The study of myocardial metabolism and its role in the pathophysiology of early diabetic cardiomyopathy

The human myocardium is a metabolic omnivore and utilises fatty acids, glucose, ketones, amino acids and lactate to produce energy. Altered metabolism results in cardiac muscle dysfunction and can play a potentially significant role in development of heart failure. Metabolic modulators like Perhexiline are potentially significant new treatments in the management of heart failure and coronary artery disease. Diabetes is a metabolic disorder that results in altered high energy phosphate kinetics in the myocardium. We demonstrate that microvascular disease plays little role in the development of impaired cardiac energetics in young patients with uncomplicated type 1 diabetes. We have shown an increase in left ventricular torsion in these patients with normal ejection fraction. Coronary microvascular disease and rotational deformation delay play a significant role in the development of increased torsion in these individuals which counteracts the early diastolic dysfunction. Furthermore the left atrial contribution to left ventricular filling is increased in these individuals. We demonstrate that Perhexiline has a differential action on insulin sensitivity in subjects with and without diabetes. It also increased plasma ketones and triglycerides in these patients. Finally we demonstrate that Perhexiline can be safely used and provides good relief of symptoms when used clinically in subjects with refractory angina and heart failure

Cloaking fabric, a confidentiality layer for hyperledger fabric

Permissioned blockchains have resulted in some unlikely collaborations between organizations that would have previously been impossible due them mutually distrusting each other. They provide a sense of trust among the parties due to the decentralized nature of their deployment that prevents censorship from a subset of the parties. Decentralization mandates that all the parties have the same view of the system, therefore it has been difficult to represent and store private data. Asynchronous Verifiable Secret Sharing(AVSS) and Secure Multi Party Computation(MPC) are techniques from cryptography that allow the sharing of secrets among multiple parties and enable arbitrary computations on the shared data without leaking any information about the data. Previously, AVSS and MPC protocols were inefficient for practical use or did not work in the same setting of blockchains where nodes of the blockchain could arbitrarily fail. Honeybadger AVSS and Honeybadger MPC are robust and scalable frameworks that make them a good candidate to be coupled with a permissioned blockchain to form a confidentiality layer on top of it. We present Cloaking Fabric, an extension to the popular permissioned blockchain Hyperledger Fabric that utilizes HoneybadgerMPC and HoneybadgerAVSS to provide a confidentiality layer that would allow smart-contracts on the blockchain to interact with private data. We present a suite of applications to demonstrate our system and measure the overhead it would have over standard MPC operations

Effect of Paclobutrazol on Fruit Quality Attributes in Mango (Mangifera indica L.) Cv. Totapuri

Paclobutrazol application restricts vegetative growth while improving flowering and fruiting in mango. In the present study, effect of soil drenching with Paclobutrazol @ 3.0ml m-1 canopy diameter, applied during the 3rd week of August, on fruit quality attributes was investigated in cv. Totapuri. Parameters like fruit weight, total soluble solids (TSS), % acidity, and content of ascorbic acid, carotenoids, lycopene and individual sugars was estimated. Paclobutrazol application increased average fruit weight, TSS and content of ascorbic acid and total carotenoids, and reduced the acidity in fruits compared to fruits in untreated trees. Lycopene content was only marginally influenced by paclobutrazol. In fruits of paclobutrazol treated trees, increase of 23.4% in total sugars, 29.6% in reducing sugars, 77.4% in glucose and 27.8% in sucrose content was recorded over fruits from the untreated trees. Results indicated that, paclobutrazol application improved quality in mango fruit

Chemical Constituents during the Main and Off-Season in Mango (Mangifera indica L.) Cv. Royal Special

Evaluation and quantification of fruit quality parameters like carbohydrates, phenolics, flavonoids, ascorbic acid, titrable acidity, Total Soluble Solids (TSS), carotenoids and lycopene content was done in fruits of mango cv. Royal Special, at ICAR-Indian Institute of Horticultural Research, Bengaluru, India, during the off-season (October, 2012) and main-season (June, 2013), respectively. 'Royal Special' is a typical off-season bearing cultivar, often characterized by multiple flushing and flowering under South Indian conditions. Major phytonutrients such as total sugars, reducing sugars, starch, total carotenoids, lycopene, total phenols, flavonoids, ascorbic acid, TSS, titrable acidity and average fruit yield per plant, were recorded during the off- and main- seasons. Results indicated that fruits from off-season were higher in the major chemical constituents studied compared to the main-season crop, except for fruit yield per plant. This may be attributed to poor competition for nutrients among the developing fruits which act as a sink, besides fluctuating environmental conditions during the off-season, compared to the main-season

Influence of Organic Practices on Growth and Fruit Yield in Papaya Cv. Surya

A field trial on organic practices in papaya cv. Surya was conducted during 2009-2011 with 10 nutrient combinations involving farm yard manure, biofertilizers and VAM along with 100% recommended dose of fertilizers and no manure/ fertilizer treatment. Vegetative parameters were recorded periodically. At 18 months after planting, plant height, plant girth and number of leaves were found to be significant. Results indicated that, crop growth was better with organic treatments compared to no manure/fertilizer treatment. Fruit yield and quality parameters were also recorded. Fruit yield and average fruit weight were found to be significant. Maximum fruit yield of 32kg/plant (80 t/ ha) was recorded under 75% recommended dose of fertilizer applied as farm yard manure+vermicompost, which was significantly superior to that in 100% recommended dose of fertilizer for the 18-month cropping period

Effect of Organic Practices on Fruit Quality in Papaya Cv. Surya

A field experiment was conducted during 2009-10 at Indian Institute of Horticultural Research, Bangalore using papaya cv. 'Surya'. Ten organic nutrient treatments along with recommended dose of fertilizers and control (no manure/fertilizer) were used totaling twelve treatment combinations of FYM, biofertilizers and vermicompost. Fruit quality parameters such as total carotenoids, lycopene, TSS, average fruit weight and ascorbic acid content were analyzed. Among the treatments, application of 50% recommended dose of fertilizers in the form of farm yard manure (FYM) applied as Azospirillum+Phosphate solubilizing bacteria+Mycorrhiza+Vermicompost showed high level of carotenoids, lycopene and low levels of ascorbic acid. TSS and average fruit weight were not affected by various organic nutrient treatments

Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy

Objectives: The aim of this study was to determine whether short-term treatment with perhexiline improves cardiac energetics, left ventricular function, and symptoms of heart failure by altering cardiac substrate utilization. Background: Perhexiline improves exercise capacity and left ventricular ejection fraction (LVEF) in patients with heart failure (HF). P cardiac magnetic resonance spectroscopy can be used to quantify the myocardial phosphocreatine/adenosine triphosphate ratio. Because improvement of HF syndrome can improve cardiac energetics secondarily, we investigated the effects of short-term perhexiline therapy. Methods: Patients with systolic HF of nonischemic etiology (n= 50, 62 ± 1.8 years of age, New York Heart Association functional class II to IV, LVEF: 27.0 ± 1.44%) were randomized to receive perhexiline 200 mg or placebo for 1 month in a double-blind fashion. Clinical assessment, echocardiography, and P cardiac magnetic resonance spectroscopy were performed at baseline and after 1 month. A substudy of 22 patients also underwent cross-heart blood sampling at completion of the study to quantify metabolite utilization. Results: Perhexiline therapy was associated with a 30% increase in the phosphocreatine/adenosine triphosphate ratio (from 1.16 ± 0.39 to 1.51 ± 0.51; p< 0.001) versus a 3% decrease with placebo (from 1.36 ± 0.31 to 1.34 ± 0.31; p=0.37). Perhexiline therapy also led to an improvement in New York Heart Association functional class compared with placebo (p= 0.036). Short-term perhexiline therapy did not change LVEF. Cross-heart measures of cardiac substrate uptake and respiratory exchange ratio (which reflects the ratio of substrates used) did not differ between patients who received perhexiline versus placebo. Conclusions: Perhexiline improves cardiac energetics and symptom status with no evidence of altered cardiac substrate utilization. No change in LVEF is seen at this early stage. (Metabolic Manipulation in Chronic Heart Failure; NCT00841139)

Increased Left Ventricular Torsion in Uncomplicated Type 1 Diabetic Patients: The role of coronary microvascular function

We used speckle tracking echocardiography to study the early changes in left ventricular (LV) torsion in young patients with uncomplicated type 1 diabetes and stress magnetic resonance imaging (MRI) to assess its interrelationships with coronary microangiopathy

Biventricular pacemaker therapy improves exercise capacity in patients with non‐obstructive hypertrophic cardiomyopathy via augmented diastolic filling on exercise

Aims Treatment options for patients with non‐obstructive hypertrophic cardiomyopathy (HCM) are limited. We sought to determine whether biventricular (BiV) pacing improves exercise capacity in HCM patients, and whether this is via augmented diastolic filling. Methods and results Thirty‐one patients with symptomatic non‐obstructive HCM were enrolled. Following device implantation, patients underwent detailed assessment of exercise diastolic filling using radionuclide ventriculography in BiV and sham pacing modes. Patients then entered an 8‐month crossover study of BiV and sham pacing in random order, to assess the effect on exercise capacity [peak oxygen consumption (VO2)]. Patients were grouped on pre‐specified analysis according to whether left ventricular end‐diastolic volume increased (+LVEDV) or was unchanged/decreased (–LVEDV) with exercise at baseline. Twenty‐nine patients (20 male, mean age 55 years) completed the study. There were 14 +LVEDV patients and 15 –LVEDV patients. Baseline peak VO2 was lower in –LVEDV patients vs. +LVEDV patients (16.2 ± 0.9 vs. 19.9 ± 1.1 mL/kg/min, P = 0.04). BiV pacing significantly increased exercise ΔLVEDV (P = 0.004) and Δstroke volume (P = 0.008) in –LVEDV patients, but not in +LVEDV patients. Left ventricular ejection fraction and end‐systolic elastance did not increase with BiV pacing in either group. This translated into significantly greater improvements in exercise capacity (peak VO2 + 1.4 mL/kg/min, P = 0.03) and quality of life scores (P = 0.02) in –LVEDV patients during the crossover study. There was no effect on left ventricular mechanical dyssynchrony in either group. Conclusion Symptomatic patients with non‐obstructive HCM may benefit from BiV pacing via augmentation of diastolic filling on exercise rather than contractile improvement. This may be due to relief of diastolic ventricular interaction. Clinical Trial Registration: ClinicalTrials.gov NCT00504647

Reverse engineering synthetic antiviral amyloids

Human amyloids have been shown to interact with viruses and interfere with viral replication. Based on this observation, we employed a synthetic biology approach in which we engineered virus-specific amyloids against influenza A and Zika proteins. Each amyloid shares a homologous aggregation-prone fragment with a specific viral target protein. For influenza we demonstrate that a designer amyloid against PB2 accumulates in influenza A-infected tissue in vivo. Moreover, this amyloid acts specifically against influenza A and its common PB2 polymorphisms, but not influenza B, which lacks the homologous fragment. Our model amyloid demonstrates that the sequence specificity of amyloid interactions has the capacity to tune amyloid-virus interactions while allowing for the flexibility to maintain activity on evolutionary diverging variants. Some human amyloid proteins have been shown to interact with viral proteins, suggesting that they may have potential as therapeutic agents. Here the authors design synthetic amyloids specific for influenza A and Zika virus proteins, respectively, and show that they can inhibit viral replication