National Strategic Reference Framework Research Articles

0892 Insomnia and poor sleep efficiency predict cognitive decline among non-demented elderly: findings from the Cretan Aging Cohort

Abstract Introduction Previous cross-sectional studies have shown that insomnia symptoms and objective short sleep are associated with disease severity in patients with Mild Cognitive Impairment (MCI) and Dementia. Our aim was to examine the longitudinal associations between sleep quality/quantity with cognitive progression in non-demented community-dwelling elderly. Methods A sub-sample of 105 participants (77.5% females) from a large population-based cohort in Crete, Greece of 3,140 older adults (>60 years; baseline) were followed up 8 years later (follow-up). All participants underwent neuropsychiatric/neuropsychological evaluation on both phases. At baseline, subjective sleep complaints and objective sleep variables based on 3-day 24 hour actigraphy were assessed. The impact of baseline objective sleep characteristics and/or insomnia (as defined by at least two subjective sleep complaints) on cognitive progression was assessed with univariate and multivariate models controlling for confounders. Results At baseline 50 participants were diagnosed as CNI and 55 as MCI; at follow-up 60 participants (57.1%) displayed clinically significant cognitive deterioration while the remaining showed relatively stable cognitive status. The frequency of persons reporting insomnia symptoms at baseline was higher among those who displayed cognitive deterioration (31.7%) than those in the cognitively stable group (13.3%, p=0.037). Logistic regression analysis showed that participants with insomnia symptoms at baseline, were significantly more likely to deteriorate cognitively at follow-up (p=0.05, OR=2.90). Also, among objective sleep variables added to the model, it was poor sleep efficiency that was associated with cognitive deterioration (p=0.035, OR=3.48). Conclusion More than half of the participants displayed significant cognitive deterioration over 8 years and this decline was predicted by insomnia symptoms and objective poor sleep efficiency at baseline. Improving both quality and quantity of sleep may significantly delay the deterioration of cognitive function in non-demented community-dwelling elderly. Support (if any) National Strategic Reference Framework (NSRF) - Research Funding Program: THALES entitled “UOC-Multidisciplinary network for the study of Alzheimer’s Disease” Grant Cod: MIS 377299 HELLENIC FOUNDATION FOR REASEARCH AND INNOVATION (HFRI)- Research Funding Program: ELIDEK entitled “Sleep Apnea (OSA) and poor sleep as Risk Factors for decreased cognitive performance in patients with Mild Cognitive Impairment: the Cretan Aging Cohort (CAC)”, Grant Cod: HFR1-FM17-4397

0893 Long objective sleep duration is a marker of cognitive impairment among older elderly: findings from the Cretan Aging Cohort

Abstract Introduction We have previously shown that although sleep duration is similar between cognitively non-impaired (CNI) elders and patients with Mild Cognitive Impairment (MCI), long sleep duration is associated with disease severity in patients with multi-domain MCI and Dementia. Our aim was to examine the associations between sleep duration and cognitive status in subjects with CNI and MCI followed 8 years later. Methods A sub-sample of 110 participants (77.3% females) were recruited from a large population-based cohort in Crete, Greece of 3,140 older adults (>60 years). Participants with an initial diagnosis of CNI (n=57) and MCI (n=53) (mean age at baseline=72.7 years [SD=6.8]) were followed-up 8 years later (mean age at follow up=80.5 years [SD=6.7]). All participants underwent neuropsychiatric/neuropsychological evaluation (baseline & follow-up) and a 7-day 24h actigraphy (follow-up). Sleep duration measured as night Total Sleep Time (TST) at follow-up was compared between the diagnostic groups using ANCOVA controlling for age, gender, depression symptom severity, psychotropic medication. Long sleep duration was defined by values >75% percentile of the total sample distribution on each sleep index. Results At follow up 62.7% of participants have deteriorated cognitively with 29 being diagnosed with CNI, 49 with MCI and 32 with dementia. Patients with dementia had significantly longer night TST (mean=493, SD=106 min) than persons with MCI (mean=453, SD=68 min, p=0.05) who in turn had longer night TST than CNI participants (mean=409, SD=58 min, p=0.02). Also, long night sleep duration was significantly more prevalent among dementia patients and MCI compared to CNI individuals [67.7% vs. 36.7% vs. 10.3%, respectively; all p< 0.02)]. Conclusion Our study confirms and expands previous findings that objective long sleep duration is a marker of worse cognitive status in elderly with MCI or Dementia and that this association is even stronger in old-old individuals. Support (if any) National Strategic Reference Framework (NSRF)-Research Funding Program: THALES entitled “UOC-Multidisciplinary network for the study of Alzheimer’s Disease” Grant Cod: MIS 377299 HELLENIC FOUNDATION FOR REASEARCH AND INNOVATION (HFRI)- Research Funding Program: ELIDEK entitled “Sleep Apnea (OSA) and poor sleep as Risk Factors for decreased cognitive performance in patients with Mild Cognitive Impairment: the Cretan Aging Cohort (CAC)”, Grant Cod: HFR1-FM17-4397

On stochastic aspects of impact modeling of the innovation incentive system and business internationalization: evidence from Portuguese SMEs

Multivariate normal distribution is base for many statistical techniques, including ordinary least square inference. Here we show that in order to make research on Internationalization of Companies, more flexible approach is needed, namely partial least squares (PLS). It is a nonparametric technique, used in Structural Equation Modeling (SEM), which makes no distributional assumptions and also may be applied with small sample sizes. In this study we discuss on regularity conditions for PLS from the perspective of semi-continuous covariance which fills the gap in the current studies. The stochastic aspects, especially those related to usage of PLS-SEM, can be well integrated to the topologically grounded regression, where jumps in the covariances can occur. The purpose of the research is to analyze and understand the impact of the Incentive System (IS) for Innovation, within the scope of the National Strategic Reference Framework (QREN) 2014-2020, on the Internationalization of Portuguese Small and Medium Enterprises (SMEs). We study stochastic aspects of theoretical model which aggregates the variables Product Innovation, Marketing Innovation, Organizational Innovation and Working Conditions as determinants of Internationalization of Companies. Data were collected based on a quantitative methodology, through a self-completion questionnaire using the Likert psychometric scale, which registered 120 participants. Organizational Innovation (exogenous latent construct) and Product Innovation have shown a statistically significant indirect effect on the Internationalization of Companies (endogenous latent construct) through Marketing Innovation. The latter has a direct effect on the Internationalization (target construct). However, Working Conditions has the greatest impact on Internationalization, meaning that measures such as increasing wages, decreasing the use of temporary work and precarious work conversion into labor effective relations have a very relevant direct effect on the Internationalization of Portuguese SMEs.

P10.23.B Polycystin-1 induces mechanotransduction pathways in gioblastoma cells under hydrostatic pressure

Abstract Background Increased mechanical load and stiffness of the tumor microenvironment are key features during progression of gliomas. Polycystin-1 (PC1) is a mechanosensitive protein which perceives extracellular mechanical cues. The aim of the study was to investigate PC1 participation in mechanisms of glioblastoma (GBM) progression under a mechanically-induced microenvironment. Material and Methods We generated monolayer cell cultures and tumor spheroids of the T98G glioblastoma cell line. Cells were subjected to continuous hydrostatic pressure (HP), inhibition of PC1 mechanical perception through functional blockage of its extracellular domain, and silencing of PKD1 expression. The level of activation of PC1 mechano-induced downstream kinases (mTOR, ERK, FAK) and transcription factors (YAP, TAZ) was evaluated via Western blot at specific time-points. Functional assays were performed to assess cell proliferation, clone formation, and cell migration. qPCR was employed to quantify the mRNA expression of markers regarding certain traits of cancer cells. Results In monolayer cell cultures, PC1 functional inhibition under HP is associated with mTOR and ERK activation and elevated expression of TAZ. On the other hand, PKD1 knockdown under HP is associated with activation of FAK, but not mTOR or ERK. In tumor spheroids, PC1 inhibition acts in synergy with HP to activate FAK and upregulate YAP, but not ERK or mTOR. PC1 inhibition under HP is associated with compact 3-dimensional spheroid structures. PC1 inhibition acts in synergy with HP to suppress cell proliferation, clone formation, and cell migration in GBM cells. The same synergistic effect is observed on the expression of respective markers of apoptosis, angiogenesis, proliferation, and epithelial-to-mesenchymal transition of GBM cells. Conclusion PC1 seems to be able to sense applied mechanical forces in GBM cells by regulating the activity of downstream molecules and enhance certain traits of tumor promotion. This work was co-financed by Operational Programme “Human Resources Development, Education and Lifelong Learning”, National Strategic Reference Framework (NSRF) 2014-2020, Ministry of Economy and Development, Greece & European Union (European Social Fund (ESF), in the context of the project “Investigation of the role of polycystin proteins in glioma neoplastic cells”; Grant/Award Number: MIS 5047967

0636 Objective sleep as a predictor of cognitive decline among non-demented elderly: preliminary results from the Cretan Aging Cohort

Abstract Introduction Sleep disturbances have been linked with cognitive decline and previous cross-sectional have shown that long sleep duration is a marker of disease severity in patients Mild Cognitive Impairment (MCI) and Dementia.Our aim was to examine the longitudinal associations between sleep quantity and quality indices and cognitive progression in non-demented community-dwelling elderly. Methods A sub-sample of 62 participants (72.6% females) were recruited from a large population-based cohort in the island of Crete, Greece of 3,140 older adults (>60yrs). Participants were followed-up 8 years later (phase III). All participants underwent neuropsychiatric/neuropsychological evaluation (phases II & III) and a 3-day 24h actigraphy (phase II).Participants were diagnosed as CNI(N=38) and MCI(N=24) during phase II, and CNI (N=22), MCI (N=27) and Dementia (N=13) during phase III. On follow-up, 28 participants progressed to a cognitively declined diagnosis compared to phase II (deteriorated group), while 34 did not (non-deteriorated group). Objective sleep variables at phase II were compared between the deteriotated/non-deteriorated groups using ANCOVA controlling for confounders. Also, differences in neuropsychological testing scores (phase II- phase III) were calculated and associations of differences with sleep variables were examined using partial correlation models controlling for confounders. Results The deteriorated group compared to non-deteriorated had significantly longer night total sleep time (TST) (442±72.6min vs. 407±53.6min, p=0.033), 24h-TST (484±8.9min vs. 434±66.4min, p=0.008), night time in bed (TMB) (537±78.7min vs. 497±62.7min, p=0.03), and 24h-TMB (603±85min vs. 539±85min, p=0.005). Episodic memory worsening was moderately correlated with night TST (r=.316), night and 24h-TMB (r=.526, and r= .442 respectively), wake time after sleep onset (r=.351), and average duration of night awakenings (r=.405). Immediate episodic memory recall decline was positively correlated with night TMB (r=.338). Conclusion Preliminary results from the Cretan aging cohort indicate that almost half of the participants deteriorated cognitively in 8 years and this decline was predicted by objective sleep duration at baseline. Long sleep at baseline may predict deterioration of clinical cognitive status in non-demented elderly at follow-up. It appears that prolonged objective sleep duration and time in bed are novel and clinically useful prognostic factors of cognitive deterioration in elderly with or without cognitive deficits. Support (If Any) National Strategic Reference Framework (NSRF) - Research Funding Program: THALES entitled “UOC-Multidisciplinary network for the study of Alzheimer’s Disease” Grant Cod: MIS 377299HELLENIC FOUNDATION FOR REASEARCH AND INNOVATION (HFRI)- Research Funding Program: ELIDEK entitled “Sleep Apnea (OSA) and poor sleep as Risk Factors for decreased cognitive performance in patients with Mild Cognitive Impairment: the Cretan Aging Cohort (CAC)”, Grant Cod: HFR1-FM17-4397

369 Insomnia with objective short sleep duration is associated with increased cortisol in patients with Mild Cognitive Impairment

Abstract Introduction Mild cognitive impairment (MCI) is frequent in the elderly and is in a continuum with dementia in a significant amount of people. Both insomnia and increased cortisol levels have been suggested as risk factors for MCI. The goal of this study was to examine whether activation of the hypothalamic-pituitary-adrenal (HPA) axis, as measured by plasma cortisol levels, is associated with the insomnia with short sleep duration (ISS) phenotype, as measured by actigraphy, in elderly with MCI. Methods A sub-sample of 109 subjects with MCI and 92 cognitively non-impaired controls 60 years or older (75.37±6.54y) was recruited from a population-based cohort residing on Crete, Greece. Subjects underwent medical history, physical examination, neuropsychiatric evaluation, neuropsychological testing, 3-day 24-h actigraphy, assessment of subjective insomnia symptoms (i.e., difficulties initiating and/or maintaining sleep), and a morning blood draw to assay for plasma cortisol levels. The ISS phenotype was defined by the presence of at least one insomnia symptom and an actigraphy-measured sleep efficiency below the median of the entire sample (i.e., ≤81%). Group differences in plasma cortisol levels between MCI subjects with and without the ISS phenotype were tested using ANCOVA adjusting for age, gender, BMI and depression. Results Subjects with MCI had higher cortisol levels compared to controls (105.34±9.34 vs. 70.3±10.02 nmol/L, p<0.05). Subjects with MCI and the ISS phenotype (138.38±16.57 nmol/L) had significantly higher cortisol levels compared to those without insomnia (97.74±19.68 nmol/L) or those with insomnia and normal sleep duration (INS; 79.97±16.02 nmol/L, p=0.044). The association between the ISS phenotype and cortisol levels was modified by amnestic symptoms (p-interaction=0.079); commensurate, the ISS phenotype was associated with higher cortisol levels among the amnestic MCI subgroup (INS: 79.12±21.93 vs. ISS: 155.55±20.40 nmol/L, p=0.040), but not among the non-amnestic MCI subgroup (INS: 64.06±23.62 vs. ISS: 89.33±29.00 nmol/L, p=0.559). Conclusion The ISS phenotype is associated with increased cortisol levels in elderly with MCI, particularly those with amnestic type. Improving sleep quality, decreasing cortisol levels and lengthening sleep duration may slow down the progression of these individuals into dementia. Support (if any) National Strategic Reference Framework(NSRF), Program: THALES entitled “UOC-Multidisciplinary network for the study of Alzheimer’s Disease” Grant Cod:MIS 377299

Agritourism entrepreneurship in Greece: policy framework, inhibitory factors and a roadmap for further development

Purpose: This paper aimed to examine how agritourism as a mild form of tourism can contribute to sustainable tourism development. Research methodology: A primary survey was conducted using a closed-type questionnaire of multiple-choice questions and sent to a respective enterprise sample. Results: The survey's output refers to the steps and measures that need to be taken for the further development of agritourism in Greece and its driving force as a pillar of sustainability growth. Limitations: The research addressed certain methodological issues, such as the difficulty of collecting the sample, since agritourism companies are not in total registered in Greece. There was also difficulty obtaining contact details (email, fax) from the list of final approved investments of the National Strategic Reference Framework. Contribution: The purpose is to present the views of agritourism entrepreneurs on their industry and identify the possible problems they encountered during their businesses' start-up and operation due to the legal or financial framework. Also, the state's role in this direction is examined and proposals are made for the further development of agritourism in Greece. Keywords: Farmer, Law 4276/2014, Legal framework of agritourism, National strategic reference framework, Rural tourism, State aid, Sustainable development

The Use of National Strategic Reference Framework Data in Knowledge Graphs and Data Mining to Identify Red Flags

Red Flags in fiscal projects are warning signs that may indicate underlying problems with their implementation. In this paper, we present how National Strategic Reference Framework Open Data can be used to take full advantage of semantic web technologies and data mining techniques to build a knowledge-based system that identifies Red Flags. We collected the data from the Open Data API provided by the Greek Ministry of Economy and Finance. Data modeling consist of two ontologies; the Vocabulary of Fiscal Projects, describing the fiscal projects and the National Strategic Reference Framework Greece Vocabulary, illustrating the Greek National Strategic Reference Framework data. We transformed the data into RDF triples and uploaded them onto an OpenLink Virtuoso Server, so that we could retrieve them via SPARQL queries. Performance indicators were defined to assess the state of the project and Density-Based Spatial Clustering of Applications with Noise, (DBSCAN) was used to identify Red Flags. User’s demands is that rejected projects should raise Red Flags, to avoid project failure and assist the auditor to organize the monitoring process efficiently, by avoiding to examine most of the non-problematic projects. We performed a use case scenario in which an auditor has to examine NSRF projects, approximately 12 months before the end of the programming period. The system retrieved the fiscal information, calculated the performance indicators and identified the Red Flags. The last update of the projects status after the end of the programming period was retrieved and extracted the number of rejected projects, to test whether the user requirements are satisfied. Rejected projects consist of 3.8% of the total projects. The results of the use case scenario show that RedFlags platform is more likely to identify project failures and not raise Red Flags on not rejected projects. Therefore, the RedFlags platform using open data, assists the auditor to organize the monitoring process better.

Nucleolin-SLe <sup>A</sup> Glycoforms as E-Selectin Ligands and Potentially Targetable Biomarkers at the Cell Surface of Gastric Cancer Cells

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide, with half of patients developing metastases within 5 years after treatment, urging the need for novel biomarkers for diagnosis and more efficient therapeutic targeting. The sialyl-Lewis A (SLeA) antigen, a terminal glycoepitope of glycoproteins and glycolipids, offers tremendous potential towards this objective. This glycan is rarely expressed by healthy tissues and blood cells but is often present in cancer cells of high metastatic potential, as well as in the metastases. The SLeA antigen is also directly involved in E-selectin mediated metastasis, making it an ideal target to control disease dissemination. To improve further on cancer specificity, we have zoomed in on the SLeA-glycoproteome of six distinct GC cell models. Emphasis was set on glycoproteins showing affinity for E-selectin. A bioinformatics-assisted algorithm, used for the first time in this study, identified nucleolin (NCL), a nuclear protein frequently observed at the cell-surface in cancer cells, as a potential targetable biomarker potentially involved in metastasis development. Several immunoassays, including western blot and in situ proximity ligation reinforced the existence of NCL-SLeA glycoforms at the cancer cells surface and in GC. The NCL-SLeA glycophenotype was associated with decreased survival and was not reflected in relevant healthy tissues, supporting its tremendous potential for precise cancer targeting with limited off-target effects. To our knowledge, this is also the first report describing SLeA in a protein preferentially found in the nucleus, setting a new paradigm for cancer biomarkers discovery and targeted therapies. Funding Statement: Portuguese Foundation for Science and Technology (FCT) for the human resources grants: PhD grant BD/103571/2014 (EF), SFRH/BD/111242/2015 (AP), SFRH/BD/146500/2019 (MRS), SFRH/BD/142479/2018 (JS), SFRH/BD/105355/2014 (RA), SFRH/BD/127327/2016 (CG); and FCT assistant researcher grant CEECIND/03186/2017 (JAF). FCT is co-financed by European Social Fund (ESF) under Human Potential Operation Programme (POPH) from National Strategic Reference Framework (NSRF). The authors also acknowledge FCT the funding for CI-IPOP research unit (PEst-OE/SAU/UI0776/201), the Portuguese Oncology of Porto Research Centre (CI-IPOP-29-2014; CI-IPOP-58-2015; CI-IPOPProj.70-bolsa2019-GPTE) and PhD Programs in Biomedical and Pathology and Molecular Genetics of ICBAS-University of Porto. The authors EF, DF and MRS also acknowledge the financial support of the Research Group of Digestive Cancers (GICD) and the “Early stage cancer treatment, driven by context of molecular imaging (ESTIMA)” framework (NORTE-01-0145-FEDER-000027), IPO-Score (DSAIPA/DS/0042/2018) and “Towards a single therapy with a synergistic combination against triple negative breast cancer and neuroblastoma by nucleolin mediated multicellular targeting” (EU joint call ENMed/0006/2015) for financial support. This article is also a result of the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior in the framework of the project Institute for Research and Innovation in Health Sciences (POCI-01-0145-FEDER-007274). Declaration of Interests: The authors declare no conflict of interests. Ethics Approval Statement: All procedures concerning the inclusion of patients were approved by the institutional Ethics Committee after patient’s informed consent.

Fostering regional development in eastern Macedonia and Thrace, Greece, through road transport projects

The purpose of the paper is to evaluate the extent to which the road transport projects implemented within the Greek National Strategic Reference Framework (NSRF) 2007–2013 contributed to the economic development of eastern Macedonia and Thrace, Greece. These projects were included in the respective regional operational programs co-financed by the European Union (EU) and national funds. The paper discusses the EU’s regional and cohesion policy which aims at reducing regional inequalities and ensuring social, economic and territorial cohesion. In Greece, cohesion policy implementation for the 2007–2013 period was achieved through the NSRF, 2007–2013, whose training philosophy and the priorities that it set are the focus of the present study. The research area concerns the region of eastern Macedonia and Thrace and, more specifically, the 21 municipalities that it consists of. One of the main conclusions of the study is that public expenditure on the projects is directly associated with the area covered by the municipalities, as well as with the length of the road network improved. However, no correlation with the population of municipalities or the gross domestic product (GDP) of each regional unit has been observed. Our findings suggest that decisions for efficient allocation of infrastructure resources in a region by policy makers should not be based on single characteristics such as regional population density, but rather on more complex considerations, such as existing natural resources, geomorphological characteristics and location.

0962 Objective Daytime Sleepiness Is Associated With Disease Severity And Inflammation In Patients With Mild To Moderate Dementia

It has been reported that patients with Dementia are sleepier and that daytime sleepiness is associated with worse cognitive performance. Inflammatory markers may be elevated in patients with cognitive impairment and have been proposed as mediators of excessive daytime sleepiness (EDS). The aim of this large, controlled study was to examine the association of sleepiness with cognitive performance and peripheral markers of inflammation in patients with dementia. A sub-sample of 46 patients with mild-to-moderate Dementia [mean age:80.3 (SD=5.6) years, 40% males] and 85 cognitively intact controls(NI) [mean age :73.0(SD=7.4) years, 37% males], were recruited from a large, population-based cohort in the island of Crete, Greece of 3,140 older adults (≥60yrs). All participants underwent medical history/physical examination, extensive neuropsychiatric and neuropsychological evaluation, 3-day 24-h actigraphy and a single morning measure of IL-6 and TNFα plasma levels. Comparisons of sleep parameters and inflammation markers between Dementia and NI, and between nappers and non-nappers within each diagnostic group, were made using ANOVA controlling for demographics. Associations between inflammatory markers, sleep variables, and neuropsychological performance were assessed within each group using Partial Correlation analysis controlling for demographics, depression, use of psychotropic medications, and sleep apnea symptoms. Dementia patients compared to NI had marginally significant longer nap total sleep time (TST) (76.7±7.0min vs. 60.9±8min, respectively, p=0.2). Also, within Dementia patients, nappers compared to non-nappers had significantly worse performance in autobiographic memory scale (p=0.002), digits reverse (p=0.007), AVLT retention (p=0.010), and assessment of daily function (p=0.012). Finally, IL-6 levels were significantly associated with nap TST within Dementia patients (r=0.500, p=0.01). , while no significant associations were found between IL-6 and sleepiness within the NI group These data indicate that IL-6 plasma levels in patients with Dementia are associated with increased daytime sleepiness. In demented patients, objective sleepiness may be a biologic marker of the severity of the disease. National Strategic Reference Framework (ESPA) 2007-2013, Program: THALES, University of Crete, title: “A multi-disciplinary network for the study of Alzheimer’s Disease” (Grant :MIS 377299)

Coloured and low conductive fabrics by in situ laccase-catalysed polymerization

Chinese Government Scholarship under China Scholarship Council [grant No. 201606790036]; and by the Chinese Foundation Key projects of governmental cooperation in international scientific and technological innovation [grant No. 2016 YFE0115700]; and by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. This work was also supported by the European Union through the European Regional Development Fund (ERDF) under the Competitiveness Operational Program [grant COP-A1.1.4-E-2015nr.30/01.09.2016]; and by the Project “Search-ON2: Revitalization of HPC infrastructure of UMinho” [grant NORTE-07-0162-FEDER-000086), co-funded by the North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF). The work was also supported by the FCT- Fundacao para a Ciencia e a Tecnologia [grant SFRH/BD/121673/2016 and IF/00186/2015]

CSR sposobem na trwałą przewagę konkurencyjną. Wpływ projektów realizowanych w Narodowych Strategicznych Ramach Odniesienia 2007-2013 na upowszechnienie społecznej odpowiedzialności biznesu w Polsce

If a company wants to be innovative and competitive in the international market, it needs to act responsibly and have good relationships throughout the supply chain. Corporate social responsibility (CSR) is a management concept that addresses those challenges. The author attempted to identify the idea of CSR and relate it to the practical aspects. The projects supporting the development of CSR in Poland, which were implemented in the National Strategic Reference Framework 2007-2013, were analyzed. An attempt was made to assess the impact of projects co-financed from the Operational Program "Human Capital" on the promotion of CSR in Poland. The study was based on data from the National Information Infrastructure which collects information about contracts from the financial perspective 2007-2013

Abstract 1716: GSTP1 promoter methylation in in-vivo isolated CTCs from high-risk prostate cancer patients

Abstract Introduction: Glutathione S-transferase 1 (GSTP1) has been reported to function as tumor suppressor gene in various types of human cancers. GSTP1 inactivation is associated with CpG island promoter hypermethylation in the majority of prostate cancers (PCs). The initiation of minimal residual disease (MRD) and especially the detection of circulating tumor cells (CTCs) in patients’ peripheral blood represents a negative prognostic parameter for recurrence-free survival. The aim of the present study was to assess the methylation status of the GSTP1 gene in CTCs that were isolated, using the CellCollector® (GILUPI, GmbH), a novel clinical device designed for the in vivo isolation of EpCAM-positive CTCs. Patients and methods: In-vivo isolation of CTCs was performed by using CellCollector® from high-risk prostate cancer patients (n=97) and 20 healthy volunteers. For all these patients, the Ab coated region of the CellCollector® was washed in PBS , cut, and stored in Trizol reagent till analysis and DNA was further prior to the analysis isolated DNA was modified by sodium bisulfite (SB) and subjected to a real time MSP assay specific for GSTP1 methylation. In all cases, peripheral blood was also collected and used for CTC analysis by Immunostaining and the CellSearch® system. Results: All DNA samples were first checked for their quality. Based on the quality evaluation of all available DNA samples, only 63 DNAs were further qualified for analysis. GSTP1 promoter was found methylated in 12/63 (19%) the EpCAM positive fraction of in-vivo isolated CTCs. Moreover, in 5/12 (41.7%) patients for which GSTP1 promoter was found methylated, CTCs were also detected by the CellSearch® and 7 /12 (58.3%) for which GSTP1 promoter was also found positive, CTCs were also detected by the Immunostaining. Conclusion: GSTP1 promoter is methylated in in-vivo isolated CTCs from high-risk prostate cancer patients. GSTP1 promoter methylation in in-vivo isolated CTCs should be prospectively validated as a novel tumor biomarker for prostate cancer patients in a large cohort of patients. Acknowledgements: This research has been co-financed by the European Union (European Regional Development Fund - ERDF) and Greek national funds through the Operational Program ‘‘Competitiveness and Entrepreneurship’’ of the National Strategic Reference Framework (NSRF) - Research Funding Program: “ERA-NET on Translational Cancer Research (TRANSCAN) Joint Transnational Call for Proposals 2011 (JTC 2011) on: “Validation of biomarkers for personalised cancer medicine Citation Format: Athina N. Markou, Panagiotis Paraskevopoulos, Marifili Lazaridou, Shukun Chen, Thomas Kroneis, Monika Świerczewska, Joanna Budna, Andra Kuske, Tobias M. Gorges, Maciej Zabel, Peter Sedlmayr, Catherine Alix-Panabieres, Klaus Pantel, Evi Lianidou. GSTP1 promoter methylation in in-vivo isolated CTCs from high-risk prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1716. doi:10.1158/1538-7445.AM2017-1716

1157 INFLAMMATION IS ASSOCIATED WITH EXCESSIVE DAYTIME SLEEPINESS AND IMPAIRED COGNITIVE PERFORMANCE IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT (MCI)

It has been shown that inflammatory markers are elevated in patients with cognitive impairment and are associated with excessive daytime sleepiness (EDS). Furthermore, we have previously shown that extended sleep/sleepiness in patients with Mild Cognitive Impairment (MCI) is associated with impaired cognitive performance. The aim of this study was to assess the associations between inflammation, objective sleep, and cognition among patients with MCI. A sub-sample of 119 patients with MCI were recruited from a large, population-based cohort in the island of Crete, Greece of 3140 older adults (>60yrs). The goal of this study was to assess the prevalence and risk factors associated with cognitive impairment. All participants underwent medical history/physical examination, extensive neuropsychiatric and neuropsychological evaluation, 3-day 24-h actigraphy and a single morning IL-6 and TNFa plasma level. Associations between (a) inflammatory markers and sleep variables and (b) inflammatory markers and cognition, were assessed using Linear Regression Analysis controlling for gender, age, BMI and depression for the former, and age, gender, and education, for the later. Peripheral levels of IL-6 were 1.2 ± 0.83 pgr/ml(mean ±SD), and TNFa were 1.18 ± 0.57pgr/ml. Regression analysis found a borderline significant association between IL-6 and daytime Total Sleep Time (r=0.186,p=0.07). Furthermore, regression analyses revealed significant associations between IL-6 and a number of episodic memory indices including immediate (β = -0.279, p = 0.003) and delayed word list recall (β = -0.25, p = .013), delayed complex figure reproduction (β = -0.26, p =0 .010), and autobiographic memory (β = -0.25, p =0 .009), and between TNFa and delayed word list recall (β= -0.217, p = -0.028). These data indicate that in patients with MCI, EDS and cognitive impairment are associated with inflammation. It appears that improvement of inflammation through pharmacologic and/or behavioral i.e. exercise, interventions may improve the prognosis in patients with MCI. Thales, University of Crete, A multi-disciplinary network for the study of the Alzheimer’s disease, National Strategic Reference Framework (ESPA) 2007–2013

New museums, exhibitions and site presentations

Since 2009 Greece has faced one of its most challenging phases in modern history; the financial and social crisis has affected all sectors of society and spending for cultural activities has been significantly cut. Although there have been museum closures and funds for research or even day-to-day needs are in short supply, nevertheless, very serious and creative work is being produced quietly, often with the aid of European Union co-funded projects, through the so-called Εθνικό Στρατηλικό Πλαίσιο Aναϕοράς (EΣΠA), or National Strategic Reference Framework. The schedule and deadlines for such projects are very tight and working conditions challenging, but the results have often been exceptional in quality, revealing hard work, effective management of people of various specialisms and scholarly expertise. The period 2015–2016 has seen the opening of many new major museums, the result of many years of planning and hard work, and the organization of temporary exhibitions, through which the finds of the last decade have become accessible to the wider public. In this feature I concentrate on a brief presentation of the new museums that have opened this past year, news that will interest not only students and academics, but also other visitors to Greece. Colleagues in the various relevant ephorates of antiquities have been very generous in providing information, and so I have decided to leave their texts largely unchanged. I begin with a brief presentation of new museums, before moving on to discuss temporary exhibitions and a few key archaeological sites.

Environmentally Progressive Road Traffic Noise Reducing Devices and Materials

This paper analyses issues of progressive road traffic noise reducing devices design and evaluating the quality of asphalt road surfaces from the perspective of the Permanent Sustainable Development, which is one of the horizontal priorities of the National Strategic Reference Framework for the period from 2007 to 2013. The horizontal priority (HP) Permanent Sustainable Development (PSD) of the National Strategic Reference Framework (NSRF) has been complementary affecting the objectives of the NSRF. The purpose of the HP is to ensure targeted achievement on several priorities of the NSRF, which cannot be provided by a single Operational Program (OP), but requires a coordinated approach combining several specific priorities / priority axes / actions, or more precisely the projects of particular OPs. Within the specific objective of enhancing the quality of the environment has been directly defined sub-goal - to reduce noise pollution of environment. The scientific paper is concerned with measurements of the noise production and sound propagation on four different roads, where the source of the noise was the same vehicle driving at five different speeds.

Can host reaction animal models be used to predict and modulate skin regeneration?

T.C.S. acknowledges Grant No. RL3-TECT-NORTE-01-0124-FEDER-000020, co-financed by the North Portugal Regional Operational Programme (ON.2-O Novo Norte), under the National Strategic Reference Framework, through the European Regional Development Fund.

Targeting urothelial tumors of upper urinary tract with drug-eluting stents impregnated by supercritical fluids

Event Abstract Back to Event Targeting urothelial tumors of upper urinary tract with drug-eluting stents impregnated by supercritical fluids Alexandre Barros1, 2, 3, Shane A. Browne3, 4, Carlos Oliveira2, 5, Rui L. Reis1, 2, Estevão E. Lima2, 5, Ana R. Duarte1, 2 and Kevin E. Healy3, 6 1 3B´s Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and, Portugal 2 ICVS/3B's - PT Government Associate Laboratory, University of Minho, Portugal 3 University of California, Berkeley, Department of Bioengineering, United States 4 National University of Ireland Galway, Centre for Research in Medical Devices (CÚRAM), Ireland 5 Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Portugal 6 University of California, Berkeley, Department of Materials Science and Engineering, United States Urothelial tumors of upper urinary tract are ranked among the most common types of cancers worldwide and it has been considered as one of the more expensive to treat due of its long-term propensity of recurrence. The current standard therapy to prevent recurrence is intravesical Bacillus Calmette–Guerin (BCG) immunotherapy, but it presents several disadvantages such as BCG failure and intolerance. Another way is to use chemotherapy, that has been reported to be generally better tolerated that BCG. In this case, drugs such as epirubicin, doxorubicin, paclitaxel and gemcitabine are used. Nevertheless, intravesical chemotherapy only prevents recurrence in the short-term[1],[2]. These failings can be partially attributed to the short residence time and low penetration of the drug within the upper urinary tract and the cancer cells, resulting in a need for frequent drug instillation[3]. To avoid these problems, biodegradable ureteral stents impregnated by supercritical fluid CO2 (SCF) with each of the four anti-cancer drugs were produced (figure 1). Four types of drug-eluting biodegradable stents were studied, impregnated with paclitaxel, epirubicin, doxorubicin and gemcitabine. The release kinetics of the impregnated drugs from the anti-cancer drug-eluting stents was measured in artificial urine solution (AUS) for 9 days. The in vitro drugs release from the impregnated biodegradable ureteral stents was analyzed using a microplate reader. The in vitro release study in AUS showed a higher release in the first 72h for the four anti-cancer drugs impregnated after this time the plateau was achieved and the stent degrades after 9 days. Regarding the amount of impregnated drugs by SCF the gemcitabine showed higher amount (109 µg) and the lower amount was obtained for paclitaxel (67 ng). The diffusion coefficient and the impregnation yield were calculated. The anti-tumoral effect of the developed stents in transitional cell carcinoma (TCC) - T24 cell lines was evaluated. T24 cell line was exposed to graded concentrations (0.01 to 2000 ng/ml) of the four drugs for both 4 and 72 hours to determine the sensitivities to each drug (IC50). Toxicity as a result of both direct and indirect contact of the cell lines with the different material conditions of biodegradable stent were studied. The four anti-cancer drugs showed a concentration-dependent inhibitory effect on the T24 and HUVEC cell lines with IC50’s for paclitaxel of 7.30ng and 501.50ng, respectively. The T24 cell line shows to be more sensitive than HUVEC cell line for all the anti-cancer drugs tested. The direct and indirect contact of the anti-cancer biodegradable stents with the T24 and HUVEC cell lines confirm the anti-tumor effect of the stents impregnated with the four anti-cancer drugs, reducing around 75% of the viability of the T24 cell line after 72h and no killing effect in the HUVEC cells. Finally, this study has shown the killing efficacy of the anti-cancer drug eluting biodegradable stents in vitro for the T24 cell lines, with no toxicity observed in the control, non-cancerous cells. Luso-American Foundation's Grant for Internships in the University of California, Berkeley, 2015/CON5/CAN8; FCT PhD Grant (SFRH/BD/97203/2013); European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° REGPOT-CT2012-316331-POLARIS; Project “Novel smart and biomimetic materials for innovative regenerative medicine approaches (Ref.: RL1 - ABMR - NORTE-01-0124-FEDER-000016)” cofinanced by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF)

Fabrication of anisotropically aligned nanofibrous scaffolds based on natural/synthetic polymer blends reinforced with cellulose nanocrystals for tendon tissue engineering

Event Abstract Back to Event Fabrication of anisotropically aligned nanofibrous scaffolds based on natural/synthetic polymer blends reinforced with cellulose nanocrystals for tendon tissue engineering Rui M. Domingues1, 2*, Silvia Chiera3, 4*, Pavel Gershovich1, 2, Antonella Motta3, 4*, Rui L. Reis1, 2* and Manuela E. Gomes1, 2* 1 University of Minho, 3B’s Research Group, Portugal 2 ICVS/3B's-PT Associate Laboratory, Portugal 3 University of Trento, Department of Industrial Engineering and Biotech Research Centre, Italy 4 European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Italy Introduction: Tendon disorders and injuries are among the most common musculoskeletal problems and their regeneration after injury remains a significant challenge. Given the prevalent fibrous nature of tendons’ ECM, which exhibits an aligned and hierarchical organization in structures from the nano to the macro scale, uniaxial aligned electrospun nanofibers produced from natural/synthetic polymer blends are among the most successful tendon scaffolds in tissue engineering (TE) strategies[1]. These biomaterials can provide the topographical cues to direct cell adhesion and proliferation, as well as positively affecting cell’s differentiation, phenotype maintenance and matrix deposition. However, the limited mechanical properties of electrospun biomaterials restrict their potential application in this field. In the present study, we propose the use of cellulose nanocrystals (CNCs), the “nature carbon nanotubes”, as a strategy for the reinforcement of electrospun poly-ɛ-caprolactone-chitosan (PCL-C) nanofiber scaffolds without compromising their biological performance and thus expand their potential range of application in tendon TE strategies. Materials and Methods: Random (reference materials) and anisotropically aligned nanocomposite nanofiber scaffolds were fabricated by electrospinning using a static plate or rotating wheel as collecting targets (Fig. 1A), respectively, and their morphology, thermodynamic, and mechanical properties were investigated. The biological performance of human derived tendon cells (TCs) on aligned PCL-C and PCL-C/CNC nanofibers was compared with those of corresponding random nanofibrous materials as composition and topographical controls, assessing their biocompatibility and influence over cell morphology and orientation (Fig. 1B). Figure1. A) Schematic representation of the nanocomposite scaffolds fabrication process. B) SEM and confocal microscopy images of TCs seeded on PCL-C scaffolds filled with 3 wt% CNCs. Red: Phalloidin-rhodamine for F-actin; Blue: DAPI for nuclei. Results and discussion: CNCs were incorporated in PCL-C nanofiber bundles, resembling the typical aligned structure of tendon EMC while raising their mechanical properties up to a tendon meaningful level. In the optimized conditions, the incorporation of 3 wt.% CNCs in the PCL-C nanofiber bundles increased the Young’s modulus to 534 MPa and the tensile strength to 39 MPa, representing an increase of 132% and 83%, respectively, compared to reference PCL-C nanofiber scaffolds, without significantly affecting the biomaterial’s ductility. The incorporation of CNCs in PCL-C nanofibers didn’t affect the cytocompatibility of the biomaterials. Moreover, the aligned nanotopography of the material surface noticeably promoted TCs to orient along the axis of the scaffold through contact guidance mechanisms (Fig. 1B). The observed actin stress fibers demonstrated longitudinal arrangement along the elongated cell shape axis, and their nuclei were evidently more elongated and elliptically shaped as well. These findings are particularly important, as actin cytoskeleton has been shown to play important role on the stage of connective tissue development[2] and elongated cell shape has been demonstrated to be essential for tenocyte function and phenotype maintenance[3]. Conclusions: Our results demonstrate that aligned PCL-C-CNC nanocomposite fibrous scaffolds meet not only the mechanical requirements for tendon TE applications but also provide mimetic ECM topographic cues which are key features for maintaining tendon cell’s morphology and behavior. The authors also acknowledge the financial support from the Project RL1 - ABMR - NORTE-01-0124-FEDER-000016 cofinanced by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF).