Evidence of dysbiosis in the intestinal microbial ecosystem of children and adolescents with primary hyperlipidemia and the potential role of regular hazelnut intake

Hyperlipidemia starts at a pediatric age and represents an unquestionable risk factor for cardiovascular disease. Modulation of the intestinal microbial ecosystem (IME), in principle, can ameliorate lipid profiles. In this study, we characterized the IME of children and adolescents with primary hyperlipidemia by analyzing fecal samples through 16S rRNA gene profiling (n\ua0=\ua015) and short chain fatty acid (SCFA) quantification (n\ua0=\ua032). The same analyses were also carried out on age-matched normolipidemic controls (n\ua0=\ua015). Moreover, we evaluated the modulatory effect of regular hazelnut intake (approximately 0.43 g of hazelnuts with skin per kg of body weight) on the IME of 15 children and adolescents with hyperlipidemia for eight weeks. We found alterations of numerous operational taxonomic units potentially associated with SCFA-producing bacteria and reductions in the fecal levels of acetate, butyrate and propionate in hyperlipidemic subjects. Furthermore, we observed that an eight-week hazelnut intervention may induce limited changes in fecal microbiota composition but can significantly modulate the fecal levels of predominant intestinal SCFAs, such as acetate. Finally, correlation analyses indicated that changes in lipidemic parameters are linked to modifications of the abundance of specific bacterial taxa, such as the families Lachnospiraceae and Ruminococcaceae and the genera Akkermansia, Bacteroides, Roseburia, and Faecalibacterium. This study suggests that children and adolescents with primary hyperlipidemia possess an altered IME. The promising results presented here support the need for future dietary interventions aimed at positively modulating the IME of hyperlipidemic subjects

Effect of short-term hazelnut consumption on DNA damage and oxidized LDL in children and adolescents with primary hyperlipidemia : a randomized controlled trial

Children with primary hyperlipidemia are prone to develop premature atherosclerosis, possibly associated with increased oxidative stress. Nutritional therapy is the primary strategy in the treatment of hyperlipidemia and associated conditions. Dietary interventions with bioactive-rich foods, such as nuts, may contribute to the modulation of both lipid profile and the oxidative/antioxidant status. Our study aimed to assess the impact of a dietary intervention with hazelnuts on selected oxidative stress markers in children and adolescents with primary hyperlipidemia. A single-blind, 8-week, randomized, controlled, three-arm, parallel-group study was performed. Children and adolescents diagnosed with primary hyperlipidemia (n=60) received dietary guidelines and were randomized into three groups: group 1 received hazelnuts with skin (HZN+S), and group 2 hazelnuts without skin (HZN-S), at equivalent doses (15-30 g/day, based on body weight); group 3 (controls) received only dietary recommendations (no nuts). At baseline and after 8 weeks, plasma oxidized low-density lipoprotein (ox-LDL) concentrations, oxidative levels of DNA damage in PBMCs and potential correlation with changes in serum lipids were examined. A reduction of endogenous DNA damage by 18.9%\ub151.3% (P=.002) and 23.1%\ub147.9% (P=.007) was observed after HZN+S and HZN-S, respectively. Oxidatively induced DNA strand breaks decreased by 16.0%\ub138.2% (P=.02) following HZN+S treatment. Ox-LDL levels did not change after HZN+S intervention but positively correlated with total cholesterol and LDL cholesterol. A short-term hazelnut intervention improves cell DNA protection and resistance against oxidative stress but not ox-LDL in hyperlipidemic pediatric patients. The trial was registered at ISRCTN.com, ID no. ISRCTN12261900

Effect of hazelnut on serum lipid profile and fatty acid composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia : a randomized controlled trial

Background & aim: Regular intake of nuts improves lipid profile and thus reduces the cardiovascular (CV) risk associated with hyperlipidemia. The aim of the study was to investigate the effect of a dietary intervention with hazelnuts (HZNs, 15-30 g/day, depending on patient weight) on serum lipid profile, anthropometric parameters and fatty acids (FAs) composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia. Methods: Eight-week randomized, single blind, controlled, three-arm, parallel-group study. Sixty-six subjects were enrolled and randomized in 3 groups receiving: 1) hazelnuts with skin (HZN+S); 2) hazelnuts without skin (HZN-S); 3) dietary advices for hyperlipidemia only (controls). Before and after intervention, clinical parameters were measured and blood samples were collected for the evaluation of serum lipid levels and phospholipid FA composition of erythrocytes. Results: Two-way ANOVA showed a significant effect of time on serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)/LDL-C ratio and non-HDL-C (p < 0.001), but not of treatment and time x treatment interaction. In particular, HZN+S and HZN-S significantly reduced the concentrations of LDL-C and increased HDL-C/LDL-C ratio. HZNs also had a favorable impact on FAs composition of erythrocyte phospholipids, as demonstrated by time x treatment interaction, with a significant increase of monounsaturated fatty acids (MUFAs) (p = 0.008) and MUFAs/saturated fatty acids (SFAs) ratio (p = 0.002) with respect to the control group. Conclusions: For the first time, we documented a positive effect of HZN consumption on lipid profile and FA composition of erythrocyte phospholipids in children with primary hyperlipidemia. Further studies are encouraged to better define HZN impact on the markers of CV risk in this population

SISTEMI DI ACCUMULO DI IDROGENO AD IDRURI DI MAGNESIO: VERIFICA SPERIMENTALE DEGLI EFFETTI DI SCALA

CESI RICERCA ha in corso un programma di ricerca per valutare le potenzialità di sistemi di accumulo di idrogenobasati su idruri di magnesio in applicazioni stazionarie. L’attività è effettuata con la collaborazione del GruppoIdrogeno dell’Università di Padova e con Venezia Tecnologie. A partire da materiali sviluppati da UNIPD e VETEC,CESI RICERCA ha progettato, realizzato e sperimentato serbatoi di accumulo di capacità diversa al fine di valutare leprestazioni del sistema in termini di capacità totale di accumulo, cinetica di absorbimento e desorbimento di idrogenoed analizzare l’eventuale degrado a valle di cicli di carica e scarica di idrogeno. In particolare, per valutare gli effettidi scala (scale-up), che sono della massima importanza in applicazioni industriali, CESI RICERCA ha progettatoe sperimentato in differenti condizioni operative un sistema di accumulo contenente 0.5 kg di idruro di magnesio.La sperimentazione sull’accumulatore ha riguardato l’attivazione delle polveri e l’esecuzione di una serie di ciclidi absorbimento e desorbimento di idrogeno; i dati sperimentali sono stati confrontati con risultati di laboratorio.L’accumulatore ha presentato una capacità massima di accumulo di idrogeno in peso del 5.35%; gli effetti di scalasono stati evidenziati da una cinetica più lenta, da sensibili effetti termici locali e da un degrado delle prestazionidopo alcuni cicli di carica e scarica di idrogeno. Al fine di identificare le cause del degrado delle prestazioni, sono stateeffettuate ulteriori attività sperimentali su accumulatori di taglia ridotta (circa 30 grammi di polvere) sviluppandoe testando nuove configurazioni degli accumulatori tali da minimizzare gli effetti negativi legati allo scale-up delsistema

Tritiated Steel Micro-Particles: Computational Dosimetry and Prediction of Radiation-Induced DNA Damage for In Vitro Cell Culture Exposures.

Biological effects of radioactive particles can be experimentally investigated in vitro as a function of particle concentration, specific activity and exposure time. However, a careful dosimetric analysis is needed to elucidate the role of radiation emitted by radioactive products in inducing cyto- and geno-toxicity: the quantification of radiation dose is essential to eventually inform dose-risk correlations. This is even more fundamental when radioactive particles are short-range emitters and when they have a chemical speciation that might further concur to the heterogeneity of energy deposition at the cellular and sub-cellular level. To this aim, we need to use computational models. In this work, we made use of a Monte Carlo radiation transport code to perform a computational dosimetric reconstruction for in vitro exposure of cells to tritiated steel particles of micrometric size. Particles of this kind have been identified as worth of attention in nuclear power industry and research: tritium easily permeates in steel elements of nuclear reactor machinery, and mechanical operations on these elements (e.g., sawing) during decommissioning of old facilities can result in particle dispersion, leading to human exposure via inhalation. Considering the software replica of a representative in vitro setup to study the effect of such particles, we therefore modelled the radiation field due to the presence of particles in proximity of cells. We developed a computational approach to reconstruct the dose range to individual cell nuclei in contact with a particle, as well as the fraction of "hit" cells and the average dose for the whole cell population, as a function of particle concentration in the culture medium. The dosimetric analysis also provided the basis to make predictions on tritium-induced DNA damage: we estimated the dose-dependent expected yield of DNA double strand breaks due to tritiated steel particle radiation, as an indicator of their expected biological effectiveness

Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants

PurposeThe purpose of this study was to enhance understanding of lysosomal acid lipase deficiency (LALD) in infancy.MethodsInvestigators reviewed medical records of infants with LALD and summarized data for the overall population and for patients with and without early growth failure (GF). Kaplan-Meier survival analyses were conducted for the overall population and for treated and untreated patients.ResultsRecords for 35 patients, 26 with early GF, were analyzed. Prominent symptom manifestations included vomiting, diarrhea, and steatorrhea. Median age at death was 3.7 months; estimated probability of survival past age 12 months was 0.114 (95% confidence interval (CI): 0.009-0.220). Among patients with early GF, median age at death was 3.5 months; estimated probability of survival past age 12 months was 0.038 (95% CI: 0.000-0.112). Treated patients (hematopoietic stem cell transplant (HSCT), n = 9; HSCT and liver transplant, n = 1) in the overall population and the early GF subset survived longer than untreated patients, but survival was still poor (median age at death, 8.6 months).ConclusionsThese data confirm and expand earlier insights on the progression and course of LALD presenting in infancy. Despite variations in the nature, onset, and severity of clinical manifestations, and treatment attempts, clinical outcome was poor.Genet Med 18 5, 452-458

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and ResultsAn lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score &gt;= 1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups &lt;0.0001); however, subjects with FH/M- and lp(a) score &gt;= 1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level &gt;= 190 mg/dL (or from 68% to 50%, considering a more conservative formula). ConclusionsOur study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH