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Meat products are generally low in omega-3 ( n -3) fatty acids, which are beneficial to human health. We describe the generation of cloned pigs that express a humanized Caenorhabditis elegans gene, fat-1, encoding an n -3 fatty acid desaturase. The hfat-1 transgenic pigs produce high levels of n -3 fatty acids from n -6 analogs, and their tissues have a significantly reduced ratio of n -6/ n -3 fatty acids ( P < 0.001).

Objective To determine whether serum concentrations of long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in the incidence rate of coronary artery calcification (CAC) between Japanese men in Japan and white men in the USA. Methods In a population based, prospective cohort study, 214 Japanese men and 152 white men aged 40–49 years at baseline (2002–2006) with coronary calcium score (CCS)=0 were re-examined for CAC in 2007–2010. Among these, 175 Japanese men and 113 white men participated in the follow-up exam. Incident cases were defined as participants with CCS≥10 at follow-up. A relative risk regression analysis was used to model the incidence rate ratio between the Japanese and white men. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline. Results Mean (SD) serum percentage of LCn3PUFA was >100% higher in Japanese men than in white men (9.08 (2.49) vs 3.84 (1.79), respectively, p<0.01). Japanese men had a significantly lower incidence rate of CAC compared to white men (0.9 vs 2.9/100 person-years, respectively, p<0.01). The incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% CI 0.150 to 0.690; p<0.01). After adjusting for age, systolic blood pressure, low density lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant (0.262, 95% CI 0.094 to 0.731; p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376, 95% CI 0.090 to 1.572; p=0.18). Conclusions LCn3PUFAs significantly contributed to the difference in the incidence of CAC between Japanese and white men.

Aims Haptoglobin (Hp) genotype 2-2 increases cardiovascular diabetes complications. In type 2 diabetes, α-tocopherol was shown to lower cardiovascular risk in Hp 2-2, potentially through HDL function improvements. Similar type 1 diabetes data are lacking. We conducted a randomized crossover pilot of α-tocopherol supplementation on HDL function [i.e., cholesterol efflux (CE) and HDL-associated lipid peroxides (LP)] and lipoprotein subfractions in type 1 diabetes. Methods Hp genotype was assessed in members of two Allegheny County, PA, type 1 diabetes registries and the CACTI cohort; 30 were randomly selected within Hp genotype, and 28 Hp 1-1, 31 Hp 2-1 and 30 Hp 2-2 were allocated to daily α-tocopherol or placebo for 8 weeks with a 4-week washout. Results Baseline CE decreased with the number of Hp 2 alleles ( p -trend = 0.003). There were no differences in LP or lipoprotein subfractions. In intention-to-treat analysis stratified by Hp, α-tocopherol increased CE in Hp 2-2 ( β  = 0.79, p  = 0.03) and LP in Hp 1 allele carriers ( β Hp 1-1  = 0.18, p  = 0.05; β Hp 2-1  = 0.21, p  = 0.07); reduced HDL particle size ( β  = −0.07, p  = 0.03) in Hp 1-1 carriers; increased LDL particle concentration in Hp 1-1; and decreased it in Hp 2-2 carriers. However, no significant interactions were observed by Hp. Conclusions In this type 1 diabetes study, HDL function worsened with the number of Hp 2 alleles. α-Tocopherol improved HDL function in Hp 2-2 carriers and appeared to adversely affect lipid peroxides and lipoprotein subfractions among Hp 1 allele carriers. As no significant interactions were observed, findings require replication in larger studies.

Background Atherosclerosis causing renal artery stenosis (RAS) is one of the most common secondary causes of hypertension in adults, but is rare in children. Case-diagnosis/treatment RAS associated with coronary artery stenosis was diagnosed in a teenage patient who presented with intermittent chest pain and elevated blood pressures for 6 years. The diagnosis of RAS was suspected after physical examination revealed an abdominal bruit. Renal ultrasound with Doppler revealed normal appearing kidneys with high velocity in the aorta and renal arteries. Computed tomography angiography (CTA) of the chest and abdomen demonstrated generalized calcified atherosclerotic narrowing of the arteries including the renal, celiac, superior mesenteric and coronary arteries in the setting of hyperlipidemia. The lipid panel revealed hypercholesterolemia with elevated serum plant sterol concentrations, suggesting the diagnosis of sitosterolemia. Cardiac catheterization demonstrated left anterior descending artery and left circumflex artery stenosis, which required bypass of the left anterior descending artery and stenting of the left circumflex artery. Aggressive lipid control was recommended and he was treated medically with a beta-blocker, low-dose angiotensin-converting enzyme inhibitor, aspirin, statin, and clopidogrel. Conclusion Although very rare, generalized atherosclerosis caused by genetic disorders should be considered an underlying cause for severe hypertension in children with hyperlipidemia.

BackgroundDepression is associated with inflammation, but the mechanisms underlying this association are unclear. We examined adiposity and smoking as potential pathways through which childhood depression may lead to an elevated inflammatory status among young adults.MethodsThe sample included 294 subjects with histories of depression (probands), 270 never-depressed siblings of probands (high-risk siblings), and 169 controls. C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) were assessed in serum samples. An adiposity score was computed from body mass index and waist circumference. Smoking behavior was evaluated during an interview. Mixed-effects models were used to test whether adiposity and smoking mediate the relationship between depression and inflammation.ResultsProbands (p = .004), but not siblings (p = .071), had higher levels of sICAM-1 compared to controls. However, depression history and risk status had no direct effects on CRP (ps > .13) or IL-6 (ps > .16). Importantly, adiposity indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on all three inflammatory markers. Smoking indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on sICAM-1 only.ConclusionsAmong young adults, the adverse inflammatory consequences of depression history are significant for sICAM-1. Adiposity and smoking are pathways through which depression can indirectly impact several inflammatory markers, suggesting possible preventive interventions to improve the immunologic and cardiovascular health of depression-prone individuals.

Recent studies suggest that the ability to produce equol, a metabolite of the soya isoflavone daidzein, is beneficial to coronary health. Equol, generated by bacterial action on isoflavones in the human gut, is biologically more potent than dietary sources of isoflavones. Not all humans are equol producers. We investigated whether equol-producing status is favourably associated with risk factors for CHD following an intervention by dietary soya isoflavones. We systematically reviewed randomised controlled trials (RCT) that evaluated the effect of soya isoflavones on risk factors for CHD and that reported equol-producing status. We searched PubMed, EMBASE, Ovid Medline and the Cochrane Central Register for Controlled Trials published up to April 2015 and hand-searched bibliographies to identify the RCT. Characteristics of participants and outcomes measurements were extracted and qualitatively analysed. From a total of 1671 studies, we identified forty-two articles that satisfied our search criteria. The effects of equol on risk factors for CHD were mainly based on secondary analyses in these studies, thus with inadequate statistical power. Although fourteen out of the forty-two studies found that equol production after a soya isoflavone intervention significantly improved a range of risk factors including cholesterol and other lipids, inflammation and blood pressure variables, these results need further verification by sufficiently powered studies. The other twenty-eight studies primarily reported null results. RCT of equol, which has recently become available as a dietary supplement, on CHD and its risk factors are awaited.

Aims/hypothesis At the same level of BMI, white people have less visceral adipose tissue (VAT) and are less susceptible to developing type 2 diabetes than Japanese people. No previous population-based studies have compared insulin resistance and insulin secretion between these two races in a standardised manner that accounts for VAT. We compared HOMA-IR, HOMA of beta cell function (HOMA-β%) and disposition index (DI) in US white men and Japanese men in Japan. Methods We conducted a population-based, cross-sectional study, comprising 298 white men and 294 Japanese men aged 40–49 years without diabetes. Insulin, glucose, VAT and other measurements were performed at the University of Pittsburgh. We used ANCOVA to compare geometric means of HOMA-IR, HOMA-β% and DI, adjusting for VAT and other covariates. Results White men had higher HOMA-IR, HOMA-β% and DI than Japanese men, and the difference remained significant ( p  < 0.01) after adjusting for VAT (geometric mean [95% CI]): 3.1 (2.9, 3.2) vs 2.5 (2.4, 2.6), 130.8 (124.6, 137.3) vs 86.7 (82.5, 91.0), and 42.4 (41.0, 44.0) vs 34.8 (33.6, 36.0), respectively. Moreover, HOMA-IR, HOMA-β% and DI were significantly higher in white men even after further adjustment for BMI, impaired fasting glucose and other risk factors. Conclusions/interpretation The higher VAT-adjusted DI in white men than Japanese men may partly explain lower susceptibility of white people than Japanese people to developing type 2 diabetes. The results, however, should be interpreted with caution because the assessment of insulin indices was made using fasting samples and adjustment was not made for baseline glucose tolerance. Further studies using formal methods to evaluate insulin indices are warranted.

This study examines the differences in circulating levels of cytokines among Japanese in Japan (JJ), Japanese Americans (JA), and whites and their associations with obesity and marine n-3 fatty acids (FA) in a cross-sectional population-based study of 297 men aged 40–49 (100 JJ, 99 whites, and 98 JA). Experimental studies show that cytokines are associated with obesity positively and marine n-3 FA inversely. Serum interleukin-1α (IL-1α), IL-1 receptor agonist (IL-1ra), IL-4, IL-8, IL-10, inducible protein-10 (IP-10), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and marine n-3 FA were determined. Body mass index (BMI), waist circumference, and computed tomography-measured visceral and subcutaneous adipose tissues were determined. The JJ had significantly lower levels of IL-1α, IL-4, IL-8, MCP-1, and TNF-α than whites and JA. Whites and JA had similar levels of IL-1α, IL-4, and IL-8 whereas whites had significantly higher levels of MCP-1 and TNF-α than JA. The JJ were least obese (BMI (kg/m2), mean ± standard deviation) 23.6 ± 2.8, 27.9 ± 4.6, and 27.9 ± 4.5 for JJ, whites, and JA, respectively. The JJ had marine n-3 FA about 100% higher than whites and JA (serum marine n-3 FA (%), median (interquartile range) 8.79 (7.41, 11.16), 3.47 (2.63, 4.83), and 4.44 (3.33, 6.01) for JJ, whites, and JA, respectively). Generally cytokines had weak and nonsignificant associations with indices of obesity and nonsignificant associations with marine n-3 FA. BMI had significant inverse associations with IL-1α, IL-4, and IL-8 in JA (P < 0.05). Marine n-3 FA had marginally significant inverse associations with IL-8 in JJ (P = 0.055) and TNF-α in whites (P = 0.076). The JJ had lower levels of many cytokines than whites and JA. Generally cytokines had weak and nonsignificant associations with indices of obesity and marine n-3 FA. Further investigation is needed to determine why JJ had lower circulating levels of cytokines.

Background Both carotid-femoral ( cf ) pulse wave velocity (PWV) and brachial-ankle ( ba) PWV employ arterial sites that are not consistent with the path of blood flow. Few previous studies have reported the differential characteristics between cf PWV and ba PWV by simultaneously comparing these with measures of pure central (aorta) and peripheral (leg) arterial stiffness, i.e., heart-femoral ( hf) PWV and femoral-ankle ( fa ) PWV in healthy populations. We aimed to identify the degree to which these commonly used measures of cf PWV and ba PWV correlate with hf PWV and fa PWV, respectively, and to evaluate whether both cf PWV and ba PWV are consistent with either hf PWV or fa PWV in their associations with cardiovascular (CV) risk factors. Methods A population-based sample of healthy 784 men aged 40–49 (202 white Americans, 68 African Americans, 202 Japanese-Americans, and 282 Koreans) was examined in this cross-sectional study. Four regional PWVs were simultaneously measured by an automated tonometry/plethysmography system. Results cf PWV correlated strongly with hf PWV (r = .81, P  < .001), but weakly with fa PWV (r = .12, P  = .001). ba PWV correlated moderately with both hf PWV (r = .47, P  < .001) and fa PWV (r = .62, P  < .001). After stepwise regression analyses with adjustments for race, cf PWV shared common significant correlates with both hf PWV and fa PWV: systolic blood pressure (BP) and body mass index (BMI). However, BMI was positively associated with hf PWV and cf PWV, and negatively associated with fa PWV. ba PWV shared common significant correlates with hf PWV: age and systolic BP. ba PWV also shared the following correlates with fa PWV: systolic BP, triglycerides, and current smoking. Conclusions Among healthy men aged 40 – 49, cf PWV correlated strongly with central PWV, and ba PWV correlated with both central and peripheral PWVs. Of the CV risk factors, systolic BP was uniformly associated with all the regional PWVs. In the associations with factors other than systolic BP, cf PWV was consistent with central PWV, while ba PWV was consistent with both central and peripheral PWVs.

Pre-pregnancy obesity has been associated with adverse birth outcomes. Poor essential fatty acid (EFA) and micronutrient status during pregnancy may contribute to these associations. We assessed the associations between pre-pregnancy BMI and nutritional patterns of maternal micronutrient and EFA status during mid-pregnancy. A cross-sectional analysis from a prospective cohort study. Women provided non-fasting blood samples at ≥ 20 weeks’ gestation that were assayed for red cell EFA; plasma folate, homocysteine and ascorbic acid; and serum retinol, 25-hydroxyvitamin D, a-tocopherol, soluble transferrin receptors and carotenoids. These nutritional biomarkers were employed in a factor analysis and three patterns were derived: EFA, Micronutrients and Carotenoids. The Antidepressant Use During Pregnancy Study, Pittsburgh, PA, USA. Pregnant women (n 129). After adjustment for parity, race/ethnicity and age, obese pregnant women were 3.0 (95% CI 1.1, 7.7) times more likely to be in the lowest tertile of the EFA pattern and 4.5 (95% CI 1.7, 12.3) times more likely to be in the lowest tertile of the Carotenoid pattern compared with their lean counterparts. We found no association between pre-pregnancy obesity and the Micronutrient pattern after confounder adjustment. Our results suggest that obese pregnant women have diminished EFA and carotenoid concentrations.