Artificial graphene as a tunable Dirac material

Artificial honeycomb lattices offer a tunable platform to study massless Dirac quasiparticles and their topological and correlated phases. Here we review recent progress in the design and fabrication of such synthetic structures focusing on nanopatterning of two-dimensional electron gases in semiconductors, molecule-by-molecule assembly by scanning probe methods, and optical trapping of ultracold atoms in crystals of light. We also discuss photonic crystals with Dirac cone dispersion and topologically protected edge states. We emphasize how the interplay between single-particle band structure engineering and cooperative effects leads to spectacular manifestations in tunneling and optical spectroscopies.Comment: Review article, 14 pages, 5 figures, 112 Reference

An innovative analytical methodology for the Therapeutic Drug Monitoring (TDM) of schizophrenic patients: Dried Blood Spots (DBS)

Schizophrenia is one of the most frequent psychiatric disorders, affecting about 1% of the world global population. The \ufb01rst antipsychotic class, the so-called \u201cclassical neuroleptics\u201d, includes agents such as Chlorpromazine, Fluphenazine and Haloperidol. These drugs are only active against positive symptoms of psychoses and tend to cause frequent and severe side effects such as extra-pyramidal syndrome, tardive dyskinesia and hyperprolactinemia. The introduction of \u201catypical antipsychotics\u201c such as Clozapine, Risperidone and Ziprasidone has allowed the treatment of schizophrenia negative symptoms as well and a reduction in the incidence and severity of side effects. However, there are some patients which are \u201cnon responder\u201d to the therapy with atypical antipsychotics, thus classical neuroleptics are still widely used, sometimes even under polypharmacy with atypical antipsychotics. Due to the complexity of schizophrenia pharmacological treatment, therapy personalization is advisable to obtain a satisfactory symptom control. Therapeutic Drug Monitoring (TDM) is one of the most important tools to personalize and optimize psychiatric therapy, dealing with drug plasma level determination, correlation of plasma levels with administered doses and correlation of therapeutic effects with side effects. Aim of this study is the development of an innovative and reliable analytical methodology for the simultaneous determination of classical and atypical antipsychotics in blood. A novel blood sampling and pre-treatnrent approach is presented herein, based on Dried Blood Spot (DBS) testing, coupled to a fast and sensitive liquid chromatography - mass spectrometry method (LC-MS/MS). The preliminary results are very promising and assays are currently in progress to fully validate the method in terms of linearity, precision and accuracy and to apply it to the TDM of several schizophrenic patients treated with classical neuroleptics and/or atypical antipsychotics

Dried Blood Spot and mass spectrometry: an analytical tool to certify Cannabis actual state of intoxication

Driving under the influence of Cannabis (DUI) has become a growing concern. Studies investigating the impact of DUI on traffic safety have shown evidence that, during the acute period of Cannabis intoxication, Cannabis diminishes driving faculties greatly increasing the risk of car accidents. However, the actual state of Cannabis intoxication is not easily assessed, particularly in specific contexts such as roadside testing. Until now, the most reliable biological matrix for this purpose in represented by blood but its sampling is invasive and requires a sanitary environment and subsequent treatments or storage precautions, such as centrifugation, refrigeration or freezing. The time lapse between the individuation of a possible intoxication and the blood sampling is very important, since a long delay can mean that, in the meantime, the drug blood levels physiologically decrease under the cut-off value. To overcome this disadvantage, Dried Blood Spots (DBSs) can be a valid alternative to the normal blood sampling by venipuncture. In fact this innovative biological matrix can be obtained after a fast and easy sampling, does not need any particular storage nor transportation precaution and is stable over time. To strictly monitor Cannabis consumption, an original LC-MS/MS method has been developed for the analysis of Cannabinoids in DBSs. Attention has been paid to the determination of \u3949- tetrahydrocannabinol (or THC, Figure 1a), the main psychoactive compound whose presence in blood can be taken as a marker of recent exposure, and its two main metabolites 11-hydroxy-\u3949-tetrahydrocannabinol (THC-OH, Figure 1b) and 11-nor-9-carboxy-\u3949-tetrahydrocannabinol. \ufffc\ufffc\ufffc\ufffc\ufffc\ufffcIn particular the intermediate hydroxylated metabolite (THC-OH) is pharmacologically active and, at the same time, it is a marker of recent Cannabis intake, since it appears in blood about 13 minutes after consumption and has a relatively short half-life. The carboxylated metabolite (THC-COOH) is not psychoactive and has a very long half-life up to one month for chronic users. For this reason the presence of this latter compound alone in blood cannot be taken as a marker of recent exposure. Is evident, therefore, that the simultaneous monitoring of all the three analytes is necessary to outline pharmacokinetic and toxicokinetic state of abusers and contribute to the assessment of psychophysical state, distinguishing between acute or former consumption. The analytical method developed has been fully validated and applied to real DBS samples from Cannabis abusers with satisfactory results, thus confirming the methodology suitability for roadside testings

Dried blood spot testing: an innovative approach to overcome cannabinoid instability in blood

Cannabis is the most widely used illicit drug around the world and among the drugs of abuse (DoA) most frequently involved in street accidents. Therefore, it is important to strictly monitor Cannabis abuse. Until now, the most reliable biological matrix for this purpose is represented by blood (whole blood/plasma), which can provide useful information about drug consumption. However, its sampling and storage require complicated and time consuming precautions, such as centrifugation and refrigeration or freezing, in order to preserve analyte stability. To overcome these disadvantages the use of Dried Blood Spots (DBSs) represents a valid alternative to the \u201cclassical\u201d blood sampling. This innovative biological matrix reproduces the composition of whole blood but its pre-treatment procedure is faster and more feasible. DBSs can be stored for months at room temperature without any appreciable sample degradation, since most enzymatic and non-enzymatic reactions are stopped by the loss of water. The aim of this work is the specific evaluation of cannabinoid stability in DBSs, namely of \u3949 tetrahydrocannabinol (THC), the most important psychoactive cannabinoid, and of its two main metabolites 11-hydroxy-\u3949-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-\u3949-tetrahydrocannabinol (THC-COOH). For this study, blank spiked DBSs were stored at room temperature for up to 3 months after sampling and then analysed by ESI-LC-MS/MS. The sample pre-treatment, based on solvent extraction, provides good extraction yields and selectivity. Preliminary results are very satisfactory, since only minimal differences were observed between the samples analysed immediately after spotting and those analysed after storage. Further assays are in progress to confirm these results and to assess cannabinoid stability in DBSs over longer periods of time

Antioxidant analysis in Vitis labrusca ("fox grape") and related products

Fox grape (Vitis labrusca, "uva fragola" in Italian) is a Vitis species closely related to V. vinifera, but with different characteristic of climactic and terrain compatibility. Moreover, fox grapes also have organoleptic properties different from those of grapevine grapes (they are usually sweeter and lack the "muscat" bouquet); the fermented beverage obtained from the former fruits (commonly called "fragolino" in Italy) cannot legally be labelled as "wine", at least in European Union countries, and cannot be commercialised. While the reasons for this distinction are largely commercial, it is also true that "fox grape wines" have a composition that is quali-quantitatively different from that of "wines"; in particular, the former contain larger amounts of methanol and of tannins. In our previous studies, we have detected and quantified the content of antioxidant compounds such as melatonin, resveratrol, ferulic acid and tryptophan in grapevine fruits and related products (juice, must, wine and grappa). Now, the aim of this study is to evaluate whether the differences in composition between grapevine and fox grape and the respective related products also extend to the mentioned antioxidant compounds, and if so, to which degree. The antioxidant content of fox grapes and "fragolino wine" were evaluated by means of a validated HPLC-F method that exploits the native fluorescence of the analytes to avoid complicated derivatisation procedures. The sample pre-treatment includes a freeze-thaw cycle followed by filtration and an advanced miniaturised procedure based on microextraction by packed sorbent (MEPS)

HPLC analysis in hematic matrices of analgesic drugs used for pain management

The use of central analgesics in pain management and palliative treatments currently involves empirical adjustments, based on observed clinical outcomes and possible adverse drug reactions. Furthermore, in recent years legislative deregulation regarding these analgesic drugs is giving rise to the problem of misuse, prolonged use and abuse. For these reasons, it is essential to develop analytical tools, allowing therapy customisation and patient compliance improvement and also controlling those cases of Driving Under the Influence (DUI) and workplace injuries. The present research aims to develop an analytical strategy to reliably identify and quantify analgesic drugs such as codeine, morphine and derivatives in haematic samples. The matrices taken into account include plasma, a classical one, and Dried Blood Spot (DBS), which is an innovative and alternative blood sampling technique. DBS guarantees reliable results in perfect agreement with those obtained from plasma samples, with the advantage of requiring a very fast and non-invasive sampling, as well as a simple conservation, without the need for any special precautions, such as freezing or centrifugation. For sample purification, a miniaturised pre-treatment procedure based on Microextraction by Packed Sorbent (MEPS) has been adopted and optimised, while analyte separation was obtained by a chromatographic system consisting of a C8 reverse phase column, as the stationary phase, and a mixture of acetonitrile, methanol and phosphate aqueous buffer, as the mobile phase. Analyte detection has been achieved by coupling the HPLC with a spectrofluorimetric detector (F) that exploits the natural fluorescence of the analytes in order to obtain high sensitivity and selectivity. Tests are currently in progress to fully validate the method, which seems to be very promising for quali-quantitative determination in haematic matrices (plasma and DBS) of analgesic drugs used for pain management

Propriet\ue0 nutraceutiche del chinotto: analisi di cumarine e altri marker

Il Chinotto (Citrus 7 myrtifolia) \ue8 un agrume del genere Citrus (famiglia Rutaceae) coltivato in Italia, principalmente in Liguria, Toscana, Lazio e Sicilia, ma le cui origini non sono ancora state accertate. La pianta produce piccoli frutti amari, tradizionalmente usati per preparare bevande, sciroppi, confetture, canditi oppure come frutti interi conservati sotto spirito. L\u2019impiego prevalente riguarda la produzione dell'omonima bevanda, commercializzata infatti con il nome di \u201cChinotto\u201d. Lo scopo dello studio \ue8 la valutazione delle propriet\ue0 nutraceutiche del chinotto mediante l\u2019analisi di importanti composti ad azione benefica sulla salute dell\u2019uomo, tra cui le cumarine. Particolare attenzione sta suscitando recentemente l\u2019auraptene (7-((E)-3,7-dimetilotta-2,6-dienilossi)-2Hcromen-2-one) che ha dimostrato potenziali azioni preventive nell'insorgenza di alcuni tipi di tumori, come melanoma, carcinoma epatico, mammario e colon-rettale. L\u2019auraptene sembra inoltre possedere propriet\ue0 antinfiammatorie e antiossidanti che potrebbero svolgere un ruolo determinante nell'azione chemiopreventiva. Altre cumarine, come l\u2019umbelliferone (7-idrossicromen-2-one), sembrano possedere interessanti attivit\ue0 biologiche, tra cui quella antinfiammatoria e chemiopreventiva. A tale scopo si stanno mettendo a punto metodi HPLC per l\u2019identificazione e la determinazione quantitativa di auraptene, umbelliferone e altri marker del potere nutraceutico sia dei frutti di Citrus 7 myrtifolia sia di diverse bevande e prodotti commerciali da essi preparati. L\u2019analisi delle cumarine pu\uf2 inoltre essere utilizzata per individuare possibili frodi commerciali, permettendo di verificare l\u2019effettivo utilizzo del frutto o dei suoi estratti, piuttosto che di semplici aromi, nelle bevande commercializzate con il nome di \u201cChinotto\u201d. Il procedimento d\u2019analisi si basa sull\u2019impiego dell\u2019HPLC con rivelazione spettrofotometrica (UV), spettrofluorimetrica (F) e accoppiata a spettrometria di massa (MS/MS), utilizzando come fase stazionaria una colonna C18 a fase inversa e come fase mobile una miscela composta da tampone fosfato e acetonitrile. Il metodo \ue8 rapido e di semplice esecuzione, come pure il pretrattamento dei campioni, e i risultati ottenuti finora sono soddisfacenti, pertanto la metodica sembra essere promettente per la valutazione delle propriet\ue0 nutraceutiche dei frutti di chinotto e per il controllo di qualit\ue0 di bevande e prodotti commerciali

Dried blood spots: Liquid chromatography\u2013mass spectrometry analysis of \u3949-tetrahydrocannabinol and its main metabolites

A sensitive and selective HPLC\u2013MS/MS method has been developed for the first time for the anal- ysis of \u3949-tetrahydrocannabinol (the most important active cannabinoid) and its hydroxylated and carboxylated metabolites in human Dried Blood Spots (DBSs). The simultaneous determination of A sensitive and selective HPLC\u2013MS/MS method has been developed for the first time for the anal- ysis of \u3949-tetrahydrocannabinol (the most important active cannabinoid) and its hydroxylated and carboxylated metabolites in human Dried Blood Spots (DBSs). The simultaneous determination of \u3949- tetrahydrocannabinol and its two main metabolites allows assessing the time elapsed after the drug intake and distinguishing between acute or former consumption. This is an important information in specific contexts such as \u201con street\u201d controls by police forces. DBSs have been chosen as the optimal biological matrix for this kind of testing, since they provide information on the actual state of intoxica- tion, without storage and transportation problems usually associated with classical blood testing. The analysis is carried out on a C8 reversed phase column with a mobile phase composed of 0.1% formic acid in a water/methanol mixture and an electrospray ionisation (ESI) source, coupled to a triple quadrupole mass spectrometer. The method was validated according to international guidelines, with satisfactory results in terms of extraction yields, precision, stability and accuracy. Application to real DBS samples from Cannabis abusers gave reliable results, thus confirming the methodology suitability for roadside testing 9- tetrahydrocannabinol and its two main metabolites allows assessing the time elapsed after the drug intake and distinguishing between acute or former consumption. This is an important information in specific contexts such as \u201con street\u201d controls by police forces. DBSs have been chosen as the optimal biological matrix for this kind of testing, since they provide information on the actual state of intoxica- tion, without storage and transportation problems usually associated with classical blood testing. The analysis is carried out on a C8 reversed phase column with a mobile phase composed of 0.1% formic acid in a water/methanol mixture and an electrospray ionisation (ESI) source, coupled to a triple quadrupole mass spectrometer. The method was validated according to international guidelines, with satisfactory results in terms of extraction yields, precision, stability and accuracy. Application to real DBS samples from Cannabis abusers gave reliable results, thus confirming the methodology suitability for roadside testing

Quantitative Evaluation of Auraptene and Umbelliferone, Chemopreventive Coumarins in Citrus Fruits, by HPLC-UV-FL-MS

An analytical strategy, based on the development of two HPLC methods with spectrophotometric (UV), spectrofluorometric (FL), and mass spectrometric (MS) detection, has been developed to investigate the presence of and to quantitate two important chemopreventive coumarins, auraptene and umbelliferone, in foodstuffs. The analytes were determined in fruits, and fruit parts, of plants belonging to the Citrus, Poncirus, and Fortunella genera, to test their nutraceutical potential. The method validation has been carried out according to international guidelines, with good results in terms of precision (RSD 91%). Application to the quantitative analysis of auraptene and umbelliferone in several kinds of citrus fruits was successful, providing reliable and consistent data. Exploiting three different kinds of detection, the analytical methodology proposed herein has been demonstrated to be sound but versatile, as well as reliable. Performances and results were compared and always found in good agreement among themselves. Thus, this approach is suitable for the identification and simultaneous quantitation of auraptene and umbelliferone in citrus fruits, with the aim of evaluating their nutraceutical potential

Bioactive compounds as markers of authenticity in Citrus-based beverages and commercial juices

Citrus-based products such as commercial beverages and juices are widely consumed around the world and, in recent years, they have received much attention because of potential therapeutic benefits associated with their high content of bioactive compounds: among them, vitamins, flavonoids and polyphenols reportedly having antioxidant, anticancer and anti-inflammatory properties. These substances also have great importance for the nutritional, organoleptic and commercial properties of fruits and derived products, contributing to their sensory characteristics (colour, sweetness, bitterness and astringency). Since commercial Citrus juices and beverages represent high-value products traded on a massive industrial scale, their adulteration is a common occurrence in the marketplace. Therefore, it is very useful to develop innovative analytical methods providing reliable measurements of their bioactive substance contents, paying attention to potentially beneficial compounds as markers of authenticity. Two methods have been developed for this purpose, based on HPLC with spectrophotometric (UV) and spectrofluorimetric (F) detection. The sample pre-treatment is carried out by means of original extraction procedures. For example, auraptene and umbelliferone, two coumarin-based molecules, can be investigated in different commercial chinotto-based “soft drinks” to exclude the use of flavours instead of fresh fruits; tartaric and citric acid can be analysed in orange juice to identify frauds in commercial products. The preliminary results are very promising and the proposed analytical methods seem suitable for these purposes