Differential effects of natural palm oil, chemically- and enzymatically-modified palm oil on weight gain, blood lipid metabolites and fat deposition in a pediatric pig model

<p>Abstract</p> <p>Background</p> <p>Increasing prevalence of obesity and overweight in the Western world, continue to be a major health threat and is responsible for increased health care costs. Dietary intervention studies show a strong positive association between saturated fat intake and the development of obesity and cardiovascular disease. This study investigated the effect of positional distribution of palmitic acid (Sn-1, 2 & 3) of palm oil on cardiovascular health and development of obesity, using weaner pigs as a model for young children.</p> <p>Methods</p> <p>Male and female weaner piglets were randomly allocated to 4 dietary treatment groups: 1) pork lard (LRD); 2) natural palm olein (NPO); 3) chemically inter-esterified PO (CPO) and 4) enzymatically inter-esterified PO (EnPO) as the fat source. Diets were formulated with 11% lard or with palm olein in order to provide 31% of digestible energy from fat in the diet and were balanced for cholesterol, protein and energy across treatments.</p> <p>Results</p> <p>From 8 weeks onwards, pigs on EnPO diet gained (P < 0.05) more weight than all other groups. Feed conversion efficiency (feed to gain) over the 12 week experimental period did not vary between treatment groups. Plasma LDL-C content and LDL-C/HDL-C ratio in pigs fed natural PO tended to be lower compared to all other diets. The natural PO lowered (P < 0.02) the plasma triglyceride (TG) content relative to the lard or EnPO diets, but was not different from the CPO diet. The natural PO diet was associated with lower (P < 0.05) saturated fat levels in subcutaneous adipose tissue than the CPO and EnPO diets that had lower saturated fat levels than the lard diet. Female pigs had lower lean and higher fat and fat:lean ratio in the body compared with male pigs. No difference in weight gain or blood lipid parameters was observed between sexes.</p> <p>Conclusions</p> <p>The observations on plasma TG, muscle and adipose tissue saturated fatty acid contents and back fat (subcutaneous) thickness suggest that natural palm oil may reduce deposition of body fat. In addition, dietary supplementation with natural palm oil containing palmitic acid at different positions in meat producing animals may lead to the production of meat and meat products with lower saturated fats. An increase in fat content and a decrease in lean content in female pigs resulted in an increased body fat:lean ratio but gender had no effect on blood lipid parameters or insulin concentrations.</p

Design Characteristics Influence Performance of Clinical Prediction Rules in Validation: A Meta-Epidemiological Study

BACKGROUND: Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules' performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics. METHODS: Electronic databases were searched for systematic reviews of clinical prediction rule studies published between 2006 and 2010. Data were extracted from the eligible validation studies included in the systematic reviews. A meta-analytic meta-epidemiological approach was used to assess the influence of design characteristics on predictive performance. From each validation study, it was assessed whether 7 design and 7 reporting characteristics were properly described. RESULTS: A total of 287 validation studies of clinical prediction rule were collected from 15 systematic reviews (31 meta-analyses). Validation studies using case-control design produced a summary diagnostic odds ratio (DOR) 2.2 times (95% CI: 1.2-4.3) larger than validation studies using cohort design and unclear design. When differential verification was used, the summary DOR was overestimated by twofold (95% CI: 1.2 -3.1) compared to complete, partial and unclear verification. The summary RDOR of validation studies with inadequate sample size was 1.9 (95% CI: 1.2 -3.1) compared to studies with adequate sample size. Study site, reliability, and clinical prediction rule was adequately described in 10.1%, 9.4%, and 7.0% of validation studies respectively. CONCLUSION: Validation studies with design shortcomings may overestimate the performance of clinical prediction rules. The quality of reporting among studies validating clinical prediction rules needs to be improved

Socioeconomic Inequalities in the Prevalence of Nine Established Cardiovascular Risk Factors in a Southern European Population

The evaluation of the gender-specific prevalence of cardiovascular risk factors across socioeconomic position (SEP) categories may unravel mechanisms involved in the development of coronary heart disease. Using a sample of 1704 community dwellers of a Portuguese urban center aged 40 years or older, assessed in 1999–2003, we quantified the age-standardized prevalence of nine established cardiovascular risk factors (diabetes mellitus, hypertension, hypercholesterolemia, smoking, sedentariness, abdominal obesity, poor diet, excessive alcohol intake and depression) across SEP and gender categories. Data on individual education and occupation were collected by questionnaire and used to characterize SEP. The prevalence of seven out of nine well-established risk factors was higher in men. Among women, the prevalence of most of the studied risk factors was higher in lower SEP groups. The main exception was smoking, which increased with education and occupation levels. Among men, socioeconomic gradients were less clear, but lower SEP was associated with a higher prevalence of diabetes, excessive alcohol intake and depression in a graded mode. The historical cultural beliefs and practices captured throughout the lifecourse frame the wide socioeconomic gradients discernible in our study conducted in an unequal European developed population. While men were more exposed to most risk factors, the clearer associations between SEP and risk factors among women support that their adoption of particular healthy behaviors is more dependent on material and symbolic conditions. To fully address the issue of health inequalities, interventions within the health systems should be complemented with population-based policies specifically designed to reduce socioeconomic gradients

Sequence variation in telomerase reverse transcriptase (TERT) as a determinant of risk of cardiovascular disease: the Atherosclerosis Risk in Communities (ARIC) study

Abstract Background Telomerase reverse transcriptase (TERT) maintains telomere ends during DNA replication by catalyzing the addition of short telomere repeats. The expression of telomerase is normally repressed in somatic cells leading to a gradual shortening of telomeres and cellular senescence with aging. Interindividual variation in leukocyte telomere length has been previously associated with susceptibility to cardiovascular disease. The aim of the present study was to determine whether six variants in the TERT gene are associated with risk of incident coronary heart disease, incident ischemic stroke, and mortality in participants in the biracial population-based Atherosclerosis Risk in Communities (ARIC) study, including rs2736100 that was found to influence mean telomere length in a genome-wide analysis. Methods ARIC is a prospective study of the etiology and natural history of atherosclerosis in 15,792 individuals aged 45 to 64 years at baseline in 1987–1989. Haplotype tagging SNPs in TERT were genotyped using a custom array containing nearly 49,000 SNPs in 2,100 genes associated with cardiovascular and metabolic phenotypes. Cox proportional hazards models were used to assess the association between the TERT polymorphisms and incident cardiovascular disease and mortality over a 20-year follow-up period in 8,907 whites and 3,022 African-Americans with no history of disease at the baseline examination, while individuals with prevalent cardiovascular disease were not excluded from the analyses of mortality. Results After adjustment for age and gender, and assuming an additive genetic model, rs2736122 and rs2853668 were nominally associated with incident coronary heart disease (hazards rate ratio = 1.20, p = 0.02, 95 % confidence interval = 1.03– 1.40) and stroke (hazards rate ratio = 1.17, p = 0.05, 95 % confidence interval = 1.00 - 1.38), respectively, in African-Americans. None of the variants was significantly associated with cardiovascular disease in white study participants or with mortality in either racial group. Conclusions Replication in additional population-based samples combined with genotyping of polymorphisms in other genes involved in maintenance of telomere length may help to determine whether genetic variants associated with telomere homeostasis influence the risk of cardiovascular disease in middle-aged adults

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era