colony-forming units). Kinetics were assessed by area under the concentration-time curve (AUC), maximum concentration (Cmax), time to maximum concentration (Tmax) and spore presence/persistence. RESULTS: In total, 22 subjects in each of the 2012 studies and 30 subjects in the 2016 study were randomised (mean age 25.0-33.8 years across studies). The mean (±SD) absolute faecal spore counts (in millions) expressed as AUC per hour were 270.7 ± 147.7 (E2 BID) and 213.8 ± 60.2 (E4 OD) in 2012 EGKINETIC4, 312.7 ± 218.0 (EC2 TID) and 319.0 ± 221.1 (ES6 OD) in 2012 EGKINETIC6, and 212.6 ± 118.0 (E6 OD) and 293.2 ± 247.2 (ES6 OD) in 2016 EGKINETIC6OP. The kinetic profiles of the different formulations of Enterogermina were similar, with superimposable AUC and daily curve profiles in each study up to the 8th day post dose. B. clausii spore presence/persistence in the intestine of healthy volunteers did not differ between the two formulations within each of the three studies. Enterogermina was well tolerated across all formulations and studies. CONCLUSION: These results show different formulations of Enterogermina had similar kinetic profiles within each study; however, they also showed that probiotics could be associated with high variability. The European Medicines Agency guidelines are the current bioequivalence reference, although only the Tmax parameter is used for high variability drugs. Due to the specific kinetics of probiotics, new parameters of bioequivalence could be necessary, considering, for example, variability via a parameter such as AUC. TRIAL REGISTRATION: EUDRACT 2010-024497-19, 2010-023187-41 and 2015-003330-27.