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Purpose: In this Report we analyse the place of civic education in the Greek Education system. The integration of civic education into education since 1982 represents a major step forward in the upgrading of general education. However the curricula are mainly characterised by teacher-centred approaches, with a strong emphasis on the achievement of cognitive objectives and little emphasis on the learning process and teaching strategy. Design/methodology/approach: This report is based on an analysis of the place of social studies in the Greek education system. We analysed the aims of the curricula, the role of teachers, the didactic approaches, the educational practices and the assessment. Findings: From our analysis we have detected a gap between the public rhetoric about the role of social sciences and their implementation in the Greek education. Although it seems that the general principles of curricula are permeated by a more democratic and flexible note which encourages critical thinking and participation, they are not implemented in practice and by and large are annulled due to the great emphasis the Greek education system places on knowledge acquisition and exams. The elimination of Social studies in some classes points to a school which is cut off from the current socio-economic reality, thus condemning students to a passive attitude towards social and educational affairs. Research limitations/implications This article reports on the research conducted on civic education since the 1990’s and onwards. The study of all these researches leads us to the conclusion that neither the curricula nor the textbooks of social studies courses have been extensively analysed, and this could be a future field of research. Another area of research is the role of school charters, the didactic approaches and the assessment in this course in the Greek education context. Practical implications Upheavals in the history of the Greek governmental system and democracy left their indelible mark on citizens’ education; changes in the title of the course, the time allotted to its teaching and the content of school knowledge evidence its dependence on the respective socio-political and ideological regime as well as its indoctrinational character. The turning points in civic education which can be pinpointed between 1982 and 2003 were linked with the educational policy of socialist governments and the gradual paradigm shift in social studies., JSSE - Journal of Social Science Education, Bd. 22 Nr. 2 (2023): Assessment and National Exams in Social Studies and Social Sciences

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

Short telomeres are recognized as risk factor for idiopathic pulmonary fibrosis (IPF). We aimed to assess the role of telomere length (TL) in fibrotic-Interstitial Lung Diseases (f-ILDs) associated with a usual interstitial pneumonia (UIP) pattern as well as in IPF acute exacerbation (IPF-AE).TL was measured from peripheral white blood cells using a multiplex quantitative polymerase chain reaction in consecutive patients with f-ILDs, all presenting UIP pattern in the high-resolution chest-computed-tomography and compared to age-matched healthy controls.Seventy-nine individuals were included (mean age 69.77 ± 0.72 years); 24 stable IPF, 18 IPF-AE, 10 combined pulmonary fibrosis and emphysema, 7 Rheumatoid arthritis-UIP-ILDs and 20 controls. TL in all patients was significantly shorter compared to controls [mean T/S ratio (SE) 0.77 (±0.05) vs 2.26 (±0.36), p 0.001] as well as separately in each one of f-ILD subgroups. IPF-AE patients presented significantly shorter TL compared to stable IPF (p = 0.029). Patients with IPF and shorter than the median TL (0-0.72) showed reduced overall survival (p = 0.004). T/S 0.72 was associated with increased risk for IPF-AE (OR = 30.787, 95% CI: 2.153, 440.183, p = 0.012) independent of age, gender, smoking and lung function impairment. A protective effect of TL was observed, as it was inversely associated with risk of death both in UIP-f-ILDs (HR = 0.174, 95%CI: 0.036, 0.846, p = 0.030) and IPF patients (HR = 0.096, 95%CI: 0.011, 0.849, p = 0.035).Shorter TL characterizes different UIP f-ILDs. Although no difference was observed in TL among diverse UIP subgroups, IPF-AE presented shorter TL compared to stable IPF. Reduced overall survival and higher hazard ratio of death are associated with shorter TL in IPF.

Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level., German Research Foundation (DFG) AL 1784/3-1, European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) 6236, Regional Government of Navarra (Spain), Regional Government of Catalonia (Catalan Institute of Oncology -ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK C864/A14136 C8221/A19170, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/N003284/1 MC-UU_12015/1 MR/M012190/1, Projekt DEAL

Background: Yoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC). Methods: We pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted. Results: The analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94–1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88–0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85–0.99) and 0.78 (95% CI = 0.73–0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91–1.02) for cardia, 1.03 (95% CI = 1.00–1.07) for non-cardia, 1.12 (95% CI = 1.07–1.19) for diffuse and 1.02 (95% CI = 0.97–1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women. Conclusions: We found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association., Fondazione AIRC per la ricerca sul cancro 21378, Unidade de Investigacao em Epidemiologia-Instituto de Saude Publica da Universidade do Porto (EPIUnit) UIDB/04750/2020, National funds from the Foundation for Science and Technology-FCT (Portuguese Ministry of Science, Technology and Higher Education), Project NEON-PC-Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline' - FEDER through the Operational Program Competitiveness and Internationalisation POCI-01-0145-FEDER-03235 PTDC/SAU-EPI/32358/2017, Fundacao para a Ciencia e a Tecnologia (FCT), EPIunit-Junior Research-Prog Financing UIDP/04750/2020, Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) 2014/26897-0, European Cancer Prevention Organization, United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI)

Purpose: Renal cell carcinoma (RCC) has the potential for cure with surgery when diagnosed at an early stage. Kidney injury molecule-1 (KIM-1) has been shown to be elevated in the plasma of RCC patients. We aimed to test whether plasma KIM-1 could represent a means of detecting RCC prior to clinical diagnosis.Experimental Design: KIM-1 concentrations were measured in prediagnostic plasma from 190 RCC cases and 190 controls nested within a population-based prospective cohort study. Cases had entered the cohort up to 5 years before diagnosis, and controls were matched on cases for date of birth, date at blood donation, sex, and country. We applied conditional logistic regression and flexible parametric survival models to evaluate the association between plasma KIM-1 concentrations and RCC risk and survival.Results: The incidence rate ratio (IRR) of RCC for a doubling in KIM-1 concentration was 1.71 [95% confidence interval (CI), 1.44–2.03, P = 4.1 × 10−23], corresponding to an IRR of 63.3 (95% CI, 16.2–246.9) comparing the 80th to the 20th percentiles of the KIM-1 distribution in this sample. Compared with a risk model including known risk factors of RCC (age, sex, country, body mass index, and tobacco smoking status), a risk model additionally including KIM-1 substantially improved discrimination between cases and controls (area under the receiver-operating characteristic curve of 0.8 compared with 0.7). High plasma KIM-1 concentrations were also associated with poorer survival (P = 0.0053).Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival. Clin Cancer Res; 24(22); 5594–601. ©2018 AACR.

Background/Aims Dementia is a major disease worldwide, with an increasing incidence rate. This study estimated the societal cost of dementia in Greece, with the aim of helping policy makers to plan health services and evaluate their efficiency. Methods This study was conducted at a specialist neurological hospital in Greece with 110 patients with dementia and 110 caregivers. Local rates were used to determine the cost of services, medicines and staff salaries. Caregivers completed a survey reporting the time spent caring for the patient and any other expenses. Results were correlated with the three stages of disease severity (mild, moderate and severe) with a multivariate regression model. Results Informal care comprised the largest proportion of the total cost of caring for a patient with dementia. Furthermore, it was found that more severe dementia was associated with higher costs in private and public social and informal care. Conclusions Informal carers provide the majority of care for patients with dementia. More support from social care services is needed to cope with the predicted increase in dementia incidence in the near future.

INTRODUCTION The EMENO (National Morbidity and Risk Factors) survey is one of the first and most representative population-based surveys in Greece due to its study design and sampling procedure. We aimed to estimate the prevalence of smoking, secondhand smoking (SHS) and their potential associations with other socioeconomic and unhealthy lifestyle risk factors. METHODS EMENO is a cross-sectional health status survey conducted in Greece from May 2013 to June 2016. The survey was performed using face-to-face interviews and enrolled 6006 adults. Data were collected through questionnaires administered by trained interviewers. Current smoking (CS) and SHS were based on self-reporting. Analysis accounted for study design. RESULTS Information on smoking was available for 5862 individuals (97.6%). Overall, 37.8% were current and 16.1% former smokers. More males (44.3%) than females (31.6%) were current smokers. CS increased during adulthood and declined sharply in the elderly (p7 glasses/ week, OR=2.52; 95% CI: 1.97–3.23) and lower education level in men were positively associated with ever smoking. Moreover, women aged >35 years and respondents with low adherence to the Mediterranean diet (MD) (high/ low, OR= 0.35; 95% CI: 0.21–0.58) had higher odds to be current smokers than former smokers. Finally, the overall prevalence of exposure to SHS at work, home and public places was 38.8%, 30% and 44.6 %, respectively. CONCLUSIONS Unhealthy lifestyles of smokers, increased rates of CS in vulnerable groups, such as females and young adults, and early age of smoking initiation constitute alarming public health issues in Greece.

Focused ultrasound (FUS) in combination with systemically injected microbubbles can be used to non-invasively open the blood-brain barrier (BBB) in targeted regions for a variety of therapeutic applications. Over the past two decades, preclinical research into the safety and efficacy of FUS-induced BBB opening has proven this technique to be transient and efficacious, propelling FUS-induced BBB opening into several clinical trials in recent years. However, as clinical trials further progress, the neuroinflammatory response to FUS-induced BBB opening needs to be better understood. In this study, we provide further insight into the relationship of microbubble cavitation and the resulting innate immune response to FUS-induced BBB opening. By keeping ultrasound parameters fixed (i.e. frequency, pressure, pulse length, etc.), three groups of mice were sonicated using a real-time cavitation controller until a target cavitation dose was reached (1 [Formula: see text] 10(7) V(2)•s, 5 [Formula: see text] 10(7) V(2)•s, 1 [Formula: see text] 10(8) V(2)•s). The change in relative gene expression of the mouse inflammatory cytokines and receptors were evaluated at three different time-points (6 h, 24 h, and 72 h) after FUS. At both 6 and 24 h time-points, significant changes in relative gene expression of inflammatory cytokines and receptors were observed across all cavitation groups. However, the degree of changes in relative expression levels and the number of genes with significant changes in expression varied across the cavitation groups. Groups with a higher cavitation dose exhibited both greater changes in relative expression levels and greater number of significant changes. By 72 h, the gene expression levels returned to baseline in all cavitation dose groups, signifying a transient inflammatory response to FUS-induced BBB opening at the targeted cavitation dose levels. Furthermore, the real-time cavitation controller was able to produce consistent and significantly different BBB permeability enhancement volumes across the three different cavitation dose groups. These results indicate that cavitation monitoring and controlling during FUS-induced BBB opening can be used to potentially modulate or limit the degree of neuroinflammation, further emphasizing the importance of implementing cavitation controllers as FUS-induced BBB opening is translated into the clinic.

in the early twentieth century, pedagogy, both as theory and practice, was revisited under the influence of two important reform movements. Pedagogy, a newly emerging discipline, established itself as an academic field and placed children, and their needs and experiences, at the core of its research. in greece, the attempt to study the physical and mental development of children was closely linked with the attainment of national goals. This article looks into the attempt of interwar greek educators to delineate and demarcate “normality” and “morbidity” with regard to the development and expression of feelings during childhood. we examine how contemporary sociopolitical conditions, as well as eugenics, influenced not only the scientific discourse on “pathological” emotions but also the ways a new signification model of “normal” and “anomalous” child emotions impacted public discourse on education and the development of the educational system in greece.

BACKGROUND: The role of allium vegetables on gastric cancer (GC) risk remains unclear. METHODS: We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach. RESULTS: Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I(2) > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata. CONCLUSIONS: In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.

Background Urban air pollution is involved in the progress of idiopathic pulmonary fibrosis (IPF). Its potential role on the devastating event of Acute Exacerbation of IPF (AE-IPF) needs to be clarified. This study examined the association between long-term personal air pollution exposure and AE- IPF risk taking into consideration inflammatory mediators and telomere length (TL). Methods All consecutive IPF-patients referred to our Hospital from October 2013-June 2019 were included. AE-IPF events were recorded and inflammatory mediators and TL measured. Long-term personal air pollution exposures were assigned to each patient retrospectively, for O3, NO2, PM2.5 [and PM10, based on geo-coded residential addresses. Logistic regression models assessed the association of air pollutants’ levels with AE-IPF and inflammatory mediators adjusting for potential confounders. Results 118 IPF patients (mean age 72 ± 8.3 years) were analyzed. We detected positive significant associations between AE-IPF and a 10 μg/m3 increase in previous-year mean level of NO2 (OR = 1.52, 95%CI:1.15–2.0, p = 0.003), PM2.5 (OR = 2.21, 95%CI:1.16–4.20, p = 0.016) and PM10 (OR = 2.18, 95%CI:1.15–4.15, p = 0.017) independent of age, gender, smoking, lung function and antifibrotic treatment. Introduction of TL in all models of a subgroup of 36 patients did not change the direction of the observed associations. Finally, O3 was positively associated with %change of IL-4 (p = 0.014) whilst PM2.5, PM10 and NO2 were inversely associated with %changes of IL-4 (p = 0.003, p = 0.003, p = 0.032) and osteopontin (p = 0.013, p = 0.013, p = 0.085) respectively. Conclusions Long-term personal exposure to increased concentrations of air pollutants is an independent risk factor of AE-IPF. Inflammatory mediators implicated in lung repair mechanisms are involved.

Objective: Focused ultrasound (FUS) has emerged as a non-invasive technique to locally and reversibly disrupt the blood-brain barrier (BBB). Here, we investigate the use of diffusion tensor imaging (DTI) as a means of detecting FUS-induced BBB opening at the absence of an MRI contrast agent. A non-human primate (NHP) was repeatedly treated with FUS and preformed circulating microbubbles to transiently disrupt the BBB (n = 4). T1- and diffusion-weighted MRI scans were acquired after the ultrasound treatment, with and without gadolinium-based contrast agent, respectively. Both scans were registered with a high-resolution T1-weighted scan of the NHP to investigate signal correlations. DTI detected an increase in fractional anisotropy from 0.21 ± 0.02 to 0.38 ± 0.03 (82.6 ± 5.2% change) within the targeted area one hour after BBB opening. Enhanced DTI contrast overlapped by 77.22 ± 9.2% with hyper-intense areas of gadolinium-enhanced T1-weighted scans, indicating diffusion anisotropy enhancement only within the BBB opening volume. Diffusion was highly anisotropic and unidirectional within the treated brain region, as indicated by the direction of the principal diffusion eigenvectors. Polar and azimuthal angle ranges decreased by 35.6% and 82.4%, respectively, following BBB opening. Evaluation of the detection methodology on a second NHP (n = 1) confirmed the across-animal feasibility of the technique. In conclusion, DTI may be used as a contrast-free MR imaging modality in lieu of contrast-enhanced T1 mapping for detecting BBB opening during focused-ultrasound treatment or evaluating BBB integrity in brain-related pathologies.

Introduction School-based tobacco control programs exhibit great variety. Our study aimed to evaluate the effectiveness of an experiential learning smoking prevention program in facilitating knowledge acquisition, forging healthy attitudes, and decreasing intention to smoke. Methods A school-based intervention-control study was implemented during the 2016-2017 academic year among middle-school students in Athens, Greece. The experiential learning intervention was delivered using an interdisciplinary approach, bridging excerpts from ancient classical Greek myths, Aesop fables and ancient classical literature (Aristotle, Herodotus, Plutarch, Xenophon, Homer's Epics), with their decoded archetypal symbols applied in a smoking and tobacco control paradigm. An anonymous self-administered questionnaire was used at baseline and at follow-up at 3 months to evaluate program effectiveness. Results A total of 351 students participated in our study; 181 (51.6%) in the intervention group and 170 (48.4%) in the control group. The mean age of student participants was 13 years (SD=0.96). Students in the intervention group were more likely to improve their knowledge of the adverse effects of smoking, develop attitudes against smoking and report a negative intention to smoke in the first year following the intervention, compared to the control group. Conclusions This study provides evidence that school-based experiential learning smoking prevention programs improve smoking-related knowledge, enhance anti-smoking attitudes and reinforce negative intentions toward tobacco products.

Karakatsani Despina, Lahlou Sofia Trantas Petros Application of Freinet Pedagogy in Greece. Research tools & evaluation of the educational experience. Evaluation survey of the Pilot Project 2017-2018 Δέσποινα Καρακατσάνη, Σοφία Λάχλου, Πέτρος Τραντάς Εφαρμογή της Παιδαγωγικής Freinet στην Ελλάδα. Ερευνητικά εργαλεία & αποτίμηση της εκπαιδευτικής εμπειρίας Έρευνα αξιολόγησης του Πιλοτικού προγράμματος επιμόρφωσης και εφαρμογής της Παιδαγωγικής Freinet στη δημόσια εκπαίδευση 2017 2018 Διοργάνωση: Ινστιτούτο Εκπαιδευτικής Πολιτικής Παιδαγωγική Ομάδα «Το Σκασιαρχείο» - Πειραματικοί ψηλαφισμοί για ένα σχολείο της κοινότητας,https://skasiarxeio.wordpress.com/ ISBN: 978-618-83056-3-2 Έτος έκδοσης: 2019 © Παιδαγωγική Ομάδα «Το Σκασιαρχείο» - Πειραματικοί ψηλαφισμοί για ένα σχολείο της κοινότητα&sigmaf

The gut has a specific vascular barrier that controls trafficking of antigens and microbiota into the bloodstream. However, the molecular mechanisms regulating the maintenance of this vascular barrier remain elusive. Here, we identified Caspase‐8 as a pro‐survival factor in mature intestinal endothelial cells that is required to actively maintain vascular homeostasis in the small intestine in an organ‐specific manner. In particular, we find that deletion of Caspase‐8 in endothelial cells results in small intestinal hemorrhages and bowel inflammation, while all other organs remained unaffected. We also show that Caspase‐8 seems to be particularly needed in lymphatic endothelial cells to maintain gut homeostasis. Our work demonstrates that endothelial cell dysfunction, leading to the breakdown of the gut‐vascular barrier, is an active driver of chronic small intestinal inflammation, highlighting the role of the intestinal vasculature as a safeguard of organ function.

Background: Monogenic and polygenic inheritances are evidenced for idiopathic pulmonary fibrosis (IPF). Pathogenic variations in surfactant protein-related genes, telomere-related genes (TRGs), and a single-nucleotide polymorphism in the promoter of MUC5B gene encoding mucin 5B (rs35705950 T risk allele) are reported. This French-Greek collaborative study, Gen-Phen-Re-GreekS in inheritable IPF (iIPF), aimed to investigate genetic components and patients’ characteristics in the Greek national IPF cohort with suspected heritability. Patients and Methods: 150 patients with familial PF, personal-family extrapulmonary disease suggesting short telomere syndrome, and/or young age IPF were analyzed. Results: MUC5B rs35705950 T risk allele was detected in 103 patients (90 heterozygous, 13 homozygous, allelic frequency of 39%), monoallelic TRG pathogenic variations in 19 patients (8 TERT, 5 TERC, 2 RTEL1, 2 PARN, 1 NOP10, and 1 NHP2), and biallelic ABCA3 pathogenic variations in 3. Overlapping MUC5B rs35705950 T risk allele and TRG pathogenic variations were shown in 11 patients (5 TERT, 3 TERC, 1 PARN, 1 NOP10, and 1 NHP2), MUC5B rs35705950 T risk allele, and biallelic ABCA3 pathogenic variations in 2. In 38 patients, neither MUC5B rs35705950 T risk allele nor TRG pathogenic variations were detectable. Kaplan-Meier curves showed differences in time-to-death (p = 0.025) where patients with MUC5B rs35705950 T risk allele alone or in combination with TRG pathogenic variations presented better prognosis. Conclusion: The Gen-Phen-Re-GreekS in iIPF identified multiple and overlapping genetic components including the rarest, underlying disease’s genetic “richesse,” complexity and heterogeneity. Time-to-death differences may relate to diverse IPF pathogenetic mechanisms implicating “personalized” medical care driven by genotypes in the near future.

Background Stroke incidence and case-fatality are reported to decline in high-income countries during the last decades. Epidemiological studies are important for health services to organize prevention and treatment strategies. Aims The aim of this population-based study was to determine temporal trends of stroke incidence and case-fatality rates of first-ever stroke in Arcadia, a prefecture in southern Greece. Methods All first-ever stroke cases in the Arcadia prefecture were ascertained using the same standard criteria and multiple overlapping sources in three study periods: from November 1993 to October 1995; 2004; and 2015–2016. Crude and age-adjusted to European population incidence rates were compared using Poisson regression. Twenty-eight days case fatality rates were estimated and compared using the same method. Results In total, 1315 patients with first-ever stroke were identified. The age-standardized incidence to the European population was 252 per 100,000 person-years (95% CI 231–239) in 1993/1995, 252 (95% CI 223–286) in 2004, and 211 (192–232) in 2015/2016. The overall age- and sex-adjusted incidence rates fell by 16% (incidence rates ratio 0.84, 95% CI: 0.72–0.97). Similarly, 28-day case-fatality rate decreased by 28% (case fatality rate ratio = 0.72, 95% CI: 0.58–0.90). Conclusions This population-based study reports a significant decline in stroke incidence and mortality rates in southern Greece between 1993 and 2016.

Background Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort. Methods Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93–1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73–0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94–1.05). Conclusions While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies.

Over the last two decades, it has become clear that classical molecules that regulate neurodevelopment also play an important role in directly regulating the development of the vascular system and vice versa. The prototypical angiogenic ligand vascular endothelial growth factor (VEGF) is by now also regarded as a molecular regulator of different neurodevelopmental processes, such as neuronal progenitor proliferation, migration and differentiation, dendritic and axonal branching and synaptogenesis. The direct effect of other classical angiogenic factors, such as angiopoietins and its receptor Tie2, on neurodevelopmental processes remains less defined. Recent work from our group indicates that the angiopoietin-Tie2 pathway does not only regulate blood vessel formation and stabilization but also simultaneously affect neuronal dendritogenesis in a cell-autonomous manner. In this mini-review, we will integrate our findings within the current understanding of the neurovascular link and within the previous knowledge of the potential effects of angiopoietins in the neuronal context.

International audience; Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.

This is the peer reviewed version of the following article: Naudin, S., Margalef, M.S., Hosnijeh, F.S., Nieters, A., Kyrø, C. Tjønneland, A. ... Ferrari, P. (2020) Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study. International Journal of Cancer, 147(6):1649-1656, which has been published in final form at https://doi.org/10.1002/ijc.32977. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL) were evaluated in a large‐scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow‐up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1‐standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1‐SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.

Background: The role of allium vegetables on gastric cancer (GC) risk remains unclear. Methods: We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the “Stomach cancer Pooling (StoP) Project”, including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach. Results: Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56–0.90), with substantial heterogeneity across studies (I2 > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55–0.86) for onions and 0.83 (95% CI, 0.75–0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29–0.86) but not European (OR 0.96, 95% CI, 0.81–1.13) and American (OR 0.66, 95% CI, 0.39–1.11) studies. Results were consistent across all other strata. Conclusions: In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation. © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

Background: Stroke incidence and case-fatality are reported to decline in high-income countries during the last decades. Epidemiological studies are important for health services to organize prevention and treatment strategies. Aims: The aim of this population-based study was to determine temporal trends of stroke incidence and case-fatality rates of first-ever stroke in Arcadia, a prefecture in southern Greece. Methods: All first-ever stroke cases in the Arcadia prefecture were ascertained using the same standard criteria and multiple overlapping sources in three study periods: from November 1993 to October 1995; 2004; and 2015–2016. Crude and age-adjusted to European population incidence rates were compared using Poisson regression. Twenty-eight days case fatality rates were estimated and compared using the same method. Results: In total, 1315 patients with first-ever stroke were identified. The age-standardized incidence to the European population was 252 per 100,000 person-years (95% CI 231–239) in 1993/1995, 252 (95% CI 223–286) in 2004, and 211 (192–232) in 2015/2016. The overall age- and sex-adjusted incidence rates fell by 16% (incidence rates ratio 0.84, 95% CI: 0.72–0.97). Similarly, 28-day case-fatality rate decreased by 28% (case fatality rate ratio = 0.72, 95% CI: 0.58–0.90). Conclusions: This population-based study reports a significant decline in stroke incidence and mortality rates in southern Greece between 1993 and 2016. © 2021 World Stroke Organization.

BACKGROUND: Evidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and gastric cancer in the Stomach cancer Pooling (StoP) Project consortium. METHODS: A total of 9438 cases and 20,451 controls from 22 studies worldwide were included. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer for regular versus non-regular tea drinkers were estimated by one and two-stage modelling analyses, including terms for sex, age and the main recognised risk factors for gastric cancer. RESULTS: Compared to non-regular drinkers, the estimated adjusted pooled OR for regular tea drinkers was 0.91 (95% CI: 0.85-0.97). When the amount of tea consumed was considered, the OR for consumption of 1-2 cups/day was 1.01 (95% CI: 0.94-1.09) and for >3 cups/day was 0.91 (95% CI: 0.80-1.03). Stronger inverse associations emerged among regular drinkers in China and Japan (OR: 0.67, 95% CI: 0.49-0.91) where green tea is consumed, in subjects with H. pylori infection (OR: 0.68, 95% CI: 0.58-0.80), and for gastric cardia cancer (OR: 0.64, 95% CI: 0.49-0.84). CONCLUSION: Our results indicate a weak inverse association between tea consumption and gastric cancer.

Objective This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls. Methods A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer. Results Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only. Conclusions These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.

Background: The coronavirus disease (COVID-19) pandemic has posed an unprecedented challenge to health systems, and has significantly affected the healthcare of lung cancer patients. The aim of our study was to assess the impact of COVID-19 on early lung cancer patients’ surgical treatment. Methods: All consecutive patients with early-stage non-small cell lung cancer eligible for surgical treatment stage I/II and resectable stage III, referred to our department during the first wave of COVID-19 between February to May 2020, were included and compared with those on the exact corresponding quarter in 2019, one year before the pandemic. Waiting time to surgical treatment, increase of tumor’s size and increase on lung cancer stage were recorded and compared. All subjects were followed up for 12 months. Multiple linear and logistic regression models were applied to assess the differences in the management of the studied groups adjusting for potential confounders. Results: Sixty-one patients with early-stage lung cancer were included in the study; 28 (median age 67 years, SD: 7.1) during the pandemic and 33 (median age 67.1 years, SD: 7.5) one year earlier. A significantly longer period of waiting for treatment and an increase in tumor size were observed during the pandemic compared to before the pandemic [median time 47 days, interquartile rate (IQR): 23–100] vs. [median time 18 days, IQR: 11–23], p < 0.001. No significant differences were detected in the increase of the stage of lung cancer between the subgroups. Conclusion: The COVID-19 pandemic had a significant impact on surgical and oncological care, leading to significant delays on treatment and an increase in tumor size in early-stage lung cancer patients.

Focused ultrasound-enhanced intranasal (IN + FUS) delivery is a noninvasive approach that utilizes the olfactory pathway to administer pharmacological agents directly to the brain, allowing for a more homogenous distribution in targeted locations compared to IN delivery alone. However, whether such a strategy has therapeutic values, especially in neurodegenerative disorders such as Parkinson’s disease (PD), remains to be established. Herein, we evaluated whether the expression of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine catalysis, could be enhanced by IN + FUS delivery of brain-derived neurotrophic factor (BDNF) in a toxin-based PD mouse model. Mice were put on the subacute dosing regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), producing bilateral degeneration of the nigrostriatal pathway consistent with early-stage PD. MPTP mice then received BDNF intranasally followed by multiple unilateral FUS-induced blood-brain barrier (BBB) openings in the left basal ganglia for three consecutive weeks. Subsequently, mice were survived for two months and were evaluated morphologically and behaviorally to determine the integrity of their nigrostriatal dopaminergic pathways. Mice receiving IN + FUS had significantly increased TH immunoreactivity in the treated hemisphere compared to the untreated hemisphere while mice receiving only FUS-induced BBB opening or no treatment at all did not show any differences. Additionally, behavioral changes were only observed in the IN + FUS treated mice, indicating improved motor control function in the treated hemisphere. These findings demonstrate the robustness of the method and potential of IN + FUS for the delivery of bioactive factors for treatment of neurodegenerative disorder.

Η ψυχιατρική περίθαλψη στον Ελλαδικό χώρο ακολούθησε παρόμοια πορεία με την υπόλοιπη Ευρώπη με μία σημαντική διαφορά, την καθυστέρηση στη δημιουργία ασύλων. Η παρούσα ερευνητική μελέτη στοχεύει στη διερεύνηση: α) της ανάπτυξης των ψυχιατρικών νοσοκομείων στο Ελληνικό κράτος και του ιστορικοκοινωνικού πλαισίου από τις αρχές έως τα μέσα του 20ου αιώνα και β) της διαμόρφωσης της Ψυχιατρικής Μεταρρύθμισης (ΨΜ). Η μεθοδολογία που ακολουθήθηκε περιελάμβανε την αναζήτηση σχετικής βιβλιογραφίας και ερευνητικών δεδομένων, τα οποία συλλέχθηκαν μέσα από την ηλεκτρονική βάση δεδομένων Google Scholar, μέσα από έντυπα, άρθρα, περιοδικά, διπλωματικές εργασίες και διδακτορικές διατριβές. Η μελέτη αναδεικνύει ότι τα προφανή κενά και οι σοβαρότατες ελλείψεις της ψυχιατρικής περίθαλψης στην Ελλάδα, κατά τις προηγούμενες δεκαετίες, δεν ήταν αρκετά για να επισημανθεί η αναγκαιότητα της ΨΜ, αλλά εκλήφθηκαν ως μία ακόμη επιβαλλόμενη υποχρέωση έναντι της πορείας προς τον εξευρωπαϊσμό., Psychiatric care in Greece followed a similar course to the rest of Europe with a significant difference, the delay in the creation of asylum. The present study aims to investigate a) the development of psychiatric hospitals in the Greek state as well as the historical and social context from the beginning to the middle of the 20th century and b) the formulation of the Psychiatric Reform (PR) program. The methodology followed included literature and research data review, which were collected through online databases, publications, articles, journals, and dissertations. A crucial outcome of the study is that the obvious gaps and the very serious shortages of psychiatric care in Greece, during the previous decades, were not enough to point out the necessity of a Psychiatric Reform (PR), but were only perceived as another imposed obligation towards europeanization.

Objective This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls. Methods A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer. Results Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only. Conclusions These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.

BackgroundMetabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk.MethodsA nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression.ResultsAmong women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity.ConclusionsThese findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

Background Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. Methods We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses’ Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. Conclusions The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.

BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies.FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively.INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.

Background To investigate the knowledge level, attitudes and perceptions of Gynecology healthcare professionals in Greece towards breastfeeding. Methods A self-administered questionnaire was provided asking to answer multiple choice questions. The study was conducted mainly at the facilities of Medical Faculty Aristotle University of Thessaloniki. The questionnaire was administered to 312 healthcare professionals (nurses, students, physicians and other healthcare professionals). Results Over 70% supported that their breastfeeding knowledge was moderate at best and could be further improved. 30% lacked knowledge concerning the management of special breastfeeding scenarios. 84% had previous personal breastfeeding experience or at least are willing to do so in the future (themselves or their partners) with 39.1% aiming to breastfeed approximately for one year. The same pattern was observed in terms of their breastfeeding recommendations to other mothers regardless of their sex. 59.6% admitted that they do not have the necessary time to properly inform mothers about breastfeeding while 72.4% acknowledged improper breastfeeding information as an important factor for the low breastfeeding rates in Greece. Finally, 80.4% stated that their education was lacking in didactic depth and their training in hands-on experience while 88.8% clearly underlined that there was definitely room for improvement in their education/training curriculum. Expert teams, well-organized educational programs and advanced computing could contribute to the personnel’s harmonization with the various breastfeeding objectives to create a “breastfeeding-friendly” social environment. Conclusions This study revealed that although most Greek gynecology healthcare professionals have very positive attitudes towards breastfeeding, their breastfeeding knowledge was moderate at best and could be further improved.

Introduction Banning smoking at home, schools, children’s playgrounds and indoor environments, constitutes an integral part of tobacco control efforts to prevent uptake of smoking among young teenagers. We aimed at exploring the role of teenagers as facilitators of change in enforcing a home no-smoking rule following school-based anti-tobacco programs and examining the effect of home no-smoking rule on teenagers’ intention to smoke. Methods A school-based intervention-control study was implemented during the 2016–2017 academic year among middle-school students in Athens, Greece. The experiential learning intervention was delivered using an interdisciplinary approach, bridging excerpts from ancient classical Greek myths and ancient classical literature, with their decoded archetypal symbols applied in a smoking and tobacco control paradigm. An anonymous selfadministered questionnaire was used at baseline, and at follow-up at 3 months to evaluate program effectiveness. A chi-squared test was used for categorical variables and a t-test for continuous variables. Cohen’s distance (d) was employed to examine the intervention effect size. A two-tailed p≤0.05 was considered statistically significant using IBM SPSS V.22. Results In all, 351 students participated. At baseline, 47.5% in the intervention group reported a home no-smoking rule and 86% indicated being unlikely to smoke, these increased to 61.3% (p=0.016) and 98.2% (p

This is a post-peer-review, pre-copyedit version of an article published in the European Journal of Epidemiology. The final authenticated version is available online at: https://doi.org/10.1007/s10654-019-00559-6. Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants’ shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e−09) and 0.77 (0.72, 0.82; ptrend = 1.7e−15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e−04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.

We find evidence that banks actively use leverage to attain RoE targets and that leverage adjustments are primarily driven by capital distributions to shareholders. Using a large group of publicly-traded commercial banks from the US and the EU for the period 2001–2013, we demonstrate that this effect particularly holds for large banks before the crisis. Such behaviour may have led banks to enter the crisis with insufficient capital buffers to absorb losses, requiring unprecedented support by the public sector to maintain their solvency. Therefore, recent policies restricting the use of RoE as a metric in remuneration schemes and introducing constraints to capital distributions unless banks maintain certain buffers above the regulatory minimum, are in the right direction.

Self-injurious and aggressive behaviors are common in fragile X syndrome (FXS). However, little is known about the persistence of these behaviors and associated risk markers. We established the prevalence and persistence of self-injurious and aggressive behaviors over eight years in males with FXS, and associations with risk markers. Results showed 77% and 69% persistence rates for self-injurious and aggressive behavior, respectively. Baseline levels of repetitive behavior predicted persistent self-injurious behavior. Chronological age, impulsivity and overactivity were associated with persistent aggressive behavior but only impulsivity predicted persistence. This is the first study to document the persistence of self-injurious and aggressive behavior in FXS over the medium to long term and to identify behavioral risk markers that might facilitate targeted early intervention.

The neuropathological hallmarks of Alzheimer's disease include amyloid plaques and neurofibrillary tangles. Tau pathology correlates well with impaired neuronal activity and dementia. Focused ultrasound coupled with systemic administration of microbubbles has previously been shown to open the blood-brain barrier and induce an immune response, which, in an amyloid AD mouse model, resulted in the reduction of the amyloid brain load. Methods: In this study, we investigated the effect of focused ultrasound at the early stages of tau pathology (pre-tangle) in the rTg4510 mouse model. Results: Reduction of phosphorylated tau from the hippocampal formation processes, and particularly the pyramidal CA1 neurons, was noted in the ultrasound-treated brains without an associated increase in the phosphorylated tau-affected cell somas, typically associated with disease progression. Attenuation of the pathology was found to correlate well with the ultrasound-initiated immune response without compromising neuronal integrity. Unilateral ultrasound application resulted in a bilateral effect indicating a broader reduction of the phosphorylated tau. Conclusion: Findings presented herein reinforce the premise of ultrasound in reducing tau pathology and thus curbing the progression of Alzheimer's disease.

Background: Air pollution affects idiopathic pulmonary fibrosis (IPF) patients and is a risk factor for IPF-Acute-Exacerbation (IPF-AE). Pathogenetic mechanisms could implicate pathways of tissue regeneration and repair following injury. Aim and objectives: To examine the association of long-term air pollution exposure with inflammatory mediators involved in lung repair, in IPF and AE-IPF. Methods: Consecutive IPF patients referred to our Department from October 2013 to June 2019 were included. Diagnoses were based on international guidelines. Long-term personal air pollution exposures were assigned to each patient retrospectively, for O3, NO2, PM2.5, PM10 based on geo-coded residential addresses. Inflammatory mediators (IL-1a, IL-1b, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, active TGF-β, TNFa, CCL2, CCL3, CCL-18, MMP-1, MMP-7, MMP-9, osteopontin) were measured in the peripheral blood by ELISA. Linear regression models were used adjusting for confounders. Results: 118 IPF patients (mean age 72±8.3 years) were included. In AE-IPF, a 10μg/m3 increase in O3 was significantly positively associated with 40.4% change of IL-4 (p=0.011) and marginally with 40% a 62.2% changes of IL-13 (p=0.052) and osteopontin (p=0.097). PM2.5, PM10 and NO2 were inversely associated with 50.6, 50.8 a 21.7% changes of IL-4 (p=0.003, p=0.003, p=0.022, respectively) and 73.2, 74.6 a 32.4% changes of osteopontin (p=0.024, p=0.022, p=0.097, respectively). In stable IPF patients, PM2.5 and PM10 were positively associated with an increase in the 76% changes of IL-13 (p=0.059, p=0.058, respectively). Conclusion: Our findings support an association of IL-4, IL-13 and osteopontin with IPF-AE related to air pollution long-term exposure. Discrepancies in the impact of different pollutants need further investigation.

Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences., National Health and Medical Research Council of Australia 1074383 209057 396414 GNT1163120, Canadian Institutes of Health Research (CIHR) Cancer Council Victoria, Cancer Research UK C570/A16491 C8221/A19170 C864/A14136, Catalan Institute of Oncology - ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission European Commission Joint Research Centre, Foundation for Alcohol Research and Education (Australia), French Ministry of Health GR-IARC-2003-09-12-01, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Junta de Andalucía, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Sante et de la Recherche Medicale (Inserm), Consiglio Nazionale delle Ricerche (CNR), Associazione Italiana per la Ricerca sul Cancro (AIRC), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MC-UU_12015/1 MR/M012190/1 MR/N003284/, Mutuelle Generale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association (UK), British Heart Foundation, Department of Health (UK), Food Standards Agency (UK), Wellcome Trust, Swedish Cancer Society, Swedish Scientific Council (Sweden), Regional Government of Skane (Sweden), Federal Ministry of Education & Research (BMBF), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), Institut Gustave Roussy

Background Urban air pollution is involved in the progress of idiopathic pulmonary fibrosis (IPF). Its potential role on the devastating event of Acute Exacerbation of IPF (AE-IPF) needs to be clarified. This study examined the association between long-term personal air pollution exposure and AE- IPF risk taking into consideration inflammatory mediators and telomere length (TL). Methods All consecutive IPF-patients referred to our Hospital from October 2013-June 2019 were included. AE-IPF events were recorded and inflammatory mediators and TL measured. Long-term personal air pollution exposures were assigned to each patient retrospectively, for O-3, NO2, PM2.5 [and PM10, based on geo-coded residential addresses. Logistic regression models assessed the association of air pollutants’ levels with AE-IPF and inflammatory mediators adjusting for potential confounders. Results 118 IPF patients (mean age 72 +/- 8.3 years) were analyzed. We detected positive significant associations between AE-IPF and a 10 mu g/m(3) increase in previous-year mean level of NO2 (OR = 1.52, 95%CI:1.15-2.0, p = 0.003), PM2.5 (OR = 2.21, 95%CI:1.16-4.20, p = 0.016) and PM10 (OR = 2.18, 95%CI:1.15-4.15, p = 0.017) independent of age, gender, smoking, lung function and antifibrotic treatment. Introduction of TL in all models of a subgroup of 36 patients did not change the direction of the observed associations. Finally, O-3 was positively associated with %change of IL-4 (p = 0.014) whilst PM2.5, PM10 and NO2 were inversely associated with %changes of IL-4 (p = 0.003, p = 0.003, p = 0.032) and osteopontin (p = 0.013, p = 0.013, p = 0.085) respectively. Conclusions Long-term personal exposure to increased concentrations of air pollutants is an independent risk factor of AE-IPF. Inflammatory mediators implicated in lung repair mechanisms are involved.