A deep transfer learning-based convolution neural network model for COVID-19 detection using computed tomography scan images for medical applications.

The Coronavirus (COVID-19) has become a critical and extreme epidemic because of its international dissemination. COVID-19 is the world's most serious health, economic, and survival danger. This disease affects not only a single country but the entire planet due to this infectious disease. Illnesses of Covid-19 spread at a much faster rate than usual influenza cases. Because of its high transmissibility and early diagnosis, it isn't easy to manage COVID-19. The popularly used RT-PCR method for COVID-19 disease diagnosis may provide false negatives. COVID-19 can be detected non-invasively using medical imaging procedures such as chest CT and chest x-ray. Deep learning is the most effective machine learning approach for examining a considerable quantity of chest computed tomography (CT) pictures that can significantly affect Covid-19 screening. Convolutional neural network (CNN) is one of the most popular deep learning techniques right now, and its gaining traction due to its potential to transform several spheres of human life. This research aims to develop conceptual transfer learning enhanced CNN framework models for detecting COVID-19 with CT scan images. Though with minimal datasets, these techniques were demonstrated to be effective in detecting the presence of COVID-19. This proposed research looks into several deep transfer learning-based CNN approaches for detecting the presence of COVID-19 in chest CT images.VGG16, VGG19, Densenet121, InceptionV3, Xception, and Resnet50 are the foundation models used in this work. Each model's performance was evaluated using a confusion matrix and various performance measures such as accuracy, recall, precision, f1-score, loss, and ROC. The VGG16 model performed much better than the other models in this study (98.00 % accuracy). Promising outcomes from experiments have revealed the merits of the proposed model for detecting and monitoring COVID-19 patients. This could help practitioners and academics create a tool to help minimal health professionals decide on the best course of therapy.

A comprehensive review of various approaches for treatment of tertiary wastewater with emerging contaminants: what do we know?

In the last few decades, environmental contaminants (ECs) have been introduced into the environment at an alarming rate. There is a risk to human health and aquatic ecosystems from trace levels of emerging contaminants, including hospital wastewater (HPWW), cosmetics, personal care products, endocrine system disruptors, and their transformation products. Despite the fact that these pollutants have been introduced or detected relatively recently, information about their characteristics, actions, and impacts is limited, as are the technologies to eliminate them efficiently. A wastewater recycling system is capable of providing irrigation water for crops and municipal sewage treatment, so removing ECs before wastewater reuse is essential. Water treatment processes containing advanced ions of biotic origin and ECs of biotic origin are highly recommended for contaminants. This study introduces the fundamentals of the treatment of tertiary wastewater, including membranes, filtration, UV (ultraviolet) irradiation, ozonation, chlorination, advanced oxidation processes, activated carbon (AC), and algae. Next, a detailed description of recent developments and innovations in each component of the emerging contaminant removal process is provided.

A mathematical model for investigation of dry band location on 22 kV bushing with and without RTV coating: Experimental study.

As different pollutants are deposited on the high voltage bushings, a dry band forms, which causes a flashover. The bushing's contaminated layer will weaken its insulation and have an impact on its electrical characteristics. The performance of bushings in dry band conditions of various lengths was investigated in this proposed piece of work, and a dynamic arc model is presented for the arc process in polluted bushings. It shows satisfactory performance in modelling the arc variables for various dry band positions. The developed dynamic open model for contaminated bushings with and without RTV coating predicted the flashover voltage and dry band positions. Any type of contamination, such as sea salt, road salt, and industrial pollutants prevalent in several sites, can be studied using the established model. Ultimately, it was discovered that there was good agreement between the model's results and the outcomes of the experiments. •Mathematical modeling of 22 kV bushing is conceded out for diverse polluted dry band location at lead-in, lead-out and middle region of bushing surface.•Dynamic arc modeling involved in bushing flashover process for different dry band location is done and flashover voltage is predicted•Experimental work is carried out to find FOV for the bushing with different dry location and compared with predicted FOV.

Identification and Classification of Prostate Cancer Identification and Classification Based on Improved Convolution Neural Network.

Prostate cancer is one of the most common cancers in men worldwide, second only to lung cancer. The most common method used in diagnosing prostate cancer is the microscopic observation of stained biopsies by a pathologist and the Gleason score of the tissue microarray images. However, scoring prostate cancer tissue microarrays by pathologists using Gleason mode under many tissue microarray images is time-consuming, susceptible to subjective factors between different observers, and has low reproducibility. We have used the two most common technologies, deep learning, and computer vision, in this research, as the development of deep learning and computer vision has made pathology computer-aided diagnosis systems more objective and repeatable. Furthermore, the U-Net network, which is used in our study, is the most extensively used network in medical image segmentation. Unlike the classifiers used in previous studies, a region segmentation model based on an improved U-Net network is proposed in our research, which fuses deep and shallow layers through densely connected blocks. At the same time, the features of each scale are supervised. As an outcome of the research, the network parameters can be reduced, the computational efficiency can be improved, and the method's effectiveness is verified on a fully annotated dataset.

Blockchain-Based Decentralized Cloud Solutions for Data Transfer.

Cloud computing has increased its service area and user experience above traditional platforms through virtualization and resource integration, resulting in substantial economic and societal advantages. Cloud computing is experiencing a significant security and trust dilemma, requiring a trust-enabled transaction environment. The typical cloud trust model is centralized, resulting in high maintenance costs, network congestion, and even single-point failure. Also, due to a lack of openness and traceability, trust rating findings are not universally acknowledged. "Blockchain is a novel, decentralised computing system. Its unique operational principles and record traceability assure the transaction data's integrity, undeniability, and security. So, blockchain is ideal for building a distributed and decentralised trust infrastructure. This study addresses the difficulty of transferring data and related permission policies from the cloud to the distributed file systems (DFS). Our aims include moving the data files from the cloud to the distributed file system and developing a cloud policy. This study addresses the difficulty of transferring data and related permission policies from the cloud to the DFS. In DFS, no node is given the privilege, and storage of all the data is dependent on content-addressing. The data files are moved from Amazon S3 buckets to the interplanetary file system (IPFS). In DFS, no node is given the privilege, and storage of all the data is dependent on content-addressing.

Analysis of Agriculture and Food Supply Chain through Blockchain and IoT with Light Weight Cluster Head.

By 2050, the world's population will have increased by 34%, to more than 9 billion people, needing a 70% increase in food production. Prepare more dishes with fewer ingredients. Therefore, the critical goal of manufacturers is to increase production while being ecologically benign. Supply chain systems that do not enable direct farmer-to-consumer connection and rising input costs influence data collection, security, and sharing. Constraints on data security, manipulation, and single-point failure are unfulfilled due to a lack of centralized IoT agricultural infrastructure. To address these issues, the article proposes a blockchain-based IoT model. This study also shows one-of-a-kind energy savings. The decentralization of data storage improves the supply chain's transparency and quality through blockchain technology, thus farmers can engage more efficiently. Blockchain technology improves supply chain traceability and security. This article provides a transparent, decentralized blockchain tracking solution and proposes an intelligent model protocol for several Internet of Things (IoT) devices that monitor crop development and the agricultural environment. A new approach has resolved the bulk of the supply chain difficulties. Smart contracts were utilized to organize all transactions in decentralized supply networks. The use of blockchain technology improves transaction quality, and customers may verify the legitimacy of an item's authenticity and legality by using the system. A total of 100 IoT nodes were distributed randomly to each 500 m2 cluster farm. The Internet of Things nodes were used to assess soil moisture, temperature, and crop disease. Network stability period and network life of the proposed method show 90.4% accuracy. The food supply chain will be more efficient and trustworthy with an intelligent model. The immutability of ledger technology and smart contract support further increases supply chain security, privacy, transparency, and trust among all stakeholders in the multi-party system. By 2050, the world's population will need a 70% increase in food production. The food supply chain will be more efficient and trustworthy with an intelligent model. This article provides a transparent, decentralized, and intelligent model protocol for several Internet of Things (IoT) devices.

Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy patients exhibit myocardial energetic impairment, but a causative role for this energy deficiency in the pathophysiology of hypertrophic cardiomyopathy remains unproven. We hypothesized that the metabolic modulator perhexiline would ameliorate myocardial energy deficiency and thereby improve diastolic function and exercise capacity. METHODS AND RESULTS: Forty-six consecutive patients with symptomatic exercise limitation (peak Vo(2) <75% of predicted) caused by nonobstructive hypertrophic cardiomyopathy (mean age, 55±0.26 years) were randomized to perhexiline 100 mg (n=24) or placebo (n=22). Myocardial ratio of phosphocreatine to adenosine triphosphate, an established marker of cardiac energetic status, as measured by (31)P magnetic resonance spectroscopy, left ventricular diastolic filling (heart rate normalized time to peak filling) at rest and during exercise using radionuclide ventriculography, peak Vo(2), symptoms, quality of life, and serum metabolites were assessed at baseline and study end (4.6±1.8 months). Perhexiline improved myocardial ratios of phosphocreatine to adenosine triphosphate (from 1.27±0.02 to 1.73±0.02 versus 1.29±0.01 to 1.23±0.01; P=0.003) and normalized the abnormal prolongation of heart rate normalized time to peak filling between rest and exercise (0.11±0.008 to -0.01±0.005 versus 0.15±0.007 to 0.11±0.008 second; P=0.03). These changes were accompanied by an improvement in primary end point (peak Vo(2)) (22.2±0.2 to 24.3±0.2 versus 23.6±0.3 to 22.3±0.2 mL · kg(-1) · min(-1); P=0.003) and New York Heart Association class (P<0.001) (all P values ANCOVA, perhexiline versus placebo). CONCLUSIONS: In symptomatic hypertrophic cardiomyopathy, perhexiline, a modulator of substrate metabolism, ameliorates cardiac energetic impairment, corrects diastolic dysfunction, and increases exercise capacity. This study supports the hypothesis that energy deficiency contributes to the pathophysiology and provides a rationale for further consideration of metabolic therapies in hypertrophic cardiomyopathy.

Performance of first pacemaker to use smart device app for remote monitoring.

BACKGROUND: High adherence to remote monitoring (RM) in pacemaker (PM) patients improves outcomes; however, adherence remains suboptimal. Bluetooth low-energy (BLE) technology in newer-generation PMs enables communication directly with patient-owned smart devices using an app without a bedside console. OBJECTIVE: To evaluate the success rate of scheduled RM transmissions using the app compared to other RM methods. METHODS: The BlueSync Field Evaluation was a prospective, international cohort evaluation, measuring the success rate of scheduled RM transmissions using a BLE PM or cardiac resynchronization therapy PM coupled with the MyCareLink Heart app. App transmission success was compared to 3 historical "control" groups from the Medtronic de-identified CareLink database: (1) PM patients with manual communication using a wand with a bedside console (PM manual transmission), (2) PM patients with wireless automatic communication with the bedside console (PM wireless); (3) defibrillator patients with similar automatic communication (defibrillator wireless). RESULTS: Among 245 patients enrolled (age 64.8±15.6 years, 58.4% men), 953 transmissions were scheduled through 12 months, of which 902 (94.6%) were successfully completed. In comparison, transmission success rates were 56.3% for PM manual transmission patients, 77.0% for PM wireless patients, and 87.1% for defibrillator wireless patients. Transmission success with the app was superior across matched cohorts based on age, sex, and device type (single vs dual vs triple chamber). CONCLUSION: The success rate of scheduled RM transmissions was higher among patients using the smart device app compared to patients using traditional RM using bedside consoles. This novel technology may improve patient engagement and adherence to RM.

Detection of unknown atrial fibrillation by prolonged ECG monitoring in an all-comer patient cohort and association with clinical and Holter variables.

OBJECTIVES: Prolonged ECG monitoring is clinically useful to detect unknown atrial fibrillation (AF) in stroke survivors. The diagnostic yield of prolonged ECG monitoring in other patient populations is less well characterised. We therefore studied the diagnostic yield of prolonged Holter ECG monitoring for AF in an unselected patient cohort referred from primary care or seen in a teaching hospital. METHODS: We analysed consecutive 7-day ECG recordings in unselected patients referred from different medical specialities and assessed AF detection rates by indication, age and comorbidities. RESULTS: Seven-day Holter ECGs (median monitoring 127.5 hours, IQR 116 to 152) were recorded in 476 patients (mean age 54.6 (SD 17.0) years, 55.9% female) without previously known AF, requested to evaluate palpitations (n=241), syncope (n=99), stroke or transient ischaemic attack (n=75), dizziness (n=29) or episodic chest pain (n=32). AF was newly detected in 42/476 (8.8%) patients. Oral anticoagulation was initiated in 40/42 (95.2%) patients with newly detected AF. Multivariate logistic regression, adjusted for age, sex and monitoring duration found four clinical parameters to be associated with newly detected AF: hypertension OR=2.54, (1.08 to 8.61) (adjusted OR (95% CI)), p=0.034; previous stroke or TIA OR=4.14 (1.81 to 13.01), p=0.001; left-sided valvular heart disease OR=5.07 (2.48 to 18.70), p<0.001 and palpitations OR=2.86, (1.33 to 10.44), p=0.015. CONCLUSIONS: Open multispeciality access to prolonged ECG monitoring, for example, as part of integrated, cross-sector AF care, can accelerate diagnosis of AF and increase adequate use of oral anticoagulation, especially in older and symptomatic patients with comorbidities.

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.

Hypoxic modulation of exogenous nitrite-induced vasodilation in humans.

BACKGROUND: It has been proposed that under hypoxic conditions, nitrite may release nitric oxide, which causes potent vasodilation. We hypothesized that nitrite would have a greater dilator effect in capacitance than in resistance vessels because of lower oxygen tension and that resistance-vessel dilation should become more pronounced during hypoxemia. The effect of intra-arterial infusion of nitrite on forearm blood flow and forearm venous volumes was assessed during normoxia and hypoxia. METHODS AND RESULTS: Forty healthy volunteers were studied. After baseline infusion of 0.9% saline, sodium nitrite was infused at incremental doses from 40 nmol/min to 7.84 mumol/min. At each stage, forearm blood flow was measured by strain-gauge plethysmography. Forearm venous volume was assessed by radionuclide plethysmography. Changes in forearm blood flow and forearm venous volume in the infused arm were corrected for those in the control arm. The peak percentage of venodilation during normoxia was 35.8+/-3.4% (mean+/-SEM) at 7.84 micromol/min (P<0.001) and was similar during hypoxia. In normoxia, arterial blood flow, assessed by the forearm blood flow ratio, increased from 1.04+/-0.09 (baseline) to 1.62+/-0.18 (nitrite; P<0.05) versus 1.07+/-0.09 (baseline) to 2.37+/-0.15 (nitrite; P<0.005) during hypoxia. This result was recapitulated in vitro in vascular rings. CONCLUSIONS: Nitrite is a potent venodilator in normoxia and hypoxia. Arteries are modestly affected in normoxia but potently dilated in hypoxia, which suggests the important phenomenon of hypoxic augmentation of nitrite-mediated vasodilation in vivo. The use of nitrite as a selective arterial vasodilator in ischemic territories and as a potent venodilator in heart failure has therapeutic implications.

Effects of bradykinin on venous capacitance in health and treated chronic heart failure.

In the present study, we investigated the effects of basal and intra-arterial infusion of bradykinin on unstressed forearm vascular volume (a measure of venous tone) and blood flow in healthy volunteers (n=20) and in chronic heart failure patients treated with ACEIs [ACE (angiotensin-converting enzyme) inhibitors] (n=16) and ARBs (angiotensin receptor blockers) (n=14). We used radionuclide plethysmography to examine the effects of bradykinin and of the bradykinin antagonists B9340 [B1 (type 1)/B2 (type 2) receptor antagonist] and HOE140 (B2 antagonist). Bradykinin infusion increased unstressed forearm vascular volume in a similar dose-dependent manner in healthy volunteers and ARB-treated CHF patients (healthy volunteers maximum 12.3+/-2.1%, P<0.001 compared with baseline; ARB-treated CHF patients maximum 9.3+/-3.3%, P<0.05 compared with baseline; P=not significant for difference between groups), but the increase in unstressed volume in ACEI-treated CHF patients was higher (maximum 28.8+/-7.8%, P<0.001 compared with baseline; P<0.05 for the difference between groups). In contrast, while the increase in blood flow in healthy volunteers (maximum 362+/-9%, P<0.001) and in ACEI-treated CHF patients (maximum 376+/-12%, P<0.001) was similar (P=not significant for the difference between groups), the increase in ARB-treated CHF patients was less (maximum 335+/-7%, P<0.001; P<0.05 for the difference between groups). Infusion of each receptor antagonist alone similarly reduced basal unstressed volume and blood flow in ACEI-treated CHF patients, but not in healthy volunteers or ARB-treated CHF patients. In conclusion, bradykinin does not contribute to basal venous tone in health, but in ACEI-treated chronic heart failure it does. In ARB-treated heart failure, venous responses to bradykinin are preserved but arterial responses are reduced compared with healthy controls. Bradykinin-mediated vascular responses in both health and heart failure are mediated by the B2, rather than the B1, receptor.

Reduced in vivo skeletal muscle oxygen consumption in patients with chronic heart failure--a study using Near Infrared Spectrophotometry (NIRS).

AIM: We used Near Infrared Spectrophotometry (NIRS) during arterial occlusion to measure resting skeletal muscle oxygen consumption in chronic heart failure (CHF) patients and in age-matched healthy volunteers (HVs). METHODS: Fifteen CHF patients (ten males) and eleven HVs (six males) had echocardiographic evaluation followed by measurement of the oxygen consumption of the brachioradialis muscle using NIRS. This involved continuous measurement of the oxygenated haemoglobin concentration ([Oxy-Hb]) and deoxy-haemoglobin concentration ([Deoxy-Hb]) with an Oxiplex TS NIRS probe first under basal overnight fasted resting conditions followed by 1 min of forearm arterial occlusion. A linear decline was observed in [Oxy-Hb-Deoxy-Hb] during the arterial occlusion and the oxygen consumption rate was calculated from the initial slope observed. RESULTS: CHF patients were 59+/-2.8 years old with Left Ventricular Ejection Fraction (LVEF) 31%+/-2.2 and the HVs were 52+/-4.8 years old with LVEF 62%+/-2.5. The resting muscle oxygen consumption rate was significantly reduced in CHF patients versus HVs (0.04+/-0.01 mlO(2)/min/100 g versus 0.07+/-0.01 mlO(2)/min/100 g) p<0.005. CONCLUSIONS: There is a significant reduction in resting oxygen consumption per gram of tissue in skeletal muscle of patients with CHF.

Insights into how to conduct a clinical trial in the UK.

New researchers may find starting and conducting clinical studies in the UK complicated and time-consuming. In this article, we describe our collective experiences and provide some pointers on how to navigate through the various committees and regulatory bodies. The article is intended to aid junior researchers in understanding the study process and to provide them with some insight on how to get through this complex system successfully.

When is a mass not a mass? An unusual presentation of prominent crista terminalis.

This case report describes a patient in whom echocardiography showed borderline left ventricular hypertrophy and a mass adjacent to the right atrial wall. This naturally caused some concern as the differential diagnoses included that of a right atrial myxoma and further investigations were organised. A subsequent cardiac MRI revealed this thickening to be a prominent crista terminalis. The crista terminalis is a variant of normal anatomical structures within the right atrium, which mimics an atrial mass.

Impact of chronic congestive heart failure on pharmacokinetics and vasomotor effects of infused nitrite.

BACKGROUND AND PURPOSE: Nitrite (NO2⁻) has recently been shown to represent a potential source of NO, in particular under hypoxic conditions. The aim of the current study was to compare the haemodynamic effects of NO2⁻ in healthy volunteers and patients with stable congestive heart failure (CHF). EXPERIMENTAL APPROACH: The acute haemodynamic effects of brachial artery infusion of NO2⁻ (0.31 to 7.8 µmol·min⁻¹) was assessed in normal subjects (n = 20) and CHF patients (n = 21). KEY RESULTS: NO2⁻ infusion was well tolerated in all subjects. Forearm blood flow (FBF) increased markedly in CHF patients at NO2⁻ infusion rates which induced no changes in normal subjects (ANOVA: F = 5.5; P = 0.02). Unstressed venous volume (UVV) increased even with the lowest NO2⁻ infusion rate in all subjects (indicating venodilation), with CHF patients being relatively hyporesponsive compared with normal subjects (ANOVA: F = 6.2; P = 0.01). There were no differences in venous blood pH or oxygen concentration between groups or during NO2⁻ infusion. Venous plasma NO2⁻ concentrations were lower in CHF patients at baseline, and rose substantially less with NO2⁻ infusion, without incremental oxidative generation of nitrate, consistent with accelerated clearance in these patients. Plasma protein-bound NO concentrations were lower in CHF patients than normal subjects at baseline. This difference was attenuated during NO2⁻ infusion. Prolonged NO2⁻ exposure in vivo did not induce oxidative stress, nor did it induce tolerance in vitro. CONCLUSIONS AND IMPLICATIONS: The findings of arterial hyper-responsiveness to infused NO2⁻ in CHF patients, with evidence of accelerated transvascular NO2⁻ clearance (presumably with concomitant NO release) suggests that NO2⁻ effects may be accentuated in such patients. These findings provide a stimulus for the clinical exploration of NO2⁻ as a therapeutic modality in CHF.

Heart team discussion in managing patients with coronary artery disease: outcome and reproducibility.

Recent ESC/EACTS revascularization guidelines advocate a 'Heart Team' (HT) approach in the decision-making process when managing patients with coronary disease. We prospectively assessed HT decision-making in 150 patients analysing personnel attendance, data presented, the 'actioning' of the HT decision and, if not completed, then the reasons why. Additionally, 50 patients were specifically re-discussed after 1 year in order to assess consistency in decision-making. We have two HT meetings each week. At least one surgeon, interventional cardiologist and non-interventional cardiologist were present at all meetings. Data presented included patient demographics, symptoms, co-morbidities, coronary angiography, left ventricular function and other relevant investigations, e.g. echocardiograms. HT decisions included continued medical treatment (22%), percutaneous coronary intervention (PCI; 22%), coronary-artery bypass grafting (CABG; 34%) or further investigations such as pressure wire studies, dobutamine stress echo or cardiac magnetic resonance imaging (22%). These decisions were fully undertaken in 86% of patients. Reasons for aberration in the remaining 21 patients included patient refusal (CABG 29%, PCI 10%) and further co-morbidities (28%). On re-discussion of the same patient data (n = 50) a year later, 24% of decisions differed from the original HT recommendations reflecting the fact that, for certain coronary artery disease pattern, either CABG or PCI could be appropriate.

The role of vascular myoglobin in nitrite-mediated blood vessel relaxation.

AIMS: This work investigates the role of myoglobin in mediating the vascular relaxation induced by nitrite. Nitrite, previously considered an inert by-product of nitric oxide metabolism, is now believed to play an important role in several areas of pharmacology and physiology. Myoglobin can act as a nitrite reductase in the heart, where it is plentiful, but it is present at a far lower level in vascular smooth muscle-indeed, its existence in the vessel wall is controversial. Haem proteins have been postulated to be important in nitrite-induced vasodilation, but the specific role of myoglobin is unknown. The current study was designed to confirm the presence of myoglobin in murine aortic tissue and to test the hypothesis that vascular wall myoglobin is important for nitrite-induced vasodilation. METHODS AND RESULTS: Aortic rings from wild-type and myoglobin knockout mice were challenged with nitrite, before and after exposure to the haem-protein inhibitor carbon monoxide (CO). CO inhibited vasodilation in wild-type rings but not in myoglobin-deficient rings. Restitution of myoglobin using a genetically modified adenovirus both increased vasodilation to nitrite and reinstated the wild-type pattern of response to CO. CONCLUSION: Myoglobin is present in the murine vasculature and contributes significantly to nitrite-induced vasodilation.

Potential of metabolic agents as adjunct therapies in heart failure.

Heart failure continues to have a significant morbidity and mortality rate despite several recent advances in treatment such as additional neurohumoral blockades and cardiac resynchronization therapy. There is emerging evidence that, irrespective of etiology, heart failure is associated with an energetic disorder and that this may contribute to the pathogenesis of the syndrome. Recently, a number of studies have suggested that some metabolic agents may have potential as adjunctive therapy in patients with heart failure. These agents cause a shift of myocardial-substrate utilization away from free fatty acids toward glucose. Free fatty acid utilization consumes more oxygen to generate an equivalent amount of energy compared with glucose. Some of these agents are also effective antianginals, presumably by reducing the myocardial oxygen requirement. In this review we will discuss some of the current issues and progresses relating to metabolic manipulation in heart failure.