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Sodium–glucose co-transporter 1 (SGLT1) and sodium-dependent neutral amino acid transporter (B0AT1) are mainly expressed on the membrane of enterocytes, a type of epithelial cell found in the intestines. In addition to their physiological role in the absorption of nutrients, a protective role in the integrity of the intestinal barrier has been established. The natural ligands of SGLT1 (d-glucose) and of B0AT1 (l-glutamine) can trigger a protective anti-inflammatory effect on the intestinal epithelium. The literature suggests the activation of common intracellular pathways upon engagement of the two transporters, whose functional forms are composed of oligomers or clusters. Simultaneous activation of these two co-transporters could lead to a potential multitarget and synergistic anti-inflammatory effect. Therefore, nanoplatforms containing multiple copies of the ligands could represent chemical tools to study the potential simultaneous activation of the two co-transporters. For these reasons, in this study, a set of different gold nanoparticles decorated with derivatives of d-glucose and of l-glutamine were designed and prepared. In particular, the synthesis of suitable sulfur-ending functionalized ligand derivatives, including a C-glucoside derivative, their anchoring to gold nanoparticles and their physical–chemical characterization have been carried out. The obtained nanostructures could represent promising multifunctional platforms for further investigation of the existence of possible multitarget and synergistic effects toward the two co-transporters SGLT1 and B0AT1.

Abstract The extracellular matrix protects biofilm cells by reducing diffusion of antimicrobials. Tobramycin is an antibiotic used extensively to treat P. aeruginosa biofilms, but it is sequestered in the biofilm periphery by the extracellular negative charge matrix and loses its efficacy significantly. Dispersal of the biofilm extracellular matrix with enzymes such as DNase I is another promising therapy that enhances antibiotic diffusion into the biofilm. Here, we combine the charge neutralization of tobramycin provided by dextran-based single-chain polymer nanoparticles (SCPNs) together with DNase I to break the biofilm matrix. Our study demonstrates that the SCPNs improve the activity of tobramycin and DNase I by neutralizing the ionic interactions that keep this antibiotic in the biofilm periphery. Moreover, the detailed effects and interactions of nanoformulations with extracellular matrix components were revealed through time-lapse imaging of the P. aeruginosa biofilms by laser scanning confocal microscopy with specific labeling of the different biofilm components.

Abstract An innovative protocol for the consolidation of ancient bone remains based on the use of nanometric HydroxyAPatite (HAP) was set up and tested through a multidisciplinary approach. A new protocol for the synthesis of HAP nanoparticles was developed, and the composition of the obtained nanomaterial was investigated through Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD); sizes, shape and morphology of the synthesized particles were studied by Scanning Electron Microscopy (SEM). The consolidation performance was evaluated by testing the new nanomaterial on degraded ancient bone findings. An increase of the mineral density and of the micro-hardness of the bone were observed. The new consolidation method was also tested to assess possible effects on the palaeogenetic analysis and radiocarbon dating on the treated bones. The consolidation treatment does not introduce any contaminations that could affect radiocarbon dating and has no general detrimental impact on the genetic characterization of the skeletal remains. This consolidation procedure represents a more compatible conservation tool with respect to traditional procedures: it has been shown that the treatment is effective, easily-applicable and compatible with post-consolidation analysis.

Naturalized dyes (NDs) are innovative and eco-friendly synthetic compounds in which a chromophore is covalently linked to a natural sugar (e.g., lactose). The sugar moiety confers water-solubility and biocompatibility to the dye molecule as a whole. NDs have demonstrated potential application in dyeing textiles and leather. The purpose of this work was to demonstrate that selected NDs can be also applied to dye wood. To that aim, two NDs were tested to color beech and poplar wood. The NDs were applied as a simple aqueous solution or mixed with a waterborne, biogenic staining agent (commercially available Gemma U50). Moreover, the effect of the application of a biogenic waterborne top coat (commercially available Resina Plus U49) was also studied. Different methods were tested to investigate the potential application of these NDs to wood. The dyeing behavior was analyzed in terms of penetration into the substrate, covering capacity and color homogeneity through macro- and microscopic observations and colorimetric measurements. The color fastness to water washout and the color stability to light, in particular by exposing the wooden samples to artificial aging (UV radiations in a Solar Box), were also investigated. The NDs, when used as water solutions, were able to afford a homogeneous coating and a pleasant appearance on the wood surface, as well as a good color fastness to washout with water. Dissolving the dyes in the stain or applying the top coat generally resulted in even better color fastness to washout. However, all the application methods tested showed limited resistance to fading in the Solar Box, which therefore remains a drawback for this type of product.

Abstract della redazione: In the social sciences literature the expressions ‘random sample’ and ‘representative sample’ are often used improperly and sometimes even interchangeably by students who seem to think that sample is representative in so far, and because, it is random. In this essay I shall discuss the proper use of ‘random’, ‘representative’ and related terms, and I shall argue that no logic nexus exists between the two concepts, nor does any causal relationship between the two sets of phenomena. The analysis begins with the term that raises the most annoying problems, and accordingly is less explored in the literature, viz, ‘representativeness’.

Mechanochemistry is an emerging and reliable alternative to conventional solution (batch) synthesis of complex molecules under green and solvent-free conditions. In this regard, we report here on the conjugation of a dextran polysaccharide with a fluorescent probe, a phenylboronic acid (PBA)-functionalized boron dipyrromethene (BODIPY) applying the ball milling approach. The ball milling formation of boron esters between PBA BODIPY and dextran proved to be more efficient in terms of reaction time, amount of reactants, and labelling degree compared to the corresponding solution-based synthetic route. PBA-BODIPY dextran assembles into nanoparticles of around 200 nm by hydrophobic interactions. The resulting PBA-BODIPY dextran nanoparticles retain an apolar interior as proved by pyrene fluorescence, suitable for the encapsulation of hydrophobic drugs with high biocompatibility while remaining fluorescent.

Chiara Falciani, 1 Fabrizia Zevolini, 1 Jlenia Brunetti, 1 Giulia Riolo, 2 Raquel Gracia, 3 Marco Marradi, 3 Iraida Loinaz, 3 Christina Ziemann, 4 Unai Cossío, 5 Jordi Llop, 5, 6 Luisa Bracci, 1 Alessandro Pini 1 1Department of Medical Biotechnologies, University of Siena, Siena, Italy; 2Setlance, Siena, Italy; 3CIDETEC, Basque Research and Technology Alliance (BRTA), Donostia-San Sebastián, Spain; 4Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany; 5CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), San Sebastian, Spain; 6Centro de Investigación Biomédica en red Enfermedades Respiratorias – CIBERES, Madrid, SpainCorrespondence: Chiara FalcianiDepartment of Medical Biotechnologies, University of Siena, via Aldo Moro 2, Siena, ItalyTel +39 0577 232022Email chiara.falciani@unisi.itIntroduction: Antibiotic-resistant bacteria kill 25,000 people every year in the EU. Patients subject to recurrent lung infections are the most vulnerable to severe or even lethal infections. For these patients, pulmonary delivery of antibiotics would be advantageous, since inhalation can achieve higher concentration in the lungs than iv administration and can provide a faster onset of action. This would allow for the delivery of higher doses and hence reduce the number of treatments required. We report here about a new nanosystem (M33-NS) obtained by capturing SET-M33 peptide on single-chain dextran nanoparticles. SET-M33 is a non-natural antimicrobial peptide synthesized in branched form. This form gives the peptide resistance to degradation in biological fluids. SET-M33 has previously shown efficacy in vitro against about one hundred of Gram-negative multidrug and extensively drug-resistant clinical isolates and was also active in preclinical infection models of pneumonia, sepsis and skin infections.Methods: The new nanosystem was evaluated for its efficacy in bacteria cells and in a mouse model of pneumonia. Toxicity and genotoxicity were also tested in vitro. Biodistribution and pharmacokinetic studies in healthy rats were carried out using a radiolabeled derivative of the nanosystem.Results: The M33-nanosystem, studied here, showed to be effective against Pseudomonas aeruginosa in time-kill kinetic experiments. Cytotoxicity towards different animal cell lines was acceptable. Lung residence time of the antimicrobial peptide, administered via aerosol in healthy rats, was markedly improved by capturing SET-M33 on dextran nanoparticles. M33-NS was also efficient in eradicating pulmonary infection in a BALB/c mouse model of pneumonia caused by P. aeruginosa.Discussion: This study revealed that the encapsulation of the antimicrobial peptide in dextran nanoparticles markedly improved lung residence time of the peptide administered via aerosol. The result has to be considered among the aims of the development of a new therapeutic option for patients suffering recurrent infections, that will benefit from high local doses of persistent antimicrobials.Keywords: antimicrobial peptides, nanoparticles, multi-drug resistance

Politics in many Western democracies have become increasingly personalized; as a consequence, the individual personalities of voters and their social identity are now essential in order to understand political choices. This essay explores the role of social and personal identity, by relating such factors as one’s family, occupation, class consciousness, religion, and personality in general to political choices in order to understand the recent cultural changes in the political scenarios in Italy and Argentina. This research is based on almost 7,000 face-to-face interviews collected between Italy and Argentina from 2014 to 2020.

This study presents proof of concept assays to validate gold nanoparticles loaded with the bacterial peptide 91–99 of the listeriolysin O toxin (GNP-LLO91–99 nanovaccines) as immunotherapy for bladder tumors. GNP-LLO91–99 nanovaccines showed adjuvant abilities as they induce maturation and activation of monocyte-derived dendritic cells (MoDCs) to functional antigen-presenting cells in healthy donors and patients with melanoma or bladder cancer (BC), promoting a Th1 cytokine pattern. GNP-LLO91–99 nanovaccines were also efficient dendritic cell inducers of immunogenic tumor death using different bladder and melanoma tumor cell lines. The establishment of a pre-clinical mice model of subcutaneous BC confirmed that a single dose of GNP-LLO91–99 nanovaccines reduced tumor burden 4.7-fold and stimulated systemic Th1-type immune responses. Proof of concept assays validated GNP-LLO91–99 nanovaccines as immunotherapy by comparison to anti-CTLA-4 or anti-PD-1 antibodies. In fact, GNP-LLO91–99 nanovaccines increased percentages of CD4+ and CD8+ T cells, B cells, and functional antigen-presenting DCs in tumor-infiltrated lymphocytes, while they reduced the levels of myeloid-derived suppressor cells (MDSC) and suppressor T cells (Treg). We conclude that GNP-LLO91–99 nanovaccines can work as monotherapies or combinatory immunotherapies with anti-CTLA-4 or anti-PD-1 antibodies for solid tumors with high T cell infiltration, such as bladder cancer or melanoma.

Background. Recent clinical guidelines have extended indications for oral appliances to subjects affected by moderate-to-severe obstructive sleep apnoea (OSA). The aim of this systematic review covering this important issue for public health is twofold: updating and summarizing the best available scientific evidence by selecting RCTs of quality only, and identifying the therapeutic pathways that can be transferred to the current clinical practice. Methods. All the abstracts which were published before February 18, 2019, have been identified in three electronic databases (PubMed, Web of Science, and Cochrane). The Cochrane Collaboration’s tool for assessing risk of bias was used as an assessment tool in order to evaluate the quality of the selected studies. Results. The search strategy yielded 2,260 studies. After removing duplicates and studies that did not comply with the inclusion criteria, 32 full-text articles were assessed for eligibility, and 17 RCTs were finally included in the qualitative synthesis. The 17 selected studies were very heterogeneous in the type of included RCTs in terms of patient inclusion criteria, sample size, distribution of the two genders in the various groups, duration of treatment, and definition of primary and secondary outcomes, without any restriction on the definition of the control group. A common finding was the positive responsiveness of oral appliance treatment in subjects affected by mild-to-moderate OSA with some evidence for cases of severe OSA. Conclusion. Higher-quality studies are needed in order to provide additional useful guidelines for dental clinicians for OSA management.

In this essay several aspects of the concept ‘indicator’ are criticized, as well as the technical consequences of those misconceptions. The most relevant among them is the pretence of measuring the validity of an indicator, e. g. the degree of semantic correspondence between the indicator and the concept which it is supposes to refer to.

Among carbohydrate-processing enzymes, Jack bean α-mannosidase (JBα-man) is the glycosidase with the best responsiveness to the multivalent presentation of iminosugar inhitopes. We report, in this work, the preparation of water dispersible gold nanoparticles simultaneously coated with the iminosugar deoxynojirimycin (DNJ) inhitope and simple monosaccharides (β-d-gluco- or α-d-mannosides). The display of DNJ at the gold surface has been modulated (i) by using an amphiphilic linker longer than the aliphatic chain used for the monosaccharides and (ii) by presenting the inhitope, not only in monomeric form, but also in a trimeric fashion through combination of a dendron approach with glyconanotechnology. The latter strategy resulted in a strong enhancement of the inhibitory activity towards JBα-man, with a Ki in the nanomolar range (Ki = 84 nM), i.e., more than three orders of magnitude higher than the monovalent reference compound.

Gold glyconanoparticles loaded with the listeriolysin O peptide 91–99 (GNP-LLO91-99), a bacterial peptide with anti-metastatic properties, are vaccine delivery platforms facilitating immune cell targeting and increasing antigen loading. Here, we present proof of concept analyses for the consideration of GNP-LLO91-99 nanovaccines as a novel immunotherapy for cutaneous melanoma. Studies using mouse models of subcutaneous melanoma indicated that GNP-LLO91-99 nanovaccines recruite and modulate dendritic cell (DC) function within the tumour, alter tumour immunotolerance inducing melanoma-specific cytotoxic T cells, cause complete remission and improve survival. GNP-LLO91-99 nanovaccines showed superior tumour regression and survival benefits, when combined with anti-PD-1 or anti-CTLA-4 checkpoint inhibitors, resulting in an improvement in the efficacy of these immunotherapies. Studies on monocyte-derived DCs from patients with stage IA, IB or IIIB melanoma confirmed the ability of GNP-LLO91-99 nanovaccines to complement the action of checkpoint inhibitors, by not only reducing the expression of cell-death markers on DCs, but also potentiating DC antigen-presentation. We propose that GNP-LLO91-99 nanovaccines function as immune stimulators and immune effectors and serve as safe cancer therapies, alone or in combination with other immunotherapies.

A novel and facile method was developed to produce hybrid graphene oxide (GO)–polyelectrolyte (PE) capsules using erythrocyte cells as templates. The capsules are easily produced through the layer-by-layer technique using alternating polyelectrolyte layers and GO sheets. The amount of GO and therefore its coverage in the resulting capsules can be tuned by adjusting the concentration of the GO dispersion during the assembly. The capsules retain the approximate shape and size of the erythrocyte template after the latter is totally removed by oxidation with NaOCl in water. The PE/GO capsules maintain their integrity and can be placed or located on other surfaces such as in a device. When the capsules are dried in air, they collapse to form a film that is approximately twice the thickness of the capsule membrane. AFM images in the present study suggest a film thickness of approx. 30 nm for the capsules in the collapsed state implying a thickness of approx. 15 nm for the layers in the collapsed capsule membrane. The polyelectrolytes used in the present study were polyallylamine hydrochloride (PAH) and polystyrenesulfonate sodium salt (PSS). Capsules where characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and Raman microscopy, the constituent layers by zeta potential and GO by TEM, XRD, and Raman and FTIR spectroscopies.

Background: This systematic review summarizes the current knowledge on the superimposition of three-dimensional (3D) diagnostic records to realize an orthodontic virtual patient. The aim of this study is to analyze the accuracy of the state-of-the-art digital workflow. Methods: The research was carried out by an electronic and manual query effectuated from ISS (Istituto Superiore di Sanità in Rome) on three different databases (MEDLINE, Cochrane Library and ISI WEB OF SCIENCE) up to 31st January 2020. The search focused on studies that superimposed at least two different 3D records to build up a 3D virtual patient—information about the devices used to acquire 3D data, the software used to match data and the superimposition method applied have been summarized. Results: 1374 titles were retrieved from the electronic search. After title-abstract screening, 65 studies were selected. After full-text analysis, 21 studies were included in the review. Different 3D datasets were used: facial skeleton (FS), extraoral soft tissues (ST) and dentition (DENT). The information provided by the 3D data was superimposed in four different combinations: FS + DENT (13 papers), FS + ST (5 papers), ST + DENT (2 papers) and all the types (FS + ST + DENT) (1 paper). Conclusions: The surface-based method was most frequently used for 3D objects superimposition (11 papers), followed by the point-based method (6 papers), with or without fiducial markers, and the voxel-based method (1 paper). Most of the papers analyzed the accuracy of the superimposition procedure (15 papers), while the remaining were proof-of-principles (10 papers) or compared different methods (3 papers). Further studies should focus on the definition of a gold standard. The patient is going to have a huge advantage from complete digital planning when more information about the spatial relationship of anatomical structures are needed: ectopic, impacted and supernumerary teeth, root resorption and angulations, cleft lip and palate (CL/P), alveolar boundary conditions, periodontally compromised patients, temporary anchorage devices (TADs), maxillary transverse deficiency, airway analyses, obstructive sleep apnea (OSAS), TMJ disorders and orthognathic and cranio-facial surgery.

Reactive oxygen and nitrogen species (RONS) are produced endogenously in our body, or introduced through external factors, such as pollution, cigarette smoke, and excessive sunlight exposure. In normal conditions, there is a physiological balance between pro-oxidant species and antioxidant molecules that are able to counteract the detrimental effect of the former. Nevertheless, when this homeostasis is disrupted, the resulting oxidative stress can lead to several pathological conditions, from inflammation to cancer and neurodegenerative diseases. In this review, we report on the recent developments of different polymeric formulations that are able to reduce the oxidative stress, from natural extracts, to films and hydrogels, and finally to nanoparticles (NPs).

The therapeutic approach for the treatment of HIV infection is based on the highly active antiretroviral therapy (HAART), a cocktail of antiretroviral drugs. Notwithstanding HAART has shown different drawbacks like toxic side effects and the emergence of viral multidrug resistance. Nanotechnology offers new tools to improve HIV drug treatment and prevention. In this scenario, gold nanoparticles are an interesting chemical tool to design and prepare smart and efficient drug-delivery systems. Here we describe the preparation and antiviral activity of carbohydrate-coated gold nanoparticles loaded with anti-HIV prodrug candidates. The nucleoside reverse transcriptase inhibitors abacavir and lamivudine have been converted to the corresponding thiol-ending ester derivatives and then conjugated to ~3 nm glucose-coated gold nanoparticles by means of “thiol-for-thiol” ligand place exchange reactions. The drugs-containing glyconanoparticles were characterized and the pH-mediated release of the drug from the nanoparticle has been determined. The antiviral activity was tested by evaluating the replication of NL4-3 HIV in TZM-bl infected cells. The proof-of-principle presented in this work aims to introduce gold glyconanoparticles as a new multifunctional drug-delivery system in the therapy against HIV.

One obvious, minimal pre-requisite in order to use Likert scores as cardinal numbers in data analysis is that they be perceived as more or less equidistant along the dimension of interest. Already 50 years ago, Johann Galtung among others raised serious doubts about the possibility that respondents actually do consider “agree” and “disagree” as equidistant from “uncertain”, given the well-known frequency of acquiescent response sets. In 1973, Benzecri maintained that the technique he had just launched on the academic market (correspondence analysis) supplied an excellent means to also control the assumption of equidistance of one of Likert’s short answers from the two adjoining ones. In the nineties, three young Italian students applied Benzecri’s technique to three different samples of respondents, and found converging results, all widely apart from the assumed equidistance. This essay replicates their survey on a larger sample of Likert scales coming from a dozen different surveys. Unlike the previous controls, the results diverge largely from one another. Yet, only a few offer a mild support to the assumption of perceived equidistance, while in their majority the results raise all sorts of further doubts about it.

The preparation of low-generation dendrimers based on a simple calix[4]arene scaffold by insertion of the iminosugar-analogue C2-symmetric 3,4-dihydroxypyrrolidine is described. This methodology allows a rapid incorporation of a considerable number of iminosugar-like moieties in a reduced volume and in a well-defined geometry. The inclusion of alkali-metal ions (sodium and potassium) in the polar cavity defined by the acetamide moieties at the lower rim of the calixarene was demonstrated, which allows also the rigidification of the dendrimer structure and the iminosugar presentation in the clusters. The combination of the supramolecular properties of calixarenes with the advantage of a dendrimeric presentation of repetitive units opens up the possibility of generating well-defined multivalent and multifaceted systems with more complex and/or biologically relevant iminosugars.

In the first part of the essay the author states that the astounding progress in physics and the natural sciences has determined an inferiority complex in social scientists, with a consequent desire to enjoy a similar measure of prestige, honours, resources, and power. That desire acted as the major premise of a sort of practical syllogism (in Von Wright’s sense) whose minor premise was the conviction that experiments, measurement, and the search for laws were the pillars of the natural sciences’ success.The consequence was the imperative to follow the same path, i. e. experimenting, measuring, and looking for laws, while totally disregarding the nature of the objects of social sciences, which hardly if ever allow for bona fide experiments or measurements, and thoroughly exclude the presence of laws, i. e. of controllable and confirmable propositions concerning men, cultures, and societies all over the planet, and from the most remote past to the most distant future.After quoting vast evidence as to the presence of that syllogism in the minds of social scientists from the Enlightenment on, the author shows how, in order to conceal the absence of bona fide laws, experiments and measurement, social scientists have resorted to a lavish (ab)use of such terms as a sort of fetishes or (self-)make believes.In the second part of the essay the author supplies vast evidence of the semantic dispersion suffered by the three terms that have been used as a sort of talisman in order to pretend having passed the sacred threshold of science.In the conclusion, the author suggests to follow a radically alternative path in order to reach a status of dignity and self respect, i. e. to develop an epistemology that should adopt as a starting point the difference of social science’s objects from physics’, rather than trying to conceal it by terminological tricks.

In the last forty, years semi-flexible pavements have been successfully employed, especially in those areas subjected to heavy and slow-moving loads. They usually comprise a wearing course of Grouted Macadam, a composite pavement material that provides significant advantages in comparison to both concrete and asphalt pavements. On the other hand, the laying process of this material is a two-stage operation, and the realization complexity leads to long realization times and high initial costs. Therefore, the use of semi-flexible pavements has been limited to some fields of application and areas. Recently, an innovative material has been developed to be used as an alternative to Grouted Macadam for semi-flexible pavement wearing course realization. This material should provide similar or even superior characteristics compared to traditional Grouted Macadam. This will reduce semi-flexible pavement construction time and avoid the need for dividing the laying process. This paper presents an experimental program involving the use of FastFWD, as an APT device, to evaluate in-situ properties and performance of this material. The achieved results regarding the validation of this new material by means of FastFWD appear promising both in terms of the material’s properties and resistance to dynamic load repetitions.

Improved detection of anti-carbohydrate antibodies is a need in clinical identification of biomarkers for cancer cells or pathogens. Here, we report a new ELISA approach for the detection of specific immunoglobulins (IgGs) against carbohydrates. Two nanometer gold glyconanoparticles bearing oligosaccharide epitopes of HIV or Streptococcus pneumoniae were used as antigens to coat ELISA-plates. A ~3,000-fold improved detection of specific IgGs in mice immunized against S. pneumoniae respect to the well known BSA-glycoconjugate ELISA was achieved. Moreover, these multivalent glyconanoparticles have been employed in solid phase assays to detect the carbohydrate-dependent binding of human dendritic cells and the lectin DC-SIGN. Multivalent glyconanoparticles in ELISA provide a versatile, easy and highly sensitive method to detect and quantify the binding of glycan to proteins and to facilitate the identification of biomarkers.

Listeriosis is a fatal infection for fetuses and newborns with two clinical main morbidities in the neonatal period, meningitis and diffused cutaneous lesions. In this study, we vaccinated pregnant females with two gold glyconanoparticles (GNP) loaded with two peptides, listeriolysin peptide 91–99 (LLO91–99) or glyceraldehyde-3-phosphate dehydrogenase 1–22 peptide (GAPDH1–22). Neonates born to vaccinated mothers were free of bacteria and healthy, while non-vaccinated mice presented clear brain affections and cutaneous diminishment of melanocytes. Therefore, these nanoparticle vaccines are effective measures to offer pregnant mothers at high risk of listeriosis interesting therapies that cross the placenta.

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BackgroundIndolizidine alkaloids widely occur in nature and display interesting biological activity. This is the reason for which their total synthesis as well as the synthesis of non-natural analogues still attracts the attention of many research groups. To establish new straightforward accesses to these molecules is therefore highly desirable.ResultsThe ring closing metathesis (RCM) of enantiopure hydroxylamines bearing suitable unsaturated groups cleanly afforded piperidine derivatives in good yields. Further cyclization and deprotection of the hydroxy groups gave novel highly functionalized indolizidines. The synthesis of a pyrroloazepine analogue is also described.ConclusionWe have developed a new straightforward methodology for the synthesis of densely functionalized indolizidines and pyrroloazepine analogues in 6 steps and 30–60% overall yields from enantiopure hydroxylamines obtained straightforwardly from carbohydrate-derived nitrones.

Discusses organizational problems in Italian state-run nursery schools. The causes of extreme variations in pupil-teacher ratios and problems concerning teacher scheduling, lunchroom management, and student transportation are examined. (AM)