Physical performance strongly predicts all-cause mortality risk in a real-world population of older diabetic patients: machine learning approach for mortality risk stratification.

Background: Prognostic risk stratification in older adults with type 2 diabetes (T2D) is important for guiding decisions concerning advance care planning. Materials and methods: A retrospective longitudinal study was conducted in a real-world sample of older diabetic patients afferent to the outpatient facilities of the Diabetology Unit of the IRCCS INRCA Hospital of Ancona (Italy). A total of 1,001 T2D patients aged more than 70 years were consecutively evaluated by a multidimensional geriatric assessment, including physical performance evaluated using the Short Physical Performance Battery (SPPB). The mortality was assessed during a 5-year follow-up. We used the automatic machine-learning (AutoML) JADBio platform to identify parsimonious mathematical models for risk stratification. Results: Of 977 subjects included in the T2D cohort, the mean age was 76.5 (SD: 4.5) years and 454 (46.5%) were men. The mean follow-up time was 53.3 (SD:15.8) months, and 209 (21.4%) patients died by the end of the follow-up. The JADBio AutoML final model included age, sex, SPPB, chronic kidney disease, myocardial ischemia, peripheral artery disease, neuropathy, and myocardial infarction. The bootstrap-corrected concordance index (c-index) for the final model was 0.726 (95% CI: 0.687-0.763) with SPPB ranked as the most important predictor. Based on the penalized Cox regression model, the risk of death per unit of time for a subject with an SPPB score lower than five points was 3.35 times that for a subject with a score higher than eight points (P-value <0.001). Conclusion: Assessment of physical performance needs to be implemented in clinical practice for risk stratification of T2D older patients.

A study protocol for identifying aging trajectories toward chronic neurodegenerative diseases by means of Marche regional administrative databases - TREND project.

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.

Impact of a Discontinuous Training Program on Sedentary Behavior in Italian Type 2 Diabetes Older Patients: The Results of the TRIPL-A Randomized Controlled Trial.

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.

Antifragility and antiinflammaging: Can they play a role for a healthy longevity?

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.

Occurrence of Idiopathic Pulmonary Fibrosis in Italy: Latest Evidence from Real-World Data.

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.

Stratification of the risk of developing severe or lethal Covid-19 using a new score from a large Italian population: a population-based cohort study.

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.

Prognostic relevance of normocytic anemia in elderly patients affected by cardiovascular disease.

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.

Connecting vascular aging and frailty in Alzheimer's disease.

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.

Measuring multimorbidity inequality across Italy through the multisource comorbidity score: a nationwide study.

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.

Associations of Lipophilic Micronutrients with Physical and Cognitive Fitness in Persons with Mild Cognitive Impairment.

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 ß-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; ß-cryptoxanthin and ß-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.

Clustering of ABCB1 and CYP2C19 Genetic Variants Predicts Risk of Major Bleeding and Thrombotic Events in Elderly Patients with Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy with Aspirin and Clopidogrel.

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; χ2 = 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; χ2 = 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.

Age-related modulation of plasmatic beta-Galactosidase activity in healthy subjects and in patients affected by T2DM.

ß-Galactosidase (ß-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 ß-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 ß-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 ß-Gal activity in young and senescent endothelial cells (HUVECs) cultured in normo- and hyper-glycaemic environment. A significant age-related increase of plasmatic ß-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. ß-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 ß-Gal activity in milieu compared to normo-glycaemic condition. Overall our data reinforce the notion that plasmatic ß-Gal activity could be a systemic biomarker of aging, whereas T2DM patients are characterized by a different age-releated trend.

Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging.

Human aging is a lifelong process characterized by a continuous trade-off between pro-and anti-inflammatory responses, where the best-adapted and/or remodeled genetic/epigenetic profile may develop a longevity phenotype. Centenarians and their offspring represent such a phenotype and their comparison to patients with age-related diseases (ARDs) is expected to maximize the chance to unravel the genetic makeup that better associates with healthy aging trajectories. Seemingly, such comparison is expected to allow the discovery of new biomarkers of longevity together with risk factor for the most common ARDs. MicroRNAs (miRNAs) and their shuttles (extracellular vesicles in particular) are currently conceived as those endowed with the strongest ability to provide information about the trajectories of healthy and unhealthy aging. We review the available data on miRNAs in aging and underpin the evidence suggesting that circulating miRNAs (and cognate shuttles), especially those involved in the regulation of inflammation (inflamma-miRs) may constitute biomarkers capable of reliably depicting healthy and unhealthy aging trajectories.

Leukocyte telomere length and mortality risk in patients with type 2 diabetes.

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.

Exercise: a "new drug" for elderly patients with chronic heart failure.

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.

Utility of video consultation to improve the outcomes of home enteral nutrition in a population of frail older patients.

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; ●●: ●●-●●.

MiR-21-5p and miR-126a-3p levels in plasma and circulating angiogenic cells: relationship with type 2 diabetes complications.

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.

Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer's disease neurodegeneration.

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.

MicroRNA-34c-5p is related to recurrence in laryngeal squamous cell carcinoma.

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.

Validation of the Italian translation of the Revised Temperament and Character Inventory--TCI-140--in adult participants and in participants with medical diseases.

INTRODUCTION: This study aimed at assessing the reliability and construct validity of the TCI-140. SAMPLE: 428 Italian participants. EXCLUSION CRITERIA: psychiatric disorders. 100 subjects - longitudinal retest study. RESULTS: The results of descriptive statistics of internal consistency reliabilities (Cronbach coefficient) of TCI-R dimensions showed: a strong internal consistence of the scales: HA (α = 0.84); RD (α = 0.70); SD (α = 0.86); C (α = 0.75); ST (α = 0.83); a low level in NS (α = 0.60). In relation to facets, internal consistency reliabilities (Cronbach coefficient) ranged from 0.14 C3 to 0.79 C4 (from 3rd to 4th facet of C scale). Correlations: highest inverse correlation between HA and SD (r = -0.56); moderate inverse correlations for: HA and PS (r = -0.37); C and RD(r = 0.32); C and SD (r = 0.44). P, SD, C and ST showed good inter class correlations (ICC) ≥ 70 maintaining a good stability of the measures over the time. Four factors accounted for 56.3% of the variance for temperament subscale. Subscales of: PS4, PS3 PS2, PS1, NS3 for factor 1; HA2, HA1, HA4, HA3 for factor 2; RD1, RD2 and RD3 for factor 3; NS4, NS1 and NS2 for factor 4. Three factors that were identified accounted for 58.3% of the variance for character subscales of: SD3, SD5, SD1, SD2 for factor 1; C4, C1, C5, SD4, C3 for factor 2; ST2, ST1, ST3, C2 for factor 3. CONCLUSION: The reliability coefficients were significantly good for some dimensions of TCI-140 and showed a good correlation after time, while some dimensions as NS have low reliability. In the principal components analysis does not saturate all dimensions in its theoretical factor. Moreover TCI-140 is a useful inventory for the evaluation of the principal dimensions of temperament and character.