High fat diet modifies the association of lipoprotein lipase gene polymorphism with high density lipoprotein cholesterol in an Asian Indian population

Background Single nucleotide polymorphisms (SNPs) in lipoprotein lipase gene (LPL) have been shown to influence metabolism related to lipid phenotypes. Dietary factors have been shown to modify the association between LPL SNPs and lipids; however, to date, there are no studies in South Asians. Hence, we tested for the association of four common LPL SNPs with plasma lipids and examined the interactions between the SNPs and dietary factors on lipids in 1,845 Asian Indians. Methods The analysis was performed in 788 Type 2 diabetes cases and 1,057 controls randomly chosen from the cross-sectional Chennai Urban Rural Epidemiological Study. Serum triacylglycerol (TAG), serum total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured using a Hitachi-912 autoanalyzer (Roche Diagnostics GmbH, Mannheim, Germany). Dietary intake was assessed using a semi-quantitative food frequency questionnaire. The SNPs (rs1121923, rs328, rs4922115 and rs285) were genotyped by polymerase chain reaction followed by restriction enzyme digestion and 20% of samples were sequenced to validate the genotypes obtained. Statistical Package for Social Sciences for Windows version 22.0 (SPSS, Chicago, IL) was used for statistical analysis. Results After correction for multiple testing and adjusting for potential confounders, SNPs rs328 and rs285 showed association with HDL-C (P = 0.0004) and serum TAG (P = 1×10−5), respectively. The interaction between SNP rs1121923 and fat intake (energy %) on HDL-C (P = 0.003) was also significant, where, among those who consumed a high fat diet (28.4 ± 2.5%), the T allele carriers (TT + XT) had significantly higher HDL-C concentrations (P = 0.0002) and 30% reduced risk of low HDL-C levels compared to the CC homozygotes. None of the interactions on other lipid traits were statistically significant. Conclusion Our findings suggest that individuals carrying T allele of the SNP rs1121923 have increased HDL-C levels when consuming a high fat diet compared to CC homozygotes. Our finding warrants confirmation in prospective studies and randomized controlled trials

5-Meth­oxy-2,2-dimethyl-6-[(2E)-2-methyl­but-2-eno­yl]-10-phenyl-2H,8H-pyrano[2,3-f]chromen-8-one (calophyllolide)

The title compound, C26H24O5, was isolated from calophyllum inophyllum seeds. In the mol­ecule, the phenyl and 2-methyl­but-2-enoyl groups are almost orthogonal to the chromene fragment [C—C—C—C torsion angles = 81.4 (3) and −90.1 (2)°, respectively]. In the crystal packing, centrosymmetrically related mol­ecules are linked by C—H⋯O contacts into dimers, which are connected via further C—H⋯O inter­actions into a double chain along [010]

Association of Hypoadiponectinemia with Hypoglutathionemia in NAFLD Subjects with and without Type 2 Diabetes

Objective: The aim of this study is to measure the extent of oxidative stress and to see whether it has any correlation to changes in adiponectin levels in NAFLD subjects with and without Type 2 diabetes.Methods: Subjects recruited from the Chennai Urban Rural Epidemiology Study comprise of 1: Normal Glucose Tolerance (NGT) subjects without NAFLD; 2: NGT with NAFLD; 3: Type 2 Diabetic patients [T2DM] without NAFLD and 4: T2DM with NAFLD. Thiobarbituric acid reactive substances (TBARS), protein carbonyl (PCO), glutathione and adiponectin levels were measured by standard methods. Ultrasound of the liver was used to diagnose NAFLD.Results: T2DM subjects with NAFLD had significantly (p&lt; 0.001) higher levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCO) but lower (p&lt; 0.001) GSH/GSSG ratio and adiponectin levels compared to other three groups. The association of hypoadiponectinemia withNAFLD/Type 2 diabetes was significant even after adjusting for age, gender and BMI, but lost when adjusted for parameters of oxidative stress. While palmitate significantly reduced GSH/GSSG ratio in hepatocytes, addition of exogenous recombinant adiponectin restored the GSH/GSSG ratio comparable to those of untreated cells.Conclusion: There exists an association of hypoglutathionemia and hypoadiponectinemia in subjects with NAFLD and/or T2DM. In addition to the known beneficial effects, out study also exposes the antioxidant nature of adiponectin.</jats:p

Multi-run concrete autoencoder to identify prognostic lncRNAs for 12 cancers

Background: Long non-coding RNA plays a vital role in changing the expression profiles of various target genes that lead to cancer development. Thus, identifying prognostic lncRNAs related to different cancers might help in developing cancer therapy. Method: To discover the critical lncRNAs that can identify the origin of different cancers, we propose the use of the state-of-the-art deep learning algorithm concrete autoencoder (CAE) in an unsupervised setting, which efficiently identifies a subset of the most informative features. However, CAE does not identify reproducible features in different runs due to its stochastic nature. We thus propose a multi-run CAE (mrCAE) to identify a stable set of features to address this issue. The assumption is that a feature appearing in multiple runs carries more meaningful information about the data under consideration. The genome-wide lncRNA expression profiles of 12 different types of cancers, with a total of 4768 samples available in The Cancer Genome Atlas (TCGA), were analyzed to discover the key lncRNAs. The lncRNAs identified by multiple runs of CAE were added to a final list of key lncRNAs that are capable of identifying 12 different cancers. Results: Our results showed that mrCAE performs better in feature selection than single-run CAE, standard autoencoder (AE), and other state-of-the-art feature selection techniques. This study revealed a set of top-ranking 128 lncRNAs that could identify the origin of 12 different cancers with an accuracy of 95%. Survival analysis showed that 76 of 128 lncRNAs have the prognostic capability to differentiate high-and low-risk groups of patients with different cancers. Conclusion: The proposed mrCAE, which selects actual features, outperformed the AE even though it selects the latent or pseudo-features. By selecting actual features instead of pseudo-features, mrCAE can be valuable for precision medicine. The identified prognostic lncRNAs can be further studied to develop therapies for different cancers

Antithrombotic therapy in atrial fibrillation associated with valvular heart disease: A joint consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology Working Group on Thrombosis, endorsed by the ESC Working Group on Valvular Heart Disease, Cardiac Arrhythmia Society of Southern Africa (CASSA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE)

Atrial fibrillation (AF) is a major public health problem1 with global prevalence rates (per 1000000 population) in 2010 being 596.2 (95% uncertainty interval (UI), 558.4-636.7) in men and 373.1 (95% UI, 347.9-402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2-95.4) in men and 59.5 (95% UI, 49.9-74.9) in women.2 Worldwide, AF in association with valvular heart disease (VHD) is also common, and management strategies for this group of patients have been less addressed by randomized trials. The latter have largely focused on 'non-valvular AF' patients leading to major uncertainties over how to define (and treat) such patients. There is also an important heterogeneity in the definition of valvular and non-valvular AF.3 Some physicians assume that any valve disease should be considered as 'valvular' AF. Others consider that only mechanical valve prosthesis and rheumatic mitral stenosis should be defined as 'valvular' AF. The term valvular AF has been arbitrarily applied and the 2016 ESC guidelines have avoided the term 'valvular AF' and refer simply to 'AF related to hemodynamically significant mitral stenosis or prosthetic mechanical heart valves'.4 AF clearly leads to an incremental risk for thromboembolism in patients with mitral valve stenosis, but there are limited data for other valvular diseases. Another proposal is to use the acronym MARM-AF as a simple acronym to designate 'Mechanical and Rheumatic Mitral AF' as an alternative to term 'valvular AF' to designate the clinical scenarios for which at the non-vitamin K antagonist oral anticoagulants (NOACs) are not indicated.5 For this document we recognize the uncertainty in terminology, and our scope largely relates to AF related to 'hemodynamically significant' rheumatic VHD (ie. severe enough to impact on patient's survival or necessitates an intervention or surgery) or prosthetic mechanical heart valves. Nonetheless, thrombo-embolic (TE) risk varies according to valve lesion and may be associated with CHA2DS2VASc score risk factor components, rather than the valve disease per se being causal.6,7 TE risk may also be influenced not only by type but also the severity of the lesion. For example, the degree of mitral regurgitation may matter when it comes to risk of TE as some studies suggest that mild (Grade 1) mitral regurgitation is associated with a 2.7-fold increased risk of stroke/TE, while severe forms may possibly have a 'protective' effect (HR = 0.45 for stroke and 0.27 for LA stasis.8 An appropriate definition of 'valvular AF' would need to identify a subgroup of patients with similar pathophysiology of thrombo-embolism, TE risk, and treatment strategies6,9; however, this would be challenging given the major heterogeneity of the condition. This consensus document proposes that the term 'valvular AF' is outdated and given that any definition ultimately relates to the evaluated practical use of oral anticoagulation (OAC) type, we propose a functional EHRA (EvaluatedHeartvalves, Rheumatic orArtificial) categorization in relation to the type of OAC use in patients with AF, as follows:Evaluated Heartvalves, Rheumatic or Artificial (EHRA) Type 1,which refers to AF patients with 'VHD needing therapy with a Vitamin K antagonist (VKA)

Harbingers of Hope: Scientists and the Pursuit of World Peace

The ongoing wars in many regions-such as the conflict between Israel and Hamas-as well as the effects of war on communities, social services, and mental health are covered in this special editorial. This article emphasizes the need for international efforts to promote peace, offer humanitarian aid, and address the mental health challenges faced by individuals and communities affected by war and violence

Yoga-Based Cardiac Rehabilitation After Acute Myocardial Infarction: A Randomized Trial

Background: Given the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly). Objectives: This study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial. Methods: The trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life–5 Dimensions–5 Level visual analogue scale at 12 weeks. Results: MACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes). Conclusions: Yoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408)