The Via Francigena as a tourist product for local development: the case of Lucca and its province

The European programmes and the local policies toward the valorization of Via Francigena have been always promoting a general diffusion of cultural heritage, both at scientific level (through numerous archeological, historical and geographic publications) and at tourist level (through specific tourist guides and the information technology communication). After a concise overview of the tourist’s features involved in this type of tourism, of this heritage usage methods and of the effort in collecting data concerning the tourists just as pilgrims, the present work has the aim to examine the level of popularity of the Via Francigena in the area of Lucca and find a possible more suitable way of promotion. This research study has been carried out through a survey involving both tourists and residents focusing on the religious or tourist relevance of the path, the advertisement efficacy and the degree of Internet use. The surrey has been carried out in different periods, between May and July 2014 in order to better understand the impact of an important event in Lucca concerning the official opening ceremony of the trail in the Province of Lucca. A particular interest has been given to the community involvement in the process of a more tourist development of the Francigena path, as a mean to highlight and capitalize also other resources and specificities of the area. The survey addressed to the residents in Lucca let us understand the perception level of Via Francigena as a resource and at what extent the community can be involved in boosting it as a tourist product for an image coming back and an economic upturn of Lucca and it’s Province

Fibrin gel: a new scaffold for cardiovascular applications

Aims: Peripheral blood endothelial progenitor cells (EPC) are promising therapies for irreversible myocardial damage, heart failure and peripheral ischemia disease. Natural biopolymers as fibrin are appealing in tissue engineering, because fibrin is biocompatible and bioresorbable. In vitro studies indicate that fibrin can support the growth migration and proliferation of several cells types. Up to date numerous studies have proved the potential of fibrin based injectable cell delivery systems. No studies are available with fibrin as scaffold for EPC. The goal of this study was to investigate if fibrin is a suitable matrix for EPC culture as compared with fibronectin and if different concentrations of fibrinogen (Fb) and thrombin (Th) can influence fibrin structure and EPC behaviour. Methods: Fibrin (Kedrion S.p.a. Lucca, Italy) was prepared mixing Fb (final 4.5-9-18-36 mg/ml) and Th (final 6-12.5-25-50 U/ml). The scaffolds were maintained for 1 hour at 37?C, 5% CO2 before cell seeding. The ultrastructure of fibrin was investigated by scanning electron microscopy (SEM), cryogenic SEM (CRYO-SEM) and atomic force microscopy (AFM) that allow the hydratating analysis of the sample, to evaluate fibre diameter and density. EPC were obtained from peripheral blood of healthy donors and cultured for 1 week on fibrin at the concentration of 1x106 cell/ml in endothelial growth medium. EPC seeded on fibronectin were used as control. Metabolic cell activity on the different scaffolds was assessed after 7 and 14 days by WST1 while cell viability by confocal microscopy (Calcein AM incorporation). Results: Fibrin polymerization rate ranged between 17 and 68 seconds and increased at higher Fb or Th concentrations. Both AFM and SEM analysis revealed a nanometric fibrous structure, with a decrease in fiber diameter with higher fibrinogen concentrations (4.5 mg/ml: 166?4 nm. vs. 36 mg/ml: 119?3 nm, p<0.005, n=5). Different concentrations of Th didn\u27t affect fibre diameter and density. CRYO-SEM suggested a reticulate structure with mesh-size up to 10?m. WST1 assay showed that EPC metabolic activity was better with lower fibrinogen concentrations (4.5 mg/ml: 0.890?0.134 a.u. vs. 36 mg/ml 0.234?0.046 a.u., p<0.05, n=5), while Th had no significant effect. Calcein staining demonstrated that EPC were viable at 14 days and even organised in cluster. Conclusions: Fibrin combines important properties of an ideal biological scaffold, like the nanometric structure, important for the growth and migration of cells. Fibrin is also an ideal scaffold for EPC but the ratio between fibrinogen and thrombin is important for cell viability

Development of a new technology for 3-D nanostructured scaffolds with potential cardiovascular applications

Aims The in situ release and maintaining of cells to promote revascularization is a new goal of cardiovascular therapy. Endothelial progenitor cells (EPC) may contribute to the process of vascular repair. Medical devices realized according to tissue engineering are composed by a cellular component and by an artificial component, usually made of a biocompatible polymer. Scaffolds may be coated with bio-polymers like fibrin to enhance cell adhesion and growth. Aim of this study was to realize nanocomposite 3D scaffolds composed by a synthetic polymer coated with fibrin to support EPC growth and to promote in vivo angiogenesis. Methods 3D PEtU-PDMS scaffolds were studied in vitro for their biocompatibility (viability and proliferation tests; citokine release). In vivo biocompatibility was studied by intramuscular implant in a rabbit model. The scaffolds were fabricated by spray-phase inversion technique. 25U/mL thrombin was sprayed during the fabrication process. The composite scaffold was then incubated o.n. at 37?C with 18mg/mL fibrinogen. The scaffold morphology was analysed by stereo-microscopy and by scanning electron microscopy (SEM). EPC obtained from peripheral blood were cultured for 1 week on the scaffolds at the concentration of 1x106 cell/ml. Fibronectin coating was used as a control. Cell viability was assessed by confocal laser (Calcein-AM incorporation). To test in vivo angiogenesis, EPC-seeded scaffolds were subcutaneously implanted into the back of rats for 14 days. After harvesting, the scaffolds were examined histologically and immunohistochemically to evaluate inflammatory response and neovascularization. Results In vitro and in vivo biocompatibility data demonstrated absence of any citotoxic effect, immunocompatibility and a slight inflammatory reaction without any sign of encapsulation and implant rejection. Morphological analyses showed an homogeneus fibrin coating of the scaffolds, tightly bound and interconnected to the PEtU-PDMS surface. SEM showed the presence of a well organized layer of fibres in a nm scale (mean diameter ~140nm). Cell viability and phenotype were not affected when EPC were seeded on PEtU-PDMS/fibrin scaffolds. The histological observation of explanted scaffolds revealed a slightly inflammatory response and a significant increased numbers of neovessels in tissues surrounding the EPC-seeded scaffold as compared to the scaffold without cells. Conclusions Our data suggest that PEtU-PDMS/fibrin scaffold obtained with a new spray manufacturing technology can support in vitro EPC growth and promote in vivo neovascularisation. Further studies are currently under way in an ischemic hindlimb rat model

Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma?

Objective: HRPT2 gene mutations are associated with parathyroid carcinomas, and absence of parafibromin immunoreactivity has been suggested as a diagnostic marker of malignancy. The aim of our study was to extend parafibromin studies in a series of benign and malignant parathyroid tumors and cross-validate the results of immunohistochemistry with those of HRPT2 analysis. Design and patients: We performed parafibromin and cyclin D1 immunostaining and HRPT2 gene analysis using loss of heterozygosity studies and sequencing analysis in parathyroid specimens from 11 patients with carcinoma (eleven primary tumors, one skin, and four lung metastases), 22 with sporadic adenomas, and 4 with atypical adenomas. Results: Ten out of eleven parathyroid cancers were negative for parafibromin staining and showed HRPT2 gene abnormalities. The remaining sample was negative for immunostaining and genetic analyses. All but one sporadic adenomas showed parafibromin immunoreactivity and no HRPT2 gene abnormalities. The sample with negative immunostaining carried an HRPT2 mutation. Two atypical adenomas were positive and two negative with parafibromin staining. No HRPT2 abnormalities were found in these samples. Cyclin D1 expression was heterogeneous and there was no relationship between expression/expression level of cyclin D1 and parafibromin expression. Conclusions: We have shown that negative parafibromin staining is almost invariably associated with HRPT2 mutations and confirm that loss of parafibromin staining strongly predicts parathyroid malignancy. In clinical practice, these tests could be particularly useful in the subset of parathyroid tumors with equivocal histological examination. However, their diagnostic value in this setting remains to be proven

Identification and functional characterization of loss-of-function mutations of the calcium-sensing receptor in four italian kindreds with familial hypocalciuric hypercalcemia

Objective: Identification and characterization of calcium-sensing receptor (CASR) mutations in four unrelated Italian kindreds with familial hypocalciuric hypercalcemia. Design: Clinical evaluation and genetic analysis of CASR gene. Functional characterization of mutated CASRs. Methods: Direct sequencing of CASR gene in genomic DNA. Studies of CASR-mediated increases in cytosolic calcium concentration [Ca2C]i in CASR-transfected COS-7 cells in vitro. Results: Four unreported heterozygous CASR mutations were identified, including three missense (H595Y, P748H, and C765W) and one splice site (IVS2C1GOC) mutation. The H595Y, P748H, and C765W mutant receptors, although expressed at normal levels on the cell surface, showed a reduced response in [Ca2C]i relative to the wildtype (WT) CASR to increasing extracellular calcium concentrations. Cotransfection experiments showed that the H595Y and P748H mutants did not affect the apparent affinity of the WT CASR for calcium, suggesting that they do not exert a dominant-negative effect. On the other hand, the co-transfected C765W mutant decreased the maximum response of the WT CASR to calcium, suggesting that it may reduce the effective concentration of the normal CASR on the cell surface or impair its maximal signaling capacity. Conclusions: Four CASR mutations were identified. The reduced functional responses to extracellular calcium and normal expression of the mutant receptors suggest that conformational changes account for altered CASR activity. Moreover, a reduced complement of normal CASRs in these heterozygous patients, perhaps combined with a mutant receptor-induced decrease in maximal activity of the WT receptor, may contribute to defective calcium-sensing in vivo.L'articolo è disponibile sul sito dell'editore http://www.euro-endo.org/default.asp

Eliciting the Demand for Long Term Care Coverage: A Discrete Choice Modelling Analysis

We evaluate the demand for long term care (LTC) insurance prospects in a stated preference context, by means of the results of a choice experiment carried out on a representative sample of the Emilia-Romagna population. Choice modelling techniques have not been used yet for studying the demand for LTC services. In this paper these methods are first of all used in order to assess the relative importance of the characteristics which define some hypothetical insurance programmes and to elicit the willingness to pay for some LTC coverage prospects. Moreover, thanks to the application of a nested logit specification with partial degeneracy, we are able to model the determinants of the preference for status quo situations where no systematic cover for LTC exists. On the basis of this empirical model, we test for the effects of a series of socio-demographic variables as well as personal and household health state indicators

Il geoitinerario come espressione del turismo postmoderno

La finalità di questo saggio introduttivo, sviluppato grazie al contributo scientifico di ambiti disciplinari affini alla Geografia (economico, sociologico, informatico), è stata quella di favorire i nuovi approcci di lettura in chiave turistica delle molteplici valenze territoriali. In particolare, è stato sottolineato il modo in cui sia possibile fare turismo attraverso gli itinerari culturali e il “viaggiare nel territorio e nel paesaggio”; un tipico di approccio, quindi, basato sul riconoscimento del valore della località e della comunità ospitante, nonchè sulla condivisione di ciò che la popolazione stessa può offrire sul piano culturale, sociale e spirituale. Di fatto, emerge il concetto stesso di geoitinerario, i cui principi ispiratori si esplicitano attraverso la concezione di un turismo sensibile verso tutto ciò che ruota intorno all’elemento territoriale, nel rispetto degli assunti della sostenibilità e della competitività. In definitiva, attraverso i sistemi di comunicazione digitale il turismo di nicchia e, in particolare, i geoitinerari hanno maggiori possibilità di affermazione, quali prodotti rivolti al turista postmoderno, che ha la capacità e la volontà di raggiungere quella che gli esperti chiamano un’iperinformazione

Composite indicators of poverty in the small area case

Nowadays there is a widespread agreement that poverty is a multifaceted phenomenon, encompassing deprivations along multiple dimensions, so that income is just one of the welfare indicators among several others that contribute to measure poverty. In this framework, our methodological choice for the measurement of multidimensional poverty responds to the notion that setting thresholds to separate the poor from the not poor is an inherently arbitrary one. The process of obtaining composite and multidimensional indicators is a very data hungry process. Moreover, current surveys on households are often unplanned to produce significant estimates at domains (target subpopulations), which do not coincide with those of interest. For all these reasons the focus of the paper is not only on the definition of indicators but also on their estimation process, with particular attention to the statistical quality of the current estimation of the indicators (quality dimension of the indicators and obviously their accuracy), and on small area estimation techniques. The proposed methods belongs to the family of M-quantile SAE models and are applied to composite indicators such as those derived under the Sen approach

Parathyroid tumorigenesis

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, mostly caused by a monoclonal parathyroid adenoma. This review primarily summarizes current knowledge concerning molecular pathogenesis of familial forms of primary hyperparathyroidism and sporadic (non familial) parathyroid tumors. The hereditary syndromes have been recognized as exhibiting Mendelian inheritance patterns and include multiple endocrine neoplasia types 1 (MEN 1) and 2A (MEN 2A), hereditary hyperparathyroidism- jaw tumor (HPT-JT) syndrome, familial isolated hyperparathyroidism (FIHP), familial hypocalciuric hypercalcemia (FHH) and severe neonatal hyperparathyroidism (NSHPT). Inactivating mutations of MEN1 tumor suppressor gene are responsible for MEN 1 in >90% of cases. MEN1 gene has also an established role in the pathogenesis of sporadic parathyroid adenomas. Allelic loss (LOH) of chromosome 11q13 occurs in about 30-40% and somatic mutation of MEN1 gene occur in about 12-20% of sporadic parathyroid adenomas. A mouse model of MEN1 deficiency causes a phenotype that includes the same range of major endocrine tumors as in MEN 1 patients, and exhibits multistage tumor progression with metastatic potential. Hormonal disturbances, such as abnormal PTH and insulin levels, were also observed in these mice. Mutations in a newly identified tumor suppressor gene, HRPT2, have been recently associated with the development of HPT-JT. HRPT2 mutations are also frequent in sporadic parathyroid carcinomas and central to their pathogenesis. MEN1 and HRPT2 genes mutations have also been found in a subset of FIHP families. FHH and NSHPT represent the mildest and severest variants of PHPT, respectively. Both cause hypercalcemia from birth and atypical PHPT that always uniquely persists after subtotal parathyroidectomy. Future identification of additional oncogenes and tumor suppressor genes will clarify the molecular basis of abnormalities of parathyroid proliferation and regulatory function and other specific features unique to the parathyroid tumorigenesis

La Toscana e la città alla svolta del Millennio

Alla fine del secondo millennio, le città toscane si presentano come trasformate da processi contradditori. La loro base economica è cambiata ; le relazioni con il territorio circostante sono mutate per fenomeni di diffusione urbana e contro-urbanizzazione ; la gerarchla mostra chiari segni di ristrutturazione, con appiattimento e maggiore selezione insieme ; lo stesso equilibrio complessivo della rete è messo in discussione da sintomi di delitoralizzazione. In un insieme di città in cui la nobile eredità del passato non rappresenta soltanto un vantaggio per il turismo, ma anche un peso per il continuo impegno di conservazione, la qualità della vita tende purtroppo a peggiorare.Cori Berardo, Cortesi Gisela, Lazzeroni Michela, Lemmi Enrica, Lombardi Daniela, Meini Monica, Spinelli Gianfranco. La Toscana e la città alla svolta del Millennio. In: Petites et grandes villes du Bassin Méditerranéen. Études autour de l’oeuvre d’Étienne Dalmasso. Rome : École Française de Rome, 1998. pp. 447-472. (Publications de l'École française de Rome, 246