L'autenticità nell'esperienza turistica. Enogastronomia, cultura e destinazione: analisi di tre casi di prodotto turistico in Italia.

In questo lavoro si studia l'autenticità, in particolare nel consumo turistico. Si individuano tre forme di autenticità e tre tipologie di prodotto turistico, di cui si illustrano le caratteristiche distintive. Attraverso lo studio di tre casi di prodotto turistico in Italia, si verifica se esiste una corrispondenza tra la tipologia di prodotto turistico individuata e la forma che l'autenticità assume nel turismo. Nello specifico, quale delle tre forme di autenticità individuate corrisponde a ciascuna delle tre tipologie di prodotto turistico. Ciascun caso esaminato è legato o avviene nel territorio, e corrisponde ad una delle tre declinazioni di turismo oggetto di interesse (prodotti tipici, patrimonio culturale ed artistico, destinazione). I casi oggetto di studio sono: Prosciutto Toscano Dop, Paniere dei Prodotti Tipici della Provincia di Torino ed il Borgo Autentico di Pietralunga (nell'ambito del Progetto Borghi Autentici d'Italia)

Preliminary assessment of fentanyl and synthetic opioids prevalence among addiction patients by means of hair analysis

Background Although the diffusion of novel synthetic opioids has become a worldwide phenomenon, their prevalence of use in Italy seems to be limited. Existing national data is mainly derived by anamnestic surveyslacking of toxicological validation and not always disclosing the use of these compounds, which might remain under-diagnosed. Methods an assessment of the metabolites of the main synthetic opioids on hair samples was carried out among patients admitted at the Addiction Treatment Unit of Trento. The analytical approach included: (a) screening by means of immunoenzymatic method for fentanyl, fentanyl analogs and oxicodone; (b) confirmation of the samples resulted positive for fentanyl and oxicodone by means of HPLC-MS/; (c) search and dosage detection of Tramadol by means of HPLC-MS/MS. Results 3 out of 309 analysed samples were found positive: one was positive to Fentanyl and two to 4-ANPP. In the same cohort, 6 samples were also found positive for Oxycodone . Tramadol was searched in 189 samples and 12 of them resulted positive. Discussion and conclusion Those found positive were mainly young adults engaging in dangerous patterns of use and lacking awareness of risks. The phenomenon requires further consideration by health professionals. Training and more evidence-based information on synthetic opioids as well as other Novel Psychoactive Substances (NPS) are urgently needed.Peer reviewe

Asthma improvement in patients treated with dupilumab for severe atopic dermatitis

IntroductionAtopic dermatitis (AD) is considered a systemic type 2 immune driven disease, and it is associated to many atopic comorbidities including asthma. The aim of our study was to prospectively evaluate the respiratory outcomes in patients with persistent allergic asthma treated with dupilumab due to severe AD (sAD).MethodsWe enrolled eligible patients with sAD for dupilumab treatment from September 2018 to December 2020. We then selected the subgroup of patients sensitized to perennial allergens. Dupilumab's efficacy and safety on AD and comorbid asthma were assessed at baseline, one month, four months, and then every 4 months up to one year.ResultsA total of 437 patients with sAD were enrolled for dupilumab treatment due to sAD, and 273 reached 48 weeks of therapy. Respiratory outcomes were evaluated in the 85 asthmatic patients with positivity only to perennial allergens. Our patients showed statistically and clinically significant improvement in asthma control (Asthma Control Test and Asthma Control Questionnaire) and airway obstruction parameters (FEV1), in addition to the expected AD-related skin outcomes. Specifically, a significant improvement was achieved at the fourth month of dupilumab therapy, and this trend was maintained up to twelve months, regardless of asthma severity.ConclusionsOur results showed the overall improvement of the clinical picture that dupilumab offers for patients with severe AD and persistent allergic asthma of any severity, highlighting the importance of a global multidisciplinary approach of type 2 driven disease

Microglia control glutamatergic synapses in the adult mouse hippocampus

Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1−/− mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in organization and activity of glutamatergic synapses

Physical function and self-rated health status as predictors of mortality: results from longitudinal analysis in the ilSIRENTE study

<p>Abstract</p> <p>Background</p> <p>Physical function measures have been shown to predict negative health-related events in older persons, including mortality. These markers of functioning may interact with the self-rated health (SRH) in the prediction of events. Aim of the present study is to compare the predictive value for mortality of measures of physical function and SRH status, and test their possible interactions.</p> <p>Methods</p> <p>Data are from 335 older persons aged ≥ 80 years (mean age 85.6 years) enrolled in the "Invecchiamento e Longevità nel Sirente" (<it>ilSIRENTE</it>) study. The predictive values for mortality of 4-meter walk test, Short Physical Performance Battery (SPPB), hand grip strength, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and a SRH scale were compared using proportional hazard models. Kaplan-Meier survival curves for mortality and Receiver Operating Characteristic (ROC) curve analyses were also computed to estimate the predictive value of the independent variables of interest for mortality (alone and in combination).</p> <p>Results</p> <p>During the 24-month follow-up (mean 1.8 years), 71 (21.2%) events occurred in the study sample. All the tested variables were able to significantly predict mortality. No significant interaction was reported between physical function measures and SRH. The SPPB score was the strongest predictor of overall mortality after adjustment for potential confounders (per SD increase; HR 0.64; 95%CI 0.48–0.86). A similar predictive value was showed by the SRH (per SD increase; HR 0.76; 95%CI 0.59–0.97). The chair stand test was the SPPB subtask showing the highest prognostic value.</p> <p>Conclusion</p> <p>All the tested measures are able to predict mortality with different extents, but strongest results were obtained from the SPPB and the SRH. The chair stand test may be as useful as the complete SPPB in estimating the mortality risk.</p

Bilateral effects of unilateral cerebellar lesions as detected by voxel based morphometry and diffusion imaging

Over the last decades, the importance of cerebellar processing for cortical functions has been acknowledged and consensus was reached on the strict functional and structural cortico-cerebellar interrelations. From an anatomical point of view strictly contralateral interconnections link the cerebellum to the cerebral cortex mainly through the middle and superior cerebellar peduncle. Diffusion MRI (dMRI) based tractography has already been applied to address cortico-cerebellar-cortical loops in healthy subjects and to detect diffusivity alteration patterns in patients with neurodegenerative pathologies of the cerebellum. In the present study we used dMRI-based tractography to determine the degree and pattern of pathological changes of cerebellar white matter microstructure in patients with focal cerebellar lesions. Diffusion imaging and high-resolution volumes were obtained in patients with left cerebellar lesions and in normal controls. Middle cerebellar peduncles and superior cerebellar peduncles were reconstructed by multi fiber diffusion tractography. From each tract, measures of microscopic damage were assessed, and despite the presence of unilateral lesions, bilateral diffusivity differences in white matter tracts were found comparing patients with normal controls. Consistently, bilateral alterations were also evidenced in specific brain regions linked to the cerebellum and involved in higher-level functions. This could be in line with the evidence that in the presence of unilateral cerebellar lesions, different cognitive functions can be affected and they are not strictly linked to the side of the cerebellar lesion

Evidence for Sub-Haplogroup H5 of Mitochondrial DNA as a Risk Factor for Late Onset Alzheimer's Disease

BACKGROUND: Alzheimer's Disease (AD) is the most common neurodegenerative disease and the leading cause of dementia among senile subjects. It has been proposed that AD can be caused by defects in mitochondrial oxidative phosphorylation. Given the fundamental contribution of the mitochondrial genome (mtDNA) for the respiratory chain, there have been a number of studies investigating the association between mtDNA inherited variants and multifactorial diseases, however no general consensus has been reached yet on the correlation between mtDNA haplogroups and AD. METHODOLOGY/PRINCIPAL FINDINGS: We applied for the first time a high resolution analysis (sequencing of displacement loop and restriction analysis of specific markers in the coding region of mtDNA) to investigate the possible association between mtDNA-inherited sequence variation and AD in 936 AD patients and 776 cognitively assessed normal controls from central and northern Italy. Among over 40 mtDNA sub-haplogroups analysed, we found that sub-haplogroup H5 is a risk factor for AD (OR=1.85, 95% CI:1.04-3.23) in particular for females (OR=2.19, 95% CI:1.06-4.51) and independently from the APOE genotype. Multivariate logistic regression revealed an interaction between H5 and age. When the whole sample is considered, the H5a subgroup of molecules, harboring the 4336 transition in the tRNAGln gene, already associated to AD in early studies, was about threefold more represented in AD patients than in controls (2.0% vs 0.8%; p=0.031), and it might account for the increased frequency of H5 in AD patients (4.2% vs 2.3%). The complete re-sequencing of the 56 mtDNAs belonging to H5 revealed that AD patients showed a trend towards a higher number (p=0.052) of sporadic mutations in tRNA and rRNA genes when compared with controls. CONCLUSIONS: Our results indicate that high resolution analysis of inherited mtDNA sequence variation can help in identifying both ancient polymorphisms defining sub-haplogroups and the accumulation of sporadic mutations associated with complex traits such as AD

Hair Cortisol in Twins : Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

A. Palotie on työryhmän jäsen.Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.Peer reviewe

Valutare la valutazione per una teoria praticabile. Il Progetto di Inclusione dei bambini rom a Napoli

Questa tesi tratta del percorso valutativo partecipato del Progetto di inclusione dei bambini rom intrapreso a Napoli. La ricerca valutativa si è sviluppata a partire non da una riflessione teorica che ha trovato riscontro nella realtà, ma a partire dalla realtà, dai limiti imposti dal mandato professionale, dai vincoli economici e di risorse umane già posti a priori, dal contesto effettivo di lavoro, dalle contraddizioni interne ed esterne al progetto, per andare ad ancorarsi ad una riflessione teorica più ampia. Un percorso che si è sviluppato attraverso deviazioni imposte e scelte, mosso a tratti da motivazioni che con la teoria della valutazione hanno poco a che vedere, in cui sono stati definiti obiettivi e costruiti strumenti attraverso la negoziazione con molteplici attori e portatori di altrettanti significati e istanze, tornando indietro, commettendo errori e aggiustamenti, fino ad arrivare ad una riflessione che, a partire dall'esperienza in questo progetto, cerca di ancorare la realtà costruita ai modelli teorici che le sottendono, andando a cercare nella teoria un sostegno alle scelte fatte ma anche una risposta agli interrogativi nati strada facendo. Una sorta di dialogo tra realtà e teoria che vuole, a partire dalla riflessione critica del modello valutativo imposto a livello nazionale e dell'analisi del piano valutativo del Progetto locale di inclusione, riflettere e andare verso una teoria praticabile, che non resti lettera morta per quanto intrigante, ma sappia destreggiarsi tra le mille contraddizioni del reale senza perdere anima e coerenza