Serum levels of advanced glycation end-products (AGEs) and the decoy soluble receptor for AGEs (sRAGE) can discriminate non-alcoholic fatty liver disease in age-, sex- and BMI-matched normo-glycemic adults

Background: Non-alcoholic fatty liver disease (NAFLD) is a serious health problem affecting ~25% of the global population. While NAFLD pathogenesis is still unclear, multiple NAFLD parameters, including reduced insulin sensitivity, impaired glucose metabolism and increased oxidative stress are hypothesised to foster the formation of advance glycation end-products (AGEs). Given the link of AGEs with end organ damage, there is scope to examine the role of the AGE/RAGE axis activation in liver injury and NAFLD. Methods: Age, sex and body mass index matched normo-glycemic NAFLD adults (n = 58) and healthy controls (n = 58) were enrolled in the study. AGEs were analysed by liquid chromatography-mass spectrometry (CML, CEL), fluorescence (pentosidine, AGE fluorescence), colorimetry (fructosamine) and ELISA (sRAGE). Their association with liver function, inflammation, fibrosis and stage of NAFLD was examined. Results: Early and advanced glycation end-products, except Nε-carboxymethyl-L-lysine (CML), were 10–30% higher, sRAGE levels 1.7-fold lower, and glycation/sRAGE ratios 4-fold higher in the NAFLD cases compared to controls. While AGEs presented weak to moderate correlations with indices of liver function and damage (AST/ALT, HOMA-IR, TNF-α and TGF-β1), including sRAGE to characterize the AGEs/sRAGE axis strengthened the associations observed. High glycation/sRAGE ratios were associated with 1.3 to 14-fold likelihood of lower AST/ALT ratios. The sum of AGEs/sRAGE ratios accurately distinguished between healthy controls and NAFLD patients (area under the curve of 0.85). Elevated AGEs/sRAGE (>7.8 mmol/pmol) was associated with a 12-fold likelihood of the presence of NAFLD. Conclusion: These findings strengthen the involvement of AGEs-RAGE axis in liver injury and the pathogenesis of NAFLD

Initial Teacher Education for Inclusion Phase 1 and 2 Report: NCSE Research Report No. 26

Executive Summary Background to the project The context for this project is a growing international consensus on the importance of policy initiatives to both raise the quality of teaching (OECD, 2005) and to better prepare teachers to respond to increasing diversity in communities and classrooms (EADSNE, 2011). The DES and the Teaching Council of Ireland developed policies requiring higher education institutions providing Initial Teacher Education (ITE) to undergo a re-accreditation process from 2012. This involved both an extension and a reconceptualization of programmes, with mandatory additional content related to inclusive education and differentiation, together with the opportunity for a wider range of school placement experiences. All concurrent (undergraduate) programmes of initial teacher education must be of four years' duration and all consecutive (postgraduate) programmes of initial teacher education must be of two years' duration. The latter were re-accredited at Masters Level 9 on the National Framework of Qualifications. Following this major reform, the National Council for Special Education (NCSE) in Ireland commissioned a study of ‘Initial Teacher Education for Inclusion’ in 2015. NCSE’s research aim was: ‘to establish what the components of inclusive/special education are within Initial Teacher Education (ITE) programmes in Ireland and to explore if the recent changes prepare newly qualified teachers to be inclusive using the indicators set out in the EASNIE’s Profile of Inclusive Teachers’. The European Agency for Special Needs and Inclusive Education (EASNIE) conducted a four-year project on Teacher Education for Inclusion, involving representatives of twenty five countries. A key output was a proposed ‘Profile of Inclusive Teachers’ (EADSNE, 2012), which outlines a range of attitudes, knowledge and skills in relation to four core values and eight areas of competence, to be addressed in initial teacher education to prepare all new teachers to become more inclusive. The NCSE proposed the EASNIE Profile of Inclusive Teachers as the baseline definition of inclusive teaching for the project and it is used by the research team as the framework and starting point for analysis. The ‘Initial Teacher Education for Inclusion’ project (ITE4I), runs from 2015-2018. The research team is led by Manchester Metropolitan University in partnership with University College Cork and University College London, Institute of Education. We understand this project may be one of the first system-wide, longitudinal studies of initial teacher education for inclusive teaching in Europe. This report relates to the first year of the project in 2015/16, which analysed the content of ITE programmes and studied the experiences of the first cohort of student teachers to graduate from the extended and reconceptualised programmes, in their final year of study. This comprised two phases of data collection: in Phase 1 we analysed programme documents and surveyed teacher educators; in Phase 2 we surveyed student teachers and interviewed a sample of student teachers and teacher educators. At the same time, a literature review was developed setting out definitional debates on inclusive education and outlining the scope of the international literature on inclusive teaching. Research design The Research Questions formulated by National Council for Special Education (NCSE) were as follows: 1. What are the components of inclusive/special education within Initial Teacher Education (ITE) programmes in Ireland for primary and post-primary teachers? 2. Do the recent changes to ITE prepare newly qualified teachers to be inclusive as identified by European Agency for Special Needs and Inclusive Education (EASNIE) Profile of Inclusive Teachers? 3. What is the intended impact of the changes in ITE on outcomes for students with special educational needs (SEN) and do student/newly qualified teachers perceive their learning during initial teacher education makes an impact on outcomes for students with SEN? 4. What gaps are there in how current ITE programmes prepare student teachers to be inclusive as per the EASNIE Profile of Inclusive Teachers and what aspects need to be strengthened to better prepare student teachers to be inclusive? 5. What lessons can be identified from this research for initial teacher education in Ireland and subsequent phases in the continuum of teacher education? The Project Phases were planned around data collection over the three years of the project: Phase 1 (Sept. – Jan. 2016): Analysing ITE Programme Content Data collection in Phase 1 included documentary analysis and a survey of teacher educators. Documentation relating to some 30 programmes (out of 59 nationally) from 13 ITE providers (out of 19 in total) was obtained with the support of the Teaching Council. These were primarily standard proforma submitted for re-accreditation, with module outlines appended in some cases; in addition, reviews of these submissions published by the Teaching Council were analysed, together with the criteria used for re-accreditation. The documentary analysis started from a typology derived from the EASNIE Profile of Inclusive Teachers, to examine how and where inclusive teaching is represented within ITE programme documents. A survey of teacher educators was conducted at the same time, to collect initial data on the range of views expressed by teacher educators in relation to issues of inclusive teaching in ITE programmes. The survey was constructed to reflect areas of competence within the EASNIE Profile of Inclusive Teachers, and to collect free-text comments. Following piloting, 21 respondents (programme leaders, module leaders, heads of departments) provided complete or near-complete responses giving information relating to 27 programmes from 13 institutions (some survey responses related to more than one programme). Phase 2 (Feb. – Aug. 2016): Understanding the ITE Student Experience Data collection in Phase 2 included a survey of student teachers, together with interviews with student teachers and with teacher educators at five case study sites. The five ITE providers were selected to represent a range of primary, post-primary, consecutive and concurrent programmes; and to provide a geographical spread of institutions. The survey of student teachers elicited data about their experiences of initial teacher education and their understandings of inclusive teaching. The questionnaire captured demographic information, key areas of experience prior to and during the respondents’ ITE programme, and a series of statements mapped to an analysis of the attitude, knowledge and skills components of the EASNIE profile. A total of 430 valid responses were received, representing a sample of approximately 13% of the national cohort of student teachers. The interviews with student teachers aimed to elicit their views about their course and how their studies related to their school placement experiences; their understandings of inclusive teaching; their approaches to inclusive teaching in practice; and their reflections on their own professional development in relation to inclusive teaching and how their courses might be developed. A total of 47 students were interviewed in person or by Skype, with 32 recruited at the five case study sites and a further 15 recruited by survey responses from other institutions. The interviews with teacher educators sought their views on issues of inclusive teaching and ITE in Ireland, and on the impact of the extension and reconceptualization of ITE programmes; their responses to emergent themes and issues arising from the survey of teacher educators and the documentary analysis; and their reflections on aspects of the EASNIE Profile of Inclusive Teachers. A total of 11 staff interviews were conducted across the five case study sites, typically including the Head of School or a Programme Leader and a lecturer in inclusive or special education

Te role of dietary habits in non alcoholic fatty liver disease

Introduction: Adherence to the Mediterranean diet (MD) has been negatively associated with insulin resistance and the metabolic syndrome. Non- alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of the metabolic syndrome.Aim: The aim of the present study was to examine the relationship between adherence to the MD and the characteristics of patients with NAFLD, as well as the contribution of the MD to the development of NAFLD.Methods: 73 non-diabetic NAFLD patients and 51 gender- age- and body mass index- matched controls were included in the study. Dietary habits were assessed using food frequency questionnaires (FFQ). Mediterranean Diet Score (MedDietScore), an index of adherence to the MD – higher values indicate higher adherence to the MD- was calculated based on data from the FFQ. Demographic data, anthropometric indices, body composition analysis (visceral fat) by bioelectrical impedance, biochemical parameters and inflammatory markers (high sensitivity CRP, interleukins-6 and -8, TNF-a and adiponectin) were available for all patients and controls. Apoptosis indices (Keratin-18, soluble fas, fas Ligand) were available only for the patients. Liver biopsy was available for 34 and liver stiffness measurements by transient elastography for 58 patients, respectively.Results: MedDietScore inversely correlated with LSM (rho=- 0,280, p= 0,034), histological stage (rho=- 0,372, p= 0,030), histological severity of steatosis (rho=- 0,523, p= 0,006), HOMA index (rho= - 0,282, p= 0,017) and keratin-18 levels (rho= -0,346, p= 0,005), while not correlating significantly with body mass index (rho= - 0,127, p= 0,147). Patients with simple fatty liver reported significantly higher MedDietScore compared to those with steatohepatitis-NASH (29,6±3,2 vs 32,9±5,0, p= 0,023). On the contrary, patients had similar adherence to the MD compared with controls (33,1±4,9 έναντι 33,0±4,7, p= 0,856, for patients and controls, respectively).Conclusions: Higher adherence to the MD is associated with the presence of simple steatosis as opposed to NASH, is inversely correlated with the stage of fibrosis, as assessed histologically or by transient elastography, with the degree of insulin resistance and with keratin 18 among NAFLD patients. Adherence to the ND is similar between patients with NAFLD and controls, implicating the role of genetic factors in the development of NAFLD.Εισαγωγή: Η υιοθέτηση της μεσογειακής διατροφής έχει σχετιστεί αρνητικά με την παρουσία αντίστασης στην ινσουλίνη και μεταβολικού συνδρόμου. Η μη αλκοολική λιπώδης νόσος του ήπατος (NAFLD) αποτελεί την ηπατική συνιστώσα του μεταβολικού συνδρόμου.Σκοπός: Σκοπός της παρούσας μελέτης ήταν να συσχετίσει την προσκόλληση στη Μεσογειακή Διατροφή (ΜΔ) με τα χαρακτηριστικά των ασθενών με NAFLD και το ρόλο της στην εμφάνιση της νόσου.Μεθοδολογία: Στη μελέτη συμπεριλήφθηκαν 73 μη διαβητικοί ασθενείς με NAFLD και 51 μάρτυρες ταιριασμένοι ένας προς έναν με αντίστοιχο αριθμό ασθενών, ως προς το φύλο, την ηλικία και το δείκτη μάζας σώματος. Η εκτίμηση των διατροφικών συνηθειών έγινε με ερωτηματολόγια συχνότητας κατανάλωσης τροφίμων, βάσει των οποίων εκτιμήθηκε ο βαθμός προσκόλλησης στη ΜΔ, με το δείκτη MedDietScore (υψηλότερες τιμές αντιστοιχούν σε καλύτερη προσκόλληση). Δημογραφικά, ανθρωπομετρικά χαρακτηριστικά, στοιχεία από ανάλυση σύστασης σώματος (με τη μέθοδο βιοηλεκτρικής εμπέδησης) καθώς και βιοχημικά χαρακτηριστικά και δείκτες φλεγμονής (υψηλής ευαισθησίας CRP, IL-6, IL-8, TNF-a, αδιπονεκτίνη). Δείκτες απόπτωσης (Keratin-18, διαλυτός υποδοχέας του fas και ο προσδέτης του fas) ήταν διαθέσιμοι μόνο για τους ασθενείς. Βιοψία ήπατος είχαν 34 και ελαστογραφία 58 ασθενείς.Αποτελέσματα: Ο βαθμός προσκόλλησης στη Μεσογειακή Διατροφή σχετίστηκε αρνητικά με το στάδιο της ίνωσης, όπως αυτό εκτιμάται ιστολογικά (rho= - 0,372, p= 0,030) ή με ελαστογραφία (rho= - 0,280, p= 0,034) και το ποσοστό ηπατικής στεάτωσης (rho= - 0,523, p= 0,006), με το βαθμό αντίστασης στην ινσουλίνη (δείκτης ΗΟΜΑ: rho= - 0,282, p= 0,017) και με την κερατίνη 18 (rho= - 0,346, p= 0,005), ενώ δε συσχετίστηκε σημαντικά με το δείκτη μάζας σώματος (rho= - 0,127, p= 0,147). Ασθενείς με NASH είχαν σημαντικά χαμηλότερη προσκόλληση στη ΜΔ, σε σύγκριση με ασθενείς με απλή ηπατική στεάτωση (29,6±3,2 έναντι 32,9±5,0, p= 0,023). Αντίθετα, ασθενείς και μάρτυρες δε διέφεραν ως προς το βαθμό προσκόλλησης στη ΜΔ (33,1±4,9 έναντι 33,0±4,7, p= 0,856, για τους ασθενείς και τους μάρτυρες, αντίστοιχα).Συμπεράσματα: Η υψηλότερη προσκόλληση στη ΜΔ σχετίζεται με την παρουσία απλής στεάτωσης σε σύγκριση με NASH, συσχετίζεται αρνητικά με το στάδιο της ίνωσης, τόσο ελαστογραφικά όσο ιστολογικά, με την αντίσταση στην ινσουλίνη και με την κερατίνη 18 σε ασθενείς με NAFLD. Ωστόσο, η προσκόλληση στη ΜΔ δε διαφέρει σημαντικά μεταξύ ασθενών με NAFLD και υγιών μαρτύρων, καταδεικνύοντας τη σημασία των γενετικών παραγόντων στην εμφάνιση της νόσου

Electronic Structure and Hole Transfer of All B-DNA Dimers and Homopolymers, via the Fishbone-Wire Model

We employ the Tight Binding Fishbone-Wire Model to study the electronic structure and coherent transfer of a hole (the absence of an electron created by oxidation) in all possible ideal B-DNA dimers as well as in homopolymers (one base pair repeated along the whole sequence with purine on purine). The sites considered are the base pairs and the deoxyriboses, with no backbone disorder. For the time-independent problem, we calculate the eigenspectra and the density of states. For the time-dependent problem after oxidation (i.e., the creation of a hole either at a base pair or at a deoxyribose), we calculate the mean-over-time probabilities to find the hole at each site and establish the frequency content of coherent carrier transfer by computing the Weighted Mean Frequency at each site and the Total Weighted Mean Frequency of a dimer or polymer. We also evaluate the main oscillation frequencies of the dipole moment along the macromolecule axis and the relevant amplitudes. Finally, we focus on the mean transfer rates from an initial site to all others. We study the dependence of these quantities on the number of monomers that are used to construct the polymer. Since the value of the interaction integral between base pairs and deoxyriboses is not well-established, we treat it as a variable and examine its influence on the calculated quantities

The reality of reality shock for inclusion: How does teacher attitude, perceived knowledge and self-efficacy in relation to effective inclusion in the classroom change from the pre-service to novice teacher year?

There is little empirical attention in the literature to how beginning teacher perceptions in relation to inclusion change as they progress from the pre-service to novice teacher year. This paper reports on a panel study of a cohort of pre-service teachers in the Republic of Ireland, which tracks their transition to the novice teacher year using a new scale. Analysis of the data indicates that this transition results in a significant drop in attitude, perceived knowledge and self-efficacy in relation to inclusion

Changes of HBsAg and interferon-inducible protein 10 serum levels in naive HBeAg-negative chronic hepatitis B patients under 4-year entecavir therapy

Background & Aims: Serum HBsAg levels might represent an important predictor of sustained off-treatment response in HBeAg-negative chronic hepatitis B (CHB). We evaluated the changes of HBsAg and interferon-inducible protein 10 (IP10) serum levels in HBeAg-negative CHB patients treated with entecavir. Methods: 114 patients received entecavir for a median of 4.3 years. HBsAg levels were determined at baseline, 6 and 12 months and every year thereafter until year-4. IP10 levels were measured at baseline and annually until year-4 in 76 patients. Results: Virological remission rates were high (year-1: 94%, after year-2: 97-98%). Compared to baseline, HBsAg levels decreased by a median of 0.03, 0.13, 0.17, 0.22, and 0.32 log(10) IU/ml at 6 months and 1, 2, 3, and 4 years, respectively (p <= 0.001 for all comparisons). The proportions of patients with HBsAg decline of >= 0.5 or >= 1 log(10) IU/ml were 9% or 6% at year-1 and 21% or 10% at the last visit. Median IP10 levels (pg/ml) did not change from baseline to year-1 or -2 (245 vs. 229 or 251), but increased at year-3 and -4 (275 and 323, p <0.030). HBsAg drop >= 0.5 log(10) was associated with baseline IP10 or IP10 >350 pg/ml (p <= 0.002). HBsAg loss occurred in 4/114 (3.5%) patients or in 1/2, 3/21, and 0/91 patients with baseline HBsAg <100, 100-1000 and >1000 IU/ml, respectively (p <0.001). Conclusions: In HBeAg-negative CHB patients, 4-year entecavir therapy decreases serum HBsAg levels, but the rate of decline is rather slow. Serum IP10 levels represent a promising predictor of HBsAg decline in this setting