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Obesity-related metabolic disorders are characterized by mild chronic inflammation, leukocyte infiltration, and tissue fibrosis as a result of adipocytokine production from the expanding white adipose tissue. Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein, which modulates systemic anti-inflammatory processes and, therefore, may be altered with increasing adiposity in humans. Paradoxically, we found that plasma AnxA1 concentrations inversely correlated with BMI, total percentage body fat, and waist-to-hip ratio in human subjects. Plasma AnxA1 was also inversely correlated with plasma concentrations of the acute-phase protein, C-reactive protein (CRP), and the adipocytoldne leptin, suggesting that as systemic inflammation increases, anti-inflanunatory AnxA1 is reduced. In addition, AnxA1 gene expression and protein were significantly up-regulated during adipogenesis in a human adipocyte cell line compared to vehicle alone, demonstrating for the first time that AnxA1 is expressed and excreted from human adipocytes. These data demonstrate a failure in the endogenous anti-inflammatory system to respond to increasing systemic inflammation resulting from expanding adipose tissue, a condition strongly linked to the development of type 2 diabetes and cardiovascular disease. These data raise the possibility that a reduction in plasma AnxA1 may contribute to the chronic inflammatory phenotype observed in [ABSTRACT FROM AUTHOR]

Elevated pulse pressure is associated with cardiovascular disorders and mortality in various populations. The genetic influence on pulse pressure has been confirmed by heritability estimates using related individuals. Recently, efforts have been made in mapping genes that are linked to the phenotype. We report results on our heritability and linkage study conducted on the Chinese population in mainland China where cardiovascular and cerebrovascular diseases are becoming the leading cause of death. A total of 630 pairs of middle-aged Chinese twins were collected for heritability analysis, from which 63 dizygotic twin pairs were randomly selected for genome-wide linkage analysis using Affymetrix 6.0 SNP array. Regression analysis reconfirmed the significant effects of age, sex, and BMI on pulse pressure. Comparison of twin models suggested the parsimonious AE model as the best model with a heritability estimate of 0.45. Genome-wide non-parametric linkage analysis identified three significant linkage peaks on chromosome 11 (lod score 4.06 at 30.5 cM), chromosome 12 (lod score 3.97 at 100.7 cM), and chromosome 18 (lod score 4.01 at 70.7 cM) with the last two peaks closely overlapping with linkage peaks reported by two American studies. In addition, multiple regions with suggestive linkage were identified with many of them overlapping with published linkage regions. Our results provide both epidemiological and molecular genetic evidence for the genetic dissection of pulse pressure in the Chinese population, which could help in fine mapping and in characterizing genes that are involved in the regulation of pulse pressure. [ABSTRACT FROM AUTHOR]

The Balance Study is a randomized controlled trial designed to reduce cardiovascular disease (CVD) risk in 200 American Indian (AI) participants with metabolic syndrome who reside in southwestern Oklahoma. Major risk factors targeted include weight, diet, and physical activity. Participants are assigned randomly to one of two groups, a guided or a self-managed group. The guided group attends intervention meetings that comprise education and experience with the following components: diet, exercise, AI culture, and attention to emotional wellbeing. The self-managed group receives printed CVD prevention materials that are generally available. The duration of the intervention is 24 months. Several outcome variables will be compared between the two groups to assess the effectiveness of the intervention program. [ABSTRACT FROM AUTHOR]

Chemoattractant cytokines or chemokines constitute a family of structurally related pro teins found in vertebrates, bacteria, or viruses. So far, 48 chemokine genes have been identified in humans, which bind to around 20 chemokine receptors.These receptors belong to the seven transmembrane G-protein-coupled receptor family. Chemokines and their receptors were originally studied for their role in cellular trafficking of leukocytes during inflammation and immune surveillance. It is now known that they exert different functions under physiological conditions such as homeostasis, development, tissue repair, and angiogenesis but also under pathological disorders including tumorigenesis, cancer metas tasis, inflammatory, and autoimmune diseases. Physicochemical properties of chemokines and chemokine receptors confer the ability to homo- and hetero-oligomerize. Many efforts are currently performed in establishing new therapeutically compounds able to target the chemokine/chemokine receptor system. In this review, we are interested in the role of chemokines in inflammatory disease and leukocyte trafficking with a focus on vascular inflammatory diseases, the operating synergism, and the emerging therapeutic approaches of chemokines. [ABSTRACT FROM AUTHOR]

This article examines the willingness of American Indian/Alaska Natives (AI/AN) to provide biological samples for research purposes. Prior cases of abuse and misuse of individuals, materials, and data highlight ethical research concerns. Investigators may be hesitant to engage AI/ANs in research projects. We conducted a survey of AI/ANs in the central plains region of the US over 1 year. This convenience sample completed a series of questions on biological samples and research. Survey results (N = 998) indicate that 70.15% of AI/ANs would be willing to provide saliva/spit for a specific study with the proper consent and control of samples. In conclusion, researchers should find ways to work with and for AI/ANs, assuring participant input in the research process. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease, diagnosed by urinary albumin excretion rate (AER), is a critical symptom of chronic vascular injury in diabetes, and is associated with dyslipidemia and increased mortality. We investigated serum lipids in 326 subjects with type 1 diabetes: 56% of patients had normal AER, 17% had microalbuminuria (20 ≤ AER < 200 μg/min or 30 ≤ AER < 300 mg/24 h) and 26% had overt kidney disease (macroalbuminuria AER ≥ 200 μg/min or AER ≥ 300 mg/24 h). Lipoprotein subclass lipids and low-molecular-weight metabolites were quantified from native serum, and individual lipid species from the lipid extract of the native sample, using a proton NMR metabonomics platform. Sphingomyelin (odds ratio 2.53, P < 10), large VLDL cholesterol (odds ratio 2.36, P < 10), total triglycerides (odds ratio 1.88, P < 10), omega-9 and saturated fatty acids (odds ratio 1.82, P < 10), glucose disposal rate (odds ratio 0.44, P < 10), large HDL cholesterol (odds ratio 0.39, P < 10) and glomerular filtration rate (odds ratio 0.19, P < 10) were associated with kidney disease. No associations were found for polyunsaturated fatty acids or phospholipids. Sphingomyelin was a significant regressor of urinary albumin ( P < 0.0001) in multivariate analysis with kidney function, glycemic control, body mass, blood pressure, triglycerides and HDL cholesterol. Kidney injury, sphingolipids and excess fatty acids have been linked in animal models-our exploratory approach provides independent support for this relationship in human patients with diabetes. [ABSTRACT FROM AUTHOR]

Purpose: To provide nurse practitioners (NPs) with an overview of prehypertension identification and management. Additionally, the article serves to highlight the prevalence and impact of prehypertension in the United States. Data sources: A comprehensive review of the literature was conducted using multiple databases, including PubMed, Medline, CINAHL, and SAGE Health Sciences databases. The review was not limited by discipline, year of publication, or type of research. Key words used to obtain relevant articles included prehypertension, nurse practitioner, health promotion, disease prevention, hypertension, and chronic disease. Conclusions: Approximately 70 million individuals have been recognized as prehypertensive in the United States, placing them at increased risk for hypertension and cardiovascular disease. Identifying and managing prehypertension has been recognized in national health policy as a priority to improve public health. Prehypertension is managed primarily by eliminating risk factors and implementing lifestyle modification. Implications for practice: Health promotion and disease prevention form the cornerstone of the NP role. The designation of prehypertension serves as an opportunity for NPs to assist in decreasing the burden on the health system from chronic disease and improve patient quality of life. [ABSTRACT FROM AUTHOR]

We narrowed chromosome 15q21-23 linkage to plasma high-density lipoprotein cholesterol (HDL-C) levels in Turkish families by fine mapping, then focused on glucuronic acid epimerase (GLCE), a heparan sulfate proteoglycan (HSPG) biosynthesis enzyme. HSPGs participate in lipid metabolism along with apolipoprotein (apo) E. Of 31 SNPs in the GLCE locus, nine analyzed by haplotype were associated with HDL-C and triglyceride levels (permuted p = 0.006 and 0.013, respectively) in families. Of five tagging GLCE SNPs in two cohorts of unrelated subjects, three (rs16952868, rs11631403, and rs3865014) were associated with triglyceride and HDL-C levels in males (nonpermuted p < 0.05). The association was stronger in APOE 2/3 subjects (apoE2 has reduced binding to HSPGs) and reached multiple-testing significance (p < 0.05) in both males and females ( n= 2612). Similar results were obtained in the second cohort ( n= 1164). Interestingly, at the GLCE locus, bounded by recombination hotspots, Turks had a minor allele frequency of SNPs resembling Chinese more than European ancestry; adjoining regions resembled the European pattern. Studies of glce apoe mice fed a chow or high-fat diet supported a role for GLCE in lipid metabolism. Thus, SNPs in GLCE are associated with triglyceride and HDL-C levels in Turks, and mouse studies support a role for glce in lipid metabolism. [ABSTRACT FROM AUTHOR]

Chronic overnutrition and modern lifestyles are causing a worldwide epidemic of obesity and associated comorbidities, which is creating a demand to identify underlying biological mechanisms and to devise effective treatments. In rats receiving a high-fat diet (HFD), we analyzed the effects of a 4-wk administration of a novel functional analog of iodothyronines, TRC150094 (TRC). HFD-TRC rats exhibited increased energy expenditure (24% vs. HFD rats; P<0.05) and body weight (BW) gain comparable to that of standard chow-fed (N) rats [N, HFD, and HFD-TRC rats,97 g,1 4 0g(P<0.05 vs. N), and9 8g(P<0.05 vs. HFD)]. HFD-TRC rats had signi?cantly less visceral adipose tissue (vs. HFD rats) and exhibited altered metabolism in two major tissues that are very active metabolically. In liver, mitochondrial fatty acid import and oxidation were increased (56 and32%, respectively; P<0.05 vs. HFD rats), and consequently the hepatic triglyceride content was lower (35%; P<0.05 vs. HFD rats). These effects were independent of the AMP-activated protein kinase-acetyl CoA-carboxylase-malonyl CoA pathway but involved sirtuin 1 activation. In skeletal muscle, TRC induced a ?ber shift toward the oxidative type in tibialis anterior muscle, increasing its capacity to oxidize fatty acids. HFD-TRC rats had lower (vs. HFD rats) plasma cholesterol and triglyceride concentrations. If reproduced in humans, these results will open interesting possibilities regarding the counteraction of metabolic dysfunction associated with ectopic/visceral fat accumulation. [ABSTRACT FROM AUTHOR]

The extracellular matrix is a key component during regeneration and maintenance of tissues and organs, and it therefore plays a critical role in successful tissue engineering as well. Tissue engineers should recognise that engineering technology can be deduced from natural repair processes. Due to advances in such distinct areas as biology, engineering, physics and chemistry and the possibility of using robotics to facilitate the search for new treatments, we can identify the basic principles and extrapolate them into tools to mimic the regenerative process. Ubiquitously distributed throughout the body, the extracellular matrix surrounding the cells plays a key instructive role, in addition to the previously recognised supportive role. In this review we will highlight the role of the extracellular matrix and discuss the latest technological possibilities to exploit the extracellular matrix in tissue engineering. [ABSTRACT FROM AUTHOR]

Objective. In a previous study, urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes. The aim of the present study was to determine whether increased UOER is associated with cardiovascular risk factors such as inflammation, impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. Material and methods. We performed a cross-sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy controls. Urinary orosomucoid was measured using a particle-enhanced immunoturbidimetric assay. Plasma interleukin-6 (IL-6), tissue plasminogen activator (tPA) and soluble intercellular adhesion molecule-1 (sICAM) were measured using ELISA. Endothelial function measured as vasodilatory capacity of the brachial artery and echocardiography were done in all participants. Results. Patients with diabetes and increased UOER had subclinically increased serum orosomucoid (p<0.001), C-reactive protein (CRP) (p<0.001), IL-6 (p<0.001), tPA (p<0.003) and sICAM (p<0.003) compared with healthy controls. In patients with type 2 diabetes, UOER was independently associated with increasing values of IL-6 (1.43 (1.06-1.93)) and tPA (1.82 (1.20-2.77)). Measurements by echocardiography showed no signs of cardiac dysfunction. Conclusions. Asymptomatic patients with type 2 diabetes and increased UOER displayed signs of chronic low-grade inflammation and endothelial dysfunction. UOER was independently related to markers of proinflammation and endothelial dysfunction in patients with type 2 diabetes. The previously shown relation between increased UOER and cardiovascular mortality is proposed to be caused by chronic low-grade inflammation and early endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Epidemiological studies report a high prevalence of type 2 diabetes and metabolic syndrome in the island nation of Mauritius. The Mauritius Family Study was initiated to examine heritable factors that contribute to these high rates of prevalence and consists of 400 individuals in 24 large extended multigenerational pedigrees. Anthropometric and biochemical measurements relating to the metabolic syndrome were undertaken in addition to family and lifestyle based information for each individual. Variance components methods were used to determine the heritability of the type 2 diabetes and metabolic syndrome related quantitative traits. The cohort was made up of 218 females (55%) and 182 males with 22% diagnosed with type 2 diabetes and a further 30% having impaired glucose tolerance or impaired fasting glucose. Notably BMI was not significantly increased in those with type 2 diabetes (P= .12), however a significant increase in waist circumference was observed in these groups (P= .02). The heritable proportion of trait variance was substantial and greater than values previously published for hip circumference, LDL and total cholesterol, diastolic and systolic blood pressure and serum creatinine. Height, weight and BMI heritabilities were all in the upper range of those previously reported. The phenotypic characteristics of the Mauritius family cohort are similar to those previously reported in the Mauritian population with a high observed prevalence rate of type 2 diabetes. A high heritability for key type 2 diabetes and metabolic syndrome related phenotypes (range 0.23 to 0.68), suggest the cohort will have utility in identifying genes that influence these quantitative traits. [ABSTRACT FROM AUTHOR]

This study ascertains the effects of zinc, a major component of particulate matter, on pulmonary and systemic endpoints using hyperlipidemic rabbits to model diet-induced human atherosclerosis. New Zealand White rabbits were fed a normal or cholesterol-enriched diet and then were intratracheally instilled 1 ×/week for 4 weeks with saline or 16 μg/kg of zinc, equal parts sulfate and oxide. Physiologic responses, blood after each exposure, and terminal bronchoalveolar lavage (BAL) were assessed. Rabbits fed a cholesterol-rich diet developed hyperlipidemia and had consistently higher circulating leukocyte counts than rabbits fed normal chow. Within minutes after zinc instillation, saturation of peripheral oxygen was decreased in hyperlipidemic rabbits and heart rate was increased in hyperlipidemic rabbits with total serum cholesterol levels greater than 200 mg/dl. Total circulating leukocytes levels were increased 24 h after the first zinc instillation, but upon repeated exposures this effect was attenuated. After repeated zinc exposures, BAL fluid (BALF) N-acetylglucosaminidase activity was increased regardless of hyperlipidemic state. Hyperlipidemic rabbits had an increase in BALF-oxidized glutathione and a decrease in serum nitrite. The study elucidates mechanisms by which the zinc metal component of PM drives cardiovascular health effects, as well as the possible susceptibility induced by hyperlipidemia. Furthermore, the study exemplifies the benefits of monitoring circulatory physiology during exposure as well as after exposure. [ABSTRACT FROM AUTHOR]

Singular value decomposition (SVD) based electrocardiogram (ECG) morphology analysis is a novel method in the assessment of subtle abnormalities in the T wave morphology of 12-lead ECG. As various types of noise contaminate the ECG signal and create a bias for the morphological analyses, this study was designed to estimate the effects of noise on the SVD method in an experimental setup. Ideal signals were generated by filtering real ECG signals several times with the Savitzky-Golay filter. Random and real noise samples were superimposed on the ideal signals. The noisy signals were filtered with a power line interference filter combined with the Savitzky-Golay or the wavelet filter. Results show that noise increased both the dipolar and non-dipolar components significantly unless filtering was applied. R-TWR (relative T wave residuum) and A-TWR (absolute T wave residuum) were four to eight times higher in noisy signals. The experiments with patient data demonstrated that certain types of noise may even lead to erroneous classification of patients. Filtering brings the median values closer to the correct ones and decreases significantly the variance of the values of parameters. [ABSTRACT FROM AUTHOR]

Background: Associations between periodontitis and cardiovascular diseases have been recognized. Material and Methods: New literature since the last European Workshop on Periodontology has been reviewed. Results: The lack of reliable epidemiological data on disease prevalence makes an assessment of the associations and risks between periodontitis and cardiovascular diseases difficult. Two recent meta-analysis reports have identified associations between periodontitis and cardiovascular diseases (odds ratios: 1.1–2.2). Different surrogate markers for both disease entities, including serum biomarkers, have been investigated. Brachial artery flow-mediated dilatation, and carotid intima media thickness have in some studies been linked to periodontitis. Studies are needed to confirm early results of improvements of such surrogate markers following periodontal therapy. While intensive periodontal therapy may enhance inflammatory responses and impair vascular functions, studies are needed to assess the outcome of periodontal therapies in subjects with confirmed cardiovascular conditions. Tooth eradication may also reduce the systemic inflammatory burden of individuals with severe periodontitis. The role of confounders remain unclear. Conclusions: Periodontitis may contribute to cardiovascular disease and stroke in susceptible subjects. Properly powered longitudinal case–control and intervention trials are needed to identify how periodontitis and periodontal interventions may have an impact on cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The article presents the 2007 European Society of Hypertension (ESH) and European Society of Cardiology (ESC) Guidelines for arterial hypertension management. These guidelines will serve as a basis for health economic, education and training, an agreement among partners involved in arterial hypertension control and detection, a reference to identify the appropriate tools for hypertension management, and others

HFE mutations have traditionally been associated with the iron overload disorder known as hemochromatosis. Recently, it has become clear that the two most common mutations in the HFE gene, H63D and C282Y, may be genetic modifiers for risk of neurodegenerative disorders and cancer, respectively. We developed human neuroblastoma stable cell lines that express either wild-type (WT) or mutant HFE to determine the cellular consequences of the mutant forms of HFE. The presence of the C282Y mutation was associated with relatively higher labile iron pool and iron regulatory protein activity than WT or H63D HFE. Targeted gene arrays revealed that the signal transduction pathway was up-regulated in the C282Y cells. H63D cells had higher levels of lipid peroxidalion, protein oxidation, and lower mitochondrial membrane potential, suggesting higher baseline stress. This cell line was also more vulnerable to exposure to oxidative stress agents and more responsive to iron chelation than the C282Y cells. These data demonstrate that the different mutations in the HFE gene have unique effects on the cells and provide insights into how the different mutations may have different clinical consequences. The results also raise multiple novel questions for future study about the function of the HFE protein. [ABSTRACT FROM AUTHOR]

Elevated C-reactive protein (CRP) levels are associated with both prevalent and incident cardiovascular disease. In this study, familial aggregation was estimated, and we tested for association between serum CRP levels and polymorphisms within the CRP and APOE genes in sib-ships with type 2 diabetes mellitus, a population at increased risk for cardiovascular disease. CRP levels were determined in 461 diabetes-affected subjects from 224 sibships from the Diabetes Heart Study (DHS). Heritability estimates of CRP levels were obtained using variance component models. Genetic influence on serum CRP levels by single nucleotide polymorphisms (SNPs) in the CRP and APOE genes was evaluated by association analysis using mixed models. Subjects were Caucasian American (84%) and African-American (16%), 53% female, and had an average age of 62.2 ± 9.2 years. The median CRP level was 3.3 mg/L (range 0 to 59.3 mg/L), and estimated heritability for CRP was approximately 40%. Estimates of heritability were significantly greater than zero (P < 0.0001) and relatively constant, despite adjustments for important modifiers (age, sex, ethnicity, diabetes duration, statin-use and anti-inflammatory use) of CRP. There was no significant evidence for association of CRP levels with CRP gene SNPs; however, consistent with previous reports, there was significant evidence of association of CRP levels with polymorphisms within the APOE gene. These data indicate CRP levels are significantly influenced by genetic (and/or environmental) factors that are shared within DHS families. While the APOE locus shows evidence of contributing to CRP levels, no evidence of CRP gene polymorphism association with CRP levels was observed. [ABSTRACT FROM AUTHOR]

Purpose. This study aims to examine the relationship between retinal arteriolar narrowing and left ventricular hypertrophy in hypertensive patients. Methods. A total of 30 patients with a recent history of hypertension (22 M, 8 F; 33±8; BMI 24,96 ± 2.8;), consecutively referred to the Hypertension Unit by their family doctors, were studied. Generalized retinal arteriolar narrowing was measured by two ophthalmologists from computer-scanned images on retinal photographs, and summarized as arteriole-to-venule ratio (AVR). Left ventricular hypertrophy was evaluated by quantitative M-mode echocardiography. Results. All patients were stratified according to the 2003 European Society of Hypertension (ESH) guidelines: 20 subjects (66.7%) were affected by hypertension grade 1, and 10 (33.3%) were affected by hypertension grade 2. Retinal vessel diameters did not differ significantly by grade 1 vs grade 2 hypertension. Echocardiographic left ventricular hypertrophy was present in 10 (33%) patients. No significant correlation was shown between arteriole-to-venule ratio (AVR) and left ventricular mass.[Spearman r  =  0.22; p  =  0.23]. Conclusions. We suggest some explanations for the fact that we did not find any correlation between AVR and left ventricular mass. Further clinical studies are required for a greater understanding as to whether early microvascular changes relate with other clinical indicators of hypertensive organ damage. [ABSTRACT FROM AUTHOR]

With improved disease survival, arterial thromboembolism has become an important cause of morbidity in patients with systemic lupus erythematosus (SLE). A number of conventional and non‐conventional risk factors are associated with accelerated atherosclerosis. Regular surveillance and control of traditional risk factors is mandatory, and so is the appropriate use of the statins, anti‐malarial agents, anti‐platelet agents, and anti‐coagulation for primary and secondary prevention of arterial thromboembolism in SLE patients. Judicious use of corticosteroids, calcineurin inhibitors, hormonal replacement therapy, and the cyclooxygenase 2 inhibitors is equally important. [ABSTRACT FROM AUTHOR]

Epigenetics involves a series of mechanisms that entail histone and DNA covalent modifications and non-coding RNAs, and that collectively contribute to programing cell functions and differentiation. Epigenetic anomalies and DNA mutations are co-drivers of cellular dysfunctions, including carcinogenesis. Alterations of the epigenetic system occur in cancers whether the initial carcinogenic events are from genotoxic (GTxC) or non-genotoxic (NGTxC) carcinogens. NGTxC are not inherently DNA reactive, they do not have a unifying mode of action and as yet there are no regulatory test guidelines addressing mechanisms of NGTxC. To fil this gap, the Test Guideline Programme of the Organisation for Economic Cooperation and Development is developing a framework for an integrated approach for the testing and assessment (IATA) of NGTxC and is considering assays that address key events of cancer hallmarks. Here, with the intent of better understanding the applicability of epigenetic assays in chemical carcinogenicity assessment, we focus on DNA methylation and histone modifications and review: (1) epigenetic mechanisms contributing to carcinogenesis, (2) epigenetic mechanisms altered following exposure to arsenic, nickel, or phenobarbital in order to identify common carcinogen-specific mechanisms, (3) characteristics of a series of epigenetic assay types, and (4) epigenetic assay validation needs in the context of chemical hazard assessment. As a key component of numerous NGTxC mechanisms of action, epigenetic assays included in IATA assay combinations can contribute to improved chemical carcinogen identification for the better protection of public health. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) often have cardiac functional and structural abnormalities which can lead to adverse cardiovascular outcomes. In this study, we investigated associations between diabetes mellitus (DM) and cardiac functional and structural parameters in patients with CKD focusing on aortic root diameter (ARD). We also investigated associations of renal outcomes with DM and cardiac functional and structural characteristics. We enrolled 419 patients with CKD stage 3–5 were enrolled. ARD was normalized to body surface area (BSA) (ARD/BSA), and the rate of decline in renal function was assessed by the estimated glomerular filtration rate (eGFR) slope (mL/min/1.73 m2/year). ARD/BSA ≥2.1 cm/m2 in men or ≥2.2 cm/m2 in women was defined as indicating aortic root dilatation. The patients with DM had lower ARD/BSA, higher left atrial dimension (LAD), lower left ventricular ejection fraction, lower ratio of peak early transmitral filling wave velocity to peak late transmitral filling wave velocity, and higher left ventricular relative wall thickness, than those without DM. After multivariable analysis, DM (vs. non-DM; coefficient β, −0.060; p = 0.018) was significantly associated with low ARD/BSA. Significantly fewer patients with DM had aortic root dilatation compared to those without DM (14.3% vs. 23.1%, p = 0.022). In the patients with DM, there were significant associations between a high left ventricular mass index (LVMI) (per 1 g/m2, β, −0.016; p = 0.040) and high LAD (per 1 cm; β, −1.965; p < 0.001) with a low eGFR slope. However, other parameters, including ARD/BSA, were not associated with eGFR slope. Furthermore, there were no associations between eGFR slope and any of the echocardiographic parameters in the patients without DM. Aortic root dilatation was attenuated in the patients with DM, but it was not associated with a decline in renal function. However, high LAD and LVMI were associated with rapid renal function decline in the CKD patients with DM. [ABSTRACT FROM AUTHOR]

Exposure to various forms of arsenic (As), the source of which may be environmental as well as occupational exposure, is associated with many adverse health effects. Therefore, methods to reduce the adverse effects of As on the human body are being sought. Research in this area focuses, among other topics, on the dietary compounds that are involved in the metabolism of this element. Therefore, the aim of this review was to analyze the influence of methionine, betaine, choline, folic acid, vitamin B2, B6, B12 and zinc on the efficiency of inorganic As (iAs) metabolism and the reduction in the severity of the whole spectrum of disorders related to As exposure. In this review, which included 62 original papers (human studies) we present the current knowledge in the area. In human studies, these compounds (methionine, choline, folic acid, vitamin B2, B6, B12 and zinc) may increase iAs metabolism and reduce toxicity, whereas their deficiency may impair iAs metabolism and increase As toxicity. Taking into account the results of studies conducted in populations exposed to As, it is reasonable to carry out prophylactic activities. In particular nutritional education seems to be important and should be focused on informing people that an adequate intake of those dietary compounds potentially has a modulating effect on iAs metabolism, thus, reducing its adverse effects on the body. [ABSTRACT FROM AUTHOR]

In this study, asthma-prone area modeling of Tehran, Iran was provided by employing three ensemble machine learning algorithms (Bootstrap aggregating (Bagging), Adaptive Boosting (AdaBoost), and Stacking). First, a spatial database was created with 872 locations of asthma patients and affecting factors (particulate matter (PM10 and PM2.5), ozone (O3), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), rainfall, wind speed, humidity, temperature, distance to street, traffic volume, and a normalized difference vegetation index (NDVI)). We created four factors using remote sensing (RS) imagery, including air pollution (O3, SO2, CO, and NO2), altitude, and NDVI. All criteria were prepared using a geographic information system (GIS). For modeling and validation, 70% and 30% of the data were used, respectively. The weight of evidence (WOE) model was used to assess the spatial relationship between the dependent and independent data. Finally, three ensemble algorithms were used to perform asthma-prone areas mapping. According to the Gini index, the most influential factors on asthma occurrence were distance to the street, NDVI, and traffic volume. The area under the curve (AUC) of receiver operating characteristic (ROC) values for the AdaBoost, Bagging, and Stacking algorithms was 0.849, 0.82, and 0.785, respectively. According to the findings, the AdaBoost algorithm outperforms the Bagging and Stacking algorithms in spatial modeling of asthma-prone areas. [ABSTRACT FROM AUTHOR]

Arterial stiffness is an important predictor of cardiovascular events, independent of traditional risk factors. Stiffening of arteries, though an adaptive process to hemodynamic load, results in substantial increase in the pulsatile hemodynamic forces that detrimentally affects the microcirculation perfusing the vital organs such as the brain, heart and kidneys. Studies have proposed that arterial stiffness precedes and may contribute to the development of hypertension in individuals with obesity. Our study sought to determine the gender-based effects on arterial stiffening in obesity which may predispose to the development of hypertension. We found female sex is associated with higher susceptibility of weight-related arterial stiffening and rise in blood pressure in obesity. Women had significantly higher carotid-femoral pulse wave velocity (CF-PWV) with higher body mass index (BMI) status (normal: 7.9 ± 2 m/s; overweight: 9.1 ± 2 m/s; obese: 9 ± 2 m/s, p < 0.001), whereas it was similar in males across all BMI categories. The linear association between arterial stiffness and BMI following adjustment for age and brachial systolic and diastolic blood pressure (BP), remained significant in females (β = 0.06; 95% CI 0.01 to 0.1; p < 0.05) but not in males (β = 0.04; 95% CI −0.01 to 0.1; p > 0.05). The mean CF-PWV values increased by 0.1 m/s for every 1 kg/m2 increase in BMI in the female subjects in the age adjusted linear model, while such effect was not seen in the male subjects. In line with arterial stiffening, the overweight and obese females demonstrated significantly higher systolic brachial BP. (BP difference: ΔBP 9−11 mmHg, p < 0.01) and central systolic pressure (ΔBP 8−10 mmHg, p < 0.05) compared to their lean counterparts, unlike the male subjects. Our results suggest that female gender is associated with higher susceptibility of weight-related arterial stiffening and rise in blood pressure. [ABSTRACT FROM AUTHOR]

Background: Cardiomyopathies are a heterogeneous group of pathologies characterized by structural and functional alterations of the heart. Aims: The purpose of this narrative review is to focus on the most important cardiomyopathies and their epidemiology, diagnosis, and management. Methods: Clinical trials were identified by Pubmed until 30 March 2021. The search keywords were "cardiomyopathies, sudden cardiac arrest, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy, arrhythmogenic cardiomyopathy (ARCV), takotsubo syndrome". Results: Hypertrophic cardiomyopathy (HCM) is the most common primary cardiomyopathy, with a prevalence of 1:500 persons. Dilated cardiomyopathy (DCM) has a prevalence of 1:2500 and is the leading indication for heart transplantation. Restrictive cardiomyopathy (RCM) is the least common of the major cardiomyopathies, representing 2% to 5% of cases. Arrhythmogenic cardiomyopathy (ARCV) is a pathology characterized by the substitution of the myocardium by fibrofatty tissue. Takotsubo cardiomyopathy is defined as an abrupt onset of left ventricular dysfunction in response to severe emotional or physiologic stress. Conclusion: In particular, it has been reported that HCM is the most important cause of sudden death on the athletic field in the United States. It is needless to say how important it is to know which changes in the heart due to physical activity are normal, and when they are pathological. [ABSTRACT FROM AUTHOR]

Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and their metabolites have long been recognized to protect against inflammation-related diseases including heart disease. Recent reports present conflicting evidence on the effects of n-3 PUFAs on major cardiovascular events including death. While some studies document that n-3 PUFA supplementation reduces the risk for heart disease, others report no beneficial effects on heart disease composite primary outcomes. Much of this heterogeneity may be related to the genetic variation in different individuals/populations that alters their capacity to synthesize biologically active n-3 and omega 6 (n-6) PUFAs and metabolites from their 18 carbon dietary precursors, linoleic acid (LA, 18:2 n-6) and alpha-linolenic (ALA, 18:3, n-3). Here, we discuss the role of a FADS gene-by-dietary PUFA interaction model that takes into consideration dietary exposure, including the intake of LA and ALA, n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in determining the efficacy of n-3 PUFA supplementation. We also review recent clinical trials with n-3 PUFA supplementation and coronary heart disease in the context of what is known about fatty acid desaturase (FADS) gene-by-dietary PUFA interactions. Given the dramatic differences in the frequencies of FADS variants that impact the efficiency of n-3 and n-6 PUFA biosynthesis, and their downstream signaling products among global and admixture populations, we conclude that large clinical trials utilizing "one size fits all" n-3 PUFA supplementation approaches are unlikely to show effectiveness. However, evidence discussed in this review suggests that n-3 PUFA supplementation may represent an important opportunity where precision interventions can be focused on those populations that will benefit the most from n-3 PUFA supplementation. [ABSTRACT FROM AUTHOR]

Resolving the interrelationships of three major extant lineages of vertebrates (hagfishes, lampreys, and gnathostomes) is a particularly important issue in evolution, because the basal resolution critically influences our understanding of primitive vertebrate characters. A consensus has emerged over the last 20 years that lampreys are the sister group to the gnathostomes and the hagfishes represent an ancient, basal lineage. This hypothesis has essentially displaced the classical hypothesis of monophyly of the cyclostomes (lampreys plus hagfishes). To test these hypotheses, we compared nearly complete ribosomal DNA sequences from each of these major lineages, as well as those from a cephalochordate and a urochordate, which represent a paraphyletic outgroup for assessing the basal vertebrate relationships. For this comparison, 92%-99% complete 28S rDNA sequences were obtained from the lancelet Branchiostoma floridae, the hagfish Eptatretus stouti, the lamprey Petromyzon marinus, and cartilaginous fishes Hydrolagus colliei and Squalus acanthias and were then analyzed with previously reported 28S and 18S rDNA sequences from other chordates. We conducted conventional (nonparametric) bootstrap analyses, under maximum-likelihood, parsimony, and minimum-evolution (using LogDet distances) criteria, of both 28S and 18S rDNA sequences considered separately and combined. All these analyses provide moderate to very strong support for the monophyly of the cyclostomes. Furthermore, the currently accepted hypothesis of a lamprey-gnathostome clade is moderately rejected by the Kishino-Hasegawa test (P = 0.099) and resoundingly rejected by parametric bootstrap tests (P < 0.01) in favor of monophyly of living cyclostomes. Another significant finding is that the hagfish E. stouti has the longest 28S rDNA gene known in any organism (> 5,200 nt). [ABSTRACT FROM PUBLISHER]

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In this study, we investigated blood lipoprotein and lipid fraction profiles, quantified using nuclear magnetic resonance, in a cohort of 844 healthy blood donors, integrating standard univariate and multivariate analysis with predictive modeling and network analysis. We observed a strong association of lipoprotein and lipid main fraction profiles with sex and age. Our results suggest an age-dependent remodulation of lipase lipoprotein activity in men and a change in the mechanisms controlling the ratio between esterified and non-esterified cholesterol in both men and women. [ABSTRACT FROM AUTHOR]

Background : Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy. Methods : A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis. Results : GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis. Conclusion : GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD. [ABSTRACT FROM AUTHOR]

Gout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the United States (U.S.), gout prevalence differentially affects certain racial groups. The objective of this proposed analysis is to compare the frequency of urate-related genetic risk alleles between Europeans (EUR) and the following major racial groups: Africans in Southwest U.S. (ASW), Han-Chinese (CHS), Japanese (JPT), and Mexican (MXL) from the 1000 Genomes Project. The Ensembl genome browser of the 1000 Genomes Project was used to conduct cross-population allele frequency comparisons of 11 SNPs across 11 genes, physiologically involved and significantly associated with SU levels and gout risk. Gene/SNP pairs included: ABCG2 (rs2231142), SLC2A9 (rs734553), SLC17A1 (rs1183201), SLC16A9 (rs1171614), GCKR (rs1260326), SLC22A11 (rs2078267), SLC22A12 (rs505802), INHBC (rs3741414), RREB1 (rs675209), PDZK1 (rs12129861), and NRXN2 (rs478607). Allele frequencies were compared to EUR using Chi-Square or Fisher's Exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.0045 for statistical significance. Risk alleles were defined as the allele that is associated with baseline or higher HU and gout risks. The cumulative HU or gout risk allele index of the 11 SNPs was estimated for each population. The prevalence of HU and gout in U.S. and non-US populations was evaluated using published epidemiological data and literature review. Compared with EUR, the SNP frequencies of 7/11 in ASW, 9/11 in MXL, 9/11 JPT, and 11/11 CHS were significantly different. HU or gout risk allele indices were 5, 6, 9, and 11 in ASW, MXL, CHS, and JPT, respectively. Out of the 11 SNPs, the percentage of risk alleles in CHS and JPT was 100%. Compared to non-US populations, the prevalence of HU and gout appear to be higher in western world countries. Compared with EUR, CHS and JPT populations had the highest HU or gout risk allele frequencies, followed by MXL and ASW. These results suggest that individuals of Asian descent are at higher HU and gout risk, which may partly explain the nearly three-fold higher gout prevalence among Asians versus Caucasians in ambulatory care settings. Furthermore, gout remains a disease of developed countries with a marked global rising. [ABSTRACT FROM AUTHOR]

Cholesterol homeostasis is essential in normal physiology of all cells. One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues. One of its main functions is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein-cholesterol (HDL-C) particles, the first step of reverse cholesterol transport (RCT). In addition, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane affecting lipid rafts, microparticle (MP) formation and cell signaling. Thus, it is not surprising that impaired ABCA1 function and altered cholesterol homeostasis may affect many different organs and is involved in the pathophysiology of a broad array of diseases. This review describes evidence obtained from animal models, human studies and genetic variation explaining how ABCA1 is involved in dyslipidemia, coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related macular degeneration (AMD), glaucoma, viral infections and in cancer progression. [ABSTRACT FROM AUTHOR]