Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes

Type-2 Diabetes (T2D), diabetic complications, and their clinical risk factors harbor a substantial genetic component but the genetic factors contributing to overall diabetes mortality remain unknown. Here, we examined the association between genetic variants at 21 T2D-susceptibility loci and all-cause mortality in an elderly cohort of 542 Italian diabetic patients who were followed for an average of 12.08 years. Univariate Cox regression analyses detected age, waist-to-hip ratio (WHR), glycosylated haemoglobin (HbA1c), diabetes duration, retinopathy, nephropathy, chronic kidney disease (CKD), and anaemia as predictors of all-cause mortality. When Cox proportional hazards multivariate models adjusted for these factors were run, three erythropoietin (EPO) genetic variants in linkage disequilibrium (LD) with each other (rs1617640-T/G, rs507392-T/C and rs551238-A/C) were significantly (False Discovery Rate < 0.1) associated with mortality. Haplotype multivariate analysis revealed that patients carrying the G-C-C haplotype have an increased probability of survival, while an opposite effect was observed among subjects carrying the T-T-A haplotype. Our findings provide evidence that the EPO gene is an independent predictor of mortality in patients with T2D. Thus, understanding the mechanisms by which the genetic variability of EPO affects the mortality of T2D patients may provide potential targets for therapeutic interventions to improve the survival of these patients

The economic impact of moderate stage Alzheimer's disease in Italy: Evidence from the UP-TECH randomized trial

Background: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families. Methods: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community. Results: The societal burden of AD, composed of public, patient, and informal care costs, was about �20,000/yr. Out of this, the cost borne by the public sector was �4,534/yr. The main driver of public cost was the national cash-for-care allowance (�2,324/yr), followed by drug prescriptions (�1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at �13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure. Conclusion: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556). Copyright � International Psychogeriatric Association 2015

Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: A multicenter cohort observational study

Background: Decline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align

Socioeconomic Predictors of the Employment of Migrant Care Workers by Italian Families Assisting Older Alzheimer's Disease Patients: Evidence from the Up-Tech Study

Background: The availability of family caregivers of older people is decreasing in Italy as the number of migrant care workers (MCWs) hired by families increases. There is little evidence on the influence of socioeconomic factors in the employment of MCWs. Method: We analyzed baseline data from 438 older people with moderate Alzheimer's disease (AD), and their family caregivers enrolled in the Up-Tech trial. We used bivariate analysis and multilevel regressions to investigate the association between independent variables - education, social class, and the availability of a care allowance - and three outcomes - employment of a MCW, hours of care provided by the primary family caregiver, and by the family network (primary and other family caregivers). Results: The availability of a care allowance and the educational level were independently associated with employing MCWs. A significant interaction between education and care allowance was found, suggesting that more educated families are more likely to spend the care allowance to hire a MCW. Discussion: Socioeconomic inequalities negatively influenced access both to private care and to care allowance, leading disadvantaged families to directly provide more assistance to AD patients. Care allowance entitlement needs to be reformed in Italy and in countries with similar long-term care and migration systems. � 2015 The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved

Increased expression of 5-lipoxygenase is common in clear cell renal cell carcinoma

The clinical behaviour of Clear Cell Renal Cell Carcinoma (CC-RCC) is often unpredictable. To fully understand the signaling pathways involved in CCRCC development, we examined whether the 5- Lipoxygenase (5-LO), which catalyzes the biosynthesis of proinflammatory leukotrienes, is involved in renal tumorigenesis. By analyzing 46 snap-frozen primary renal cell carcinomas and their corresponding normal renal cortex biopsies, 5-LO protein levels were found to be significantly increased in the majority of CC-RCCs (P<0.001). Quantitative 5-LO mRNA expression analysis revealed up to 3-fold increased expression in the tumor tissues. There was no association between 5-LO and gender, grade or vein invasion. In contrast, increased 5-LO protein and mRNA correlated with large tumor size (>4 cm) and age of patients (P<0.001). 5-LO was frequently overexpressed in von Hippel-Lindau protein (pVHL)–reduced tumors and in Vascular Endothelial Growth Factor (VEGF)-positive tumors, which represent two frequent alterations in CC-RCC. Cell culture experiments demonstrated that VEGF expression was strongly inducible by 5-LO metabolites in RCC cell lines. The loss of pVHL expression led to high basal 5- LO and VEGF expression, which were markedly reduced by transfection with 5-LO small interfering RNA (siRNA). These results suggest that 5-LO upregulation is an important step in renal cancer progression

Effect of 4G/5G PAI-1 polymorphism on the response of PAI-1 activity to vitamin E supplementationin Type 2 diabetic patients

Plasminogen activator inhibitor type 1 (PAI-1) is an independent cardiovascular risk factor and increases in patients with Type 2 diabetes mellitus. The 4G/5G polymorphism of PAI-1 has been reported to be involved in the incidence of cardiovascular disease by regulation of PAI-1 levels, but this relation is still under debate. The aim of the study was to test the effect of 4G/5G polymorphism on the lowering of PAI-1 levels in Type 2 diabetic patients during vitamin E supplementation. Ninety-three Type 2 diabetic subjects (age+/-SD, 62.1+/-6.1 yr) were enrolled and treated with vitamin E (500 IU/die) for 10 weeks. We determined the 4G/5G polymorphism and PAI-1 activity at baseline, during (5(th) and 10(th) week) and after (30(th) week) vitamin E supplementation. No significant differences were found in PAI-1 and its determinants among the three genotypic groups at baseline. Decrements were detected in the whole group in PAI-1 at the 5(th) and the 10(th) week from baseline followed by an increase at the 30(th) week (p&lt;0.001). Patients with 4G/4G and 4G/5G genotypes showed a different trend with respect to those with 5G/5G in PAI-1. In particular, there was a decrease in 4G/4G and 4G/5G PAI-1 levels from the loth week, while a decrease in 5G/5G PAI-1 was observed from the 5(th) week (p&lt;0.01). The delayed decrease, found in patients with at least one 4G allele with respect to those with 5G/5G genotype, demonstrates that 4G/5G polymorphism mainly influences the rate of decrease of PAI-1 after supplementation with vitamin E in Type 2 diabetic subjects

Paraoxonase activity and genotype predispose to successful aging.

The paraoxonase 1 codon 192 R allele has been previously reported to have a role in successful aging. The relationship between PON1 genotypes, enzymatic activity, and mass concentration was evaluated in a group of 229 participants from 22 to 104 years of age, focusing our attention on nonagenarian/centenarian participants. We found a genetic control for paraoxonase activity that is maintained throughout life, also in the nonagenarians/centenarians. This activity decreases significantly during aging and shows different mean values among R and M carriers, where R+ and M- carriers have the significant highest paraoxonase activity. Results from the multinomial regression logistic model show that paraoxonase activity as well as R+ and M- carriers contribute significantly to the explanation of the longevity phenotype. In conclusion, we show that genetic variability at the PON1 locus is related to paraoxonase activity throughout life, and suggest that both parameters affect survival at extreme advanced age. Copyright 2006 by The Gerontological Society of America