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Background: Vitamin D deficiency has been associated with dry eye development during Sjögren’s syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. Methods: 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C−) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). Results: The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C−), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. Conclusions: Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye.

The author analyses the European souls starting from the documents of his first conceptualization: the Ventotenemanifesto to touch on the problems of the European political crisis and fundamental rights, L’autore analizza le diverse anime europee a partire dal documento della sua prima concettualizzazione: ilmanifesto di Ventotene sino a toccare i problemi della crisi politica europea e dei diritti fondamentali

The essay studies the construction of the concept of jurist in Emilio Betti as an organic representative of society. He is not a political representative, with or without mandate constraint, nor a legal representative, who transfers interests and relates them. The organic representative is a longa manus, an authoritative extension of the best of society. Its authority, disregarding political power, can reconcile the interests at stake, say the law with the sentence, rebalancing social imbalances, which can also be caused by the laws themselves. The function of social rebalancing combined with equity understood not only as formal but substantial justice makes Betti’s theoretical tension a methodological tool possible for all the sciences of knowledge and also for the associated life in the footsteps of Aristotle’s Nicomachean Ethichs, Politics and Rhetoric. The decision-making choice of the jurist emerges as one of the most relevant legal issues of our time, that of due process. Its necessary solution, both on the level of the legislation of each state, and on the level of all the individual narratives of each procedural event, can find solid references in Betti’s Romanesque studies, starting from those on the seven Kings of Rome, up to those on the Roman praetor. It makes possible to distinguish the gnoseological and thoughtful decision-making of the jurist from that which puts an end to the state of exception of the politician theorized by Carl Schmitt. And it also makes allows to distinguish a logic based on a broad ethical and cultural vision of society, from a logic emptied of deontology and based only on syllogistic argumentation, in which the means can replaces the end., L’articolo studia la costruzione concettuale del giurista in Emilio Betti come un rappresentante organico della società. Non è un rappresentante politico, con o senza vincolo di mandato, né un rappresentante legale, che trasferisce interessi e li relaziona. Il rappresentante organico è una longa manus, un’estensione autorevole del meglio della società. La sua autorevolezza, disinteressandosi del potere politico, può contemperare gli interessi in gioco, dire il diritto con la sentenza, riequilibrando gli squilibri sociali, provocati anche dalle stesse leggi. La funzione di riequilibrio sociale, capace di coniugarsi con l’equità, nella potenzialità di quest’ultima di porsi non solo come giustizia formale, ma sostanziale, è ciò che rende capace la tensione teoretica bettiana di divenire strumento metodologico possibile per tutte le scienze del sapere, ma anche per la vita associata, sulle orme dell’Etica nicomachea, della Politica e della Retorica di Aristotele. La scelta decisionale del giurista emerge come una delle più rilevanti questioni giuridiche del nostro tempo, quella del giusto processo. La sua soluzione necessaria, sia sul piano della legislazione di ciascuno stato, sia sul piano di tutte le singole narrazioni di ciascuna vicenda processuale, può trovare riferimenti solidi negli studi romanistici di Betti, a partire da quelli sui Sette Re di Roma, fino a giungere a quelli sul Pretore romano. Permette di distinguere il decisionismo gnoseologico e ponderato del giurista da quello che mette fine allo stato d’eccezione del politico, teorizzato da Carl Schmitt. E permette anche di distinguere una logica fondata su una visione etica e culturale ampia della società, da una logica svuotata di deontologia e fondata soltanto sull’argomentazione sillogistica, nella quale il mezzo può sostituire il fine. &nbsp

Purpose. To evaluate the efficacy of intravitreal dexamethasone implant (DEX) for the treatment of macular oedema secondary to vitrectomy for epiretinal membrane (ERM) and retinal detachment (RD) by conducting a systematic review with meta-analysis of published studies. Methods. Studies reporting clinical outcomes of DEX use for the treatment of macular oedema secondary to ERM and RD vitrectomy were searched on PubMed and Embase databases. The primary outcome was best-corrected visual acuity (BCVA) change between baseline and post-DEX treatment, reported as mean difference (MD) with 95% confidence interval (CI). Mean central macular thickness (CMT) change was assessed as a secondary outcome. Postimplant adverse events, including intraocular pressure rise and cataract development, were reported as well. Results. Five uncontrolled studies, 1 nonrandomized controlled study, and 1 randomized controlled study were included, with a total of 5 cohorts and 3 cohorts in the ERM group and RD group, respectively. Considering the last available follow-up, a significant improvement in postimplant BCVA was found in the overall population, irrespective of the indication for vitrectomy (MD = −0.28, 95% CI = −0.37, −0.20; p

Sono fonti imprescindibili dell’ermeneutica giuridica bettiana le contaminazioni tra gli studi di Friedrich Schleiermacher e Friedrich Carl Savigny. Lo si coglie soprattutto se si tiene conto del think tank voluto da Friedrich von Humboldt, che vide i due pensatori intorno allo stesso tavolo all’Accademia delle Scienze di Berlino dal 1810 al 1835. La peculiarità della teoria generale ermeneutica bettiana, proprio riconsiderando la costruzione concettuale delle fonti, si rivela pienamente, nella sua essenza di metodologia giuridicoermeneutica, fruibile per tutti i campi del sapere. The contamination between the studies of Friedrich Schleiermacher and Friedrich Carl Savigny are essential sources of the bettian legal hermeneutics. This is especially true when one takes into account the think tank wanted by Friedrich von Humboldt, who saw the two thinkers around the same table at the Academy of Sciences in Berlin from 1810 to 1835. The peculiarity of the general Bettian hermeneutic theory, precisely by reconsidering the conceptual construction of the sources, is fully revealed in its essence of legal-hermeneutic metodology, usable for all fields of knowledge.

Legal positivism of modernity, built on the will of the legislature, today is interesting, considering its differences with the logical legal positivism, because it is based on a political decision. Because of its construction on willed decision, is intertwined with the need a constant recourse to the courts of justice to settle questions pre or post legal, reguarding radical anthropological or existential problems of one man or of the whole policy society. The Swedish example can be used as an important model for understanding where a possible corrective methodology legal-hermeneutics of the high courts of justice is going. It also helps to better understand the recent security legislations, in some countries - including European countries - against terrorism, without any opposition of national and supranational political and legal systems. Key words: Legal-positivism of modernity, Legal-hermeneutics, Security state. Riassunto Il positivismo giuridico della modernità, costruito sulla volontà del legislatore, trova nuovo interesse, se considerato nelle sue differenze con il positivismo giuridico logico, proprio per il suo affondare le radici nella decisione politica. Il suo fondamento volitivo-decisionista lo vede intrecciarsi con la necessità odierna del ricorso costante alle Corti di Giustizia per risolvere questioni pre-giuridiche o post-giuridiche, attinenti, per esempio, a radicali problematiche antropologiche o esistenziali di soggetti singoli, ma anche di intere società politiche. L'esempio svedese si rivela modello di forte rilievo per cogliere fino in fondo la direzione di senso della metodologia giuridico-ermeneutica correttiva possibile delle alte Corti di Giustizia, ma anche per comprendere fino in fondo, dal punto di vista giuridico oltre che politico, il recente ricorso da parte di alcuni stati, anche europei, a legislazionidi sicurezza contro il terrorismo, senza resistenza da parte degli ordinamenti giuridico-politici nazionali e sovranazionali. Parole chiave: Positivismo giuridico della modernità, ermeneutica giuridica, sicurezza dello Stato, Società e diritti, V. 1, N. 2 (2016): Diritto: dalla forma alla struttura

Legal positivism of modernity, built on the will of the legislature, is today an interesting issue, considering its differences with logical legal positivism, because it is based on a political decision. Being constructed on a willed decision, it is intertwined with the need for constant recourse to the courts of justice to settle pre- or post- legal questions, regarding radical anthropological or existential problems of one individual or of the whole society. The studies on legal decision-making help us also to better understand recent security legislation, in some countries - including European countries - against terrorism, without any opposition from national and supranational political and legal systems.

The content relating to the protection of the landscape in the planning tools are not alwais set according to a plan for convergence and synergies. In the paper the following possible solution aimed at activating unifying process to the overall territorial variables, including rural.

The plans for sustainable development and the role of the parks. The involvement of the population in the management, protection and enhancement of the territory. The development of rural areas and the action of the park.

For a qualitative leap in the processes of land reorganization, the territory and the community should be regarded as part of an information process through which the human capital deploys all its potential (information society). As a natural consequence, a new identity can be sketched as territory-community-development, resting upon the capability to absorb, process and transfer knowledge for a participated representation of reality, that is reality proposes itself as a social construction synthetically mirrored in a text-project. In this paper we tried essentially to propose some solutions to identify the models needed to match programmatic 'agreements' and linguistic 'agreements'. The aim is twofold: 1) to implement land reorganization through a semeiotic design in order to plan a path whereby individual needs and interests can comply with community needs and interests; 2) on account of the sustainability prerequisite, to allow innovation and conservation to coexist in the town centre in order to respond more effectively to the growing and ever more urgent needs of population.

Background: Vitamin D deficiency has been associated with dry eye development during Sjögren’s syndrome (SS). Here, we investigated whether repeated oral vitamin D3 supplementation could prevent the corneal epithelium damage in an SS mouse model. Methods: 30 female mouse knock-out for the thrombospondin 1 gene were randomized (six per group) in untreated mice euthanized at 6 weeks as negative control (C−) or at 12 weeks as the positive control for dry eye (C+). Other mice were sacrificed after 6 weeks of oral vitamin D3 supplementation in the drinking water (1000, 8000, and 20,000 IU/kg/week, respectively). Results: The C+ mice showed alterations in their corneal epithelial morphologies and thicknesses (p < 0.01 vs. C−), while the mice receiving 8000 (M) and 20,000 (H) IU/kg/week of vitamin D3 showed preservation of the corneal epithelium morphology and thickness (p < 0.01 vs. C+). Moreover, while the C+ mice exhibited high levels and activity of corneal tumor necrosis factor alpha converting enzyme (TACE), neovascularization and fibrosis markers; these were all reduced in the M and H mice. Conclusions: Oral vitamin D3 supplementation appeared to counteract the negative effect of TACE on corneal epithelium in a mouse model of SS-associated dry eye.

The aim of this study was to investigate the effects of the lipid mediator Resolvin D1 in experimental keratitis. C57BL/6J mice were injected with lipopolysaccharide (2 µg/eye), and after 24 hours, the corneal damage was assessed. Clinical score was quantified, and corneal inflammatory biomarkers were detected by immunohistochemistry. A robust accumulation of sub‐epithelial macrophages and polymorphonuclear leucocytes, chemokine (C‐X‐C motif) ligand 1 (also known as keratinocyte‐derived chemokine), interleukin‐10 and promoters of apoptosis was also observed in lipopolysaccharide‐treated mice. Formyl peptide receptor 2 corneal expression was also assessed. The corneal stroma treated with lipopolysaccharide was characterized by presence of macrophages of M1‐like subtype and immature fibroblastic cells, marked with Ki67, not fully differentiated in fibroblasts. Indeed, the staining of the cornea with anti‐vimentin antibodies, a marker of differentiated myofibroblasts, was very faint. Resolvin D1 attenuated all the inflammatory parameters assessed in the present study, except for IL‐10. In conclusion, the data presented here seem to be consistent with the hypothesis that Resolvin D1 protected the cornea from the lipopolysaccharide‐induced keratitis by acting on several inflammatory components of this damage, pivoted by Formyl peptide receptor 2 (FPR2) activation and macrophages‐leucocytes activity.

Topical administration is the most convenient route for ocular drug delivery, but only a minor fraction is retained in the precorneal pocket. To overcome this limitation, numerous drug delivery systems (DDS) have been developed. The protein corona (PC) is the layer of biomolecules (e.g., proteins, sugars, lipids, etc.) that forms around DDS in physiological environments by non-covalent interaction. The PC changes the DDS physical–chemical properties, providing them with a completely novel biological identity. The specific involvement of PC in ocular drug delivery has not been addressed so far. To fulfill this gap, here we explored the interaction between a library of four cationic liposome-DNA complexes (lipoplexes) and mucin (MUC), one of the main components of the tear film. We demonstrate that MUC binds to the lipoplex surface shifting both their size and surface charge and reducing their absorption by primary corneal epithelial cells. To surpass such restrictions, we coated lipoplexes with two different artificial PCs made of Fibronectin (FBN) and Val-Gly-Asp (VGA) tripeptide that are recognized by receptors expressed on the ocular surface. Both these functionalizations remarkedly boosted internalization in corneal epithelial cells with respect to pristine (i.e., uncoated) lipoplexes. This opens the gateway for the exploitation of artificial protein corona in targeted ocular delivery, which will significantly influence the development of novel nanomaterials.