Metabolic fate and cardiometabolic effects of phenolic compounds from red-fleshed apple in hypercholesterolemic rats: A comparative study with common white-fleshed apple. The AppleCOR Study

The present study aims to investigate the metabolic fate and the cardiometabolic effects of phenolic compounds provided by a red-fleshed apple variety biofortified in anthocyanins (ACN). Wistar rats are fed with high-fat diet (HFD) to induce hypercholesterolemia and supplemented with red-fleshed apple (HFD+R), white-fleshed apple (HFD+W), or an ACN-rich infusion from aronia fruit (HFD+A) providing matched content and profile of ACN. Plasma biochemical parameters, histological analysis, and phenol biological metabolites are determined. Plasma, urine, and feces show a significant increase of ACN metabolites after HFD+R andHFD+A, while flavan-3-ols are significantly increased after HFD+W and dihydrochalcones derivatives increased after both apples supplementation. A cardioprotective effect sobserved after both apples and aronia infusion supplementation in the reduction of aortic thickness. The kidney function is improved after all supplementations and a decrease in insulin plasma concentration after both apples supplementation (HFD+R andHFD+W) is also observed. The findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3-ols, together with dihydrochalcones, compose a phenolic phytocomplex in red- and white-fleshed apples, respectively, which can act synergistically in the attenuation of cardiovascular outcomes in hypercholesterolemic rats.This study was supported by the Spanish Ministry of Industry, Economy and Competitiveness through the AGL2016-76943-C2-1-R and AGL2016-76943-C2-2-R projects (co-funded by the European Social Fund, European Union). I.A.L. enjoyed a post-doctoral contract (2017PMF-POST2-19) from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement and from the Universitat Rovira i Virgili (URV). S.Y. was supported by a grant from the University of Lleida. Ú.C. has a Pla estratègic de recerca i innovació en salut (PERIS) post-doctoral grant (SLT002/16/00239; Catalunya, Spain) from Generalitat de Catalunya. A.P. enjoys a post-doctoral grant (PTQ-15-08068; Spain). L.R. is a Serra Húnter Fellow. In addition, the authors were grateful to NUFRI SAT (Mollerussa, Lleida, Catalonia, Spain) for providing the red-fleshed apples; to Ana Martínez (Department of Medicine, University of Lleida) for helpful with the histological stains; and finally, to SCT-Estabulari of the University of Lleida where the animal experiment was carried out. A few spelling and layout mistakes were corrected on May 14, 2021

Effectiveness of a physical activity program on cardiovascular disease risk in adult primary health-care users: the "Pas-a-Pas" community intervention trial

Intervention program; Physical activity; Cardiovascular disease risk prevention; Primary care programActivitat física; Prevenció de riscos de malalties cardiovasculars; Programa d'atenció primàriaActividad física; Prevención de riesgos de enfermedades cardiovasculares; Programa de atención primariaBACKGROUND: Physical activity is a major, modifiable, risk factor for cardiovascular disease (CVD) that contributes to the prevention and management of CVD. The aim of this study was to assess the short- and medium-term effectiveness of 9 months of a supervised physical activity program, including sociocultural activities, on CVD risk in adults. METHODS: Multicentered, randomized, controlled community intervention involving 364 patients in four primary care centers. The participants were randomly assigned to a Control Group (CG = 104) or Intervention Group (IG = 260); mean age 65.19 years; 76.8% women. The intervention consisted of 120 min/week walking (396 METs/min/week) and sociocultural gathering once a month. Clinical history, physical activity, dietary intake, CVD risk factors (smoking, systolic and diastolic blood pressure, weight, waist circumference, BMI, total cholesterol, LDL- and HDL-cholesterol, triglycerides, glycosylated hemoglobin and glucose) and global CVD risk were assessed at baseline and at the end of the intervention and multivariate models were applied to the data. Incidence of adverse cardiovascular events and continued adherence to the physical activity were assessed 2 years after intervention. RESULTS: At the end of the intervention period, in the IG relative to the CG group, there was a significant increase in physical activity (774.81 METs/min/week), a significant change during the intervention period in systolic blood pressure (-6.63 mmHg), total cholesterol (-10.12 mg/dL) and LDL-cholesterol (-9.05 mg/dL) even after adjustment for potential confounders. At 2 years after the intervention, in the IG, compared with the CG, tthe incidence of adverse cardiovascular events was significantly lower (2.5% vs. 10.5%) and the adherence to regular physical activity was higher (72.8% vs 27.2%) in IG compared to CG. CONCLUSIONS: This community-based physical activity program improved cardiovascular health in the short- as well as medium-term, and promoted regular physical activity in the medium-term in older Spanish adults. TRIALS REGISTRATION: Clinicaltrials.gov ID NCT02767739 . Trial registered on May 5th, 2016. Retrospectively registered

Virgin olive oil phenolic compounds modulate the HDL lipidome in hypercholesterolaemic subjects: a lipidomic analysis of the VOHF study

Scope The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function.Methods and results A randomized, controlled, double-blind, crossover trial (33 hypercholesterolaemic subjects) is performed with a control virgin olive oil (VOO), VOO enriched with its own phenolic compounds (FVOO), or VOO enriched with additional phenolic compounds from thyme (FVOOT) for 3 weeks. HDL lipidomic analyses are performed using the Lipidyzer platform. VOO and FVOO intake increase monounsaturated-fatty acids (FAs) and decrease saturated and polyunsaturated FAs in triacylglyceride (TAG) species, among others species. In contrast, FVOOT intake does not induce these FAs changes. The decrease in TAG52:3(FA16:0) after VOO intake and the decrease in TAG52:5(FA18:2) after FVOO intake are inversely associated with changes in HDL resistance to oxidation. After FVOO intake, the decrease in TAG54:6(FA18:2) in HDL is inversely associated with changes in HDL cholesterol efflux capacity.Conclusion VOO and FVOO consumption has an impact on the HDL lipidome, in particular TAG species. Although TAGs are minor components of HDL mass, the observed changes in TAG modulated HDL functionality towards a cardioprotective mode. The assessment of the HDL lipidome is a valuable approach to identify and characterize new biomarkers of HDL function.Proteomic

ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization

BackgroundWhole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts.MethodsWe developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient's standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA).ResultsClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes.ConclusionsClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses