Evaluation of polygenic determinants of non-alcoholic fatty liver disease (NAFLD) by a candidate genes resequencing strategy

NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into the genetic architecture of NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 and TM6SF2 genes were resequenced by next generation sequencing in a cohort of 218 NAFLD subjects and 227 controls, where PNPLA3 rs738409 and MBOAT7 rs641738 genotypes were also obtained. A total of 168 sequence variants were detected and 47 were annotated as functional. When all functional variants within each gene were considered, only those in TM6SF2 accumulate in NAFLD subjects compared to controls (P = 0.04). Among individual variants, rs1260326 in GCKR and rs641738 in MBOAT7 (recessive), rs58542926 in TM6SF2 and rs738409 in PNPLA3 (dominant) emerged as associated to NAFLD, with PNPLA3 rs738409 being the strongest predictor (OR 3.12, 95% CI, 1.8-5.5, P 0.28 was associated with a 3-fold increased risk of NAFLD. Interestingly, rs61756425 in PPP1R3B and rs641738 in MBOAT7 genes were predictors of NAFLD severity. Overall, TM6SF2, GCKR, PNPLA3 and MBOAT7 were confirmed to be associated with NAFLD and a score based on these genes was highly predictive of this condition. In addition, PPP1R3B and MBOAT7 might influence NAFLD severity

Use of by-products of the olive oil industry for bread fortification: Effect of health claims on consumer liking

In this study the possibility to utilize by-products of the olive oil industry for bread fortification was investigated. In particular, when using a specific decanter made by Pieralisi (Italy) for olive oil extraction it is possible to obtain a by-product having the physical consistency of a pat\ue9, whose polyphenols content is very high [about 9600 ppm (f.w.)] and that could find an use in the food industry. After several tests at industrial level to identify the maximum allowable addition of pat\ue9 that would not cause technological problems in the production of a typical bread loaf, the dough fortification was carried out at 600 ppm. The cooking step caused a 14% polyphenols loss, but due to the water removal the final concentration in the bread was about 2600 ppm. The bread acceptability was then assessed in comparison with a traditional bread loaf using a panel of 110 consumers, giving no information about the bread characteristics. While the data showed higher preference of the traditional bread as far as color and general appearance, the fortified bread was preferred for taste and aroma. The test was then repeated giving the panelist information about the polyphenols content and their beneficial effects on the human health. In this case the fortified bread scored a higher acceptability vs the regular bread. The bread was also analyzed to assess the polyphenols bioavailability after baking and the results indicate that by eating 100 g of fortified bred the polyphenols daily intake would be about 4 times higher than the minimum quantity recommended by EFSA in order to exert a positive influence on consumers\u2019 health. The overall results indicate that fortification of bread with phenolic compounds resulting from the production of olive oil is feasible and that consumers are positively influenced in their choice by the information received

Il problema della longitudine nel VXII secolo: auge e declino nel metodo geomagnetico

Submitted to "Nuncius"SIGLEITItal

Joint effect of insulin signaling genes on all-cause mortality

Objective: We have previously reported the combined effect of SNPs perturbing insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular events. We here investigated whether such a combined effect affects also all-cause mortality in a sample of 1851 Whites of European ancestry. Methods: We investigated a first sample of 721 patients, 232 deaths, 3389 person-years (py). Replication was assessed in two samples of patients with T2D: the Gargano Mortality Study (GMS) of 714 patients, 127 deaths, 5426 py and the Joslin Kidney Study (JKS) comprising 416 patients, 214 deaths, 5325 py. Results: In the first sample, individuals carrying 1 or 2 risk alleles had 33% (p ¼ 0.06) and 51% (p ¼ 0.02) increased risk of mortality, as compared with individuals with no risk alleles. A similar, though not significant, trend was obtained in the two replication samples only for subject carrying 2 risk alleles. In a pooled analysis, individuals carrying 2 risk alleles had higher mortality rate as compared to those carrying 0 risk alleles (HR ¼ 1.34, 95%CI ¼ 1.08e1.67; p ¼ 0.008), and as compared to those carrying only one risk allele (HR ¼ 1.41, 95% CI ¼ 1.13e1.75; p ¼ 0.002). This association was independent from several possible confounders including sex, age, BMI, hypertension and diabetes status. Conclusion: Our data suggest that variants affecting insulin signaling exert a joint effect on all-cause mortality and is consistent with a role of abnormal insulin signaling on mortality ris