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Background: People are living longer but an increasing number of older people experience chronicity and disability in the latest years of their life. The Marche region is one of the Italian regions where people live the longest lives; therefore, the number of people with age-related chronic diseases is expected to be at least similar, if not higher, compared to the rest of Italy. The identification of the aging trajectories is of huge interest in the arena of public health. Administrative healthcare databases represent valuable reservoirs for reconstructing the trajectories of aging. Here, we present the protocol for a study (TREND project) aimed to integrate existing administrative databases into a Marche regional dataset in order to estimate the prevalence and incidence rates of age-related neurodegenerative diseases (ND), with a specific focus on Parkinsonism and Dementia., Methods: The TREND Project is a retrospective cross-sectional study. The source population includes permanent residents in the Marche region aged 40 years and older. A minimal dataset has been built up linking data on drug prescriptions, outpatient services, and diagnosis for hospital admission, from 2014 to 2021 in the Marche Region. Data on clinical outcomes (re-hospitalization, mortality, comorbidities), and therapeutic approaches (drugs and medicines) have been integrated with state-of-the-art statistical methods to define patients into different risk clusters and to analyze the aging trend by assessing the Comorbidity Index (CI) as a proxy for chronicity., Discussion: Our research contributes to the integration of existing administrative databases on ND to create a Marche regional ND database, support regional health policy, and better understand patients' needs and their aging trajectories. This approach could be implemented also at the National level. Moreover, by linking different administrative data sources, this study sheds light on important issues related to ND, such as early-onset dementia; ethical aspects such as anticipated wills; problems of dementia in patients still in the job market, etc. The results of this study will contribute to the successful implementation of integrated care for patients affected by ND at regional or national levels., Competing Interests: FB and LP were employed by the company Tech4Care srl. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Spazzafumo, Sabbatinelli, Biscetti, Balducci, Lilla, Ramini, Giuliani, Paciello, Rupelli, Pompili, Pelliccioni, Recchioni and Olivieri.)

Background : Physical activity is an important predictor of quality of life in older adults with type 2 diabetes (T2D). Unfortunately, most T2D adults adopt a sedentary lifestyle. The randomized, controlled TRIPL-A trial aims to verify the effect of a personalized, discontinuous exercise program on a sedentary lifestyle of T2D older adults. Methods : A total of 305 T2D patients (mean age ± SD: 68.8 ± 3.3 years) were divided into a control arm receiving only behavioral counseling and an intervention arm of an 18-month supervised discontinuous exercise program (ERS). The primary outcomes were the changes in sitting time (ST) and metabolic equivalent (MET) values, both evaluated by the International Physical Activity Questionnaire short form. A repeated measures ANOVA with Bonferroni correction for multiple comparisons was used to compare study outcomes. Results : The ST and MET differed significantly during the study compared to the control group ( p = 0.028 and p = 0.004, respectively). In the intervention group, a decrease from baseline in ST at 6 months ( p = 0.01) and an increase in MET values at 6 months ( p = 0.01) up to 12 months ( p < 0.01) were found. No significant differences were found for the other variables. Conclusions : Beneficial lifestyle changes were found within the first year of intervention. These results align with the theory of change.

One of the most exciting challenges of the research on aging is to explain how the environmental factors interact with the genetic background to modulate the chances to reach the extreme limit of human life in healthy conditions. The complex epigenetic mechanisms can explain both the interaction between DNA and environmental factors, and the long-distance persistence of lifestyle effects, due to the so called "epigenetic memory". One of the most extensively investigated theories on aging focuses on the inflammatory responses, suggesting that the age-related progression of low-grade and therefore for long time subclinical, chronic, systemic, inflammatory process, named "inflammaging", could be the most relevant risk factor for the development and progression of the most common age-related diseases and ultimately of death. The results of many studies on long-lived people, especially on centenarians, suggested that healthy old people can cope with inflammaging upregulating the antiinflammaging responses. Overall, a genetic make-up coding for a strong antiinflammaging response and an age-related ability to remodel key metabolic pathways to cope with a plethora of antigens and stressors seem to be the best ways for reach the extreme limit of human lifespan in health status. In this scenario, we wondered if the antifragility concept, recently developed in the framework of business and risk analysis, could add some information to disentangle the heterogeneous nature of the aging process in human. The antifragility is the property of the complex systems to increase their performances because of high stress. Based on this theory we were wondering if some subjects could be able to modulate faster than others their epigenome to cope with a plethora of stressors during life, probably modulating the inflammatory and anti-inflammatory responses. In this framework, antifragility could share some common mechanisms with anti-inflammaging, modulating the ability to restrain the inflammatory responses, so that antifragility and antiinflammaging could be viewed as different pieces of the same puzzle, both impinging upon the chances to travel along the healthy aging trajectory., Competing Interests: Conflict of interest The authors have no conflict of interests to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The aim of the study was to evaluate the trend in the incidence of idiopathic pulmonary fibrosis (IPF) in a real-world setting of the Marche region, a region of Central Italy, between 2014 and 2019. This observational prospective study was based on administrative databases of hospital discharges and drug prescriptions. All adult residents in the Marche Region with a first prescription of antifibrotic drugs, or a first hospitalization with a diagnosis of IPF during the study period, were identified as incident cases of IPF. A multiple Poisson regression analysis was used to estimate the IPF incidence trend, adjusted for age, sex, and health conditions. The mean incidence rate was 9.8 cases per 100,000 person-years. A significant increasing trend of 6% per year was observed. The incidence rates were significantly higher in males than females, older subjects, and those with poorer health conditions. To our knowledge, this is the first study evaluating incidences of IPF over a 6-year period in Italy, combining hospital discharge and drug prescription databases. The study highlights that the combined use of two secondary sources is a reliable strategy to accurately identify new cases of IPF when the appropriate disease registry is lacking.

Objectives: To develop a population-based risk stratification model (COVID-19 Vulnerability Score) for predicting severe/fatal clinical manifestations of SARS-CoV-2 infection, using the multiple source information provided by the healthcare utilisation databases of the Italian National Health Service., Design: Retrospective observational cohort study., Setting: Population-based study using the healthcare utilisation database from five Italian regions., Participants: Beneficiaries of the National Health Service, aged 18-79 years, who had the residentship in the five participating regions. Residents in a nursing home were not included. The model was built from the 7 655 502 residents of Lombardy region., Main Outcome Measure: The score included gender, age and 29 conditions/diseases selected from a list of 61 conditions which independently predicted the primary outcome, that is, severe (intensive care unit admission) or fatal manifestation of COVID-19 experienced during the first epidemic wave (until June 2020). The score performance was validated by applying the model to several validation sets, that is, Lombardy population (second epidemic wave), and the other four Italian regions (entire 2020) for a total of about 15.4 million individuals and 7031 outcomes. Predictive performance was assessed by discrimination (areas under the receiver operating characteristic curve) and calibration (plot of observed vs predicted outcomes)., Results: We observed a clear positive trend towards increasing outcome incidence as the score increased. The areas under the receiver operating characteristic curve of the COVID-19 Vulnerability Score ranged from 0.85 to 0.88, which compared favourably with the areas of generic scores such as the Charlson Comorbidity Score (0.60). A remarkable performance of the score on the calibration of observed and predicted outcome probability was also observed., Conclusions: A score based on data used for public health management accurately predicted the occurrence of severe/fatal manifestations of COVID-19. Use of this score may help health decision-makers to more accurately identify high-risk citizens who need early preventive or treatment interventions., Competing Interests: Competing interests: GC received research support from the European Community (EC), the Italian Agency of Drug (AIFA), the Italian Ministry of Education, University and Research (MIUR), and the Italian Health Ministry. He took part in a variety of projects that were funded by pharmaceutical companies (ie, Novartis, GSK, Roche, AMGEN and BMS). He also received honoraria as member of Advisory Board from Roche. GM received honoraria for participation as speaker/chairman in national/international meetings from Boehringer Ingelheim, Ferrer, Medtronic, Menarini, Merck Serono, Recordati and Servier., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Anemia associated with cardiovascular diseases (CVD) is a common condition in older persons. Prevalence and prognostic role of anemia were extensively studied in patients with myocardial infarction (MI) or congestive heart failure (CHF) whereas limited data were available on patients with atrial fibrillation (AF). This study was conducted to assess the clinical prevalence and prognostic relevance of anemia in elderly patients affected by AF and other CVDs., Methods: A total of 866 elderly patients (430 men and 436 women, age: 65-98 years, mean age: 85 ± 10 years) were enrolled. Among these patients, 267 patients had acute non-ST-segment elevation MI (NSTEMI), 176 patients had acute CHF, 194 patients had acute AF and 229 patients were aged-matched healthy persons (CTR). All parameters were measured at the hospital admission and cardiovascular mortality was assessed during twenty-four months of follow-up., Results: The prevalence of anemia was higher in NSTEMI, CHF and AF patients compared to CTR subjects (50% vs. 15%, P < 0.05), with normocytic anemia being the most prevalent type (90%). Adjusted mortality risk was higher in anemic patient versus non-anemic patient in all the groups of patients [NSTEMI: hazard ratio (HR) = 1.81, 95% CI: 1.06-2.13; CHF: HR = 2.49, 95% CI: 1.31-4.75; AF: HR = 1.98, 95% CI: 1.01-3.88]. Decreased hemoglobin levels ( P = 0.001) and high reticulocyte index ( P = 0.023) were associated with higher mortality in CVD patients., Conclusions: The significant associations between CVD and anemia and the prognostic relevance of anemia for elderly patients with CVD were confirmed in this study. The presence of anemia in AF patients is associated with a two-fold increased mortality risk compared with non-anemic AF patients. Low hemoglobin and high reticulocyte count independently predict mortality in elderly patients with CVD., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

Aging plays an important role in the etiology of the most common age-related diseases (ARDs), including Alzheimer's disease (AD). The increasing number of AD patients and the lack of disease-modifying drugs warranted intensive research to tackle the pathophysiological mechanisms underpinning AD development. Vascular aging/dysfunction is a common feature of almost all ARDs, including cardiovascular (CV) diseases, diabetes and AD. To this regard, interventions aimed at modifying CV outcomes are under extensive investigation for their pleiotropic role in ameliorating and slowing down cognitive impairment in middle-life and elderly individuals. Evidence from observational and clinical studies confirm the notion that the earlier the interventions are conducted, the most favorable are the effects on cognitive function. Therefore, epidemiological research should focus on the early detection of deviations from a healthy cognitive aging trajectory, through the stratification of adult individuals according to the rate of aging. Here, we review the interplay between vascular and cognitive dysfunctions associated with aging, to disentangle the complex mechanisms underpinning the development and progression of neurodegenerative disorders, with a specific focus on AD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Multimorbidity is a growing concern for healthcare systems, with many countries experiencing demographic transition to older population profiles. A simple multisource comorbidity score (MCS) has been recently developed and validated. A very large real-world investigation was conducted with the aim of measuring inequalities in the MCS distribution across Italy., Methods: Beneficiaries of the Italian National Health Service aged 50-85 years who in 2018 were resident in one of the 10 participant regions formed the study population (15.7 million of the 24.9 million overall resident in Italy). MCS was assigned to each beneficiary by categorizing the individual sum of the comorbid values (i.e. the weights corresponding to the comorbid conditions of which the individual suffered) into one of the six categories denoting a progressive worsening comorbidity status. MCS distributions in women and men across geographic partitions were compared., Results: Compared with beneficiaries from northern Italy, those from centre and south showed worse comorbidity profile for both women and men. MCS median age (i.e. the age above which half of the beneficiaries suffered at least one comorbidity) ranged from 60 (centre and south) to 68 years (north) in women and from 63 (centre and south) to 68 years (north) in men. The percentage of comorbid population was lower than 50% for northern population, whereas it was around 60% for central and southern ones., Conclusion: MCS allowed of capturing geographic variability of multimorbidity prevalence, thus showing up its value for addressing health policy in order to guide national health planning., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Age-associated cognitive impairment in general and dementia in particular are a global concern. Preventive lifestyle strategies are highly used but there is a lack of information on the reciprocal relationships between nutrition biomarkers and measures of both cognitive and physical performance. To fill this gap of knowledge, the relationship between plasma levels of the robust nutrition- and antioxidant defense-related biomarkers carotenoid and tocopherols and both indicators of cognitive and physical performance was investigated in a group of persons with mild cognitive impairment participating in the NeuroExercise Study at the German Sport University in Cologne, Germany. In 56 participants with full dataset, significant correlations independently of fruit and vegetable intake were found between plasma levels of β-cryptoxanthin and Timed Up&Go test ( p < 0.05), γ-tocopherol and number of daily steps ( p < 0.01), as well as between four out of six measured carotenoids-lutein; zeaxanthin; β-cryptoxanthin and β-carotene-and the computerized CogState International Shopping List subtest ( p < 0.01). In light of the increasing attention towards the nutritional cognitive neuroscience of carotenoids, computerized measures of cognitive performance might be further implemented in future studies investigating the effects of lifestyle interventions against cognitive and physical impairment.

Objective: The clinical efficacy of clopidogrel in secondary prevention of vascular events is hampered by marked inter-patient variability in drug response, which partially depends on genetic make-up. The aim of this pilot prospective study was to evaluate 12-month cardiovascular outcomes in elderly patients with acute coronary syndrome (ACS) receiving dual antiplatelet therapy (aspirin and clopidogrel) according to the clustering of CYP2C19 and ABCB1 genetic variants., Methods: Participants were 100 consecutive ACS patients who were genotyped for CYP2C19 (G681A and C-806T) and ABCB1 (C3435T) polymorphisms, which affect clopidogrel metabolism and bioavailability, using PCR-restriction fragment length polymorphism. They were then grouped as poor, extensive and ultra-rapid metabolisers based on the combination of CYP2C19 loss-of-function (CYP2C19*2) and gain-of-function (CYP2C19*17) alleles and ABCB1 alleles. The predictive value of each phenotype for acute vascular events was estimated based on 12-month cardiovascular outcomes., Results: The poor metabolisers were at an increased risk of thrombotic events (OR 1.26; 95% CI 1.099-1.45; χ 2  = 5.676; p = 0.027), whereas the ultra-rapid metabolisers had a 1.31-fold increased risk of bleeding events compared with the poor and extensive metabolisers (OR 1.31; 95% CI 1.033-1.67; χ 2  = 5.676; p = 0.048). Logistic regression model, including age, sex, BMI and smoking habit, confirmed the differential risk of major events in low and ultra-rapid metabolisers., Conclusions: Our findings suggest that ACS patients classified as 'poor or ultra-rapid' metabolisers based on CYP2C19 and ABCB1 genotypes should receive alternative antiplatelet therapies to clopidogrel.

β-Galactosidase (β-Gal) activity has been the most extensively utilized biomarker for the detection of cellular senescence. It can be measured also in plasma, and few recent evidence showed an altered plasmatic β-Gal activity in patients affected by some age-related diseases (ARDs). Since T2DM is one of the most common ARDs, we aimed to investigate if plasmatic β-Gal activity is modulated in T2DM patients and if "age" could affect such modulation. To gain mechanistic insights we paralleled this investigation with the evaluation of β-Gal activity in young and senescent endothelial cells (HUVECs) cultured in normo- and hyper-glycaemic environment. A significant age-related increase of plasmatic β-Gal activity was observed in healthy subjects (n. 230; 55-87 years), whereas the enzymatic activity was significantly reduced in T2DM patients (n. 230; 55-96 years) compared to healthy subjects. β-Gal activity detectable both in cells and in the culture medium was significantly increased in senescent cells compared to the younger ones, both under normo- and hyper-glycaemic condition. However, the hyper-glycaemic condition was not associated with an increased β-Gal activity in milieu compared to normo-glycaemic condition. Overall our data reinforce the notion that plasmatic β-Gal activity could be a systemic biomarker of aging, whereas T2DM patients are characterized by a different age-releated trend., Competing Interests: CONFLICTS OF INTEREST None of the authors has competing interests.

Leukocyte telomere length (LTL) shortening is found in a number of age-related diseases, including type 2 diabetes (T2DM). In this study its possible association with mortality was analyzed in a sample of 568 T2DM patients (mean age 65.9 ± 9 years), who were followed for a median of 10.2 years (interquartile range 2.2). A number of demographic, laboratory and clinical parameters determined at baseline were evaluated as mortality risk factors. LTL was measured by quantitative real-time PCR and reported as T/S (telomere-to-single copy gene ratio). Age, gender, creatinine, diabetes duration at baseline, and LTL were significantly different between T2DM patients who were dead and alive at follow-up. In the Cox regression analysis adjusted for the confounding variables, shorter LTL, older age, and longer disease duration significantly increased the risk of all-cause mortality (HR = 3.45, 95%CI 1.02-12.5, p = 0.004). Kaplan-Maier analysis also found a different cumulative mortality risk for patients having an LTL shorter than the median (T/S ≤0.04) and disease duration longer than the median (>10 years) (log-rank = 11.02, p = 0.011). Time-dependent mortality risk stratification showed that T2DM duration and LTL combined was a fairly good predictor of mortality over the first 76 months of follow-up.In conclusion, LTL combined with clinical parameters can provide additive prognostic information on mortality risk in T2DM patients., Competing Interests: None of the authors have any competing interests.

Aim: To determine whether the outcomes of home enteral nutrition for frail older patients can be improved by video consultation between home visiting staff and a hospital physician, specialized in clinical nutrition, during monthly home visits., Methods: A randomized prospective study out of patients aged older than 65 years receiving home enteral nutrition from the Department of Clinical Nutrition of an Italian geriatric hospital in 2013 was carried. A total of 100 patients were randomly assigned to receive video consultation in addition to regular monthly home visits, 88 patients only had regular monthly home visits. Therapy outcomes - incidence rates of complications, outpatient hospital visits and hospitalizations - were compared between two groups. A logistic regression analysis was carried out to evaluate the usefulness of the video consultation to improve therapy outcomes., Results: Incidence rates for metabolic and gastrointestinal complications were significantly lower for patients who received a video consultation, respectively: 0.032/year "video consultation" versus 0.055/year "no video consultation" (P = 0.0001) and 0.006/year "video consultation" versus 0.028/year "no video consultation" (P < 0.0001). No differences were found for incidence rates of mechanical complications, outpatient hospital visits and hospitalizations. Logistic regression showed that the video consultation was significantly correlated with a reduction of metabolic complications (OR 2.63, 95% CI 1.00-6.91; P = 0.049 after adjustment for duration of home enteral nutrition and diabetes mellitus 2)., Conclusion: The present study provides evidence that a video consultation between home visiting staff and hospital physicians specialized in clinical nutrition during monthly home visits is associated with a reduction of metabolic complications in a population of frail older patients. Geriatr Gerontol Int 2015; ●●: ●●-●●., (© 2015 Japan Geriatrics Society.)

Patients with chronic heart failure (CHF) experience progressive deterioration of functional capacity and quality of life (QoL). This prospective, randomized, controlled trial assesses the effect of exercise training (ET) protocol on functional capacity, rehospitalization, and QoL in CHF patients older than 70 years compared with a control group. A total of 343 elderly patients with stable CHF (age, 76.90±5.67, men, 195, 56.9%) were randomized to ET (TCG, n=170) or usual care (UCG, n=173). The ET protocol involved supervised training sessions for 3 months in the hospital followed by home-telemonitored sessions for 3 months. Assessments, performed at baseline and at 3 and 6 months, included: ECG, resting echocardiography, NT-proBNP, 6-minute walk test (6MWT), Minnesota Living with Heart Failure Questionnaire, and comprehensive geriatric assessment with the InterRAI-HC instrument. As compared to UCG, ET patients at 6 months showed: i) significantly increased 6MWT distance (450±83 vs. 290±97 m, p=0.001); ii) increased ADL scores (5.00±2.49 vs. 6.94±5.66, p=0.037); iii) 40% reduced risk of rehospitalisation (hazard ratio=0.558, 95%CI, 0.326-0.954, p=0.033); and iv) significantly improved perceived QoL (28.6±12.3 vs. 44.5±12.3, p=0.001). In hospital and home-based telemonitored exercise confer significant benefits on the oldest CHF patients, improving functional capacity and subjective QoL and reducing risk of rehospitalisation.

Innovative biomarkers are required to manage type 2 diabetic patients (T2DM). We focused our study on miR-126-3p and miR-21-5p levels, as biomarkers of endothelial function and inflammation. MiRNAs levels were measured in plasma from 107 healthy subjects (CTR) and 193 diabetic patients (T2DM), 76 without (T2DM NC) and 117 with (T2DM C) complications. When diabetic complication were analysed as a whole, miR-126-3p and miR-21-5p levels declined significantly from CTR to T2DM NC and T2DM C patients. When miRNAs levels were related to specific complications, significantly higher miR-21-5p levels (0.46 ± 0.44 vs. 0.26 ± 0.33, p < 0.001) and significant lower miR-126-3p levels (0.21 ± 0.21 vs. 0.28 ± 0.22, p = 0.032) were found in T2DM with previous major cardiovascular events (MACE) vs. all the others T2DM patients. To confirm these results we focused on circulating angiogenic cells (CACs) from a subgroup of 10 CTR, 15 T2DM NC and 15 T2DM patients with MACE. CACs from T2DM patients expressed higher miR-21-5p and lower miR-126-3p levels than CACs from CTR. Furthermore, CACs from T2DM + MACE showed the highest levels of miR-21-5p. Circulating miR-21-5p and miR-126-3p emerge as dynamic biomarkers of systemic inflammatory/angiogenic status. Their expression levels in CACs from T2DM with MACE suggest a shift from a proangiogenic to a proinflammatory profile.

Objectives/hypothesis: Altered microRNA expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). We investigated the association of LSCC-related miR-34c-5p with disease-free survival and overall survival., Study Design: Retrospective cohort study., Methods: Expression levels of miR-34c-5p were detected in 90 LSCC formalin-fixed paraffin-embedded tissues by reverse-transcription quantitative polymerase chain reaction. Overall survival and disease-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis., Results: A downregulation of miR-34c-5p expression significantly correlated with worse disease-free and overall survival. In the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence., Conclusions: A downregulation of miR-34c-5p in LSCC is independently associated with unfavorable disease-free survival, suggesting that miR-34c-5p might be a promising marker for evaluating the risk of recurrences., Level of Evidence: NA., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

The objective of our study was to demonstrate that living with a person affected by mild to moderate Alzheimer's disease can lead to an increased perception of the caregiver's burden using the Caregiver Burden Inventory (CBI). The sample consisted of 153 dyads, caregiver-patient. At baseline, a greater perception of the caregiver's burden was observed in the live-in caregivers. A further increase in the total burden of the live-in caregivers was noticed at the 6-month follow-up. More specifically, with the inclusion of correction factors such as the caregiver's age and the CBI subscales at baseline, the social and emotional burden becomes statistically significant (P < .001). The present paper confirms our hypothesis that live-in caregivers perceive a greater burden than nonlive-in, and this difference increases further after 6 months. The difference in involvement between live-in and nonlive-in caregivers could be the foundation to tailor more specific interventions., (© The Author(s) 2015.)

Objectives: To assess the impact of a personalized diet, with or without addition of VSL#3 preparation, on biomarkers of inflammation, nutrition, oxidative stress and intestinal microbiota in 62 healthy persons aged 65-85 years., Design: Open label, randomized, multicenter study., Primary Endpoint: High-sensitivity C-reactive protein., Setting: Community., Interventions: Eight week web-based dietary advice (RISTOMED platform) alone or with supplementation of VSL#3 (2 capsules per day). The RISTOMED diet was optimized to reduce inflammation and oxidative stress., Measurements: Blood and stool samples were collected on days 1 and 56., Results: Diet alone reduced ESR (p = 0.02), plasma levels of cholesterol (p < 0.01) and glucose (p = 0.03). Addition of VSL#3 reduced ESR (p = 0.05) and improved folate (p = 0.007), vitamin B12 (p = 0.001) and homocysteine (p < 0.001) plasma levels. Neither intervention demonstrated any further effects on inflammation. Subgroup analysis showed 40 participants without signs of low-grade inflammation (hsCRP<3 mg/l, subgroup 1) and 21 participants with low-grade inflammation at baseline (hsCRP≥3 mg/l, subgroup 2). In subgroup 2 addition of VSL#3 increased bifidobacteria (p = 0.005) in more participants and improved both folate (p = 0.015) and vitamin B12 (p = 0.035) levels compared with subgroup 1. The increases were positively correlated to the change in the bifidobacteria concentration for folate (p = 0.023) and vitamin B12 (p = 0.001). As expected change in homocysteine correlated negatively to change in folate (r = -0.629, p = 0.002) and vitamin B12 (r = -0.482, p = 0.026)., Conclusions: Addition of VSL#3 increased bifidobacteria and supported adequate folate and vitamin B12 concentrations in subjects with low-grade inflammation. Decrease in homocysteine with VSL#3 was clinically relevant. suggesting protective potentials for aging-associated conditions, e.g. cardiovascular or neurological diseases. ClinicalTrials.gov: NCT01069445-NCT01179789., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Alzheimer's disease (AD) is the most common form of dementia in the elderly. The vast majority of cases are not linked to a known genetic defect and the molecular mechanisms underlying AD pathogenesis are still elusive. Evidence suggests that mitochondrial dysfunction is a prominent feature of the disease, and that mitochondrial DNA (mtDNA) alterations may represent a possible starting point of the pathophysiological cascade. Although specific mtDNA alterations have been reported in AD patients both in brain and peripheral tissues, such as D-loop mutations, 4977-bp deletion and poly-C tract D310 cytosine insertion, a generalized subtle allelic shift has also been demonstrated. This shift is significant for a few nucleotide positions (nps), but it is also detectable for most nps, although at a lower level. As single allelic substitutions can unlikely be determinant, it is proposed that the combination of all of them could lead to a less efficient oxidative phosphorylation, thus influencing AD development and course.

Background: Glycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome., Methods: We enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.6±8.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.5±12.4 years). N-glycome was evaluated in serum glycoproteins., Results: We found significant changes in N-glycan composition in the sera of T2DM patients. In particular, α(1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P<0.001) compared with CTRs. Macro vascular-complications were found to be related with decreased levels of NG1(6)A2F. In addition, NG1(6)A2F and NG1(3)A2F, identifying, respectively, monogalactosylated N-glycans with α(1,6)- and α(1,3)-antennary galactosylation, resulted strongly correlated with most MS parameters. The plasmatic levels of these two glycans were lower in T2DM as compared to healthy controls, and even lower in patients with complications and MS, that is the extreme "unhealthy" phenotype (T2DM+ with MS)., Conclusions: Imbalance of glycosyltransferases, glycosidases and sugar nucleotide donor levels is able to cause the structural changes evidenced by our findings. Serum N-glycan profiles are thus sensitive to the presence of diabetes and MS. Serum N-glycan levels could therefore provide a non-invasive alternative marker for T2DM and MS.

Aim: The study of the determinants of loss of autonomy during hospitalization may be valuable in the identification of the most effective interventions and to achieve better outcomes. The aim of this study was to describe changes in the level of autonomy of the elderly admitted to the hospital at the entrance and at discharge in relation to a rehabilitation program., Methods: Prospective observational study conducted at the INRCA Geriatric Hospital of Ancona. The study included patients aged 65 years and over, daily admitted to INRCA Hospital of Ancona between September and December 2010. Criteria for inclusion were age ≥ 65 years, length of stay > 24 hours and signed informed consent. Patients admitted for less than 24 hours or in day hospital or day surgery were excluded from the beginning. A total of 1266 elderly patients were recruited in the period. From this sample, 74 people who died during hospitalization were excluded. At the time of hospitalization (within 24 hours) and at discharge, patients were evaluated with the Barthel Index (BI), the Rankin scale, and a short assessment of cognitive status derived from the Mini Mental State Examination (MMSE)., Results: Referring to 1192 subjects who participated to the study, the mean age was 82.13 years ±7.39, age range between 65 and 100 years. The average BI was 56.6±36.16 (SD) (median value =60) at admission and 63.84±34.7 (SD) (median value=70) at discharge. The average Rankin score at admission was 2.63±1.5 (SD) (median value=3)., Conclusion: Patients presented better score of the BI at discharge and this figure was associated to the implementation of a rehabilitation treatment. Hospitalization of the elderly patient in a suitable environment, such as a geriatric hospital, contrary to some theories highlighting only the negative aspects of removal from the living environment, can be a measure of benefit for the reduction of disability and the recovery of compromised activities along and after the acute event. The collection of data on the level of autonomy of the subjects before and after hospitalization can be a useful element for clinical evaluation in a geriatric hospital.

Circulating miR-126-3p levels were determined in 136 healthy subjects (CTRs) aged 20-90 years and 193 patients with type-2 diabetes mellitus (T2DMs) aged 40-80 years, to explore the combined effect of age and glycemic state on miR-126-3p expression. Moreover, intra/extracellular miR-126-3p levels were measured in human endothelial cells (HUVECs) undergoing senescence under normo/hyper-glycemic conditions. Plasma miR-126-3p was significantly higher in the oldest compared with the youngest CTRs ( <45 vs. >75 years; relative expression: 0.27±0.29 vs. 0.48±0.39, p=0.047). Age-based comparison between CTRs and T2DM demonstrated significantly different miR-126-3p levels only in the oldest (0.48±0.39 vs. 0.22±0.23, p<0.005). After multiple adjustments, miR-126-3p levels were seen to be lower in patients with poor glycemic control, compared with age-matched CTRs. The age-related increase in plasma miR-126-3p found in CTRs was paralleled by a 5/6-fold increase in intra/extracellular miR-126-3p in in vitro-cultured HUVECs undergoing senescence. Notably, significant down- regulation of SPRED-1 protein, a validated miR-126-3p target, was found in senescent HUVECs. Moreover, miR-126-3p expression was down-regulated in intermediate-age HUVECs grown in high-glucose medium until senescence. Aging/senescence-associated miR-126-3p up-regulation is likely a senescence-associated compensatory mechanism that is blunted when endothelial cells are exposed to high glucose levels, a phenomenon that probably occurs in vivo in T2DM patients.

Background: Body composition has been shown to be correlated with physical performance, but data in older persons with diverse chronic diseases are lacking., Objective: We aimed at investigating the associations of body composition to gait speed and nutritional status of older people in different stages of chronic obstructive pulmonary disease (COPD)., Design, Setting and Subjects: Cross-sectional analysis of data from Pulmonary Rehabilitation Geriatric Unit at INRCA in Casatenovo, Italy including 132 consecutively admitted COPD patients (mean age: 75 years) with data on body composition, walking speed and respiratory parameters., Methods: Body mass parameters were assessed using bioelectrical impedance analysis. Pulmonary function tests included spirometry and arterial blood gases. Differences among body composition markers were compared according to gender. Separate multivariate linear regression models with gait speed as the dependent variable were used to test for independent associations with body composition markers after adjusting for multiple confounders., Results: Walking speed deteriorated with increasing severity of COPD. Men were heavier and had more lean mass than women. Participants in the fastest gait tertile were younger, had lower body mass index and fat mass (FM); higher lean-to-fat ratio and albumin levels and better respiratory function (FEV1, FVC) compared with those in the slower tertiles. Total body FM was an independent determinant of walking speed, while fat-free mass and lean-to-fat ratio were not., Conclusions: Excess body fat may be harmful for physical functioning among elders with COPD., (© The Author 2013. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

To re-examine the correlation between mtDNA variability and longevity, we examined mtDNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high-resolution classification, while about 1300 mtDNA molecules (650 ultranonagenarians and an equal number of controls) were completely sequenced. Sequences, unlike standard haplogroup analysis, made possible to evaluate for the first time the cumulative effects of specific, concomitant mtDNA mutations, including those that per se have a low, or very low, impact. In particular, the analysis of the mutations occurring in different OXPHOS complex showed a complex scenario with a different mutation burden in 90+ subjects with respect to controls. These findings suggested that mutations in subunits of the OXPHOS complex I had a beneficial effect on longevity, while the simultaneous presence of mutations in complex I and III (which also occurs in J subhaplogroups involved in LHON) and in complex I and V seemed to be detrimental, likely explaining previous contradictory results. On the whole, our study, which goes beyond haplogroup analysis, suggests that mitochondrial DNA variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mtDNA genes., (© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here we examined the signal intensity of the four alleles of each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls using MitoChip v2.0 array. Our analysis identified 270 significantly different nps which, with one exception, showed an increased contribution of non-reference alleles in AD patients. Principal component analysis (PCA) and cluster analysis showed that five of these nps could discriminate AD from control subjects with 80% of cases correctly classified. Our data support the hypothesis of mtDNA alterations as an important factor in the etiology of AD.

T2DM is today considered as world-wide health problem, with complications responsible of an enhanced mortality and morbidity. Thus, new strategies for its prevention and therapy are necessary. For this reason, the research interest has focused its attention on TLR4 and its polymorphisms, particularly the rs4986790. However, no conclusive findings have been reported until now about the role of this polymorphism in development of T2DM and its complications, even if a recent meta-analysis showed its T2DM association in Caucasians. In this study, we sought to evaluate the weight of rs4986790 polymorphism in the risk of the major T2DM complications, including 367 T2DM patients complicated for the 55.6%. Patients with A/A and A/G TLR4 genotypes showed significant differences in complication's prevalence. In particular, AG carriers had higher risk prevalence for neuropathy (P = 0.026), lower limb arteriopathy (P = 0.013), and the major cardiovascular pathologies (P = 0.017). Their cumulative risk was significant (P = 0.01), with a threefold risk to develop neuropathy, lower limb arteriopathy, and major cardiovascular events in AG cases compared to AA cases. The adjusted OR for the confounding variables was 3.788 (95% CI: 1.642-8.741). Thus, the rs4986790 polymorphism may be an indicative of prevalence of complications in T2DM patients.

Purpose: We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina., Methods: An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated., Results: Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA., Conclusions: This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.

Background: Geriatric patients with acute non-ST elevation myocardial infarction (NSTEMI) can frequently present atypical symptoms and non-diagnostic electrocardiogram. The detection of modest cardiac troponin T (cTnT) elevation is challenging for physicians needing to routinely triage these patients. Unfortunately, non-coronary diseases, such as acute heart failure (CHF), may cause cTnT elevation. Circulating microRNAs (miRs) have emerged as biomarkers of MI. However, their diagnostic potential needs to be determined in elderly NSTEMI patients., Methods: 92 NSTEMI patients (82.6 ± 6.9 years old; complicated by CHF in 74% of cases) and 81 patients with acute CHF without AMI (81.3 ± 6.8 years old) were enrolled at presentation. A third group comprised 99 age-matched healthy control subjects (CTR). Plasma levels of miR-1, -21, -133a, -208a, -423-5p and -499-5p were analyzed., Results: MiR-1, -21 -133a and -423-5p showed a 3- to 10-fold increase and miR-499-5p exhibited >80-fold increase in acute NSTEMI patient vs. CTR. MiR-499-5p and -21 showed a significantly increased expression in NSTEMI vs. CHF. Interestingly, mir-499-5p was comparable to cTnT in discriminating NSTEMI vs. CTR and CHF patients. Its diagnostic accuracy was higher than conventional and hs-cTnT in differentiating NSTEMI (n=31) vs. acute CHF (n=32) patients with modest cTnT elevation at presentation (miR-499-5p AUC=0.86 vs. cTnT AUC=0.68 and vs. hs-cTnT AUC=0.70)., Conclusions: Circulating miR-499-5p is a sensitive biomarker of acute NSTEMI in the elderly, exhibiting a diagnostic accuracy superior to that of cTnT in patients with modest elevation at presentation., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Tumor suppressor protein p53 has been demonstrated to regulate genes involved in energy generating metabolic pathways and apoptosis. To date, a new field of research is the involvement of TP53 codon 72 (Arg72Pro) polymorphism in the diabetic disease. The aim of this study was to evaluate whether the genotype and the related genetic models of Arg72Pro polymorphism of TP53 (rs1042522) are associated with insulin resistance and its metabolic parameters in diabetic and non-diabetic subjects. We examined 335 type 2 diabetic patients (65.5 ± 8.4 years) and 367 non-diabetic subjects (60.5 ± 11.7 years). The results were validated in a validation sample consisting of 199 type 2 diabetic (66.2 ± 8.5 years) and 224 non-diabetic subjects (61.2 ± 12.7 years). In the study sample, the analysis of covariance, adjusted for the effects of age, gender and BMI, showed a significant genotype-diabetes effect on insulin resistance evaluated by HOMA-IR (p = 0.038). This result was mediated by variations in fasting plasma insulin (p = 0.027), as no TP53 genotype-diabetes effects were detected for fasting plasma glucose. In particular, in the diabetic subjects, Pro/Pro genotype was associated with lower values of HOMA-IR with respect to Arg/Arg (p = 0.013) and Arg/Pro (p = 0.006) carriers. No difference in HOMA-IR between diabetic and non-diabetic Pro/Pro carriers was found. Significant recessive model-diabetes interaction effects on fasting insulin and HOMA-IR adjusted for age, sex and BMI were found (p = 0.007 and p = 0.029, respectively). Linear regression analyses, based on the assumption of an additive genetic model adjusted for age, sex and BMI, highlight p53 gene-diabetes interaction effects on fasting insulin (β = -1.27; p = 0.001) and HOMA-IR (β = -0.22; p = 0.006). The results of statistical analyses on fasting insulin and HOMA-IR were all confirmed in the validation sample. Furthermore, the logistic regression models confirmed that the effect of HOMA-IR levels on diabetes was moderated by Pro/Pro genotype in both study and validation samples (OR = 0.29, p = 0.034, 95 % CI = 0.09-0.91, OR = 0.37, p = 0.035, 95 % CI = 0.15-0.93, respectively). Our findings suggest that p53 codon 72 (Arg72Pro) polymorphism influences insulin resistance in type 2 diabetic patients independently of body mass.

Background: The epidemic of Alzheimer's disease (AD) represents a significant challenge for the health care and social service systems of many developed countries. AD affects both patients and family caregivers, on whom the main burden of care falls, putting them at higher risk of stress, anxiety, mortality and lower quality of life. Evidence remains controversial concerning the effectiveness of providing support to caregivers of AD patients, through case management, counseling, training, technological devices and the integration of existing care services. The main objectives of the UP-TECH project are: 1) to reduce the care burden of family caregivers of AD patients; and 2) to maintain AD patients at home., Methods/design: A total of 450 dyads comprising AD patients and their caregivers in five health districts of the Marche region, Italy, will be randomized into three study arms. Participants in the first study arm will receive comprehensive care and support from a case manager (an ad hoc trained social worker) (UP group). Subjects in the second study arm will be similarly supported by a case manager, but in addition will receive a technological toolkit (UP-TECH group). Participants in the control arm will only receive brochures regarding available services. All subjects will be visited at home by a trained nurse who will assess them using a standardized questionnaire at enrollment (M0), 6 months (M6) and 12 months (M12). Follow-up telephone interviews are scheduled at 24 months (M24). The primary outcomes are: 1) caregiver burden, measured using the Caregiver Burden Inventory (CBI); and 2) the actual number of days spent at home during the study period, defined as the number of days free from institutionalizations, hospitalizations and stays in an observation unit of an emergency room., Discussion: The UP-TECH project protocol integrates previous evidence on the effectiveness of strategies in dementia care, that is, the use of case management, new technologies, nurse home visits and efforts toward the integration of existing services in an ambitious holistic design. The analysis of different interventions is expected to provide sound evidence of the effectiveness and cost of programs supporting AD patients in the community., Trial Registration: ClinicalTrials.gov: NCT01700556.

Importance: The use of proton pump inhibitors (PPIs) has rapidly increased during the past several years. However, concern remains about risks associated with their long-term use in older populations., Objective: To investigate the relationship between the use of PPIs and the risk of death or the combined end point of death or rehospitalization in older patients discharged from acute care hospitals., Design: We investigated the relationship between PPI use and study outcomes using time-dependent Cox proportional hazards regression in patients 65 years or older discharged from acute care medical wards from April 1 to June 30, 2007., Setting: Eleven acute care medical wards., Participants: Four hundred ninety-one patients (mean [SD] age, 80.0 [5.9] years)., Main Outcome Measures: Mortality and the combined end point of death or rehospitalization. RESULTS The use of PPIs was independently associated with mortality (hazard ratio, 1.51 [95% CI, 1.03-2.77]) but not with the combined end point (1.49 [0.98-2.17]). An increased risk of mortality was observed among patients exposed to high-dose PPIs vs none (hazard ratio, 2.59 [95% CI, 1.22-7.16])., Conclusions and Relevance: In older patients discharged from acute care hospitals, the use of high-dose PPIs is associated with increased 1-year mortality. Randomized controlled studies including older frail patients are needed. In the meantime, physicians need to use caution and balance benefits and harms in long-term prescription of high-dose PPIs.

Factor structure analyses have revealed the presence of specific biological system markers in healthy humans and diseases. However, this type of approach in very old persons and in type 2 diabetes (T2DM) is lacking. A total sample of 2,137 Italians consisted of two groups: 1,604 healthy and 533 with T2DM. Age (years) was categorized as adults (≤65), old (66-85), oldest old (>85-98) and centenarians (≥99). Specific biomarkers of routine haematological and biochemical testing were tested across each age group. Exploratory factorial analysis (EFA) by principal component method with Varimax rotation was used to identify factors including related variables. Structural equation modelling (SEM) was applied to confirm factor solutions for each age group. EFA and SEM identified specific factor structures according to age in both groups. An age-associated reduction of factor structure was observed from adults to oldest old in the healthy group (explained variance 60.4% vs 50.3%) and from adults to old in the T2DM group (explained variance 57.4% vs 44.2%). Centenarians showed three-factor structure similar to those of adults (explained variance 58.4%). The inflammatory component became the major factor in old group and was the first one in T2DM. SEM analysis in healthy subjects suggested that the glucose levels had an important role in the oldest old. Factorial structure change during healthy ageing was associated with a decrease in complexity but showed an increase in variability and inflammation. Structural relationship changes observed in healthy subjects appeared earlier in diabetic patients and later in centenarians.

Background: To assess heat production using osteotomes under conditions simulating implant placement in D3, D4 bone., Material and Methods: Implant osteotomes were tested (Winsix, Biosafin, Italy). Site preparations were performed on porcine ribs through a compressive fashion. The ribs were partially immersed in a custom-made water bath/water pump system that maintained the baseline temperature at 36 °C. Temperatures generated at different depths (2, 5, and 9 mm) during a series of 25 osteotomies were measured using 3 thermocouples connected to a digital thermometer., Results: The mean temperatures never exceeded 37 °C and were all significantly lower than those reported during preparation with standard implant drills. Statistical evaluation of the temperature during implant site preparation showed slight significant variations between the baseline values and those of the different depth preparations., Conclusions: Within the limits of this study, the production of heat during implant preparation using osteotomes shows significant variations at different depths. However, these variations are not clinically relevant because they never increased over the values that negatively affect bone that may jeopardize osseointegration.

Background: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). Increased levels of ADMA cause impaired vasodilation, leading to endothelial dysfunction and a higher risk for cardiovascular events. In patients with a chronic kidney disease, increased ADMA levels are reported to play a role in the pathogenesis of accelerated atherosclerosis and are an independent risk marker leading to end-stage renal disease and mortality. Circulating ADMA is metabolized by the action of dimethylarginine dimethylamino hydrolase (DDAH) and DDAH2 isoform is the most prevalent in tissues expressing endothelial NOS. DDAH and NOS are co-expressed in the same kidney regional sites supporting the hypothesis that a strict and specific regulation of intracellular ADMA levels is crucial for NO generation in the kidney. Starting from these findings, the study aims to investigate the role of DDAH2 gene promoter polymorphism at position -1151 A/C in determining the levels of ADMA in type 2 diabetic patients (T2DM) with chronic renal impairment., Methods: Three groups of carefully selected subjects of both sexes were enrolled and compared. The first group (control subjects) comprised 286 non-diabetic subjects (mean age 55.8 ± 11.4 years), the second group (T2DM uncomplicated subjects) was made up of 322 T2DM subjects without complications (mean age 64.9 ± 9.6 years) whereas the third group (T2DM CRF subjects) included 110 T2DM patients with chronic renal impairment. The rs805304 DDAH2-1151 A/C promoter polymorphism was determined by a polymerase chain reaction-restriction fragment length polymorphism approach. Results T2DM CRF subjects showed significant increased plasma levels of ADMA with respect to those of T2DM uncomplicated subjects and control subjects (0.51 versus 0.39 versus 0.37 μmol/L, P = 0.002, respectively). Analysis of variance showed an interaction between DDAH2-1151 C carrier and groups on ADMA plasma levels (F = 4.36; P < 0.05). ADMA plasma levels were also dependent on groups (F = 4.96; P < 0.01)., Conclusions: Our work demonstrates that rs805304 DDAH2-1151 polymorphism plays a central role in determining ADMA in diabetic renal impairment, where patients with DDAH2-1151 C carriers showed the highest ADMA levels. This unfavourable genetic profile is highlighted by pathological kidney conditions such as diabetic CRF. These findings could open new insights on the pathways involving ADMA/DDAH/NOS in the development and progression of chronic renal impairment and therefore of the other micro- macrovascular diabetic complications.

Physical education (PE) at school is an important starting point for long-term interventions improving quality of life in elderly. To evaluate the effectiveness of professionally led PE on motor and health-related abilities of Italian primary schoolchildren (3rd-5th graders), three schools were assigned to the experimental groups "A" (38 pupils, 17 M, 21 F) and "B" (37 pupils, 16 M, 21 F), and to control group "C" (26 pupils, 18 M, 8 F). All groups underwent a six-month, twice-a-week (60 min each session) PE intervention. The PE program of the EGs was age-tailored, included strength training and was administered by specialised teachers. Group A and B programs differed in the strength training devices used, while they were identical in terms of training load. The control group program was not structured and administered by generalist teachers. At baseline and follow-up, children underwent a motor and health-related abilities test battery. At follow-up, children in group C gained significantly more weight than children in the EGs and scored significantly less than the children in the EGs in the following assessments: counter movement jump (C:+0.15% vs. A:+4.1% and B:+6.99%), plate tapping (C:+13.56% vs. A:+19.37% and B:+36.12%), sit-and-reach (C:-311.15% vs. B:+409.57%), pinch strength (C:+2.39% vs. B:+10.83, on average) and sit-up (C:+29.69% vs. A:+72.61%). In conclusion, specialist-led pupils demonstrated greater increases in some motor and health-related abilities tests compared to generalist-led peers, while different strength training devices produced comparable increases of strength in both EGs.

Background: Elderly people are particularly vulnerable to the effects of social reduction, so there is an urgent need to identify the risks associated with social isolation. The aim of this paper was to analyze associations between psychological, socio-demographic, functional aspects on the risk of social isolation, mortality and re-hospitalization in older persons., Methods: This is a longitudinal study on 580 hospitalized elderly sample aged ≥70yrs recruited from 2005 to 2007 in the Geriatrics Operative Unit of INRCA in Fermo, Italy. The comprehensive geriatric assessment (CGA) was used. Outcome measures included 36-month mortality and re-hospitalization., Results: In all patients, approximately 20% (n=112) of the subjects were socially isolated. Women perceived their social support significantly worse than men (77.7 vs. 22.3%; p<0.001). A multiple logistic regression analysis (goodness of fit χ(2)=102.86, p<0.001) with risk of social isolation as the dependent variable, showed that women were at a greater risk than men for social isolation (OR=1.99, 95% CI=1.13-3.50). Furthermore, patients with a higher number of family components (OR=0.72, 95% CI=0.59-0.88) and good parameters of quality of life (PCS-12: OR=0.94, 95% CI=0.91-0.98; MCS-12: OR=0.94, 95% CI=0.92-0.97) were less likely to be socially isolated. Cox regression models adjusted for gender, quality of life and number of family components, showed that the social isolation did not predict mortality (HR=1.44, 95% CI=0.84-2.46, p=0.19), but was associated with higher re-hospitalization rates (HR=1.28, 95% CI=1.02-1.59, p=0.03)., Conclusions: Our findings highlight several aspects related to the risk of social isolation and re-hospitalization in a specific group of older persons., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Circulating microRNAs (miRs) have been investigated as diagnostic/prognostic biomarkers in human diseases. However, little is known about their expression throughout the aging process. Eleven healthy individuals aged 20, 80 and 100 years underwent miR plasma profiling. The validation cohort consisted of 111 healthy adults (CTR) aged 20-105 years and included 30 centenarians. In addition, 34 patients with cardiovascular disease (CVD) and 15 healthy centenarian offspring (CO) were enrolled. An exploratory factorial analysis grouped the miRs into three main factors: factor 1 primarily higher in 20-year-old subjects, but these differences did not reach statistical significance, factor 2 primarily higher in octogenarians and factor 3 primarily higher in centenarians. MiR-21, the most highly expressed miR of factors 2 and 3, was further validated, confirming the differences in the age groups. MiR-21 expression was higher in the CVD patients and lower in the CO compared to the age-matched CTR. MiR-21 was correlated with C-reactive protein and fibrinogen levels. TGF-β signaling was the predicted common pathway targeted by miRs of factors 2 and 3. TGF-βR2 mRNA, a validated miR-21 target, showed the highest expression in the leukocytes from a subset of the octogenarians. Our findings suggest that miR-21 may be a new biomarker of inflammation., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

We compared the diagnostic accuracy of 3-lead tele-ECGs to both 12-lead tele-ECGs and a conventional 12-lead ECG device (the gold standard). The subjects were older people (n = 107) with a mean age of 66 years. The overall agreement between two cardiologists on interpreting the 3-lead tele-ECG recordings was 97% (kappa = 0.96, P < 0.001) and it was 91% for the 12-lead tele-ECGs (kappa = 0.90, P < 0.001). We also found excellent agreement on the interpretation of the 3-lead tele-ECGs compared to the gold standard: 98% (kappa = 0.96, P < 0.001) and for the 12-lead tele-ECG compared to the gold standard: 98% (kappa = 0.96, P < 0.001). Bland-Altman plots showed that the apparent differences between the techniques were not clinically relevant. The use of a 3-lead tele-ECG device may be useful for reducing the delay in treating specific heart disease conditions, e.g. in older people affected by chronic heart disease who need frequent ECG monitoring.

The present study examines the leisure style and leisure satisfaction of a sample of older people at baseline and after a period of 5 years. Three groups were identified by factorial and cluster analyses and labelled under the headings of: organised style, surrounding style and indoor style. Each group represented a different typology of leisure, according to the demand for physical and organizational commitment. Results indicated that the Organized Style group was the most active and satisfied with their leisure time, and differed from the other two by being predominantly male, younger, better educated and in good health. Follow-up analyses revealed a decline in the size of both the organised style and surrounding style groups, and an increase in the size of the less active group, suggesting that advancing very old age with deteriorating health influenced older peoples' choices toward an increment of indoor activities. This pattern may be softened through the implementation of mechanisms of selection and optimisation.

It is well known that serum paraoxonase (PON1) plays an important role in the protection of LDL from oxidation. PON1 55 polymorphism is currently investigated for its possible involvement in cardiovascular diseases. The objective of our study is to verify if PON1 55 polymorphism is associated with risk of acute coronary syndrome (ACS) and with biochemical myocardial ischemia markers, such as troponin I, creatine kinase (CK)-MB, myoglobin, and C-reactive protein. We analysed PON1 55 polymorphism in a total of 440 elderly patients who underwent an ACS episode: 98 patients affected by unstable angina (UA), 207 AMI (acute myocardial infarction) patients affected by STEMI (ST elevation), and 135 AMI patients affected by NSTEMI (no ST elevation). We found that individuals carrying PON1 55 LL genotype are significantly more represented among AMI patients affected by NSTEMI; moreover, the patients carrying LL genotype showed significantly higher levels of myoglobin in comparison to LM + MM carriers patients. Our study suggests that PON1 55 polymorphism could play a role in the pathogenesis of cardiac ischemic damage. In particular, the significant association between PON1 55 LL genotype and the occurrence of a NSTEMI may contribute to improve the stratification of the cardiovascular risk within a population.

We aimed to demonstrate that depression and hypertension are associated independently of each other with disability and cognitive impairment in older subjects and that such an association is not attributable to number and severity of comorbidities. An observational study was performed on elderly patients admitted to the Hospital Network of the Italian National Research Center on Aging (INRCA) from January 2005 to December 2006. Depression was defined according to 15-item geriatric depression scale (GDS) score; physical disability according to activities of daily living (ADL) and instrumental activities of daily living (IADL) scores; cognitive impairment on the mini-mental state examination (MMSE) test; the number and severity of comorbidities by means of physician-administered cumulative illness rating scale (CIRS). Among 6180 older subjects (age=79.3 ± 5.8 years; 47% men), 48.3% were normotensive, 21.8% normotensive depressed, 21.7% hypertensive, and 8.2% hypertensive and depressed. Both depression and hypertension remained significantly associated with functional disability and cognitive impairment. When controlling for age, gender, the number and severity of comorbidities, hypertension was associated with a significantly higher likelihood of having functional disability or cognitive impairment only in the presence of depression (odds ratio=OR=2.02, 95% confidence interval=95%CI=1.60-2.54, p<0.001 for functional disability; OR=2.21, 95%CI=1.79-2.74, p<0.001 for cognitive impairment) as compared to normotensive controls without depression. We conclude that depression per se' or co-occurrence of hypertension and depression is associated with higher functional disability and cognitive impairment in older subjects. This effect is not attributable to the number or to the severity of comorbidities., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: In this study, we consider spirituality in terms of interpersonal, transpersonal, and intrapsychic processes. The goal of this study is to establish whether a spiritual perspective is correlated with more effective coping skills and intrapsychic processes., Patients: Lung (n = 88, n. (age 62.8±10.1)) and large bowel cancer (n = 56; age (age 60.1±11.4)) (all stages)., Tests: SASB Questionnaire by L.S. Benjamin-intrapsychic processes; Scale of Coping Styles by A. Jalowiech; Brief Measure of Spirituality (BMMS); Spiritual Well Being Index by T. Daaleman and B. Bruce., Results: There is a significant correlation among inner spirituality (IS) (Cronbach's α = 0.692), spiritual coping (SC) (Cronbach's α = 0.935) (described total variability-BMMS) and Spiritual Well Being (SWB) (Cronbach's α = 0.759). (Significant correlation among the three scales, Cronbach's α = 0.676.)The patients with high spirituality are more prone to develop their potentialities and capacities. They (with IS and SC) have more effective coping mechanisms with stressful situations (SASB Cl 3: Self-supporting and appreciate and IS = p<0.002; and SC = p<0.001. They care for themselves by developing their own capacities and potentialities-SASB Cl 5: Self-control and IS p = 0.033; and SC p = 0.037. The profile of patients with lower intrinsic spirituality and SC scores suggest ineffective coping with high risk of depression, self-neglect both in the physical and emotional dimensions, and of self-abuse (SASB Cl 8: Self-criticism and IS p = 0.033; SC p = 0.044)., Conclusion: The presence of a spiritual dimension may be a marker of patients with a good adaptation to cancer treatment., (Copyright © 2010 John Wiley & Sons, Ltd.)

Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure.

Aims: Circulating microRNAs (miRNAs) may represent a novel class of biomarkers; therefore, we examined whether acute myocardial infarction (MI) modulates miRNAs plasma levels in humans and mice., Methods and Results: Healthy donors (n = 17) and patients (n = 33) with acute ST-segment elevation MI (STEMI) were evaluated. In one cohort (n = 25), the first plasma sample was obtained 517 ± 309 min after the onset of MI symptoms and after coronary reperfusion with percutaneous coronary intervention (PCI); miR-1, -133a, -133b, and -499-5p were ~15- to 140-fold control, whereas miR-122 and -375 were ~87-90% lower than control; 5 days later, miR-1, -133a, -133b, -499-5p, and -375 were back to baseline, whereas miR-122 remained lower than control through Day 30. In additional patients (n = 8; four treated with thrombolysis and four with PCI), miRNAs and troponin I (TnI) were quantified simultaneously starting 156 ± 72 min after the onset of symptoms and at different times thereafter. Peak miR-1, -133a, and -133b expression and TnI level occurred at a similar time, whereas miR-499-5p exhibited a slower time course. In mice, miRNAs plasma levels and TnI were measured 15 min after coronary ligation and at different times thereafter. The behaviour of miR-1, -133a, -133b, and -499-5p was similar to STEMI patients; further, reciprocal changes in the expression levels of these miRNAs were found in cardiac tissue 3-6 h after coronary ligation. In contrast, miR-122 and -375 exhibited minor changes and no significant modulation. In mice with acute hind-limb ischaemia, there was no increase in the plasma level of the above miRNAs., Conclusion: Acute MI up-regulated miR-1, -133a, -133b, and -499-5p plasma levels, both in humans and mice, whereas miR-122 and -375 were lower than control only in STEMI patients. These miRNAs represent novel biomarkers of cardiac damage.

Background: The mechanisms related to cognitive impairment in older persons with Type 2 diabetes (DM) remains unclear. We tested if adiposity parameters and body fat distribution could predict cognitive decline in older persons with DM vs. normal glucose tolerance (NGT)., Methodology: 693 older persons with no dementia were enrolled: 253 with DM in good metabolic control; 440 with NGT (age range:65-85 years). Longitudinal study comparing DM and NGT individuals according to the association of baseline adiposity parameters (body mass index (BMI), waist-hip-ratio (WHR), waist circumference (WC) and total body fat mass) to cognitive change (Mini Mental State Examination (MMSE), a composite score of executive and attention functioning (CCS) over time., Findings: At baseline, in DM participants, MMSE correlated with WHR (beta = -0.240; p = 0.043), WC (beta = -0.264; p = 0.041) while CCS correlated with WHR (beta = -0.238; p = 0.041), WC (beta = -0.326; p = 0.013) after adjusting for confounders. In NGT subjects, no significant correlations were found among any adiposity parameters and MMSE, while CCS was associated with WHR (beta = -0.194; p = 0.036) and WC (beta = -0.210; p = 0.024). Participants with DM in the 3(rd) tertile of total fat mass showed the greatest decline in cognitive performance compared to those in 1(st) tertile (tests for trend: MMSE(p = 0.007), CCS(p = 0.003)). Logistic regression models showed that 3(rd) vs. 1(st) tertile of total fat mass, WHR, and WC predicted an almost two-fold decline in cognitive function in DM subjects at 2(nd) yr (OR 1.68, 95%IC 1.08-3.52)., Conclusions: Total fat mass and central adiposity predict an increased risk for cognitive decline in older person with DM.

Although the role of environmental factors in the development of acute myocardial infarction (AMI) has been clearly established, the role of genetic factors is still undefined. The aim of this study was to investigate the association between various gene polymorphisms in the haemostatic system and the risk of myocardial infarction in a very genetic restricted area population of Sardinian young adults with AMI. The study case-control involved 71 patients who had survived a first MI at a mean age of 47,2 years and 150 healthy subjects. No differences in the allele or genotype frequencies were seen between the study groups for the fibrinogen, prothrombin, factor V, factor VII, vWF, TM, PAI-1, TPO gene, and PLA and HPA-2 genes polymorphisms. Indeed differences statistically significant were detected for A5709G in the TPO gene (P= 0,041), and I/D dimorphism in the eNOS gene (P= 0,016). We therefore conclude that among all the investigated polymorphisms only the 5709G and eNOS4a alleles seem to confer protection against MI in the young age of Sardinian people.

It is well known that oxidative stress plays an important role in atherosclerosis and age-related diseases. The antioxidant properties of the Human Paraoxonase gene family (PON1, 2, 3) have been widely investigated, as well as a possible role of the such gene family in cardiovascular disease. In this study, we investigated the relationship between the C311S PON2 polymorphism and the prognosis of acute myocardial infarction (AMI). We analyzed the PON2 C311S polymorphism in 442 elderly patients who had experienced an AMI. PON2 C311S genotypes were identified by PCR based analysis and analyzed as C- (SS genotype) or C+ (CS+CC) carriers. After 1 year of follow-up, the cardiovascular mortality rate in a sub-group of 295 AMI patients was calculated. We found that AMI patients carrying CS+CC genotypes (C+ carriers) had a history of type 2 diabetes mellitus, low levels of HDL-cholesterol and higher levels of TroponinT (TnT). Furthermore, we found that C+ carrier patients with low levels of HDL-cholesterol had an increased risk for mortality after 1 year of follow-up (Log Rank=11.45, p=0.001). Our study suggests a possible role for PON2 C311S polymorphism in the pathogenesis of cardiac ischemic damage. Patients with at least one C allele (C+ carriers) represent a category of subjects at a higher risk for the development of AMI with a worse prognosis. Our findings suggest the need for a more careful clinical monitoring in older persons with such characteristics.

Objective: We performed a cross-sectional study to examine the differences in leukocyte telomere length among three groups of subjects: patients with type 2 diabetes mellitus without history of previous myocardial infarction (Type2DM), patients with type 2 diabetes mellitus with evidence of previous myocardial infarction (Type2DM+MI), and healthy control subjects (CTR). The main objective of the present study is to investigate differences in telomere length between the studied groups of subjects, with the aim to clarify if telomere length could be a reliable marker associated with MI in Type2DM patients. Secondary end point is the identification of associations between leukocyte telomere length and selected variables related to glycemic control, pro-inflammatory status and lipidic profile., Research Design and Methods: A total of 272 elderly subjects, 103 Type2DM (mean age 70+/-4 years, 59% males), 65 Type2DM+MI (mean age 68+/-7 years, 68% males), and 104 CTR (mean age 69+/-7 years, 50% males) were studied. Telomere length, defined as T/S (Telomere-Single copy gene ratio), was determined in leukocytes by quantitative real-time polymerase chain reaction (real-time PCR)-based assay. Moreover, we assessed: (1) high sensitive C reactive protein (hsCRP), fibrinogen and plasminogen-activator inibitor-1 (PAI-1) as inflammatory markers; (2) fasting glucose, insulin, glycated haemoglobin (HbA1C) and waist-to-hip ratio as markers of glycemic control; (3) total-cholesterol, HDL-cholesterol and triglycerides as markers of lipidic profile, in all sample population. The use of statins and sulfonylurea, as well as the presence of some relevant diabetes complications (nephropathy and retinopathy) were also assessed., Conclusion: Type2DM+MI elderly patients have leukocyte telomere lengths shorter than those of Type2DM (without MI) and healthy CTR. Moreover, glucose, HbA1C and waist-to-hip ratio, variables related to glycemic control, showed a significant inverse correlation with leukocyte telomeres length.

Objectives: To perform a psychometric evaluation of the Carers Assessment of Difficulties Index, Carers Assessment of Satisfactions Index and the Carers Assessment of Managing Index (CADI-CASI-CAMI)., Method: Data was collected in three European countries from informal carers of older people (n = 295) via a common protocol. Carers completed: (a) a questionnaire containing items on demographics and caregiving characteristics and (b) the CADI-CASI-CAMI indices. Principal component analysis of the CADI-CASI-CAMI indices was followed by internal consistency analysis of emergent components. Scales derived by summing items loading on the components were analysed for their association with the demographic and caregiving characteristic variables., Results: CADI produced six internally consistent and interpretable components, CASI five and CAMI seven. Subscales derived from the components were significantly associated with the demographic and caregiving characteristic variables, providing initial support for construct validity., Conclusion: The CADI-CASI-CAMI indices are recommended as an assessment tool for in-depth work with family carers of older people and as a research tool for large-scale studies of family care.