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The impaired ability of the elderly to mount an efficient immune response after exposure to microbes or vaccines represents a major challenge in protection against pathogens in ageing. Recently studies have shown that stimulation of Toll-like receptors (TLRs), using stimulatory ligands, can enhance vaccine efficacy by a number of mechanisms, including the activation of innate immune cells and the consequent production of inflammatory cytokines.

The objective of this study was to validate two interviewer-led food frequency questionnaires (FFQs) of very different lengths: a medium-length FFQ (medium-FFQ) of 36 items and a short-length FFQ (short-FFQ) of 18 items, intending to measure levels of intakes in a local population. Both FFQs were validated against intakes derived from a 3-day dietary record (3-day DR). Sixty-five non-diabetic adults with no known cardiovascular, renal or other systemic diseases were included. High correlation coefficients between the FFQ and the 3-day DR (0.45-0.73) were observed for energy intake, carbohydrates and lipid and protein intake. Bland-Altman plots showed good agreement between the methods. Low (0.26-0.37) correlation coefficients of the different nutrient intakes obtained with the short-FFQ and the 3-day DR were observed, with the exception of alcohol intake (rho = 0.49). This study showed promising evidence for the use of a medium-FFQ as a potentially useful tool for investigating the relationship between habitual diet and diseases in clinical and research settings.

BACKGROUND:Endothelial dysfunction is involved in the pathogenesis of atherosclerosis. Consumption of fish is associated with reduced cardiovascular risk, but there is paucity of data concerning its effect on endothelial function. Furthermore, investigation of the effects of fish consumption on health must take into account the ingestion of contaminants, including transition metals and some metalloids, which may have unfavorable effects on health, including those on the cardiovascular system. We investigated the association between fish consumption, endothelial function (flow mediated dilation of the brachial artery), and serum concentration of some toxic metals in apparently healthy people. METHODS:Twenty-nine high fish consumers (at least 3 portions a week) were compared with 25 low fish consumers (less than 1 portion a week). All participants were free of diabetes, cardiovascular or other systemic diseases. Serum metal (antimonium, arsenic, mercury, lead, cobalt, copper, zinc, selenium, strontium) concentrations were measured in subgroups of 24 high fish consumers and 19 low fish consumers. RESULTS:Both groups exhibited similar habitual dietary patterns, age and anthropometric characteristics. The high fish consumers had higher flow mediated dilation (9.7 ± 1.8 vs. 7.3 ± 1.9%; P

Aims: Resting energy expenditure (REE) plays a critical role in the regulation of body weight, with important implications in type 2 diabetes (T2D). However, the relationships between REE and T2D have not been extensively evaluated. We compared REE in persons with diabetes and in persons without diabetes. We also investigated the acute effect of insulin on REE and venous lactate, the latter an indirect measure of neoglucogenetic activity. Methods: REE was measured using indirect calorimetry in 14 newly diagnosed, untreated T2D adults and in 14 non-diabetic age-, gender- and body mass index-matched persons. The REE and lactate venous concentrations were also measured in a subgroup of 5 T2D patients in the hour following an IV insulin bolus. Results: The REE normalized for fat-free mass (FFM) was significantly higher in T2D patients than in the group without diabetes (mean SD: 27.6 1.9 vs. 25.8 1.9 kcal/kg-FFM 24 h; P = 0.02). REE normalized for FFM was correlated with fasting plasma glucose concentration (r = 0.51; P = 0.005). Following the insulin venous bolus REE (00: 2048 242; 100: 1804 228; 200: 1684 230; 300: 1634 212; 450: 1594 179; 600: 1625 197 kcal/24 h; P < 0.001) and both glucose (P < 0.001) and lactate (P < 0.001) concentrations progressively declined in the ensuing hour. Conclusions: Patients with diabetes have a higher energy expenditure, likely a consequence of higher gluconeogenetic activity. This study may contribute to recognizing the nature of body weight reduction that occurs in concomitance with poorly controlled diabetes, and of body weight gain as commonly observed when hypoglycemic treatment is started.

This work presents preliminary results of the international project: “Effect of the environment on reinforced concrete durability: DURACON”, which shows the physical, mechanical and chemical characterization of two different concrete mixtures prepared in the participating countries, as well as the environment to which the specimens are exposed. These results show the potentiality and probability of future reinforcement corrosion, depending on the type of mixture and the environment to which the structure is exposed. To that effect, concrete specimens, with and without reinforcement, were prepared for electrochemical and physical/mechanical/chemical testing using the existing materials in each participating country, following premises that enabled the preparation of similar concrete specimens. Two water/cement ratios (0.45 and 0.65) were selected, where the concrete with w/c=0.45 had to have a minimum cement content of 400 kg m−3, and the other with w/c=0.65, a minimum compressive strength of 21 MPa. Ordinary Portland Cement (OPC), crushed coarse aggregate, and silica sand were used for concrete preparation. The specimens were exposed to several microenvironments including urban and marine conditions (at least two testing sites in each country), resulting into a total of 46 test sites distributed among 11 countries (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Mexico, Spain, Uruguay, Portugal, and Venezuela). The environment was evaluated using ISO Standard 9223 and the concrete was characterized by measuring compressive strength, modulus of elasticity, total and effective porosity, and rapid chloride permeability according to ASTM standards, as well as resistance to water absorption, using the Fagerlund method. After 1-year exposure, some results of the corrosion potentiality and probability analysis of the reinforcement in several test sites based on environmental meteorochemical parameters show that, for specific microclimates like those in marine atmospheres, the most aggressive environment is that at Cabo Raso test site in Portugal, inducing the greater steel-corrosion probability. The least aggressive is the one at Valparaíso in Chile. It was also determined that Maracaibo, Venezuela, is the one that has the greatest probability of early rebar corrosion initiation by carbonation, with the test site at Cali, Colombia being the one that would induce the least corrosion probability.

Background The cerebral innate immune system has a critical role in control processes of viral replication in the brain after primary infactivo and immunologic disregulation and inflammation has been reported as a primary determinant of pathogenesis and prognosis of subsequent HSV-1 related encephalitis (HSE). Interaction linking LTR3-activated DCs is also represented by the killer Ig-like receptor (KIR) + pathways on NK cells. Only a few studies analyzed the role of of MMP-9 activity regulating genetic polymorphism on clinical outcome of viral infections. Susceptibility to symptomatic encephalitis depends on SNC viral invasion and BBB disruption. We hypothesize that certain KIR genes and MMP allele may help to characterize a risk profile of developing an acute encephalitis due to HSV 1. Aim of the study Analyze the frequency of KIR genes and the C(−1562)T MMP-9 allels in subjects with HSV-1 encephalitis and to analyze their interaction with regard of the risk of occurrence of a symptomatic encephalitis. Materials and methods Between November 2014 and January 2019, all consecutive patients with symptomatic acute encephalitis were recruited from three wards (Internal Medicine, Neurology, and Infectious Diseases) of “P. Giaccone” University Hospital, Palermo. Results Patients with acute viral encephalitis in comparison to controls showed a higher frequency AA KIR haplotype, HLA-C2 and of HLA-A-Bw4 alleles. With regard of HLA allele frequency patients with acute viral encephalitis In comparison to controls also showed a higher frequency of HLA-C2 and of HLA-A-Bw4 alleles. With regard of MMP-9 alleles, subjects with acute viral encephalitis were more likely to have the TT genotype. The multiple logistic regression analysis considering variables predictive of the occurrence of acute viral encephalitis showed the detrimental effect of AA KIR, HLA C1, HLA-A-BW4 and HLA-B-BW4T and of TT aplotype of MMP-9 genotype. Conclusions Our study shows that in immunocompetent adult subjects there is an association between some KIR genes, MMP-9 alleles and HLA-ligand alleles and susceptibility to develop a symptomatic acute viral encephalitis. Definition of the genetic and immunological background of acute viral encephalitis can play a key role to determine personalized medicine.

Strong evidence suggests that systemic inflammation and central adiposity contribute to and perpetuate metabolic syndrome. All of these alterations predispose individuals to type 2 diabetes mellitus (T2DM), cardiovascular disease, as well as Alzheimer's disease (AD), all characterized by chronic inflammatory status. On the other hand, extensive abnormalities in insulin and insulin-like growth factor I (IGF-I) and IGF-II signaling mechanisms in brains with AD have been demonstrated, suggesting that AD could be a third form of diabetes. The Src homology domain-containing inositol 5-phosphatase 2 (SHIP2) has an important role in the insulin pathway because its over-expression causes impairment of insulin/IGF-1 signaling. Because some single-nucleotide polymorphisms (SNP) of the gene encoding SHIP2 were significantly associated in T2DM patients with metabolic syndrome and some related conditions, we decided to conduct a case-control study on this gene, analyzing AD and T2DM subjects as cases and young, old, and centenarians as controls. Our results suggest a putative correlation between the the rs144989913 SNP and aging, both successful and unsuccessful, rather than age-related diseases. Because this SNP is an insertion/deletion of 28 bp, it might cause an alteration in SHIP2 expression. It is noteworthy that SHIP2 has been demonstrated to be a potent negative regulator of insulin signaling and insulin sensitivity. Many studies demonstrated the association of the insulin/IGF1 pathway with aging and longevity, so it is tempting to speculate that the found association with SHIP2 and aging might depend on its effect on the insulin/IGF-1 pathway.

A typical feature of ageing is a chronic, low-grade inflammation characterized by a general increase in the production of pro-inflammatory cytokines and inflammatory markers ("inflamm-ageing"). This status may slowly damage one or several organs, especially when unfavorable genetic polymorphisms and epigenetic alterations are concomitant, leading to an increased risk of frailty together with the onset of age-related chronic diseases. The contribution of different tissues (adipose tissue, muscle), organs (brain, liver), immune system and ecosystems (gut microbiota) to age-related inflammation ("inflamm-ageing") will be discussed in this review in the context of its onset/progression leading to site-restricted and systemic effects. Moreover, some of the possible strategies and therapies to counteract the different sources of molecular mediators which lead to the age-related inflammatory phenotype will be presented.

The major trait characterizing offspring in centenarians is a reduction in the prevalence of cardiovascular disease. Because a pro-inflammatory genotype seems to contribute significantly to the risk of coronary heart disease, alleles associated with disease susceptibility would not be included in the genetic background favoring longevity, as suggested by our previous studies on inflammatory cytokines. To confirm whether genotypes of inflammatory molecules play an opposite role in atherosclerosis and longevity, we are studying the role of other proinflammatory alleles, such as pyrin and CCR5, in acute myocardial infarction and longevity. The results support the hypothesis that the genetic background favoring cardiovascular diseases is detrimental to longevity. In addition, they suggest that the centenarian genetic background may be useful for investigating genetic key components of age-associated diseases that are characterized by a multifactorial etiology.

Fresh vegetables and fruits have always been the mainstays of good nutrition as providers of fiber, beneficial phytochemicals (such as vitamins and phenolic compounds), and minerals. Today and in the future, biofortification is a promising strategy to increase the concentration of these compounds. Considering the importance of minerals in human health, the enrichment of fresh produce for consumption has been considered through specific agronomic approaches. This review discusses, in detail, the latest findings on vegetable agronomic biofortification, aimed at increasing the concentration of crucial minerals, such as iron (Fe), zinc (Zn), iodine (I), selenium (Se), molybdenum (Mo), and silicon (Si), in edible portions, focusing on the direct and indirect effects of this strategy. Although agronomic biofortification is considered a feasible technique, the approach is complex due to the many interactions between the microelement bioavailability for both plants and consumers. Therefore, the effects of biofortification on human health and the influence of beneficial and antinutritional compounds were discussed in detail to analyze the advantages and disadvantages of this practice.

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.

The pro-inflammatory cytokine interleukin(IL)-1β is a main component in inflammatory pathways and is overexpressed in the brain of Alzheimer's disease (AD) patients. Several studies report associations between IL-1β polymorphisms and AD, but findings from different studies are controversial. Our aim was to verify the correlation between the single nucleotide polymorphisms (SNPs) of the IL-1β, at sites − 511 and + 3953, and AD by meta-analysis. Computerized bibliographic searches of PUBMED and AlzGene database ( http://www.alzgene.org ) were supplemented with manual searches of reference lists. There is evidence for association between IL-1β + 3953 SNP and AD, with an OR = 1.60 (95% C.I.: 1.16–2.22; Z = 2.83 p = 0.005) for TT genotype. No significant difference in genotype distribution of the IL-1β − 511 SNP in AD was obtained, but high between-study heterogeneity was found. To reduce heterogeneity, subgroup analyses were performed using, as stratifying variables, characteristics of the population under study (age, gender, type of AD diagnosis, Mini Mental State Examination of the controls) and characteristics related to the study design (statistical power of individual studies). The frequency of the IL-1β − 511 TT genotype resulted significantly higher than other genotypes only when the Caucasian studies with the highest statistical power were included in the subgroup analysis (OR = 1.32; 95% C.I.: 1.03–1.69; p = 0.03), with no evidence of between-study heterogeneity. Our data support an association between the TT genotype of IL-1β + 3953 SNP and AD, and suggest a possible association of the − 511 TT genotype. Unreplicability of the results seems to be due mainly to the lack of statistical power of the individual studies.

Udgivelsesdato: 2009-Jan Several studies have assessed changes in frequency of -174 interleukin (IL)-6 single nucleotide polymorphism (SNP) with age. If IL-6 tracks with disability and age-related diseases, then there should be reduction, in the oldest old, of the frequency of homozygous GG subjects, who produce higher IL-6 levels. However, discordant results have been obtained. To explore the relationship between this polymorphism and longevity, we analyzed individual data on long-living subjects and controls from eight case-control studies conducted in Europeans, using meta-analysis. There was no significant difference in the IL-6 genotype between the oldest old and controls (Odds Ratio [OR]=0.96; 95% C.I.: 0.77-1.20; p=0.71), but there was significant between-study heterogeneity (I2=55.5%). In a subgroup analyses when male centenarians from the three Italian studies were included, the frequency of the IL-6 -174 GG genotype was significantly lower than the other genotypes (OR=0.49; 95% C.I.: 0.31-0.80; p=0.004), with no evidence of heterogeneity (I2=0%). Our data supports a negative association between the GG genotype of IL-6 SNP and longevity in Italian centenarians, with males who carry the genotype being two times less likely to reach extreme old age compared with subjects carrying CC or CG genotypes. These findings were not replicated in other European groups suggesting a possible interaction between genetics, sex and environment in reaching longevity.