NGF modulates trkANGFR/p75NTR in αsMA-expressing conjunctival fibroblasts from human ocular cicatricial pemphigoid (OCP)

OBJECTIVE: In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkANGFR expression in Ocular Cicatricial Pemphigoid (OCP), an inflammatory and remodeling eye disease. Herein, we hypothesize a potential NGF-driven mechanism on fibroblasts (FBs) during OCP remodeling events. To verify, human derived OCP-FBs were isolated and characterized either at baseline or after NGF exposure. MATERIALS AND METHODS: Conjunctival biopsies were obtained from 7 patients having OCP and 6 control subjects (cataract surgery). Both conjunctivas and primary FB cultures were characterised for αSMA, NGF and trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for αSMA, NGF, trkANGFR/p75NTR expression as well as TGFβ1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. RESULTS: OCP-conjunctivas showed αSMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher αSMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. αSMA expression was in keeping with disease severity and correlated to p75NTR. NGF exposure did not affect trkANGFR levels in early OCP-FBs while decreased both αSMA/p75NTR expression and TGFβ1/IL4 release. These effects were not observed in advanced OCP-FBs. CONCLUSIONS: Taken together, these data are suggestive for a NGF/p75NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75NTR might be viewed as a potential therapeutic target

Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva

Purpose: To evaluate the role of nerve growth factor (NGF) in remodeling processes of vernal keratoconjunctivitis (VKC). VKC is a chronic inflammatory disorder of the conjunctiva and is characterized by marked tissue remodeling. NGF, a pleiotrophic factor with documented profibrogenic activities, is produced by inflammatory and structural cells populating the VKC conjunctiva and is increased in the serum and tears of VKC patients.Methods: Primary cultures of VKC-derived fibroblasts (VKC-FBs) were exposed to increasing NGF concentrations (1500 ng/ml) to evaluate and compare the expression of alpha-smooth muscle actin (alpha SMA, a defining myofibroblast marker), collagens (types I and IV), and metalloproteinases and tissue inhibitors (MMP9/TIMP1, MMP2/TIMP2) at the biochemical as well as molecular levels.Results: Endogenous NGF was increased in the VKC-FB supernatant, as compared to healthy-FB supernatant. VKC-FBs expressed aSMA and increased types I and IV collagens. VKC-FBs, and in particular all aSMA positive cells, expressed both trkA(NGFR) and p75(NTR), while healthy-FBs only expressed trkA(NGFR). Exogenous NGF did not change aSMA expression, while aSMA expression was enhanced by specific neutralization of p75(NTR). NGF (10 ng/ml) exposure significantly decreased type I collagen expression, without affecting type IV collagen, and increased MMP9mRNA and protein.Conclusions: The autocrine modulation of differentiation and response of VKC-FBs to NGF exposure with downregulation of type I collagen and upregulation of MMP9 expression supports a relevant role for NGF in tissue remodeling of VKC

Age-Related Changes to Human Tear Composition.

Purpose We characterize age-associated alterations in the expression of inflammatory mediators and tissue remodeling factors in human tears. Methods A total of 75 consecutive volunteers (32 male/44 female; 19-93 years) underwent clinical assessment of ocular surface status, ocular surface disease index (OSDI) grading and tear sampling. The volunteers were categorized into three groups: young (18-40 years), middle-aged (41-60 years), and old (>60 years). Total protein profiles and chip-based protein array evaluations were conducted to investigate the expression of 60 potential candidates, including pro-/anti-inflammatory mediators and tissue remodeling factors. Appropriate validations were performed using conventional assays. Multiple comparisons for regression between potential candidates and age were performed, as well as statistical analyses among the three age groups. Nonpooled samples were used for quantifications. Results Pearson analysis of chip-arrays identified 9 of 60 potential candidates. Specifically, IL-8, IL-6, and regulated on activation, normal T cell expressed and secreted (RANTES; P < 0.0083) protein as well as matrix metalloproteinase (MMP)-1, IL-3, and TNF-α (P < 0.05) correlated positively with aging. MIP-3β showed an opposite tendency. Western blot and ELISA analysis corroborated the array data. OSDI grading did not correlate with aging. Conclusions Dynamic changes to tear protein profiles occur with aging. Our study identifies the expression of IL-8, IL-6, RANTES, MMP-1, and MIP-3β as increasing with age. These select inflammatory and matrix remodeling factors may be relevant to the development of novel diagnostic tools and therapeutics in the context of age-related ocular surface disease

Design strategies to improve patient motivation during robot-aided rehabilitation

BACKGROUND: Motivation is an important factor in rehabilitation and frequently used as a determinant of rehabilitation outcome. Several factors can influence patient motivation and so improve exercise adherence. This paper presents the design of two robot devices for use in the rehabilitation of upper limb movements, that can motivate patients during the execution of the assigned motor tasks by enhancing the gaming aspects of rehabilitation. In addition, a regular review of the obtained performance can reinforce in patients' minds the importance of exercising and encourage them to continue, so improving their motivation and consequently adherence to the program. In view of this, we also developed an evaluation metric that could characterize the rate of improvement and quantify the changes in the obtained performance. METHODS: Two groups (G1, n = 8 and G2, n = 12) of patients with chronic stroke were enrolled in a 3-week rehabilitation program including standard physical therapy (45 min. daily) plus treatment by means of robot devices (40 min., twice daily) respectively for wrist (G1) and elbow-shoulder movements (G2). Both groups were evaluated by means of standard clinical assessment scales and the new robot measured evaluation metric. Patients' motivation was assessed in 9/12 G2 patients by means of the Intrinsic Motivation Inventory (IMI) questionnaire. RESULTS: Both groups reduced their motor deficit and showed a significant improvement in clinical scales and the robot measured parameters. The IMI assessed in G2 patients showed high scores for interest, usefulness and importance subscales and low values for tension and pain subscales. CONCLUSION: Thanks to the design features of the two robot devices the therapist could easily adapt training to the individual by selecting different difficulty levels of the motor task tailored to each patient's disability. The gaming aspects incorporated in the two rehabilitation robots helped maintain patients' interest high during execution of the assigned tasks by providing feedback on performance. The evaluation metric gave a precise measure of patients' performance and thus provides a tool to help therapists promote patient motivation and hence adherence to the training program

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Le alleanze strategiche nel settore alberghiero: teorie interpretative ed evidenze empiriche

Negli ultimi anni, l’industria turistica ha conosciuto una crescita tendenziale e costante, che ha provocato bruschi cambiamenti tecnologici, una globalizzazione dei mercati, della concorrenza ed una maggiore velocità nella divulgazione delle informazioni. Tutto ciò ha contribuito a generare un contesto caratterizzato da elevata incertezza ed imprevedibilità, in cui la dinamica competitiva tende a trasformarsi rapidamente secondo modalità ed intensità di non semplice previsione e valutazione preventiva. E’ in quest’ambito che si stanno diffondendo alleanze strategiche tali da rendere il settore turistico come un network industry, in quanto caratterizzato dalla presenza di prodotti, il cui valore dipende dal valore delle singole componenti della filiera e dalla condivisione di risorse, che i vari attori riescono a realizzare. Da qui l’esigenza di allearsi sia a livello orizzontale, creando così catene alberghiere multi-unit, che possono godere di vantaggi: economici, finanziari, commerciali ed organizzativi; sia a livello verticale, per esempio con i tour operator, le agenzie di viaggio, le compagnie aeree o i cosiddetti fornitori di servizi turistici elementari, ottenendo vantaggi connessi alla maggiore flessibilità, alla distribuzione, alla programmazione dei prodotti turistici complessi ed alla destagionalizzazione del business alberghiero. Con specifico riferimento alle catene alberghiere, intese come alleanze strategiche orizzontali, una delle problematiche da affrontare è quella di scegliere una forma di governance idonea a garantire il raggiungimento di un vantaggio competitivo sostenibile. Le scelte di governo di una catena alberghiera possono spaziare da forme di tipo equity (catene proprietarie) o non-equity (franchising e management contract). In questo senso lo scopo del lavoro di ricerca è quello di rispondere a due quesiti fondamentali: 1. In funzione di quali variabili le catene alberghiere prediligono una particolare forma di governance (alleanze equity, in franchising e in management contract) per gestire gli alberghi della catena? 2. Come la struttura di governance prescelta tra i singoli alberghi della catena, influenza le alleanze strategiche con gli altri operatori del settore turistico? Per rispondere a queste domande l’approccio teorico sviluppato nel lavoro di ricerca combina la Transaction Cost Theory con la Resource-Based Theory. Dunque, la forma di governo delle catene alberghiere è determinata considerando congiuntamente le variabili degli approcci transaction cost e resource-based. Inoltre è stato esaminato, come la struttura di governance prescelta dalle catene alberghiere può influenzare la strategia dell’impresa. Ci si è soffermati sulla capacità delle singole strutture alberghiere, che compongono la catena, di realizzare alleanze locali o centralizzate con gli altri operatori della filiera turistica, in funzione della forma di governo adottata. In definitiva partendo dal background teorico descritto, l’obiettivo di fondo del progetto di ricerca è stato quello di fornire un quadro teorico delle scelte di sviluppo dimensionale collegate alle alleanze strategiche ed inoltre, individuare possibili interpretazioni ed approcci relativi ai processi di decisione, di gestione e sviluppo delle alleanze delle imprese del settore alberghiero. Ad un livello – normativo – la ricerca potrebbe essere di supporto e di suggerimento per alcune delle decisioni dei manager delle imprese alberghiere, in relazione alle alleanze poste in essere da queste ultime sia con altre strutture alberghiere, sia con gli altri operatori della filiera turistica

Integration management in networks’ value creation. An empirical analysis of high quality tourist offer in Southern Italy

The new competitive environment has generated an increasing recourse to cooperation in tourism, almost aimed at local development (Beccatini, 1991; Putman, 1993; Cappellin, 1998). Particularly, the paper will value the strategic elasticity and flexibility degree in inter-firms networks, and the advantage of taking part to a network, also in terms of systemic resources and competences (Gulati, Nohria, Zaheer, 2000; Gulati, 2007). This overview, starting from the typical resource-based theory (Barney, 1991) setting, is also its progress, because it gets reference to both “owned or controlled” resources and competences (Wernerfelt, 1984; Barney, 2002) by firms and to those anyway “available” for firms involved in a network (networks interactions and relationships). This is with the aim of developing offers able to create a higher total value than individual one, in a continuous interactive relationship with clients

Low cost airlines' Marketing choices. Some empirical cases.

This paper analyzes how Low Cost Airlines (LCA) choose marketing strategies and how they decide where to compete in the air transportation market. Liberalization has brought about numerous advantages to European travellers, both in terms of higher quality offered by airlines and drastic price reductions. However, one of the main and most interesting aspects of the free market has been the entry in the industry of LCA. Our main research hypothesis is to verify if some strategic resources for LCAs lie in their different marketing polices (product, price, promotion and placement) and in the way they are mixed. Therefore, this study is focused to analyze whether there is a significant difference in LCAs' strategies, with particular reference to product differentiation, price level and the choice of innovative channels in promoting places and products. A double level analysis is applied, through the case study method, to compare marketing strategies of the main LCAs in European airlines industry: 1) marketing choices and connected resources; 2) deep interviewing process to CEO/general managers/marketing managers, aimed at pointing out more hidden sources of competitive advantage, under completion