CONSIDERAZIONI E RICERCHE SU UN CALICE GOTICO VENDUTO ILLEGALMENTE A PIEMONTE D’ISTRIA

Tutte le guide turistiche che parlano del paese di Piemonte d’Istria menzionano un prezioso calice sacro di epoca medievale che fu venduto dal parroco del paese sul finire dell’Ottocento. Passato di mano in mano, il calice sarebbe arrivato ad un prezzo esorbitante nelle mani della facoltosa famiglia Rothschild. Alla notizia, scarsissima di dettagli, di nomi o di riferimenti cronologici certi, si è voluto dedicare una ricerca toriografica che tracciasse quanto più possibile l’accaduto.Svi turisticki vodici koji govore o mjestu Završje spominju dragocjeni sveti kalež iz srednjeg vijeka, kojeg je lokalni župnik prodao krajem 19. stoljeca. Nakon što je prošao kroz ruke raznih vlasnika, kalež je za prekomjernu cijenu dospio u vlasništvo bogate obitelji Rothschild. Za ovu vijest postoji vrlo malo detalja, imena i sigurnih kronoloških podataka. Stoga joj je posveceno historiografsko istraživanje kojim se željelo otkriti što više dogadaja i postaviti temelje za konacnu lokalizaciju dragulja. Osim možda najpoznatijeg bibliografskog izvora, knjige Istria Nobilissima Giuseppea Caprina, prouceni su i drugi tiskani materijali. Povijesno istraživanje se zatim bavilo i kontekstom u kojem je kalež dospio u Završje 1474. zahvaljujuci donaciji portugalskog kapetana Pietra Funesa koji je takoder uspostavio službu za održavanje jednog oltara i slavljenje mise jednom tjedno za vlastiti spomen. Prisutan stoljecima u crkvenim inventarima, kalež je postao predmet nelegalne prodaje oko 1880. Ono što je izazvalo negodovanje, pored nezakonitog djelovanja župnika, bila je i niska prodajna cijena koja je naglo porasla nakon što se predmet pojavio na medunarodnom tržištu umjetnina. Polazeci od pretpostavke da tako dragocjeni predmet ne može proci neopaženo, istražene su arhive nekoliko velikih medunarodnih muzeja, u potrazi za svetim kaležem ciji izgled odgovara opisima

CONSIDERAZIONI E RICERCHE SU UN CALICE GOTICO VENDUTO ILLEGALMENTE A PIEMONTE D’ISTRIA

Tutte le guide turistiche che parlano del paese di Piemonte d’Istria menzionano un prezioso calice sacro di epoca medievale che fu venduto dal parroco del paese sul finire dell’Ottocento. Passato di mano in mano, il calice sarebbe arrivato ad un prezzo esorbitante nelle mani della facoltosa famiglia Rothschild. Alla notizia, scarsissima di dettagli, di nomi o di riferimenti cronologici certi, si è voluto dedicare una ricerca toriografica che tracciasse quanto più possibile l’accaduto.Svi turisticki vodici koji govore o mjestu Završje spominju dragocjeni sveti kalež iz srednjeg vijeka, kojeg je lokalni župnik prodao krajem 19. stoljeca. Nakon što je prošao kroz ruke raznih vlasnika, kalež je za prekomjernu cijenu dospio u vlasništvo bogate obitelji Rothschild. Za ovu vijest postoji vrlo malo detalja, imena i sigurnih kronoloških podataka. Stoga joj je posveceno historiografsko istraživanje kojim se željelo otkriti što više dogadaja i postaviti temelje za konacnu lokalizaciju dragulja. Osim možda najpoznatijeg bibliografskog izvora, knjige Istria Nobilissima Giuseppea Caprina, prouceni su i drugi tiskani materijali. Povijesno istraživanje se zatim bavilo i kontekstom u kojem je kalež dospio u Završje 1474. zahvaljujuci donaciji portugalskog kapetana Pietra Funesa koji je takoder uspostavio službu za održavanje jednog oltara i slavljenje mise jednom tjedno za vlastiti spomen. Prisutan stoljecima u crkvenim inventarima, kalež je postao predmet nelegalne prodaje oko 1880. Ono što je izazvalo negodovanje, pored nezakonitog djelovanja župnika, bila je i niska prodajna cijena koja je naglo porasla nakon što se predmet pojavio na medunarodnom tržištu umjetnina. Polazeci od pretpostavke da tako dragocjeni predmet ne može proci neopaženo, istražene su arhive nekoliko velikih medunarodnih muzeja, u potrazi za svetim kaležem ciji izgled odgovara opisima

Combination quetiapine therapy in the long-term treatment of patients with bipolar I disorder

OBJECTIVE: Determine the long-term effectiveness of quetiapine in combination with standard treatments in preventing relapses for patients with bipolar I disorders METHOD: Twenty-one outpatients with type I bipolar disorder who had inadequate responses to ongoing standard therapies were treated with add-on quetiapine in an open-label study. The quetiapine dose was increased until clinical response occurred. Illness response was assessed using the Clinical Global Impression (CGI) scale. Relapse rates before and during quetiapine treatment were compared by calculating incidence risk ratios. RESULTS: Quetiapine was added to ongoing standard therapy for 26 to 78 weeks. Thirteen patients received combination therapy for at least 52 weeks. The mean quetiapine dose received was 518 ± 244 mg/day. There were highly significant improvements in overall relapse rate, manic/mixed relapse rate, and depression relapse rate in the period during quetiapine treatment compared with the period before quetiapine was initiated. The calculated relative risk of relapse in the absence of quetiapine treatment was 2.9 overall (95% confidence interval, 1.5~5.6), 3.3 for manic/mixed relapse (95% confidence interval, 1.5~7.1), and 2.4 for depressive relapse (95% confidence interval, 1.3~4.4). The mean Clinical Global Impression scores improved significantly from baseline during 26 weeks of quetiapine treatment in 21 patients (p = 0.002) and remained significantly better during a 52-week treatment period in 13 patients (p = 0.036). CONCLUSION: Long-term treatment with quetiapine combination therapy reduced the probability of manic/mixed and depressive relapses and improved symptoms in patients with bipolar I disorder who had inadequate responses to ongoing standard treatment

Fermentation of Microalgal Biomass for Innovative Food Production

Fermentation is an ancient method used worldwide to process and preserve food while enhancing its nutraceutical profile. Alga‐based fermented products have recently been developed and tested due to growing interest in healthy sustainable diets, which demands the development of innovative practices in food production, operating for both human health and Earth sustainability. Algae, particularly microalgae such as Arthrospira platensis, Chlorella vulgaris, and Dunaliella salina, are already cultivated as sources of food due to their valuable compounds, including proteins, pigments, lipids, carotenoids, polyunsaturated fatty acids, steroids, and vitamins. Due to their nutritional composition, functional diversity, and flexible metabolism, microalgae represent good fermentation substrates for lactic acid bacteria (LAB) and yeasts. This review presents an overview of the scientific studies on microalga fermentation underlining microalgae’s properties and health benefits coupled with the advantages of LAB and yeast fermentation. The potential applications of and future perspectives on such functional foods are discussed

The glycoside oleandrin reduces glioma growth with direct and indirect effects on tumor cells

Oleandrin is a glycoside that inhibits the ubiquitous enzyme Na(+)/K(+)-ATPase. In addition to its known effects on cardiac muscle, recent in vitro and in vivo evidence highlighted its potential for anticancer properties. Here, we evaluated for the first time the effect of oleandrin on brain tumors. To this aim, mice were transplanted with human or murine glioma and analyzed for tumor progression upon oleandrin treatment. In both systems, oleandrin impaired glioma development, reduced tumor size, and inhibited cell proliferation. We demonstrated that oleandrin does the following: (1) enhances the brain-derived neurotrophic factor (BDNF) level in the brain; (2) reduces both microglia/macrophage infiltration and CD68 immunoreactivity in the tumor mass; (3) decreases astrogliosis in peritumoral area; and (4) reduces glioma cell infiltration in healthy parenchyma. In BDNF-deficient mice (bdnftm1Jae/J) and in glioma cells silenced for TrkB receptor expression, oleandrin was not effective, indicating a crucial role for BDNF in oleandrin's protective and antitumor functions. In addition, we found that oleandrin increases survival of temozolomide-treated mice. These results encourage the development of oleandrin as possible coadjuvant agent in clinical trials of glioma treatment.SIGNIFICANCE STATEMENT In this work, we paved the road for a new therapeutic approach for the treatment of brain tumors, demonstrating the potential of using the cardioactive glycoside oleandrin as a coadjuvant drug to standard chemotherapeutics such as temozolomide. In murine models of glioma, we demonstrated that oleandrin significantly increased mouse survival and reduced tumor growth both directly on tumor cells and indirectly by promoting an antitumor brain microenvironment with a key protective role played by the neurotrophin brain-derived neurotrophic factor

Quetiapine as add-on treatment for bipolar I disorder: efficacy in preventing relapse of depressive episodes

<p>Abstract</p> <p>Objective</p> <p>To assess the long-term response to add-on quetiapine therapy in patients with bipolar I disorder who were not adequately responding to standard medications.</p> <p>Methods</p> <p>Outpatients with bipolar I disorder (DSM-IV-TR) responding inadequately to standard treatment were observed before and after the addition of quetiapine. Symptom severity was evaluated using the Clinical Global Impressions scale for Bipolar Disorder (CGI-BP) each month. Relapses included hospitalization, treatment in a day hospital or clinic, scores ≥ 1 point higher than previous CGI-BP scores and/or upward titration of quetiapine or other medications.</p> <p>Results</p> <p>Sixty-one patients (age range of 18–68 years) were observed prospectively for an average of 7.5 months (range 3–18 months) prior to addition of quetiapine and subsequently followed for an average of 15.7 months (range 6–42 months). The final mean quetiapine dose was 537.1 ± 91.7 mg/d. Prior to quetiapine addition, an annual relapse rate of 2.09 episodes was recorded, relating to 0.94 depressive and 1.15 manic or mixed episodes. Following quetiapine addition, annual relapse rates were reduced to 0.61 episodes, representing 0.14 depressive and 0.46 manic or mixed episodes. Compared with the period of add-on quetiapine treatment, the relative risk of relapse <it>prior </it>to quetiapine therapy was 3.4 for all episodes (χ²= 24.8, <it>P </it>< 0.001), 6.7 for depressive episodes (χ²= 24.7, <it>P </it>< 0.001), and 2.5 for manic or mixed episodes (χ²= 9.0, <it>P </it>< 0.05).</p> <p>Conclusion</p> <p>This naturalistic follow-up study provides preliminary evidence for the efficacy of long-term add-on quetiapine treatment in the prevention of relapses of manic or mixed and depressive episodes of bipolar I disorder, and particularly in the prevention of depressive episodes.</p

Autophagy generates citrullinated peptides in human synoviocytes: a possible trigger for anti-citrullinated peptide antibodies

OBJECTIVES: Autophagy may represent a functional processing event that creates a substrate for autoreactivity. In particular, autophagy may play a role in the pathogenesis of RA, since autophagy is a key cellular event involved in the generation of citrullinated peptides, with consequent breakage of tolerance. Thus, in RA, autophagy may be the common feature in several situations (including smoking, joint injury and infection) that may drive the adaptive responses to citrullinated self-proteins. The aim of this study was the analysis, in vitro, of the role of autophagy in the generation of citrullinated peptides and, in vivo, of the relationship between autophagy and the production of anti-CCP antibodies (Abs). METHODS: For autophagy induction, fibroblast-like synoviocytes, primary fibroblasts and monocytes were stimulated with tunicamycin or rapamycin. Peptidyl arginine deiminase activity was tested by enzyme-linked immunosorbent assay, and protein citrullination was evaluated by western blotting. The main citrullinated RA candidate antigens, vimentin, α-enolase and filaggrin, were demonstrated by immunoprecipitation. The relationship between autophagy and anti-CCP Abs was analysed in 30 early-active RA patients. RESULTS: Our results demonstrated in vitro a role for autophagy in the citrullination process. Cells treated with tunicamycin or rapamycin showed peptidyl arginine deiminase 4 activation, with consequent protein citrullination. Immunoblotting and immunoprecipitation experiments, using specific Abs, identified the main citrullinated proteins: vimentin, α-enolase and filaggrin. In vivo, a significant association between levels of autophagy and anti-CCP Abs was observed in treatment-naïve early-active RA patients. CONCLUSION: These findings support the view that the processing of proteins in autophagy generates citrullinated peptides recognized by the immune system in RA

Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice

Mice exposed to standard (SE) or enriched environment (EE) were transplanted with murine or human glioma cells and differences in tumour development were evaluated. We report that EE exposure affects: (i) tumour size, increasing mice survival; (ii) glioma establishment, proliferation and invasion; (iii) microglia/macrophage (M/Mφ) activation; (iv) natural killer (NK) cell infiltration and activation; and (v) cerebral levels of IL-15 and BDNF. Direct infusion of IL-15 or BDNF in the brain of mice transplanted with glioma significantly reduces tumour growth. We demonstrate that brain infusion of IL-15 increases the frequency of NK cell infiltrating the tumour and that NK cell depletion reduces the efficacy of EE and IL-15 on tumour size and of EE on mice survival. BDNF infusion reduces M/Mφ infiltration and CD68 immunoreactivity in tumour mass and reduces glioma migration inhibiting the small G protein RhoA through the truncated TrkB.T1 receptor. These results suggest alternative approaches for glioma treatment

Ca2+-activated K+ channels modulate microglia affecting motor neuron survivalin hSOD1G93A mice

Recent studies described a critical role for microglia in amyotrophic lateral sclerosis (ALS), where these CNS-resident immune cells participate in the establishment of an inflammatory microenvironment that contributes to motor neuron degeneration. Understanding the mechanisms leading to microglia activation in ALS could help to identify specific molecular pathways which could be targeted to reduce or delay motor neuron degeneration and muscle paralysis in patients. The intermediate-conductance calcium-activated potassium channel KCa3.1 has been reported to modulate the "pro-inflammatory" phenotype of microglia in different pathological conditions. We here investigated the effects of blocking KCa3.1 activity in the hSOD1G93AALS mouse model, which recapitulates many features of the human disease. We report that treatment of hSOD1G93A mice with a selective KCa3.1 inhibitor, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), attenuates the "pro-inflammatory" phenotype of microglia in the spinal cord, reduces motor neuron death, delays onset of muscle weakness, and increases survival. Specifically, inhibition of KCa3.1 channels slowed muscle denervation, decreased the expression of the fetal acetylcholine receptor γ subunit and reduced neuromuscular junction damage. Taken together, these results demonstrate a key role for KCa3.1 in driving a pro-inflammatory microglia phenotype in ALS

Preliminary Validation of the CI-FRA Checklist: A Simple Screening Tool for Measuring the Early Signs of Reading and Spelling Disorders in Italian Primary Students

Although several screening tests for recognizing early signs of reading and spelling difficulties have been developed, brief and methodologically grounded tools for teachers are very limited. The present study aimed to lay the foundation for a new screening tool for teachers: the Checklist for early Indicators of risk Factors in Reading Ability (CI-FRA). The proposed checklist consists of 20 items, based on a 7-point Likert scale, and it investigates five domains: reading, writing, attention, and motor skills. Six hundred sixtyseven children were evaluated by 40 teachers during the first year of primary school and, longitudinally, in the second year. Exploratory factor analysis and confirmatory factor analysis (CFA) were applied to verify structural validity. Concurrent validity was assessed by Spearman correlation to analyze the link between CI-FRA and reading and spelling standardized tests and cognitive tests. Reliability was assessed by Cronbach a and interclass correlation coefficient. The CFA reported a three-factor structure as the optimal solution, including language (reading and writing), visuospatial attention, and fine motor skills subscales. Good reliability, good internal consistency, and acceptable test\u2013 retest indices were found. Concurrent validity was confirmed by significant correlations between CI-FRA total score and standardized reading and spelling test, as well as by correlations between CI-FRA subscales and neuropsychological standardized test scores. Preliminary evaluation of sensitivity by receiver operating characteristic curves showed that the CI-FRA score has particularly high sensitivity and specificity for word reading speed deficit. In conclusion, the results confirm that CI-FRA is a theoretically grounded and statistically valid tool that could help the teachers to screen for early signs of reading and spelling difficulties