The Impact of Education and Culture on Poverty Reduction: Evidence from Panel Data of European Countries.

The 2030 Agenda has among its key objectives the poverty eradication through increasing the level of education. A good level of education and investment in culture of a country is in fact necessary to guarantee a sustainable economy, in which coexists satisfactory levels of quality of life and an equitable distribution of income. There is a lack of studies in particular on the relations between some significant dimensions, such as education, culture and poverty, considering time lags for the measurement of impacts. Therefore, this study aims to fill this gap by focusing on the relationship between education, culture and poverty based on a panel of data from 34 European countries, over a 5-year period, 2015-2019. For this purpose, after applying principal component analysis to avoid multicollinearity problems, the authors applied three different approaches: pooled-ordinary least squares model, fixed effect model and random effect model. Fixed-effects estimator was selected as the optimal and most appropriate model. The results highlight that increasing education and culture levels in these countries reduce poverty. This opens space to new research paths and policy strategies that can start from this connection to implement concrete actions aimed at widening and improving educational and cultural offer.

Telomeric nucleosomes: forgotten players at chromosome ends.

Telomeres are the special nucleoprotein structures that protect chromosome ends from both recombination and degradation. In most organisms, telomeric DNA consists of short sequences repeated in tandem ending in single-stranded G-rich overhangs. In higher eukaryotes, about 80% of telomeric DNA is organized in tightly packed nucleosomes separated by 10-20 bp of linker DNA. Several specific proteins contribute to telomeric structure. At the moment, a satisfactory description of telomere organization is still lacking. Whereas the role played by telomeric proteins in telomere function and regulation has been widely investigated, little is known about the contribution of nucleosomes to the protection of chromosome ends. In this review we present an overview on the chromatin organization in lower and higher eukaryotes, and discuss the recent results on the peculiar features of telomeric nucleosomes and on the epigenetic status of mammalian telomeres.

Establishment and characterization of SV40 T-antigen immortalized human esophageal epithelial cells.

Normal human esophageal autopsy tissue was explanted in serum-free medium. The epithelial outgrowths were subcultured and then transfected by strontium phosphate coprecipitation with plasmid pRSV-T consisting of the RSV-LTR promoter and the sequence encoding the simian virus 40 large T-antigen. The transfected cells, but not the sham-transfected controls, formed multilayered colonies within 3-4 weeks, after which the colonies were transferred and cell strains (HE-451 and HE-457) developed. Both cell strains grew exponentially for 8-10 weeks and then senesced. After a "crisis" of 6-8 months, growth resumed in isolated colonies. One line, HET-1A from HE-457, was developed and has now undergone more than 250 population doublings. This line has retained epithelial morphology, stains positively for cytokeratins and the simian virus 40 T-antigen gene by immunofluorescence, and has remained nontumorigenic in athymic, nude mice for more than 12 months. Karyotypic analysis by Giemsa banding has shown that HET-1A is hypodiploid (34-40 chromosomes). Growth factor studies have shown that HET-1A is stimulated by Ca2+, and inhibited by fetal bovine serum, transforming growth factor-beta 1, and transforming growth factor-beta 2. This serum-free immortalized esophageal cell system will be useful for investigating the action of putative esophageal carcinogens.

Inhibitory effects of phenethyl isothiocyanate on N-nitrosobenzylmethylamine carcinogenesis in the rat esophagus.

F-344 rats fed diets containing phenethyl isothiocyanate (PEITC; 3 and 6 mumol/g diet), a naturally occurring constituent of cruciferous vegetables, before and during treatment with the carcinogen N-nitrosobenzylmethylamine (NBMA), developed 99-100% fewer esophageal tumors than NBMA-treated control rats. PEITC exhibited inhibitory effects against both preneoplastic lesions (acanthosis and hyperkeratosis, leukoplakia, leukokeratosis) and neoplastic lesions (papilloma, carcinoma). Tumors were not observed in rats treated with PEITC alone. The effects of PEITC (10, 25, 50, 100 microM) on the metabolism and DNA binding of NBMA in cultured explants of rat esophagus were also investigated. PEITC produced a marked (53-97%) dose-dependent inhibition in the binding of NBMA metabolites to DNA and in the levels of DNA methylation at the N7 (20-89%) and O6 (55-93%) positions of guanine. This isothiocyanate also reduced the metabolism of NBMA by esophageal tissues as indicated by increased amounts of unmetabolized NBMA in the medium of cultures containing PEITC. Collectively, these data indicate that PEITC is a potent inhibitor of NBMA-induced esophageal carcinogenesis in rats.

Adenomas induced by polycyclic aromatic hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels.

The induction of DNA adducts and adenomas in the lungs of strain A/J mice has been investigated following the single i.p. administration of each of the following polycyclic aromatic hydrocarbons (PAH): pyrene, dibenz[a,h]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, 5-methylchrysene, and cyclopenta[c,d]pyrene. DNA adducts were measured by 32P-postlabeling at times between 1 and 21 days following injection, while adenomas were counted at 240 days after treatment. Pyrene did not induce either DNA adducts or lung adenomas at any of the doses examined. Each of the remaining PAH induced both adenomas and DNA adducts in a dose-dependent manner, with dibenz[a,h]anthracene > 5-methylchrysene > cyclopenta[c,d]pyrene > benzo[a]pyrene > benzo[b]fluoranthene. DNA adducts reached maximal levels between 3 and 9 days after injection, followed by a gradual decrease. The time-integrated DNA adduct level (TIDAL) was calculated by numerically integrating the areas under the adduct persistence curves extrapolated to 240 days for each PAH at each dose level. This value represents the effective total molecular dose of PAH that was delivered to the lung DNA over the entire course of tumorigenesis. A strong correlation of lung adenoma induction with the TIDAL values was observed for each PAH. The slopes of the tumors versus TIDAL value relationships were essentially identical for 5-methylchrysene, cyclopenta[cd]pyrene, benzo[a]pyrene, and benzo[b]fluoranthene. The slope of this relationship for dibenz[a,h]anthracene was markedly greater. The essentially identical induction of adenomas as a function of TIDAL values for these PAH suggests that the formation and persistence of DNA adducts determines their carcinogenic potency.

Prognostic value of high dose dipyridamole echocardiography in patients with chronic coronary artery disease and preserved left ventricular function.

OBJECTIVES: The prognostic value of dipyridamole echocardiography was assessed in patients with chronic coronary artery disease and preserved left ventricular function. BACKGROUND: Few data are available on the prognostic value of dipyridamole echocardiography in patients with a low risk of cardiac events. METHODS: Two hundred sixty-eight consecutive patients with stable, proven or suspected coronary artery disease and ejection fraction > or = 0.40 underwent high dose (up to 0.84 mg/kg body weight) dipyridamole echocardiography. In 204 patients definite exercise electrocardiographic (ECG) results were also available. RESULTS: During a mean (+/- SD) follow-up period of 16 +/- 8 months (range 6 to 36), 33 spontaneous events occurred: 15 "hard" events (cardiac death [n = 6], myocardial infarction [n = 9]) and 18 "soft" events (unstable angina). Events occurred more frequently in patients with positive findings on dipyridamole echocardiography (59% vs. 3%, p < 0.001; hard events 24% vs. 2%, p < 0.01). A positive response at the low dose (up to 0.56 mg/kg) identified patients with a high incidence of hard events (7 of 16 patients, sensitivity 50%, specificity 96%). In patients with an exercise ECG, a comparable sensitivity for cardiac events was found (89% vs. 93%, p = NS), but dipyridamole echocardiography was more specific (91% vs. 61%, p < 0.01). A positive response on the low work load exercise ECG (< 8 min) and a positive response to low dose dipyridamole echocardiography had similar accuracy (82% vs. 90%, p = NS). Cox analysis identified dipyridamole echocardiography as the best predictor of cardiac events (odds ratio [OR] 20.9, 95% confidence interval [CI] 10.8 to 37.9); the highest risk of hard events was found in patients with a positive response to low dose dipyridamole echocardiography (OR 25.4, 95% CI 12.2 to 54.1). CONCLUSIONS: In patients with chronic coronary artery disease and a low incidence of cardiac events, dipyridamole echocardiography was effective in prognostic stratification, and positive low work load exercise ECG results were a reliable predictor of subsequent events. Consequently, dipyridamole echocardiography should be considered a complementary tool in the presence of high work load positivity or ambiguous exercise ECG results.

Value of pharmacologic stress echocardiography in risk stratification of patients with single-vessel disease: a report from the Echo-Persantine and Echo-Dobutamine International Cooperative Studies.

OBJECTIVES: This study sought to verify the effectiveness of pharmacologic stress echocardiography in risk stratification of patients with single-vessel disease. BACKGROUND: Noninvasive prognostic assessment of single-vessel disease is an unresolved issue to date. METHODS: The study evaluated prospectively collected data from 754 patients with angiographic single-vessel disease who underwent either dipyridamole (n = 576) or dobutamine (n = 178) stress echocardiography. Invasive treatment (coronary revascularization within 3 months of stress testing) was performed in 260 patients and medical treatment in 494. RESULTS: Echocardiographic positivity was observed in 421 patients (56%). Patients treated invasively had a higher incidence of stress test positivity (69% vs. 49%, p < 0.001) and left anterior descending coronary artery involvement (60% vs. 46%, p < 0.001) than patients maintained with medical therapy. During a mean follow-up of 37 months, 54 hard cardiac events occurred (14 deaths, 40 nonfatal infarctions): 37 in medically and 17 in invasively treated patients (7.5% vs. 6.5%, p = NS). On Cox analysis, a positive result on stress testing was the only independent prognostic predictor in medically treated patients (relative risk 2.92, 95% confidence interval 1.29 to 6.59). The 4-year infarction-free survival rate was higher for a negative than a positive stress test result in medically (93.9% vs. 87.3%, p = 0.009) but not invasively treated patients (92.7% vs. 97.1%, p = 0.545). Moreover, a significantly higher 4-year infarction-free survival rate was found in invasively versus medically treated patients with a positive (p = 0.012), but not in those with a negative, stress test result (p = 0.853). CONCLUSIONS: Pharmacologic stress echocardiography is effective in risk stratification of single-vessel disease and can accurately discriminate patients in whom coronary revascularization can have the maximal beneficial effect. These findings have a potential favorable impact on the cost-effectiveness of invasive procedures.

The atropine factor in pharmacologic stress echocardiography. Echo Persantine (EPIC) and Echo Dobutamine International Cooperative (EDIC) Study Groups.

OBJECTIVES: This study sought to compare, head to head, the two most popular pharmacologic stress echocardiographic tests--dipyridamole and dobutamine--with state of the art protocols in a large multicenter prospective study. BACKGROUND: In the continuing quest for ideal diagnostic accuracy, pharmacologic stress echocardiography has quickly moved over the years from low to high dose regimens and is currently performed with atropine coadministration. METHODS: Dobutamine (up to 40 microgram/kg body weight per min) plus atropine (up to 1 mg over 4 h) and dipyridamole (up to 0.84 mg/kg per min over 10 h) plus atropine (up to 1 mg over 4 h) stress echocardiography was performed on different days, in random order and within 1 week in 360 patients with chest pain syndrome. Thirteen different echocardiographic laboratories, all fulfilling quality control criteria for stress echocardiographic reading, contributed to the study. RESULTS: No major complications occurred during either test. The test was interrupted before achievement of predetermined end points for limiting side effects in 37 dobutamine-atropine and 7 dipyridamole-atropine stress echocardiographic studies (feasibility 90% vs. 98%, p < 0.01). Diagnostic accuracy was assessed in a subset of 110 patients with no obvious rest dyssynergy (akinesia or dyskinesia) who underwent coronary angiography independently of test results and within 1 week of testing. Significant coronary artery disease (> or = 50% diameter reduction in at least one major coronary vessel by quantitative coronary angiography) was found in 92 patients. Sensitivity for detection of coronary artery disease was 84% (77 of 92) for dobutamine-atropine and 82% (75 of 92) for dipyridamole-atropine stress echocardiography (p = NS), with a specificity of 89% (16 of 18) for dobutamine-atropine and 94% (17 of 18) for dipyridamole-atropine stress echocardiography (p = NS). A significant correlation was present between peak wall motion score index during dipyridamole-atropine and dobutamine-atropine stress echocardiography (r = 0.83, p < 0.0001). CONCLUSIONS: Dobutamine-atropine and dipyridamole-atropine stress echocardiography are safe and feasible, although submaximal studies are more frequent with dobutamine. The two stresses have comparable accuracy in the detection of angiographically assessed coronary artery disease, although dobutamine is marginally more sensitive and dipyridamole marginally more specific. Stratification of the ischemic response in the space domain is also comparable with the two stresses.

Prognostic interaction between viability and residual myocardial ischemia by dobutamine stress echocardiography in patients with acute myocardial infarction and mildly impaired left ventricular function.

Dobutamine stress echocardiography (DSE) accurately detects viable myocardium and residual ischemia in patients with acute myocardial infarction (AMI). The prognostic interaction of viability and ischemia has not been completely clarified in these patients. This study assesses the long-term effect of viability, ischemia, or their combination on survival in patients with AMI and mildly impaired left ventricular (LV) function. Four hundred eleven patients (age 57 +/- 9 years) underwent predischarge DSE (up to 40 microg/kg/min plus atropine if needed) after uncomplicated AMI and were prospectively followed for 23 months (range 1 to 78). According to DSE findings, patients were divided into 4 groups: viability only, ischemia only, combination of viability and ischemia, and scar. Adverse outcome occurred in 64 patients: 34 patients had hard events (9 cardiac deaths, 25 nonfatal AMI) and 30 patients had unstable angina requiring hospitalization. The combination of viability and ischemia, diabetes mellitus, and non-Q-wave AMI were significant predictors of all events at univariate and multivariate analysis. The same variables were also univariate predictors of hard events, but multivariate analysis indicated only the combination of viability and ischemia and diabetes as independent predictors. The event-free survival of patients with combined viability and ischemia was significantly lower (hazard ratio 3 [95% confidence interval 1.8 to 11]) compared with patients with ischemia only. Thus, viability and ischemia show a significant adverse prognostic interaction in patients with AMI and preserved LV function.

Dobutamine-induced ST-segment elevation in patients with acute myocardial infarction and the role of myocardial ischemia, viability, and ventricular dyssynergy.

We analyzed the relation between dobutamine-induced Q-wave ST-segment elevation and regional contraction during low (5 to 10 microg/kg/min) and high doses (20 to 40 microg/kg/min) of dobutamine in a series of 391 dobutamine echocardiographic tests performed 10 +/- 2 days after a first uncomplicated acute myocardial infarction (AMI). ST-segment elevation was defined as > or = 1 mm new or additional J-point elevation with a horizontal or upsloping ST segment lasting 80 ms. Wall motion score index at rest was derived using a 16 segment-4 grade score model. Patients with dobutamine-induced ST-segment elevation had a higher wall motion score index at rest (anterior wall AMI: 1.67 +/- 0.27 vs 1.43 +/- 0.30, p = 0.0001; inferior wall AMI: 1.44 +/- 0.27 vs 1.30 +/- 0.18, p = 0.0001) and similar incidence and extent of myocardial viability and homozonal ischemia in comparison with those without ST-segment elevation. The sensitivity, specificity, and accuracy of dobutamine-induced ST-segment elevation for detecting residual homozonal ischemia were 51%, 55%, and 54%, respectively, in patients with anterior wall AMI, and 42%, 68%, and 58%, respectively, in patients with inferior wall AMI. In conclusion, dobutamine-induced ST-segment elevation is not associated with higher incidence and extent of viable or jeopardized myocardium but rather to a greater extent of wall motion abnormalities at rest. Thus, this finding does not represent a clinically reliable discriminator for selecting patients for coronary angiography and possible revascularization procedures.

Different clinical and prognostic significance of painful and silent myocardial ischemia detected by exercise electrocardiography and dobutamine stress echocardiography after uncomplicated myocardial infarction.

Prevalence and prognostic significance of painful and silent ischemia detected by exercise electrocardiography (ECG) and dobutamine stress echocardiography (DSE) were evaluated in 407 consecutive patients recovering from acute myocardial infarction. Painful ischemia assessed by both tests was not associated with different clinical characteristics of patients; on the other hand, it identified a higher risk subgroup compared with silent ischemia during exercise ECG but not during DSE.

Dose-related inhibition by dietary phenethyl isothiocyanate of esophageal tumorigenesis and DNA methylation induced by N-nitrosomethylbenzylamine in rats.

The purpose of this investigation was to establish a dose response for the effects of dietary phenethyl isothiocyanate (PEITC) on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis and DNA methylation. Groups of 13-27 rats were randomly assigned to AIN-76A diets containing 0, 0.325, 0.75, 1.5 or 3.0 mumol PEITC/g. Two weeks later, rats were administered NMBA subcutaneously at a dose of 0.5 mg/kg once a week for 15 weeks. Animals were maintained on control or experimental diets for an additional 8 weeks and were terminated at week 25 of the experiment. No significant effects on weight gain or food intake were noted for any of the experimental diets when compared with control values. Animals receiving only NMBA developed 9.3 +/- 0.9 tumors/rat, with an incidence of 100%. Dietary PEITC at concentrations of 0.75, 1.5 and 3.0 mumol/g inhibited NMBA-induced esophageal tumor multiplicity by 39%, 90% and 100%, respectively. Esophageal tumor incidence in these groups was reduced by 0%, 40% and 100%, respectively. The 0.325 mumol/g PEITC diet did not significantly affect NMBA-induced esophageal tumorigenesis. These results indicate that the minimum inhibitory dietary concentration of PEITC is between 0.325 and 0.75 mumol/g. Groups of 20 rats were assigned to diets containing 0-3.0 mumol PEITC/g for two weeks as described above, and then sacrificed 24 hours after administration of [3H-methyl]NMBA. The esophageal DNA was isolated, purified, hydrolyzed, and analyzed by HPLC. PEITC inhibited DNA methylation in a dose-dependent manner, as was found in the tumor bioassay. The inhibition of tumor incidence was highly correlated with the percentage inhibition of either 7-methylguanine or O6-methylguanine. These latter results suggest that the inhibitory activity of PEITC in this model is manifested, at least in part, during the functional equivalent of tumor initiation.

Lung tumorigenic interactions in strain A/J mice of five environmental polycyclic aromatic hydrocarbons.

The binary, ternary, quaternary, and quintary interactions of a five-component mixture of carcinogenic environmental polycyclic aromatic hydrocarbons (PAHs) using response surface analyses are described. Initially, lung tumor dose-response curves in strain A/J mice for each of the individual PAHs benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), dibenz[a,h]anthracene (DBA), 5-methylchrysene (5MC), and cyclopenta[cd]pyrene (CPP) were obtained. From these data, doses were selected for the quintary mixture study based on toxicity, survival, range of response, and predicted tumor yields. The ratios of doses among PAHs were designed to simulate PAH ratios found in environmental air and combustion samples. Quintary mixtures of B[a]P, B[b]F, DBA, 5MC, and CPP were administered to male strain A/J mice in a 2(5) factorial 32-dose group dosing scheme (combinations of five PAHs each at either high or low doses) and lung adenomas were scored. Comparison of observed lung adenoma formation with that expected from additivity identified both greater than additive and less than additive interactions that were dose related i.e., greater than additive at lower doses and less than additive at higher doses. To identify specific interactions, a response surface analysis using response addition was applied to the tumor data. This response surface model contained five dose, ten binary, ten ternary, five quaternary, and one quintary parameter. This analysis produced statistically significant values of 16 parameters. The model and model parameters were evaluated by estimating the dose-response relationships for each of the five PAHs. The predicted dose-response curves for all five PAHs indicated a good estimation. The binary interaction functions were dominated for the most part by DBA and were inhibitory. The response surface model predicted, to a significant degree, the observed lung tumorigenic responses of the quintary mixtures. These data suggest that although interactions between PAHs do occur, they are limited in extent.

Coronary flow reserve of normal left anterior descending artery in patients with ischemic heart disease: A transesophageal Doppler study.

The aim of this study was to investigate the flow reserve of a normal left anterior descending coronary artery (LAD) in patients with coronary artery disease (CAD) of other epicardial vessels by Doppler transesophageal echocardiography (TEE). Thirty-one consecutive patients (age 59 +/- 8 years; 23 men) referred for TEE were considered. Eighteen patients had CAD and a 70% or greater LAD stenosis (group 1); 13 patients had right and/or circumflex CAD (>/=70% stenosis) and normal or minimally diseased LAD (group 2). Ten patients (age 54 +/- 11 years) with normal coronary arteries constituted group 3. Baseline and adenosine (0.160 microg/kg per minute intravenously over 60 minutes) flow velocities in the LAD were measured by pulsed Doppler examination during TEE. Peak and mean systolic and diastolic flow velocities were calculated. Adenosine/baseline peak and mean velocity ratios were used for evaluating blood flow reserve in the LAD. Heart rate and arterial pressure values were similar in the 3 groups at baseline and during adenosine infusion. Baseline and adenosine-related flow velocities were comparable in the 3 groups. Peak and mean diastolic velocity ratios were lower in groups 1 and 2 compared with group 3 (peak velocity ratio 1.68 +/- 0.81 and 1.93 +/- 0.35 vs 2.62 +/- 0.32, P <. 05; mean velocity ratio 1.71 +/- 0.86 and 2.01 +/- 0.41 vs 2.84 +/- 0.74, P <.05), whereas no differences were found between groups 1 and 2. No significant differences were found in systolic flow velocity ratios among the 3 groups. Patients with ischemic heart disease have a reduced diastolic flow velocity reserve in the LAD independent from the presence of significant LAD stenosis. Thus the adenosine TEE-Doppler study should be considered a screening test for CAD rather than for LAD disease.

Sister-chromatid exchanges in human bronchial epithelial cells.

One method of assessing the genotoxic effects of exposure to environmental agents is by determining the frequency of sister chromatid exchanges in exposed cells. In the present study, a procedure for observing sister chromatid exchanges in adult human bronchial epithelial cells exposed to a carcinogen has been developed. Using this procedure, the frequencies of sister chromatid exchanges in untreated cells from two individuals were found to be 5.1 +/- 1.8 and 6.5 +/- 1.4 per metaphase (mean +/- SD). Cells from the first individual exposed to 7,12-dimethylbenz[a]anthracene at 0.5, 1 and 2 mug/ml had 7.8 +/- 2.2, 13 +/- 3.1, 18.7 +/- 3.7 sister chromatid exchanges per metaphase, respectively. This method is likely to be particularly useful for observing sister chromatid exchanges in cells that have a relatively slow growth rate in the presence of bromodeoxyuridine and for which preparation of a large number of metaphase chromosomes is difficult. In addition, the procedure provides a means of assessing genotoxic effects in the lung by examining the direct effects of pollutants on the chromosomes of the target cells for human lung cancer.