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There is substantial evidence linking disturbed gastrointestinal motility to inflammation. Thus, it is not surprising that abnormalities of gastrointestinal motility play a role in inflammatory bowel disease (IBD), affecting patient outcomes. We performed a review of the literature to investigate the relationship between abnormal gut motility and IBD. With an extensive literature search, we retrieved the pertinent articles linking disturbed gut motility to IBD in various anatomical districts. The evidence in the literature suggests that abnormal gastrointestinal motility plays a role in the clinical setting of IBD and may confuse the clinical picture. Abnormal gut motility may be important in the clinical setting of IBD. However, additional data obtained with modern techniques (e.g., magnetic resonance imaging) are needed to individuate in a more precise manner gastrointestinal motor dysfunctions, to understand the nature of clinical manifestations and properly tailor the treatment of patients.

Background Aging is characterized by an insidious decline in cognitive function. Several genetic and lifestyle factors have been implicated in the increased risk or early onset of dementia. Aim We sought to assess the role of tumor necrosis factor (TNF) and angiotensin-converting enzyme (ACE) polymorphisms on the development of impaired mental health in respect to indices of arterial aging in nonagenarian individuals. Design 178 consecutive subjects above 75 years that permanently inhabit in the island of IKARIA, Greece were recruited. Methods Aortic distensibility (AoD) was calculated and genetic evaluation was performed on the ACE Insertion/Deletion gene polymorphism (intron 16) and the G/A transition (position -308) of the TNF gene. Cognitive function was evaluated using the Mini-mental State Examination (MMSE). Results The DD genotype for ACE was independently associated ( b = -0.44, P = 0.007) with AD while AoD remained an independent determinant of mental status (OR = 1.82, P = 0.036). Interestingly though, when a combined genetic index (GI) was calculated for both genes (ACE and TNF), subjects being double homozygous (DD for ACE and GG for TNF) for these loci presented significantly decreased MMSE (adjusted OR = 0.259, P = 0.033). This GI independently associated with AD (beta coefficient = -0.785, P = 0.002). When AoD was included, GI lost its predictive role (OR = 0.784, P = 0.783) towards MMSE. AoD has marginal indirect mediating effect in the association of the GI with MMSE ( P = 0.07). Conclusion Vascular aging may modulates the genetic substrate of elderly subjects on the risk for developing dementia.

De nombreuses etudes se sont interessees aux centenaires, considerant ceux-ci comme des exemples d’un vieillissement en bonne sante. L’identification de populations longevives a egalement attire l’interet des scientifiques et plus encore celui des medias. Dans le cadre des activites de l’International Database on Longevity, une aire de longevite exceptionnelle a ete identifiee en Sardaigne. Nous avons introduit le concept de Blue Zones comme etant des zones relativement limitees dans l’espace, ou la population partage un meme mode de vie et environnement et montre une longevite exceptionnelle scientifiquement validee. A ce jour, quatre Blue Zones ont ete identifiees : une region montagneuse de Sardaigne, l’ile d’Okinawa, la peninsule de Nicoya au Costa Rica et l’ile d’Ikaria en Grece. Comparer les populations de ces Blue Zones permet de mieux mettre en evidence les determinants de la longevite exceptionnelle qu’elles ont en commun car la plupart de ces personnes sont nees, et ont vecu, dans le meme environnement. Cette contribution presente egalement un projet mis en œuvre aux Etats-Unis visant a transferer les lecons des Blue Zones a l’echelle de communautes locales afin d’ameliorer l’etat de sante et le bien-etre de ces populations.

Probiotics have proven to be useful in the treatment of a number of gastrointestinal diseases. Probiotics may compete directly with Helicobacter pylori, possibly by interference with adherence or by the production of antimicrobial molecules. Lactobacillus reuteri has been shown to inhibit H. pylori in vitro and in vivo, and theoretically may play a role in eradication therapy. The aim of this study was to examine the efficacy of L. reuteri in H. pylori eradication therapy. This was an open label single center study. H. pylori infection was defined as positive gastric histopathology and (13)C-UBT. Intervention consisted of L. reuteri (DSM 17938) 10(8) cfu plus pantoprazole 20 mg twice a day for 8 weeks. Eradication was defined as a negative (13)C-UBT, 4-6 weeks post therapy. Compliance was considered good if at least 90% of the total number of the pills were taken. 21 of 22 subjects completed the study without protocol violation (mean age 52 years; 36% men). L. reuteri plus pantoprazole twice a day cured 13.6% (3/22; 95% CI 2.9-34.9%) of patients with H. pylori infection by ITT analysis and 14.2% (3/21; 95% CI 3.0-36%) by PP analysis. Overall urease activity assessed before and 4-6 weeks post therapy showed a significant reduction with a difference of mean of 38.8 vs. 25.4 by one-tailed test (P = 0.002). In conclusion, L. reuteri may have a potential role in H. pylori eradication therapy if the cure rate can be improved by changes in dose, dosing interval, or duration of therapy.

The question of whether mothers' fertility history influences their post-reproductive survival has been addressed frequently in the scientific literature. Using data from Villagrande Strisaili, Sardinia, where longevity is higher than anywhere else in Europe, we analyzed the relationship between the fertility pattern of mothers who survived past age 50 (n = 539) and their post-reproductive lifespan. We find that, after adjustment for potential confounders (mothers' birth cohort, survival of spouse), the mothers who on average delivered their children later displayed a reduced mortality risk (‒2.9 percent for each additional year), supporting previously reported findings. We also find that a male-skewed offspring ratio was associated with decreased mortality risk of mothers, with longer survival of mothers who delivered their sons above age 35 (p = 0.005), a result not found for daughters. So far, no biological explanation has been suggested for the positive effect of delivering sons later in life. We conjecture that in our dataset stronger nonbiological factors such as gender-specific sociocultural and economic factors may have masked the negative effect reported in other populations, for which a biological explanation was proposed.

24 páginas, 7 figuras. Borras C, et al. Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging. Aging (Albany NY). 2016 Oct 28;8(12):3185-3208. doi: 10.18632/aging.101078., Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl-xL as an important gene up-regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune response, all associated to healthy aging. Indeed, centenarians display lower plasma cytochrome C levels, higher mitochondrial membrane potential and also less cellular damage accumulation than septuagenarians. Leukocyte chemotaxis and NK cell activity are significantly impaired in septuagenarians compared with young people whereas centenarians maintain them. To further ascertain the functional role of Bcl-xL in cellular aging, we found that lymphocytes from septuagenarians transduced with Bcl-xL display a reduction in senescent-related markers. Finally, to demonstrate the role of Bcl-xL in longevity at the organism level, C. elegans bearing a gain of function mutation in the Bcl-xL ortholog ced-9, showed a significant increase in mean and maximal life span. These results show that mRNA expression in centenarians is unique and reveals that Bcl-xL plays an important role in exceptional aging., This work was supported by grants SAF2013-44663-R, from the Spanish Ministry of Education and Science (MEC); ISCIII2012-RED-43-029 from the “Red Tematica de investigacion cooperative en envejecimiento y fragilidad” (RETICEF); PROMETEOII/2014/056 from "Conselleria d’Educació, Cultura I Esport de la Generalitat Valenciana"; and EU Funded CM1001 and FRAILOMIC-HEALTH.2012.2.1.1-2 (To J.V) APM-03/15 from Conselleria de Sanitat, AICO/2016/067 and from Conselleria d’Educació, Cultura i Esport de la Generalitat Valenciana, Intramural Grant from INCLIVA (to C.B.),VAL i+d Fellowship from Generalitat Valenciana (to C.L.-F.) and Marie Curie Career Integration Grant (to N.F). This study has been co-financed by FEDER funds from the European Union.

A healthy diet should balance caloric intake (quality calories) with a variety of foods poor in simple sugars, such as cereals and legumes, fruits and vegetables, nuts, low-fat dairy products, fish, meat, and eggs prepared with culinary skills and minimally processed. This paper investigates the eating habits of school children of Villagrande, Italy, a rural village characterized by the remarkable longevity of its inhabitants, and makes a comparison with a sample of school children of the same age from an urban setting in the island. A specific questionnaire was used to collect demographic data, meals structure and composition, frequency of food consumption, and characteristic of the usual diet. The frequency of healthy eating habits, according to the current standards, was superior in the rural compared to the urban setting. The consumption of vegetables was higher in rural than in urban students (≥ once a week, 94% vs 54%, p

This paper aims to discuss the validation and family determinants affecting the longevity of Sardinian centenarians, using a genealogical approach. This preliminary study presents the first results of a genealogical tree reconstruction of selected centenarians aged 105 and over, from certain areas. These are mostly situated in the province of Nuoro, an area with the highest rate of centenarians and where the female-to-male sex ratio tends to be male-biased. An accurate centenarian age validation was performed that required a meticulous examination of numerous civil status records and parish registers. An important finding was that longevity occurs among the ascendants of a particular branch of the family. The data used are still provisional but, should it apply to other validated cases, it would provide empirical evidence of a genetic component in longevity. A more thorough examination of the data available may yield deeper insights into the role played by endogamy and consanguinity.

The identification of a hot spot of exceptional longevity, the Longevity Blue Zone (LBZ), in the mountain population of Sardinia has aroused considerable interest toward its traditional food as one of the potential causal factors. This preliminary study on the traditional Sardinian diet has been supported by the literature available, which has been carefully reviewed and compared. Up to a short time ago, the LBZ population depended mostly upon livestock rearing, and consumption of animal-derived foods was relatively higher than in the rest of the island. The nutrition transition (NT) in urbanized and lowland areas began in the mid-1950s, fueled by economic development, whereas in the LBZ it started later owing to prolonged resistance to change by a society organized around a rather efficient pastoral economy. Even nowadays a large proportion of the population in this area still follows the traditional diet based on cereal-derived foods and dairy products. The LBZ cohorts comprising individuals who were of a mature age when NT began may have benefited both from the high-quality, albeit rather monotonous, traditional diet to which they had been exposed most of their life and from the transitional diet, which introduced positive changes such as more variety, increased consumption of fruits and vegetables and moderate meat intake. It could be speculated that these changes may have brought substantial health benefits to this particular aging group, which was in need of nutrient-rich food at this specific time in life, thereby resulting in a decreased mortality risk and, in turn, life-span extension.

Gender accounts for important differences in the incidence and prevalence of a variety of age-related diseases. Considering people of far advanced age, demographic data document a clear-cut prevalence of females compared to males, suggesting that sex-specific mortality rates follow different trajectories during aging. In the present investigation, we report data from a nationwide study on Italian centenarians (a total of 1162 subjects), and from two studies on centenarians living in two distinct zones of Italy, i.e., the island of Sardinia (a total of 222 subjects) and the Mantova province (Northern Italy) (a total of 43 subjects). The female/male ratio was about 2:1 in Sardinia, 4:1 in the whole of Italy, and about 7:1 in the Mantova province. Thus, a complex interaction of environmental, historical and genetic factors, differently characterizing the various parts of Italy, likely plays an important role in determining the gender-specific probability of achieving longevity. Gender differences in the health status of centenarians are also reported, and an innovative score method to classify long-lived people in different health categories, according to clinical and functional parameters, is proposed. Our data indicate that not only is this selected group of people, as a whole, highly heterogeneous, but also that a marked gender difference exists, since male centenarians are less heterogeneous and more healthy than female centenarians. Immunological factors regarding the age-related increase in pro-inflammatory status, and the frequency of HLA ancestral haplotypes also show gender differences that likely contribute to the different strategies that men and women seem to follow to achieve longevity. Concerning the different impact of genetic factors on the probability of reaching the extreme limits of the human life-span, emerging evidence (regarding mtDNA haplogroups, Thyrosine Hydroxilase, and IL-6 genes) suggests that female longevity is less dependent on genetics than male longevity, and that female centenarians likely exploited a healthier life-style and more favorable environmental conditions, owing to gender-specific cultural and anthropological characteristics of the Italian society in the last 100 years.

Usually women live longer than men and female centenarians largely outnumber male centenarians. The findings of previous studies identifying a population with a femininity ratio close to 1.0 among centenarians in the mountainous region of Sardinia was the starting point of an in-depth investigation in order to compare mortality trajectories between men and women in that population. The exceptional survival of men compared to women emerges from the comparison with similar Italian data. Age exaggeration for men has been strictly excluded as a result of the age validation procedure. The discussion suggests that besides biological/genetic factors, the behavioral factors including life style, demographic behavior, family support, and community characteristics may play an important role. No single explanation is likely to account for such an exceptional situation and a fully integrated multidisciplinary approach is urgently needed. © 2011 Michel Poulain et al.

The effect of proton pump inhibitor (PPI) therapy on extraesophageal or atypical manifestations of gastroesophageal reflux disease (GERD) remains unclear. This study aimed to evaluate the prevalence of atypical manifestations in patients with acid reflux disease and the effect of PPI treatment. Patients with symptoms and signs suggestive of reflux were enrolled. Erosive esophagitis was stratified using the Los Angeles classification. Demographic data and symptoms were assessed using a questionnaire and included typical symptoms (heartburn, regurgitation, dysphagia, odynophagia), and atypical symptoms (e.g., chest pain, sialorrhea, hoarseness, globus sensation, chronic coughing, episodic bronchospasm, hiccup, eructations, laryngitis, and pharyngitis). Symptoms were reassessed after a 3-month course of b.i.d. PPI therapy. A total of 266 patients with a first diagnosis of GERD (erosive, 166; non-erosive, 100) were entered in the study. Presentation with atypical symptoms was approximately equal in those with erosive GERD and with non-erosive GERD, 72% vs 79% (P = 0.18). None of the study variables showed a significant association with the body mass index. PPI therapy resulted in complete symptom resolution in 69% (162/237) of the participants, 12% (28) had improved symptoms, and 20% (47) had minimal or no improvement. We conclude that atypical symptoms are frequent in patients with GERD. A trial of PPI therapy should be considered prior to referring these patients to specialists.

The clinical expression of heterozygous familial hypercholesterolemia (FH) is highly variable even in patients carrying the same LDL receptor (LDL-R) gene mutation. This variability might be due to environmental factors as well as to modifying genes affecting lipoprotein metabolism. We investigated Apo E (2, 3, 4), MTP (-493G/T), Apo B (-516C/T), Apo A-V (-1131T/C), HL (-514C/T and -250G/A), FABP-2 (A54T), LPL (D9N, N291S, S447X) and ABCA1 (R219K) polymorphisms in 221 unrelated FH index cases and 349 FH relatives with defined LDL-R gene mutations. We found a significant and independent effect of the following polymorphisms on: (i) plasma LDL-C (Apo E, MTP and Apo B); (ii) plasma HDL-C (HL, FABP-2 and LPL S447X); (iii) plasma triglycerides (Apo E and Apo A-V). In subjects with coronary artery disease (CAD+), the prevalence of FABP-2 54TT genotype was higher (16.5% versus 5.2%) and that of ABCA1 219RK and KK genotypes lower (33.0% versus 51.5%) than in subjects with no CAD. Independent predictors of increased risk of CAD were male sex, age, arterial hypertension, LDL-C level and FABP-2 54TT genotype, and of decreased risk the 219RK and KK genotypes of ABCA1. These findings show that several common genetic variants influence the lipid phenotype and the CAD risk in FH heterozygotes.

The method, developed by modifying the FOX methods described by Wolff (Methods Enzymol. 233, 182-189, 1994), involves the oxidation of Fe2- by peroxides at low pH in the presence of both the ferric-complexing dye xylenol orange and sucrose, the amplifier of the reaction. The method proved to be a convenient, simple and efficient assay for the direct measurement of both water and lipid soluble peroxides. In fact it improves by about 60% the sensitivity of the FOX1 method for water soluble peroxides, and by 7-8 times that of the FOX2 method for lipid soluble peroxides. It allows the detection of 0.1 microM peroxide in the test solution. The method is suitable to measure the lipid hydroperoxides present in phosphatidylcholine liposomes and in human LDL. The data obtained allowed us to define a mathematical expression to calculate the lipid hydroperoxide content of liposomes knowing their oxidation index.