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Osteoarthritis is the most widespread joint-affecting disease. The management of persistent pain remains inadequate and demands new therapeutic strategies. In this study, we explored the pain relieving and protective properties of a single intra-articular (i.a.) injection of khellin loaded in nanovesicles (K-Ves) based on ascorbyl decanoate plus phosphatidylcholine in a rat model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA) treatment. The developed nanovesicles (approximately 136 nm) had a narrow size distribution (PdI 0.26), a good recovery (about 80%) and a worthy encapsulation efficiency (about 70%) with a ζ-potential of about −40 mV. The stability of K-Ves was assessed in simulated synovial fluid. Seven days after the articular damage with MIA, both K-Ves and a suspension of khellin (K, 50 μL) were i.a. injected. K-Ves significantly counteracted MIA-induced hypersensitivity to mechanical noxious (paw pressure test) and non-noxious stimuli (von Frey test) and significantly reduced the postural unbalance related to spontaneous pain (incapacitance test) and the motor alterations (beam balance test) 7 and 14 days after the i.a. injection. K was partially active only on day 7 after the treatment. The histology emphasized the improvement of several morphological factors in MIA plus K-Ves-treated animals. In conclusion, K-Ves could be successfully used for the local treatment of osteoarthritis.

In this work, an innovative coating strategy that is able to prolong the shelf-life of fresh-cut kiwifruit was proposed, and the effectiveness of the procedure was evaluated for a period of ten days under cold storage (4 °C). Alginate (2% m/v) functionalized with green extracts from hop (Humulus lupulus, L.) cones (HE, 0.5 and 1%, v/v) was used as a coating material in order to assess the best performing strategy, leading to the most stable product. At the concentrations used to formulate the edible coatings, no contribution related to hop bitterness on the final product was recorded. The results were compared to control samples (without edible coating and coated only with alginate at 2% m/v). The plant extract was characterized by its main chemical traits and by 1H NMR profiling, revealing the presence of antioxidant and antimicrobial bioactive compounds (i.e., alpha and beta hop acids, xanthohumol). Furthermore, the characteristics of the samples during cold storage were evaluated by physico-chemical (i.e., weight loss, soluble solid content, titratable acidity, pH, color attributes) and nutraceutical (i.e., total polyphenol, ascorbic acid content, total carotenoids, chlorophylls) traits. The results showed that the incorporation of hop extracts into the edible coatings tested was able to preserve the quality and nutraceutical traits of fresh-cut kiwifruit during cold storage, thus prolonging their shelf life and marketability.

A3 adenosine receptor (A3AR) agonists have emerged as potent relievers of neuropathic pain by a T cell-mediated production of IL-10. The H4 histamine receptor (H4R), also implicated in pain modulation, is expressed on T cells playing a preeminent role in its activation and release of IL-10. To improve the therapeutic opportunities, this study aimed to verify the hypothesis of a possible cross-talk between A3AR and H4R in the resolution of neuropathic pain. In the mouse model of Chronic Constriction Injury (CCI), the acute intraperitoneal co-administration of the A3AR agonist IB-MECA (0.5 mg/kg) and the H4R agonist VUF 8430 (10 mg/kg), were additive in counteracting mechano-allodynia increasing IL-10 plasma levels. In H4R−/− mice, IB-MECA activity was reduced, lower pain relief and lower modulation of plasma IL-1β, TNF-α, IL-6 and IL-10 were shown. The complete anti-allodynia effect of IB-MECA in H4R−/− mice was restored after intravenous administration of CD4+ T cells obtained from naïve wild type mice. In conclusion, a role of the histaminergic system in the mechanism of A3AR-mediated neuropathic pain relief was suggested highlighting the driving force evoked by CD4+ T cells throughout IL-10 up-regulation.

Numerous experimental tests showed that ductile square hollow structural sections (HSS) are susceptible to premature fracture under design-level earthquake ground motions. In addition, recent research has highlighted the vulnerability of column splices to reach their full strength once ductile square HSS braces experience a fracture in braced frames. In this study, the performance of column splices in 5-and 13-story special concentrically braced frames (SCBFs), with X-bracing configuration, located at a distance permitted by the seismic design provisions (i.e., four feet over the concrete floor level), is evaluated under a large number of ground motion excitations. The performance of identical SCBFs with conventional HSS braces and innovative buckling controlled HSS braces is compared. Overall, results from this research indicate that the prevention of brace buckling in SCBFs yields a substantial reduction in the seismically induced bending demands on the column splices, leading to a large margin of safety to remain elastic.

Aboveground steel storage tanks are large vessels employed to store various liquids, including water, food, fertilizers, oil, and other hazardous chemicals. The damage and collapse of storage tanks can generate long-lasting consequences on built environment and communities. The seismic behavior of storage tanks is often evaluated employing fragility functions obtained simulating the tank under a variety of ground motion records. However, the computational demand of high-fidelity simulation models makes risk assessment a burdensome task. The use of data-driven surrogate models could represent a suitable solution to evaluate the seismic vulnerability of steel tanks rapidly. In this context, this paper presents an open dataset composed of 204 aboveground cylindrical steel liquid storage tanks with different geometric properties. The dataset was assembled based on past earthquake reconnaissance reports. In the dataset, different types of damage experienced by the steel tanks are divided into four classes, ranging from no damage to complete failure. Eight different machine learning algorithms are trained to predict the damage class of a steel tank as a function of its geometric properties and seismic excitation parameters. Stratified 5-fold cross-validation is used to split the dataset into training and testing subsets and to assess the prediction capability of the machine learning models. Results showed that the Support Vector Machine algorithm yielded the most accurate predictions, followed by Random Forest, XGBoost, and LightBoost. Overall, the paper demonstrated the feasibility of using machine learning models to predict the damage level of steel liquid storage tanks subjected to seismic hazard.

Platinum-based chemotherapy is widely used for the treatment of different tumors but is associated with serious side effects, among which neuropathic pain. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitors have recently been validated as therapeutic agents in neuropathic pain and as antitumor agents. We report the synthesis of new organochalcogenides bearing the benzensulfonamide moiety acting as potent inhibitors of several human CA isoforms and, in particular, against hCA II and VII endowed with potent neuropathic pain attenuating effects. Moreover, in combination with cisplatin or doxorubicin, some of the new CA inhibitors enhanced the effects of the anticancer drugs capability in counteracting breast cancer MCF7 cell viability. The concomitant anti-neuropathic pain and antiproliferative effects of the new chalcogenide-based CA inhibitors represent an innovative approach for the counteraction and management of side effects associated with clinically platinum drugs as antitumor agents.

Chemotherapy-induced neuropathy (CIN) is a major dose-limiting side effect of anticancer therapy that can compel therapy discontinuation. Inadequate analgesic efficacy of current pharmacological approaches requires the identification of innovative therapeutics and, hence, the purpose of this study is to conduct a preclinical evaluation of the efficacy of DDD-028, a versatile pentacyclic pyridoindole derivative, against paclitaxel-induced neuropathic pain. In two separate experiments, DDD-028 was administered per os acutely (1–25 mg kg−1) or repeatedly (10 mg kg−1) in paclitaxel-treated rats. The response to mechanical noxious stimulus (paw pressure) as well as to non-noxious mechanical (von Frey) and thermal (cold plate) stimuli was investigated. Acute administration of DDD-028 induced a dose-dependent anti-neuropathic pain effect in all tests performed. Further, repeated daily treatment for 18 consecutive days (starting the first day of paclitaxel administration) significantly reduced the development of pain over time without the development of tolerance to the anti-hyperalgesic effect. Ex vivo analysis showed that DDD-028 was able to reduce oxidative damage of dorsal root ganglia as evidenced by the increase in the level of carbonylated proteins and the decrease in catalase activity. In the lumbar spinal cord, periaqueductal gray matter, thalamus, and somatosensory cortex 1, DDD-28 significantly prevented the activation of microglia and astrocytes. The pharmacodynamic study revealed that the pain-relieving effects of DDD-028 were fully blocked by both the non-selective nicotinic receptor (nAChR) antagonist mecamylamine and by the selective α7 nAChR antagonist methyllycaconitine. In conclusion, DDD-028 was active in reducing paclitaxel-induced neuropathic pain after single or repeated administrations without tolerance development and displaying a double symptomatic and neuroprotective profile. DDD-028 could represent a valuable candidate for the treatment of CIN. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01069-8.

Neuroinflammation is a key pathological event shared by different diseases affecting the nervous system. Since the underlying mechanism of neuroinflammation is a complex and multifaceted process, current pharmacological treatments are unsatisfactory—a reason why new therapeutic approaches are mandatory. In this context, the endocannabinoid system has proven to possess neuroprotective and immunomodulatory actions under neuroinflammatory status, and its modulation could represent a valuable approach to address different inflammatory processes. To this aim, we evaluated the efficacy of a repeated treatment with NSD1819, a potent β-lactam-based monoacylglycerol lipase inhibitor in a mouse model of neuroinflammation induced by lipopolysaccharide (LPS) injection. Mice were intraperitoneally injected with LPS 1 mg/kg for five consecutive days to induce systemic inflammation. Concurrently, NSD1819 (3 mg/kg) was daily per os administered from day 1 until the end of the experiment (day 11). Starting from day 8, behavioral measurements were performed to evaluate the effect of the treatment on cognitive impairments, allodynia, motor alterations, anhedonia, and depressive-like behaviors evoked by LPS. Histologically, glial analysis of the spinal cord was also performed. The administration of NSD1819 was able to completely counteract thermal and mechanical allodynia as highlighted by the Cold plate and von Frey tests, respectively, and to reduce motor impairments as demonstrated by the Rota rod test. Moreover, the compound was capable of neutralizing the memory loss in the Passive avoidance test, and reducing depressive-like behavior in the Porsolt test. Finally, LPS stimulation caused a significant glial cells activation in the dorsal horn of the lumbar spinal cord that was significantly recovered by NSD1819 repeated treatment. In conclusion, NSD1819 was able to thwart the plethora of symptoms evoked by LPS, thus representing a promising candidate for future applications in the context of neuroinflammation and related diseases.

Brassicaceae are natural sources of bioactive compounds able to promote gut health. Belonging to this plant family, Camelina sativa is an ancient oil crop rich in glucosinolates, polyunsaturated fatty acids, and antioxidants that is attracting renewed attention for its nutraceutical potential. This work aimed at investigating the therapeutic effects of a defatted seed meal (DSM) of Camelina sativa on the colon damage and the persistent visceral hypersensitivity associated with colitis in rats. Inflammation was induced by the intrarectal injection of 2,4-dinitrobenzenesulfonic acid (DNBS). The acute administration of Camelina sativa DSM (0.1–1 g kg−1) showed a dose-dependent pain-relieving effect in DNBS-treated rats. The efficacy of the meal was slightly enhanced after bioactivation with myrosinase, which increased isothiocyanate availability, and drastically decreased by pre-treating the animals with the selective peroxisome proliferator-activated receptor alpha (PPAR α) receptor antagonist GW6471. Repeated treatments with Camelina sativa DSM (1 g kg−1) meal counteracted the development, as well as the persistence, of visceral hyperalgesia in DNBS-treated animals by reducing the intestinal inflammatory damage and preventing enteric neuron damage. In conclusion, Camelina sativa meal might be employed as a nutraceutical tool to manage persistent abdominal pain in patients and to promote gut healing.

Chemotherapy-induced neuropathic pain is a clinically relevant adverse effect of several anticancer drugs leading to dose reduction or therapy discontinuation. The lack of knowledge about the mechanisms of neuropathy development and pain chronicization makes chemotherapy-induced neuropathic pain treatment an unmet medical need. In this context, the vascular endothelial growth factor A (VEGF-A) has emerged as a neurotoxicity biomarker in a model of chemotherapy-induced neuropathy, and its decrease has been related to pain relief. Aim of this study was to clarify the VEGF-A-dependent pain signaling in the CNS for individuating new targeted therapeutic approaches. In mice, the intrathecal infusion of VEGF-A induced a dose-dependent noxious hypersensitivity mediated by the VEGF receptor 1 (VEGFR-1) as demonstrated by pharmacological and genetic tools. In electrophysiological study, VEGF-A stimulated the spinal nociceptive neurons activity through VEGFR-1. In the dorsal horn of the spinal cord, VEGF-A increased in astrocytes of animals affected by neuropathy suggesting this cell population as a source of the potent pain mediator. Accordingly, the selective knockdown of astrocytic VEGF-A, by shRNAmir, blocked the development of oxaliplatin-induced neuropathic pain. Besides, the anti-VEGFR-1 mAb D16F7 (previously described as anticancer) effectively relieved neuropathic pain induced by chemotherapeutic agents. In conclusion, astrocyte-released VEGF-A is a new player in the complex neuron-glia network that oversees physiological and pathological pain and D16F7 mAb rises as a potent pain killer strategy.

Configurationally stable 5-aza[6]helicene (1) was envisaged as a promising scaffold for non-conventional ionic liquids (IL)s. It was prepared, purified, and separated into enantiomers by preparative HPLC on a chiral stationary phase. Enantiomerically pure quaternary salts of 1 with appropriate counterions were prepared and fully characterized. N-octyl-5-aza[6]helicenium bis triflimidate (2) was tested in very small quantities as a selector in achiral IL media to perform preliminary electrochemical enantiodifferentiation experiments on the antipodes of two different chiral probes. The new organic salt exhibited outstanding enantioselection performance with respect to these probes, thus opening the way to applications in the enantioselective electroanalysis of relevant bioactive molecules.

In this work, we shed new light on ultrasound contrast agents applied to the field of cultural heritage as an invaluable fine-tune cleaning tool for paper artworks. In this context, one of the primary and challenging issues is the removal of modern adhesives from paper artifacts. Modern adhesives are synthetic polymers whose presence enhances paper degradation and worsens its optical features. A thorough analytical and high-spatial-resolution combined study was successfully performed to test the capability of poly(vinyl alcohol)-based microbubbles stimulated by a proper noninvasive 1 MHz ultrasound field exposure in removing these adhesives from paper surfaces, in the absence of volatile invasive and toxic chemicals and without damaging paper and/or leaving residues. We demonstrate that poly(vinyl alcohol)-shelled microbubbles are suitable for interacting with paper surfaces, targeting and boosting in a few minutes the nondamaging removal of adhesive particles from paper samples thanks to their peculiar shell composition together with their ultrasound dynamics.

This article proposes an approach for smart monitoring of the life cycle of innovative graphene-based filters for water remediation in the presence of pollutants. The measurement technique is based on suitable figures of merit that analyze the time variation of the electrical impedance frequency spectrum. The proposed study considers the remediation of two toxic industrial pollutants, such as the acetonitrile and the 2,4-dichlorophenol. The contribution of this article is twofold. The first is the demonstration of a reliable monitoring setup that is able, for the selected use cases, to correlate in real time the behavior of the electrical impedance of the filter to its status, defined as “absence of pollutants” and/or “saturation.” The second contribution is the proposal of suitable figures of merit, based on measurement of the impedance frequency spectrum, able to increase the measurement sensitivity and the reliability and to mitigate some sources of uncertainty typically associated with these kinds of setups and measurements. Results show that the proposed graphene-based filters combine very good filtering capability and high sensitivity of the electrical impedance to the considered pollutants. These results suggest further investigations with other pollutants and the potential use of this technique for the predictive maintenance of the water filters in industrial applications, by endowing the graphene filters of smart sensing devices.

A3 adenosine receptor (A3AR) agonists have emerged as potent relievers of neuropathic pain by a T cell-mediated production of IL-10. The H4 histamine receptor (H4R), also implicated in pain modulation, is expressed on T cells playing a preeminent role in its activation and release of IL-10. To improve the therapeutic opportunities, this study aimed to verify the hypothesis of a possible cross-talk between A3AR and H4R in the resolution of neuropathic pain. In the mouse model of Chronic Constriction Injury (CCI), the acute intraperitoneal co-administration of the A3AR agonist IB-MECA (0.5 mg/kg) and the H4R agonist VUF 8430 (10 mg/kg), were additive in counteracting mechano-allodynia increasing IL-10 plasma levels. In H4R−/− mice, IB-MECA activity was reduced, lower pain relief and lower modulation of plasma IL-1β, TNF-α, IL-6 and IL-10 were shown. The complete anti-allodynia effect of IB-MECA in H4R−/− mice was restored after intravenous administration of CD4+ T cells obtained from naïve wild type mice. In conclusion, a role of the histaminergic system in the mechanism of A3AR-mediated neuropathic pain relief was suggested highlighting the driving force evoked by CD4+ T cells throughout IL-10 up-regulation.

This paper deals with low-cost sensors to detect the presence of organic pollutants, based on the voltammetric response of Screen Printed Electrodes (SPE). Modified SPEs are here proposed, by using graphene nanoplatelets that represent a low cost version of graphene, characterized by an easier and more scalable production compared to pure graphene. Improved sensing performance are experimentally observed with these surface modifications to the detection of an aromatic organic compound.

Aqueous cleaning of works of art on paper is one of the most important and delicate steps in a conservation process. It allows the removal of inorganic (metals) and organic substances, such as degradation products and other contaminants. These substances are responsible for yellowing, weakening, and loss of mechanical properties of paper. In this article, the cleaning effect of gellan gum was assessed on xuan paper, a traditional Chinese paper different in composition and papermaking technology compared to many Western papers. To assess the effect of gellan gum on xuan paper, its characteristics were studied before and after cleaning utilizing non-invasive and micro-invasive techniques. Results were compared to those obtained when treating Western papers and indicated that gellan gum can be applied effectively for aqueous cleaning of xuan paper.

Deep Eutectic Solvents (DESs) offer advantages similar to ionic liquid (IL) ones, with easier and more sustainable synthesis; moreover, bio-based DESs often include chiral components, surprisingly underexploited. A proof of concept is now offered of the impressive potential of enantiopure chiral DESs as chiral media for enantioselective electroanalysis. Three chiral DESs, consisting of a molecular salt with bio-based chiral cation [NopolMIm]+ combined with three natural and/or low-cost partners (levulinic acid, glycerol and urea), are introduced and investigated as chiral voltammetry media. Significant potential differences are observed for the enantiomers of a model chiral probe, with a dramatic tuning depending on the achiral DES component, reaching an impressive ~0.5 V in the levulinic acid case (while less efficient appears [NopolMIm]+ as chiral additive in IL). With the same medium good enantiodiscrimination is also observed for aminoacid tryptophan, a quite different probe and of applicative interest. These findings can be considered as a remarkable step further in chiral electroanalysis as well as in the development of task-specific enantioselective media.

Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing postinflammatory visceral pain persistence. Colitis was induced in mice by intrarectally injecting 2,4-dinitrobenzenesulfonic acid (DNBS). The effect of faecal microbiota transplantation from viscerally hypersensitive DNBS-treated and naive donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. Faecal microbiota transplantation from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition of gut microbiota and short chain fatty acids. By contrast, no significant alterations of colon histology, permeability, and monoamines levels were detected. Finally, by manipulating the gut microbiota of DNBS-treated animals, a counteraction of persistent visceral pain was achieved. The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota-targeted interventions.

Screen-printed electrodes are the most recent generation of low-cost, mass-produced, sensitive and portable devices for the measurement of analytes of interest. The responses of these platforms, in terms of current intensity and reproducibility, are strongly influenced by factors such as printing procedures, type of ink, substrates, etc. In this paper, an improved inverse-designed screen-printed electrode (IDSPE) is proposed. The electrochemical performance is compared with that obtained using classical screen printed electrodes (SEPs), showing enhanced sensitivity and signal-to-noise ratio (background current minimization 32 ± 3nA and 0.64 ± 0.01nA, for SPE and IDSPE, respectively). A full comparison between inverse and classical screen-printed electrodes is carried out using various electroactive species (potassium ferricyanide, ascorbic acid, hexaammineruthenium(III) chloride and NADH) and two different electrochemical techniques (cyclic and square-wave voltammetry). In tests conducted with potassium ferricyanide the sensitivity of the IDSPE shows a nearly four-fold improvement, and a limit of detection three times better than the values obtained employing the classical SPE. The reproducibility (RSD%) in tests conducted with ascorbic acid is 6% and 12% for IDSPE and SPE, respectively. Moreover, surface modification of both screen-printed electrodes (SPE and IDSPE) with biochar obtained from recycled brewers waste (Bio-SPEs and Bio-IDSPEs), further improves their electrochemical performance, in terms, for example, of the heterogeneous electron transfer constant (0.0024 and 0.0018 for Bio-SPE and Bio-IDSPE, respectively).

Osteoarthritis (OA) is one of the most frequent degenerative joint diseases characterized by joint pain and stiffness traditionally treated with symptomatic drugs such as oral nonsteroidal anti-inflammatory drugs (NSAIDs )and, in extreme cases, with intra-articular corticoids. However, both these drugs are not exempt from adverse effects. Curcumin (Cur) has proven its anti-inflammatory properties and its potential as an anti-osteoarthritic drug. However, its low solubility hinders its usage and limits its therapeutic efficacy. To overcome this issue, drug-in-cyclodextrin–double-loaded liposomes (DCL–DL) were developed. These liposomes contained free drug in the lipid bilayer and drug–cyclodextrin complex in the aqueous compartment. The aim of this work was to evaluate the actual effectiveness of Cur–DCL–DL formulations in the OA treatment by intra-articular treatment. For this purpose, the monoiodoacetate (MIA) model of OA pain in rats was used. A single dose of samples containing Cur as DCL–DL, conventional liposomes (SL), and empty liposomes (EL, as control) were injected once intra-articularly. Paw pressure, beam balance, and incapacitation tests were performed to evaluate OA progression at 7 and 14 days. After ending the assay, animals were sacrificed, and histological evaluation of the ankle-joint tissue was performed. Results showed that DCL–DL significantly reduced pain and ameliorated the balance and gait of rats over the 14 days, compared to SL. Histological tests showed that DCL–DL had protective properties in some aspects of OA.

High-performance control systems (HPCS) are sophisticated vibration-mitigation devices that include active, semiactive, and hybrid systems. HPCS leverage feedback mechanisms to dynamically ...

Performance-based design (PBD) is becoming a benchmark approach for design and performance assessment of civil structures because it facilitates communication between stakeholders and desig...

New methodologies for the characterization of chemical composition and the monitoring of cleaning processes of paper and wood artifacts are based on tuned electrochemical sensors based on screen printed electrodes (SPE) coupled with a portable instrumentation1,2. Electrochemical biosensors, based on enzymes, have been successfully applied in many fields from environment to medicine, from foods to pharmaceuticals but the use of them in the cultural heritage field is still an almost unexplored world. Many of these biosensors are well suitable to be used for the characterization of several important materials used in cultural heritage such as paper, paintings, textiles, metals or glass, with the aim of determining their composition, health state and/or the effectiveness of conservation or restoration interventions. Opportune biosensors could be indeed applied to determine both inorganic than organic compounds present as components, pollutants or degradation products of artworks. In this work, several application of sensors coupled with hydrogel is presented to underline the potentiality of these tools in cultural heritage. Mazzuca, C., Carbone, M., Cancelliere, R., Prati, S., Sciutto, G., Mazzeo, R., Tositti, L., Regazzi, R., Mostacci, D., Micheli, L. (2018) A new analytical approach to characterize the effect of γ-ray sterilization on wood Microchemical Journal, 143, pp. 493-502. DOI: 10.1016/j.microc.2018.08.001 18) Micheli, L., Mazzuca, C., Palleschi, A., Palleschi G. (2016) Development of a diagnostic and cleaning tool for paper artworks: a case of study Microchemical Journal, 126, 32-41 DOI: 10.1016/j.microc.2015.11.052

The use of nanomaterials in sensor and biosensor field is one of the hottest topics today in analytical chemistry. The advantage of using nanomaterials leads to sensors characterized by high sensitivity, stability, and an improved repeatability1. Screen-printed electrodes (SPEs) are recognized as successful sensor platforms in modern electroanalytical chemistry due to their low background, wide potential window, cost-effectiveness, and easiness of surface modification. This last property allows modifying the screen-printed electrodes (SPEs) with several nanomaterials such as carbon nanotubes, graphene, nanoparticles, graphene nanoplates (GNPs)2, etc3,4. In this work, a comparative study using these devices (SPEs) modified with different nanomaterials via drop-casting procedure is reported (Figure 1). Moreover, the modified SPEs have been morphologically and electrochemically characterized. The research activity carried out for the development of sensors and biosensors based on SPEs modified with nanomaterials will be presented. Among the different feasible applications, the use of these nano-engineered biosensors for uric acid quantification based on SPEs modified with carbon nanotubes (bare or functionalized) and graphene nanoplatelets (GNPs) will be introduced. Significant improvements in analytical parameters have been obtained, when using nano-modified SPEs with respect to biosensors based on bare SPEs. Limit of detection (LOD), linear range and Km (Michaelis-Menten Constant) undergo remarkable ameliorations (LOD going from 48 μM to 12 μM, linear range from 0.05-2 mM to 0.02-5 mM and Km from 0.43 to 1.31 mM for bare and -CO2H MWNT based biosensors, respectively). Figure1 Schematic representation of nanomaterial-modified SPE: a) by drop casting and then used to set up a biosensor, b) enzyme immobilization. Electrochemical measurements can be performed using portable instrumentation (c).

The purpose of this study was to correlate the chemical composition of four commercial concentrated glycerine macerates (C-GMs), produced through the same extraction method, with their in vitro antimicrobial, antioxidant, and immunomodulatory properties, in order to evaluate their potential for healing upper airway diseases. C-GMs of Carpinus betulus (CB), Ficus carica (FC), Alnus glutinosa (AG) and Ribes nigrum (RN) were studied. The quality was evaluated using HPLC and IM-SPME/GC-MS systems, anti-oxidant and anti-microbial activities were assessed by the respective DPPH test, and micro-broth dilution test performed against 10 strains of Streptococcus pyogenes and 10 probiotic strains. ELISA and MTT tests were used to assess the immunomodulatory activity and the cytotoxicity of C-GMs, respectively. A significant correlation was found between the number of active compounds and the in vitro C-GMs effectiveness. Furthermore, the C-GMs of AG showed the best anti-microbial activity on pathological strains and, together with CB, the best anti-oxidant activity. The ELISA test exhibited a good immunomodulatory activity of RN. In vitro data support the integrated use of C-GMs of CB, AG, and RN in presence of airway diseases, and highlight the importance of standard procedures in cultivation, harvest and post-harvest treatments, as a premise for C-GMs with consistent characteristics.

Background: Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing the persistence of visceral hypersensitivity consequent to colitis induced by the intra-rectal injection of 2,4-dinitrobezenesulfonic acid (DNBS) in rats. Results: The effect of faecal microbiota transfer (FMT) from viscerally hypersensitive DNBS and naïve donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. FMT from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition and structure of the gut microbiota at phylum (Proteobacteria and Firmicutes to Bacteroides ratio) and family levels (Enterobacteriaceae, Akkermansiaceae and Lachnospiraceae). Acetic acid was significantly increased in the recipients FMT from DNBS donors. Gut cytokine profile, as well as tryptophan metabolism were similarly altered after FMT from both DNBS and naïve donors. By contrast, no significant alterations of colon histology, permeability and monoamines levels were detected. Finally, following FMT from healthy donors to DNBS-treated animals, a counteraction of persistent visceral pain was achieved. Conclusions: The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota modulation on persistent abdominal pain.

Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the clinical practice. Unfortunately, together with analgesia, a number of adverse effects can occur such as nausea, vomiting, constipation, gastrointestinal alterations and cognitive impairments. Naltrexone is a competitive antagonist of opioids receptors commonly used to treat opioids addiction, its oral use against agonists side effects is limited by the decrease of opioids-therapeutic efficacy and own adverse effects. The intranasal delivery of naltrexone could offer a quick and effective achievement of CNS based on extracellular mechanisms including perineural and perivascular transport. Aim of the study was to test the efficacy of intranasal low-dose naltrexone in reducing intraperitoneal morphine and oxycodone side effects in rodents. In mice, 1 g naltrexone intranasally administered 30 min before opioids, reduced cognitive impairments and motor alteration induced by 10 mg kg-1 morphine and 60 mg kg-1 oxycodone in the Passive avoidance and Rota rod tests, respectively. Moreover, naltrexone rebalanced opioids-induced reduction of the intestinal transit and latency of feces expulsion as well as food intake inhibition. Importantly, 1 g naltrexone instillation did not block analgesia as demonstrated by the Hot plate test. In rats, intranasal naltrexone counteracted the opioid-induced pica phenomenon related to emesis and increased water and palatable food intake. The effects were comparable to that achieved by metoclopramide used as reference drug. Treatments did not influence body weight. Lastly, the safety of the intranasal delivery has been checked by hematoxylin-eosin staining that did not show histological alterations of the nasal cavity. In conclusion, intranasal low-dose naltrexone counteracted morphine and oxycodone induced gastrointestinal and CNS side effects without impairing opioids analgesia. It is candidate to be a valid clinical strategy deserving deeply analysis.

Advances in x-ray techniques, including x-ray optics, have paved the way to obtain challenging results in several research fields thanks to the improvement in terms of spatial resolution. This is particularly true for x-ray fluorescence (XRF), where the combination of conventional x-ray sources with polycapillary optics has permitted to have high flux and high focused beams. However, XRF spectroscopy applied to archeological samples at a lab scale is mainly dedicated to qualitative studies. At the same time, quantitative analysis still remains a strong hurdle mainly due to important matrix effects that affect the signal related to the chemical components under evaluation. In this respect the adoption of x-ray optics on both the source and the detector represents a way to improve the signal to noise ratio, necessary for quantitative analysis. At LNF XLab Frascati the expertise, gained on x-ray techniques and on polycapillary lenses, has allowed researchers to carry out advanced μXRF studies. RXR (Rainbow X-ray), is the experimental station dedicated to 2D/3D XRF micro-imaging and TXRF analysis, being equipped with 2 detectors of different energy efficiency (covering a full spectrum from 800 eV to 25 keV) and working in confocal mode with the source coupled with a full-lens and both the detectors combined with dedicated half-lenses. This report aims in depicting the RXR potentialities through the results obtained in 2 case studies dedicated to carry out a semi-quantitative analysis of 2 different artifacts (an ancient book, a Buddhist scroll) by μXRF characterization.

Vegetable wastes represent an inexpensive and sustainable source of valuable bioproducts for several applications. Natural micro-porous and fibrous materials can be obtained from a very cheap and abundant cellulosic bio-waste. Here we demonstrated that vegetable waste derivatives can be suitable as scaffolds for biosensors and 3D cell growth. Many studies have been addressed to fabricate biocompatible 3D scaffolds for mammalian stem cells cultures and develop novel systems able to reproduce the complexity of the in vivo microenvironment. Many of these products are proprietary, expensive or require chemical synthesis. The recycling and revaluation of vegetable derived tissues to fabricate scaffolds for analytical biosensors 3D stem cell cultures platforms may represent a very low-cost approach for toxicological and environmental analyses. In this approach, potential applications of vegetable-derived tissue for biosensing and 3D stem cell cultures were investigated. Micro-structured scaffolds from stalk of broccoli, named BrcS, were either functionalized for production of enzymatic 3D-biosensors or preconditioned to be used them as 3D-scaffolds for human mesenchymal stem cells cultures. The conditions to fabricate 3D-biosensors and scaffolds for cell growth were here optimized studying all analytical parameters and demonstrating the feasibility to combine these two properties for an innovative solution to ennoble vegetable wastes.

Multifactorial pathogenesis of non-alcoholic steatohepatitis (NASH) disease, a wide-spread liver pathology associated with metabolic alterations triggered by hepatic steatosis, should be hit by multitarget therapeutics. We tested a multicomponent food supplement mixture (AP-NHm), whose components have anti-dislipidemic, antioxidant and anti-inflammatory effects, on in vitro and in vivo models of NASH. In vitro, hepatic cells cultures were treated for 24 h with 0.5 mM oleic acid (OA): in the co-treatment set cells were co-treated with AP-NH mixtures (AP-NHm, 1:3:10 ratio) and in the post-injury set AP-NHm was added for 48 h after OA damage. In vivo, C57BL/6 mice were fed with high-fat diet (HFD) for 12 weeks, inducing NASH at 7th week, and treated with AP-NHm at two dosages (1:3 ratio) in co-treatment or post-injury protocols, while a control group was fed with a standard diet. In in vitro co-treatment protocol, alterations of redox balance, proinflammatory cytokines release and glucose uptake were restored in a dose-dependent manner, at highest dosages also in post-injury regimen. In both regimens, pathologic dyslipidemias were also ameliorated by AP-NHm. In vivo, high-dose-AP-NHm-co-treated-HFD mice dose-dependently gained less body weight, were protected from dyslipidemia, and showed a lower liver weight. Dose-dependently, AP-NHm treatment lowered hepatic LDL, HDL, triglycerides levels and oxidative damage, co-treatment regimen was anti-inflammatory, reducing TNF-&alpha, and IL-8 levels. Hepatic lipidic infiltration significantly decreased in co-treated and post-injury-AP-NHm-HFD animals. The multitarget approach with AP-NHm was effective in preventing and reducing NASH-related pathologic features, warranting for the clinical development of this compound.

The management of chronic visceral pain related to Inflammatory Bowel Diseases or Irritable Bowel Syndrome is still a clinical problem and new therapeutic strategies continue to be investigated. In the present study, the efficacy of a pomegranate decoction and of its polysaccharide and ellagitannin components in preventing the development of colitis-induced abdominal pain in rats was evaluated. After colitis induction by 2,4-dinitrobenzenesulfonic acid (DNBS), the pomegranate decoction (300 mg kg−1), polysaccharides (300 mg kg−1), and ellagitannins (45 mg kg−1) were orally administered for 14 days. Repeated treatment with decoction reduced visceral hypersensitivity in the colitic animals both at 7 and 14 days. Similar efficacy was shown by polysaccharides, but with lower potency. Ellagitannins administered at dose equivalent to decoction content showed higher efficacy in reducing the development of visceral pain. Macroscopic and microscopic evaluations performed on the colon 14 days after the damage showed that all three preparations reduced the overall amount of mast cells, the number of degranulated mast cells, and the density of collagen fibers in the mucosal stroma. Although ellagitannins seem to be responsible for most of the beneficial effects of pomegranate on DNBS-induced colitis, the polysaccharides support and enhance its effect. Therefore, pomegranate mesocarp preparations could represent a complementary approach to conventional therapies for promoting abdominal pain relief.

Objectives The creation of a new valid preclinical model of articular pain by the intra-articular (i.a.) injection of mucilages for the screening of new treatments against arthritis. Methods A single intra-articular injection (20 μl) of mucilages (from Althaea officinalis roots and Linum usitatissimun seeds) or vegetal components (Amorphophallus konjac gum powder and β-glucan, used as reference standard) were assessed in the rat. The pathology progression was monitored by behavioural measurements (paw pressure test, von Frey test, incapacitance test and beam balance test) and compared to that induced by the i.a. injections of monoiodioacetate (MIA) and Complete Freund's Adjuvant (CFA), well-recognized models of osteoarthritis and rheumatoid arthritis, respectively. Key findings Among all, the mucilage of L. usitatissimun showed the best pro-algic profile inducing a painful long-lasting condition. Hypersensitivity was characterized as a mixed form of inflammatory and neuropathic pain by the responsiveness to ibuprofen (100 mg/kg, p.o.) and pregabalin (30 mg/kg, p.o.). The histological evaluation of joint showed a damage that represents both MIA and CFA features. Conclusions In conclusion, a single i.a. injection of L. usitatissimun mucilage can represent a valid model to assess articular pain in the rat for the screening of new treatments against arthritis.

Hydrochlorothiazide (HCT) is widely used in pediatrics for hypertension management. Due to the lack of pediatric commercial forms, community or hospital pharmacies generally prepare HCT extemporaneous pediatric suspensions by dispersing in water a portion of a crushed tablet or the drug powder; however, any dose or stability control is usually done on these preparations. Obtaining stable HCT solutions is very challenging, due to its low water-solubility and pH-dependent degradation. The aim of this work was to develop a stable 2 mg/mL-HCT oral pediatric solution without using co-solvents. Combined use of cyclodextrins (CD) and hydrophilic polymers was exploited to improve poor HCT solubility and stability. HPβCD and SBEβCD were selected, considering their safe toxicological profiles, while PVP resulted the best among the tested polymers. Low PVP concentrations (0.2–1.0%) improved the solubilizing efficiency of both CDs, allowing to reach the prefixed HCT concentration. Different CD-PVP concentrations were used to prepare several 2 mg/mL-HCT solutions in pH 5.5 buffer. The best stability was shown by solutions containing the highest SBEβCD concentration (25 mM), which allowed a 3-months stability at 4 °C. In vivo studies on rats showed that such formulation allowed a more pronounced and more reproducible diuretic effect than the corresponding HCT suspension.

High-performance control systems (HPCSs) are sophisticated vibration mitigation strategies that include active, semi-active and hybrid systems. They generally outperform passive supplemental damping systems by relying on a feedback mechanism enabling adaptability, resulting in better control reachability over a wide excitation frequency bandwidth. HPCSs are therefore ideal for multi-hazard mitigation. However, the performance of these systems is highly dependent on the controller design, which requires appropriate tuning based on assumptions or on knowledge of dynamic parameters, long-term performance of sensors, excitations, etc. The quantification of performance based on possible uncertainties on such assumptions and/or knowledge could be a powerful tool in financially or technically justifying the use of an HPCS, or simply to benchmark the long-term performance of a given control algorithm. This paper investigates a methodology to assess the performance of control algorithms under various sources of uncertainties. To reduce the computational demand of the uncertainty quantification process, surrogate models are employed to map the nonlinear relationship between structural response and controller configurations. Long-term performance is quantified using life-cycle cost analysis. The investigation is conducted on a 39-story building, located in Boston (MA), and equipped with a set of semi-active friction devices. Results demonstrate that the proposed framework can be used to assess the performance of a given control algorithm considering various sources of uncertainties.

Current pharmacological therapies for the management of chronic articular diseases are far from being satisfactory, so new strategies need to be investigated. We tested the intra-articular pain relieving properties of a system of molecules from a characterized Centella asiatica extract (14G1862) in a rat model of osteoarthritis induced by monoiodoacetate (MIA). 14G1862 (0.2–2 mg mL−1) was intra-articularly (i.a.) injected 7 days after MIA, behavioural and histological evaluations were performed 14, 30 and 60 days after treatments. Moreover, the effect of 14G1862 on nitrate production and iNOS expression in RAW 264.7 macrophages stimulated with LPS was assessed. In vitro, 14G1862 treatment attenuated LPS-induced NO production and iNOS expression in a comparable manner to celecoxib. In vivo, 14G1862 significantly reduced mechanical allodynia and hyperalgesia, spontaneous pain and motor alterations starting on day 14 up to day 60. The efficacy was higher or comparable to that evoked by triamcinolone acetonide (100 μg i.a.) used as reference drug. Histological evaluation highlighted the improvement of several morphological parameters in MIA + 14G1862-treated animals with particularly benefic effects on joint space and fibrin deposition. In conclusion, i.a. treatment with Centella asiatica is a candidate to be a novel effective approach for osteoarthritis therapy.

We present a combined spectroscopic and computational approach aimed to elucidate the mechanism of formation and activity of etoposide nanoaggregates upon release from dextran–etoposide conjugates. Etoposide is an anticancer drug that inhibits cell growth by blocking Topoisomerase II, the key enzyme involved in re-ligation of the DNA chains during the replication process. In silico and spectroscopic analysis indicate that released etoposide nanoaggregates have a different structure, stability, and bioactivity, which depend on the pH experienced during the release. Molecular dynamics simulation and in silico docking of etoposide dimers suggest that the aggregation phenomena inhibit etoposide bioactivity, yet without drastically preventing Topoisomerase II binding. We correlated the diminished cytotoxic activity exerted by dextran–etoposide conjugates on the A549 lung cancer cells, compared to the free drug, to the formation and stability of drug nanoaggregates.

In the present paper, we investigate the effects of alkali and operational temperature on NiO capacitive and optical properties. The NiO samples were prepared by a straightforward, surfactant-free hydrothermal synthesis, employing Ni(NO3)2 and either urea or moderately sterically hindered triethylamine (TEA). The syntheses were followed by calcinations at either 400 or 600 &deg, C. NiO samples were characterized by XRD, scanning electron microscopy, and nitrogen adsorption isotherms. The optical properties were investigated by reflectance spectroscopy, and the pseudocapacitance was studied by cyclic voltammetry and galvanostatic charge charge-discharge measurements. We found that the synthesis with TEA yielded nanoflowers whereas the morphology of the synthesis with urea varied with the calcination temperature and resulted in nanoparticles or nanoslices at calcination temperatures of 400 and 600 &deg, C, respectively. The NiO samples prepared at a lower temperature displayed a favorable combination of surface area and porosity that allowed for high performance with capacitances of 502 and 520 F g&minus, 1 at a current density of 1 A g&minus, 1 for nanoflowers and nanoparticles, respectively. The band gaps of all the samples were compatible with the estimated nanoparticle sizes. Finally, we used the synthesized NiO samples for the preparation of screen-printed electrodes (SPEs) modified by drop-casting and probed them against a [Fe(CN)6]3&minus, /4&minus, probe.

Of wide interest for health is the relation existing between depression, a very common psychological illness, accompanied by anxiety and reduced ability to concentrate, and adult neurogenesis. We will focus on two neurogenic stimuli, fluoxetine and physical exercise, both endowed with the ability to activate adult neurogenesis in the dentate gyrus of the hippocampus, known to be required for learning and memory, and both able to counteract depression. Fluoxetine belongs to the class of selective serotonin reuptake inhibitor (SSRI) antidepressants, which represent the most used pharmacological therapy; physical exercise has also been shown to effectively counteract depression symptoms in rodents as well as in humans. While there is evidence that the antidepressant effect of fluoxetine requires its pro-neurogenic action, exerted by promoting proliferation, differentiation and survival of progenitor cells of the hippocampus, on the other hand fluoxetine exerts also neurogenesis-independent antidepressant effects by influencing the plasticity of the new neurons generated. Similarly, the antidepressant action of running also correlates with an increase of hippocampal neurogenesis and plasticity, although the gene pathways involved are only partially coincident with those of fluoxetine, such as those involved in serotonin metabolism and synapse formation. We further discuss how extra-neurogenic actions are also suggested by the fact that, unlike running, fluoxetine is unable to stimulate neurogenesis during aging, but still displays antidepressant effects. Moreover, in specific conditions, fluoxetine or running activate not only progenitor but also stem cells, which normally are not stimulated; this fact reveals how stem cells have a long-term, hidden ability to self-renew and, more generally, that neurogenesis is subject to complex controls that may play a role in depression, such as the type of neurogenic stimulus or the state of the local niche. Finally, we discuss how fluoxetine or running are effective in counteracting depression originated from stress or neurodegenerative diseases.

The beneficial effects of isothiocyanate-based compounds, as well as their safety, have been shown in neuropathological disorders, such as neuropathic pain. Aim of the present work was to study the efficacy of the glucosinolate glucoraphanin (GRA) and the derived isothiocyanate sulforaphane (SFN), secondary metabolites occurring exclusively in Brassicales, on chemotherapy-induced neuropathic pain. Mice were repeatedly treated with oxaliplatin (2.4 mg kg-1 ip) for 14 days to induce neuropathic pain. GRA and SFN effects were evaluated after a single administration on Day 15 or after a daily repeated oral and subcutaneous treatment starting from the first day of oxaliplatin injection until the 14th day. Single subcutaneous and oral administrations of GRA (4.43-119.79 μmol kg-1 ) or SFN (1.33-13.31 μmol kg-1 ) reduced neuropathic pain in a dose-dependent manner. The repeated administration of GRA and SFN (respectively 13.31 and 4.43 μmol kg-1 ) prevented the chemotherapy-induced neuropathy. The co-administration of GRA and SFN in mixture with the H2 S binding molecule, haemoglobin, abolished their pain-relieving effect, which was also reverted by pretreating the animals with the selective blocker of Kv7 potassium channels, XE991. GRA and SFN reduce neuropathic pain by releasing H2 S and modulating Kv7 channels and show a protective effect on the chemotherapy-induced neuropathy.

Disposable non-invasive and compatible real time monitoring tool was developed in order to follow the cleaning process of paper artwork directly in situ. This tool was based on a biocompatible cleaning hydrogel coupled with flow electrochemical diagnostic tool, suitable to verify in situ and in a simple way the assessment of degradation of artwork and the efficiency of cleaning process. In this paper, the results obtained by applying this tool on a great format artwork with a lining as support, “Le Nozze di Psiche”, engraved by Diana Scultori, printed in 1613, are reported. This opera was affected by a structural and chromatic deterioration due to a strong oxidative degradation. Such deterioration was probably accelerated by the adhesive (a mixture of starch paste and animal glue) used in a previous lining intervention. In this case, the cleaning agents used are rigid hydrogels of Gellan gum, modified with hydrolytic enzymes. By using the flow sampling system, all materials removed by the gel was carried up to a thin layer cell containing a selective electrochemical biosensors, suitable to monitor both treatments, the cleaning process and the removal of lining. These were monitored, allowing understanding when both processes were completed, thus avoiding lengthy and unnecessary cleaning applications. The effectiveness of cleaning with Gellan gel was assessed quantitatively by using non-invasive optical reflectance spectroscopy by a portable instrumentation, elaborating data with an improved version of the Kubelka-Munk theory in order to recover the absorption coefficient of the cellulose fibers of “Le Nozze di Psiche”. The concentration of oxidized groups acting as chromophores was obtained by comparing the experimental optical absorption spectra to those simulated computationally by using TDDFT-based calculations. By following the cleaning with Gellan gel the results indicate a large decrease of the concentration of degradation product of cellulose. Moreover, chromatographic analysis were carried out in order to evaluate the amount of acid compound, produced during the aging and present on the graphic artwork, using the Gellan gel after cleaning step. The results obtained from the restoration of “Le Nozze di Psiche” have allowed the restorers to evaluate innovative methods for cleaning treatment of paper artworks with a highly specialized scientific-diagnostic approach

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies. Neuropathies are associated to aberrant excitability of DRG neurons due to the alteration in the expression or function of a variety of ion channels. In this regard, Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are overexpressed in inflammatory and neuropathic pain states, and HCN blockers have been shown to reduce neuronal excitability and to ameliorate painful states in animal models. However, HCN channels are critical in cardiac action potential, and HCN blockers used so far in pre-clinical models do not discriminate between cardiac and non-cardiac HCN isoforms. In this work, we show an HCN current gain of function in DRG neurons from oxaliplatin-treated rats. Biochemically, we observed a downregulation of HCN2 expression and an upregulation of the HCN regulatory beta-subunit MirP1. Finally, we report the efficacy of the selective HCN1 inhibitor MEL57A in reducing hyperalgesia and allodynia in oxaliplatin-treated rats without cardiac effects. In conclusion, this study strengthens the evidence for a disease-specific role of HCN1 in CIPN, and proposes HCN1-selective inhibitors as new-generation pain medications with the desired efficacy and safety profile.

An Enzyme Linked ImmunoMagnetic Electrochemical assay (ELIME) was developed for the detection of the hepatitis A virus (HAV). This system is based on the use of new polydopamine-modified magnetic nanobeads as solid support for the immunochemical chain, and an array of 8 screen-printed electrodes as a sensing platform. Enzymatic-by-product is quickly measured by differential pulse voltammetry. For this purpose, all analytical parameters were optimized; in particular, different blocking reagents were evaluated in order to minimize the nonspecific interaction of bioreagents. Using the ELIME assays, a quantitative determination of HAV can be achieved with a detection limit of 1·10−11 IU mL−1 and a working range between 10−10 – 5 × 10−7 IU mL−1. The cross-reactivity of the commercial monoclonal antibodies against HAV used in ELIME assays was tested for Coxsackie B4, resulting very low. The sensitivity was also investigated and compared with spectrophotometric sandwich ELISA. The average relative standard deviation (RSD) of the ELIME method was less than 5% for the assays performed on the same day, and 7% for the measurements made on different days. The proposed system was applied to the cell culture of HAV, which title was quantified by Real-Time Quantitative Reverse Transcription PCR (RT¬qPCR). To compare the results, a correlation between the units used in ELIME (IU mL−1) and those used in RT¬qPCR (genome mL−1) was established using a HAV-positive sample, resulting in 1 IU mL−1–10−4 gen mL−1 (R2 = 0.978). The ELIME tool exhibits good stability and high biological selectivity for HAV antigen detection and was successfully applied for the determination of HAV in tap water.

The quantitative evaluation of chemical elements from X-ray Fluorescence (XRF) analysis still remains a strong hurdle in X-ray Spectrometry, mainly due to significant matrix effects involved in the processes. The Fundamental Parameter Method (FPM) is a valid tool for the calculation of analyte concentration unless the primary source comes from a Synchrotron Radiation facility or the experimental design is based on a confocal layout. The approximation of an infinitely thin sample represents a feasible way to apply the FPM approach along with dedicated X-ray optics implemented in the XRF apparatus to improve the performance of the primary beam (and also of the fluorescence signal reaching the detector). This is routinely available at the XLab Frascati of INFN-LNF thanks to the ”Rainbow X-ray” (RXR) facility, the μXRF station opened to users and optimized for most of X-ray analytical research fields. The basic principle of the station is in the use of various geometrical combinations of polycapillary optics for X-ray beam shaping (focusing/collimation) applied to specially designed laboratory units. The flexible RXR layout allows investigating specimens of the dimensions ranging from several millimeters up to half meter and weighting up to several tens of kilograms with the main advantage of having a detection system able to work separately both at high and low X-ray energies. The aim of the present work is to show the results obtained in quantitative XRF analysis by applying the FPM approach to the RXR experimental layout in a study of the pigments covering two different Japanese scrolls, n.142 838 (also known as Engi Jizo Emakimono) and n. 142 846, coming from the private Ragusa Collection presently stored at Pigorini Museum in Italy.

The FOLFOX family of chemotherapy regimens are hampered by the development of a painful neuropathy. Current clinical treatments are inadequate, and furthermore, the research of innovative drugs is strongly disadvantaged by the absence of a preclinical model based on the complete mixture of FOLFOX components. The aim of this study was to set up a rat model of FOLFOX-induced neuropathy in rats, validate its predictability by reference drugs, and evaluate the effectiveness of the new anti-neuropathic compound dimiracetam. Male Sprague–Dawley rats were treated intraperitoneally with the FOLFOX components (6 mg kg−1 oxaliplatin, 50 mg kg−1 5-FU, 90 mg kg−1 leucovorin calcium salt) or oxaliplatin alone (6 mg kg−1) on days 0, 7, 14, and 21, whereas a separate group received one more injection of FOLFOX on day 28. Pain behavioural measurements (paw pressure, cold plate, and electronic Von Frey tests) and motor coordination (Rota-rod test) were assessed before and after treatments. Behavioural, motor, neurological, and autonomic parameters (open field and Irwin tests) were evaluated. FOLFOX reduced the pain threshold in response to mechanical noxious and thermal (cold) non-noxious stimuli beginning from day 14 up to day 42 comparably to oxaliplatin alone. A fifth FOLFOX injection enhanced the severity but not the duration of painful alterations. Spontaneous activity, behavioural, autonomic, and neurological functions were also affected, whereas the motor coordination was not altered. On day 22, duloxetine (15 mg kg−1, per os), morphine (10 mg kg−1, subcutaneously), or pregabalin (20 mg kg−1, per os), acutely administered, reduced the FOLFOX-dependent hypersensitivity. Repeated treatments with dimiracetam (150 mg kg−1, per os, twice daily, from day 22) significantly protected rats from FOLFOX-induced alterations of pain threshold as well as from autonomic and neurological impairments taking effect after 7 days treatment. Pregabalin repeatedly administered (20 mg kg−1, per os, twice daily, from day 22) was less effective in reducing mechanical hypersensitivity. A clinically consistent model of FOLFOX-induced neurotoxicity has been developed in rats. Dimiracetam fully reduced hypersensitivity and neurological alterations showing a relevant profile as anti-neuropathic resource.

Hypothesis Due to their highly retentive properties, innovative recently developed, semi-interpenetrated hydrogels made up of poly(vinyl pyrrolidone) (PVP) chains embedded in a poly(2-hydroxyethyl methacrylate) (p(HEMA)) network should be efficiently used as cleaning material for fragile and degraded paper artworks. In restoration practice, indeed the wet cleaning of these artworks is usually performed by immersion of paper in water, a procedure which may lead to several drawbacks, including paper fibers swelling and dissolution of water-soluble original components. Experiments This class of gels were yet presented in literature, but their interactions with paper materials and ability to be spiked with active enzymes (as cleaning agents), have not been analyzed. To establish the suitability of these hydrogels as paper cleaning materials, first, a rheological and microstructural characterization of the gels was performed. Moreover, diffusion of macromolecules inside gels was studied using fluorescence microscopy, to check if these innovative hydrogels can be used as carriers for hydrolytic enzymes. Indeed, pastes and glues are usually found in old paper artworks, and their removal is a very delicate operation that requires a selective action, which is granted by specific hydrolytic enzymes. At the same time, spectroscopic analyses on paper samples under investigation before and after cleaning treatment has been performed, thus assessing the capabilty of these gels as cleaning materials. Findings With the aim of demonstrating the versatility of these hydrogels, several case studies, i.e., the removal of grime and water-soluble cellulose degradation byproducts, the removal of animal glue and the removal of starch paste from real samples, are presented. Results obtained with these gels have been compared to those obtained by using another gel used for paper artworks cleaning, i.e., Gellan gel.