A Multimodal Assistive-Robotic-Arm Control System to Increase Independence After Tetraplegia.

Following tetraplegia, independence for completing essential daily tasks, such as opening doors and eating, significantly declines. Assistive robotic manipulators (ARMs) could restore independence, but typically input devices for these manipulators require functional use of the hands. We created and validated a hands-free multimodal input system for controlling an ARM in virtual reality using combinations of a gyroscope, eye-tracking, and heterologous surface electromyography (sEMG). These input modalities are mapped to ARM functions based on the user's preferences and to maximize the utility of their residual volitional capabilities following tetraplegia. The two participants in this study with tetraplegia preferred to use the control mapping with sEMG button functions and disliked winking commands. Non-disabled participants were more varied in their preferences and performance, further suggesting that customizability is an advantageous component of the control system. Replacing buttons from a traditional handheld controller with sEMG did not substantively reduce performance. The system provided adequate control to all participants to complete functional tasks in virtual reality such as opening door handles, turning stove dials, eating, and drinking, all of which enable independence and improved quality of life for these individuals.

An online learning algorithm for adapting leg stiffness and stride angle for efficient quadruped robot trotting.

Animals adjust their leg stiffness and stride angle in response to changing ground conditions and gait parameters, resulting in improved stability and reduced energy consumption. This paper presents an online learning algorithm that attempts to mimic such animal behavior by maximizing energy efficiency on the fly or equivalently, minimizing the cost of transport of legged robots by adaptively changing the leg stiffness and stride angle while the robot is traversing on grounds with unknown characteristics. The algorithm employs an approximate stochastic gradient method to change the parameters in real-time, and has the following advantages: (1) the algorithm is computationally efficient and suitable for real-time operation; (2) it does not require training; (3) it is model-free, implying that precise modeling of the robot is not required for good performance; and (4) the algorithm is generally applicable and can be easily incorporated into a variety of legged robots with adaptable parameters and gaits beyond those implemented in this paper. Results of exhaustive performance assessment through numerical simulations and experiments on an under-actuated quadruped robot with compliant legs are included in the paper. The robot platform used a pneumatic piston in each leg as a variable, passive compliant element. Performance evaluation using simulations and experiments indicated that the algorithm was capable of converging to near-optimal values of the cost of transport for given operating conditions, terrain properties, and gait characteristics with no prior knowledge of the terrain and gait conditions. The simplicity of the algorithm and its demonstrably improved performance make the approach of this paper an excellent candidate for adaptively controlling tunable parameters of compliant, legged robots.

Cytokine profiling in pulmonary arterial hypertension: the role of redox homeostasis and sex.

Pulmonary arterial hypertension (PAH) is a fatal disease with a well-established sexual dimorphism. Activated inflammatory response and altered redox homeostasis, both known to manifest in a sex-specific manner, are implicated in the pathogenic mechanisms involved in PAH development. This study aimed to evaluate the impact of sex and plasma redox status on circulating cytokine profiles. Plasma oxidation-reduction potential (ORP), as a substitute measure of redox status, was analyzed in male and female Group 1 PAH and healthy subjects. The profiles of 27 circulating cytokines were compared in 2 PAH groups exhibiting the highest and lowest quartile for plasma ORP, correlated with clinical parameters, and used to predict patient survival. The analysis of the PAH groups with the highest and lowest ORP revealed a correlation between elevated cytokine levels and increased oxidative stress in females. In contrast, in males, cytokine expressions were increased in the lower oxidative environment (except for IL-1b). Correlations of the increased cytokine expressions with PAH severity were highly sex-dependent and corresponded to the increase in PAH severity in males and less severe PAH in females. Machine learning algorithms trained on the combined cytokine and redox profiles allowed the prediction of PAH mortality with 80% accuracy. We conclude that the profile of circulating cytokines in PAH patients is redox- and sex-dependent, suggesting the vital need to stratify the patient cohort subjected to anti-inflammatory therapies. Combined cytokine and/or redox profiling showed promising value for predicting the patients' survival.

Limited utility of plasma elafin as a biomarker for skin graft-versus-host disease following allogeneic stem cell transplantation.

BACKGROUND: Acute cutaneous graft-versus-host disease (acGVHD) following haematopoietic stem cell transplant (HSCT) is common but difficult to distinguish from other causes of rash. Plasma elafin has been proposed as a diagnostic and prognostic biomarker of skin GVHD. AIM: To evaluate the role of plasma elafin as a biomarker in acGVHD in an Indian population. METHODS: Plasma elafin was evaluated in a prospective study of HSCT recipients, conducted over 2 years, taking measurements at baseline and at onset of skin rash after HSCT. Patients were categorized into those with GVHD rash, those with non-GVHD rash and those with no rash and the three groups were compared. RESULTS: Two hundred and sixty-one patients with a median age of 16 years (range 1-61 years) and a male predominance (175 : 86 M/F) underwent HSCT during the study period: 56 patients in the GVHD group, 49 in the non-GVHD group and 156 in the no-rash group. The median baseline elafin was similar in all three groups. At the onset of rash, median elafin level was similar between GVHD and non-GVHD rash (34 549 vs. 32 077 pg/mL; P = 0.58) and between GVHD and no rash (34 549 vs. 26 197 pg/mL; P = 0.08). A rise in elafin from baseline was significantly different between GVHD and no rash (P < 0.001) but not between GVHD and non-GVHD rash (P = 0.44). CONCLUSION: The utility of plasma elafin as a biomarker of skin GVHD is very limited. Plasma elafin, although elevated in cutaneous GVHD, is not helpful in distinguishing between GVHD rash and other causes of rash following HSCT.

Shared Prosthetic Control Based on Multiple Movement Intent Decoders.

SIGNIFICANCE: A number of movement intent decoders exist in the literature that typically differ in the algorithms used and the nature of the outputs generated. Each approach comes with its own advantages and disadvantages. Combining the estimates of multiple algorithms may have better performance than any of the individual methods. OBJECTIVE: This paper presents and evaluates a shared controller framework for prosthetic limbs based on multiple decoders of volitional movement intent. METHODS: An algorithm to combine multiple estimates to control the prosthesis is developed in this paper. The capabilities of the approach are validated using a system that combines a Kalman filter-based decoder with a multilayer perceptron classifier-based decoder. The shared controller's performance is validated in online experiments where a virtual limb is controlled in real-time by amputee and intact-arm subjects. During the testing phase subjects controlled a virtual hand in real time to move digits to instructed positions using either a Kalman filter decoder, a multilayer perceptron decoder, or a linear combination of the two. RESULTS: The shared controller results in statistically significant improvements over the component decoders. Specifically, certain degrees of shared control result in increases in the time-in-target metric and decreases in unintended movements. CONCLUSION: The shared controller of this paper combines the good qualities of component decoders tested in this paper. Herein, combining a Kalman filter decoder with a classifier-based decoder inherits the flexibility of the Kalman filter decoder and the limited unwanted movements from the classifier-based decoder, resulting in a system that may be able to perform the tasks of everyday life more naturally and reliably.

Single Mutation in the NFU1 Gene Metabolically Reprograms Pulmonary Artery Smooth Muscle Cells.

OBJECTIVE: NFU1 is a mitochondrial iron-sulfur scaffold protein, involved in iron-sulfur assembly and transfer to complex II and LAS (lipoic acid synthase). Patients with the point mutation NFU1G208C and CRISPR/CAS9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9)-generated rats develop mitochondrial dysfunction leading to pulmonary arterial hypertension. However, the mechanistic understanding of pulmonary vascular proliferation due to a single mutation in NFU1 remains unresolved. Approach and Results: Quantitative proteomics of isolated mitochondria showed the entire phenotypic transformation of NFU1G206C rats with a disturbed mitochondrial proteomic landscape, involving significant changes in the expression of 208 mitochondrial proteins. The NFU1 mutation deranged the expression pattern of electron transport proteins, resulting in a significant decrease in mitochondrial respiration. Reduced reliance on mitochondrial respiration amplified glycolysis in pulmonary artery smooth muscle cell (PASMC) and activated GPD (glycerol-3-phosphate dehydrogenase), linking glycolysis to oxidative phosphorylation and lipid metabolism. Decreased PDH (pyruvate dehydrogenase) activity due to the lipoic acid shortage is compensated by increased fatty acid metabolism and oxidation. PASMC became dependent on extracellular fatty acid sources due to upregulated transporters such as CD36 (cluster of differentiation 36) and CPT (carnitine palmitoyltransferase)-1. Finally, the NFU1 mutation produced a dysregulated antioxidant system in the mitochondria, leading to increased reactive oxygen species levels. PASMC from NFU1 rats showed apoptosis resistance, increased anaplerosis, and attained a highly proliferative phenotype. Attenuation of mitochondrial reactive oxygen species by mitochondrial-targeted antioxidant significantly decreased PASMC proliferation. CONCLUSIONS: The alteration in iron-sulfur metabolism completely transforms the proteomic landscape of the mitochondria, leading toward metabolic plasticity and redistribution of energy sources to the acquisition of a proliferative phenotype by the PASMC.

Compensation of Temperature Effects on Lamb Waves Using Mode Decomposition and a Nonlinear Model.

Active Lamb-wave-based structural health monitoring techniques have been widely studied to inspect large structures using permanently installed arrays of sensors and actuators. Most of these methods depend on comparing baseline signals recorded from the structure before going into service and test signals acquired during inspection. Temperature changes affect the propagation of the wave in a nonlinear and mode-dependent manner. As a result, baseline comparison methods fail when the test and baseline signals are acquired at vastly different temperatures. Approximate methods that compensate for the effects of temperature on the waves using signal stretch models have been introduced in the literature. These methods are effective when the temperature changes are small and the propagation distances are short. However, they perform poorly when these conditions are not satisfied. Consequently, there is a need for better temperature compensation algorithms than presently available. This article presents a data-driven approach that separately compensates for the effects of temperature on different mode components of the sensor signals. The performance of the temperature compensation algorithm of this article is compared with that of a commonly used baseline signal stretch (BSS) algorithm using experimental signals measured from an aluminum panel and a unidirectional composite panel. Analysis results indicate that the method of this article outperforms the BSS algorithm for large temperature differences. The usefulness of the temperature compensation algorithm is further validated by demonstrating the ability of compensated signals to accurately reconstruct anomaly maps associated with damaged composite structures.

A Nonlinear Latching Filter to Remove Jitter From Movement Estimates for Prostheses.

Continuous movement intent decoders are critical for precise control of hand and wrist prostheses. Noise in biological signals (e.g., myoelectric or neural signals) can lead to undesirable jitter in the output of these types of decoders. A low-pass filter (LPF) at the output of the decoder effectively reduces jitter, but also substantially slows intended movements. This paper introduces an alternative, the latching filter (LF), a recursive, nonlinear filter that provides smoothing of small-amplitude jitter but allows quick changes to its output in response to large input changes. The performance of a Kalman filter (KF) decoder smoothed with an LF is compared with that of both an KF decoder without an additional smoother and a KF decoder smoothed with a LPF. These three algorithms were tested in real-time on target holding and target reaching tasks using surface electromyographic signals recorded from 5 non-amputee subjects, and intramuscular electromyographic and peripheral neural signals recorded from an amputee subject. When compared with the LPF, the LF provided a statistically significant improvement in amputee and non-amputee subjects' ability to hold the hand steady at requested positions and achieve movement goals faster. The KF decoder with LF provided a statistically significant improvement in all subjects' ability to hold the prosthetic hand steady, with only slightly lower speeds, when compared to the unsmoothed KF.

Necrosis-Released HMGB1 (High Mobility Group Box 1) in the Progressive Pulmonary Arterial Hypertension Associated With Male Sex.

Damage-associated molecular patterns, such as HMGB1 (high mobility group box 1), play a well-recognized role in the development of pulmonary arterial hypertension (PAH), a progressive fatal disease of the pulmonary vasculature. However, the contribution of the particular type of vascular cells, type of cell death, or the form of released HMGB1 in PAH remains unclear. Moreover, although male patients with PAH show a higher level of circulating HMGB1, its involvement in the severe PAH phenotype reported in males is unknown. In this study, we aimed to investigate the sources and active forms of HMGB1 released from damaged vascular cells and their contribution to the progressive type of PAH in males. Our results showed that HMGB1 is released by either pulmonary artery human endothelial cells or human pulmonary artery smooth muscle cells that underwent necrotic cell death, although only human pulmonary artery smooth muscle cells produce HMGB1 during apoptosis. Moreover, only human pulmonary artery smooth muscle cell death induced a release of dimeric HMGB1, found to be mitochondrial reactive oxygen species dependent, and TLR4 (toll-like receptor 4) activation. The modified Sugen/Hypoxia rat model replicates the human sexual dimorphism in PAH severity (right ventricle systolic pressure in males versus females 54.7±2.3 versus 44.6±2 mm Hg). By using this model, we confirmed that necroptosis and necrosis are the primary sources of circulating HMGB1 in the male rats, although only necrosis increased circulation of HMGB1 dimers. Attenuation of necrosis but not apoptosis or necroptosis prevented TLR4 activation in males and blunted the sex differences in PAH severity. We conclude that necrosis, through the release of HMGB1 dimers, predisposes males to a progressive form of PAH.

Deep Learning Movement Intent Decoders Trained With Dataset Aggregation for Prosthetic Limb Control.

SIGNIFICANCE: The performance of traditional approaches to decoding movement intent from electromyograms (EMGs) and other biological signals commonly degrade over time. Furthermore, conventional algorithms for training neural network based decoders may not perform well outside the domain of the state transitions observed during training. The work presented in this paper mitigates both these problems, resulting in an approach that has the potential to substantially improve the quality of life of the people with limb loss. OBJECTIVE: This paper presents and evaluates the performance of four decoding methods for volitional movement intent from intramuscular EMG signals. METHODS: The decoders are trained using the dataset aggregation (DAgger) algorithm, in which the training dataset is augmented during each training iteration based on the decoded estimates from previous iterations. Four competing decoding methods, namely polynomial Kalman filters (KFs), multilayer perceptron (MLP) networks, convolutional neural networks (CNN), and long short-term memory (LSTM) networks, were developed. The performances of the four decoding methods were evaluated using EMG datasets recorded from two human volunteers with transradial amputation. Short-term analyses, in which the training and cross-validation data came from the same dataset, and long-term analyses, in which the training and testing were done in different datasets, were performed. RESULTS: Short-term analyses of the decoders demonstrated that CNN and MLP decoders performed significantly better than KF and LSTM decoders, showing an improvement of up to 60% in the normalized mean-square decoding error in cross-validation tests. Long-term analyses indicated that the CNN, MLP, and LSTM decoders performed significantly better than a KF-based decoder at most analyzed cases of temporal separations (0-150 days) between the acquisition of the training and testing datasets. CONCLUSION: The short-term and long-term performances of MLP- and CNN-based decoders trained with DAgger demonstrated their potential to provide more accurate and naturalistic control of prosthetic hands than alternate approaches.

Lamb Wave Mode Decomposition Based on Cross-Wigner-Ville Distribution and Its Application to Anomaly Imaging for Structural Health Monitoring.

Lamb waves are characterized by their multimodal and dispersive propagation, which often complicates analysis. This paper presents a method for separation of the mode components and reflected components in sensor signals in an active structural health monitoring (SHM) system. The system is trained using linear chirp signals but works for arbitrary excitation signals. The training process employs the cross-Wigner-Ville distribution (xWVD) of the excitation signal and the sensor signal to separate the temporally overlapped modes in the time-frequency domain. The mode decomposition method uses a ridge extraction algorithm to separate each signal component in the time-frequency distribution. Once the individual modes are separated in the time-frequency domain, they are reconstructed in the time domain using the inverse xWVD operation. The propagation impulse response associated with each component can be directly estimated for chirp inputs. The estimated propagation impulse response can be used to separate the modes resulting from arbitrary excitation signals as long as their frequency components fall in the range of the chirp signal. The usefulness of the mode decomposition algorithm is demonstrated on a new health monitoring system for composite structures. This system performs anomaly imaging using the first arriving mode extracted from sensor array signals acquired from the structure. The anomaly maps are computed using a sparse tomographic reconstruction algorithm. The reconstructed map can locate anomalies on the structure and estimate their boundaries. Comparisons with methods that do not employ mode decomposition and/or sparse reconstruction techniques indicate a substantially better performance for the method of this paper.

Utility of tissue elafin as an immunohistochemical marker for diagnosis of acute skin graft-versus-host disease: a pilot study.

BACKGROUND: The skin is the most common organ involved in acute graft-versus-host disease (GvHD). Because histopathology has limited utility in ruling out clinical mimics of acute skin GvHD, more accurate diagnostic techniques are required. AIM: To evaluate the utility of elafin expression in skin by immunohistochemistry (IHC) for accurate diagnosis of acute skin GvHD. METHODS: Consecutive allogeneic haematopoietic stem cell transplant (HSCT) recipients during a 6-month period who developed rash within the first 100 days post-transplant were recruited. Skin biopsies were taken on the day the rash developed. IHC for epidermal elafin was performed and interpreted by a pathologist blinded to the histopathological diagnosis. Staining of ≥ 50% of epidermis was considered positive. Final diagnosis of the rash was assigned using clinical features supported by histopathology. The accuracy of elafin IHC in predicting the final diagnosis of acute GvHD was evaluated. RESULTS: In total, 23 patients (20 male, 3 female; median age 16 years, range 3-53 years) with 27 episodes of skin rash were recruited. Skin rash post-HSCT occurred at a median of 20 days (range 5-45 days). A diagnosis of GvHD was made in 16 episodes (59.26%) while the remaining 11 episodes (40.74%) were judged to be non-GvHD rash. Elafin IHC was positive in all patients with GvHD. Of the 11 episodes of non-GvHD rash, elafin was negative in 8. Thus, the sensitivity and specificity of elafin IHC for predicting acute skin GvHD was 100% and 75%, respectively. CONCLUSION: Tissue elafin is a useful immunohistochemical marker for acute skin GvHD. However, larger studies are needed to validate these results.

Correction: Population pharmacokinetics of fludarabine in patients with aplastic anemia and Fanconi anemia undergoing allogeneic hematopoietic stem cell transplantation.

This article was originally published under a CC BY-NC-ND 4.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the article have been modified accordingly.

Long-term outcome of mixed chimerism after stem cell transplantation for thalassemia major conditioned with busulfan and cyclophosphamide.

Mixed chimerism (MC) occurs frequently after allogeneic hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) and may be associated with rejection. We report the outcome of MC in 132 TM patients conditioned with Busulphan/Cyclophosphamide, who had successful engraftment and had ⩾1 year follow-up. Chimerism was first assessed at day +28, then every 3-9 months or more frequently if there was MC. If rejection was suspected, immunosuppression was stopped and donor-lymphocyte infusion (DLI) was given if there was no response. Among 132 patients, aged 7 years (range: 2-24), 46/132 (34.8%) had MC in the first year, 32/46 (69.6%) at day +28 and another 14 (30%) between day +28 and 1 year post HSCT. MC was quantified at level 1 (residual host chimerism (RHC) <10%) in 20 (43.5%), level II (RHC 10-25%) in 14 (30.4%) and level III (RHC >25%) in 12 (26.1%). On tapering immunosuppression, 15 (32.6%) developed acute GvHD and 8 (17.4%) had chronic GvHD with reversal to complete chimerism (CC). DLI was administered to 5/46 (10.9%), 1 evolved to CC but 4 rejected the graft. At median follow-up of 60 months (range: 16-172), 20/46 (43.5%) had CC, 18/46 (39.1%) had persistent MC with hemoglobin of 11.5 g/dL (range: 8.4-13.6), whereas 8 (17.4%) rejected the graft. Close monitoring and early intervention is needed with increasing recipient chimerism. Novel strategies are required for preventing graft rejection.

Systolic blood pressure variability in patients with early severe sepsis or septic shock: a prospective cohort study.

BACKGROUND: Severe sepsis and septic shock are often lethal syndromes, in which the autonomic nervous system may fail to maintain adequate blood pressure. Heart rate variability has been associated with outcomes in sepsis. Whether systolic blood pressure (SBP) variability is associated with clinical outcomes in septic patients is unknown. The propose of this study is to determine whether variability in SBP correlates with vasopressor independence and mortality among septic patients. METHODS: We prospectively studied patients with severe sepsis or septic shock, admitted to an intensive care unit (ICU) with an arterial catheter. We analyzed SBP variability on the first 5-min window immediately following ICU admission. We performed principal component analysis of multidimensional complexity, and used the first principal component (PC1) as input for Firth logistic regression, controlling for mean systolic pressure (SBP) in the primary analyses, and Acute Physiology and Chronic Health Evaluation (APACHE) II score or NEE dose in the ancillary analyses. Prespecified outcomes were vasopressor independence at 24 h (primary), and 28-day mortality (secondary). RESULTS: We studied 51 patients, 51% of whom achieved vasopressor independence at 24 h. Ten percent died at 28 days. PC1 represented 26% of the variance in complexity measures. PC1 was not associated with vasopressor independence on Firth logistic regression (OR 1.04; 95% CI: 0.93-1.16; p = 0.54), but was associated with 28-day mortality (OR 1.16, 95% CI: 1.01-1.35, p = 0.040). CONCLUSIONS: Early SBP variability appears to be associated with 28-day mortality in patients with severe sepsis and septic shock.

Population pharmacokinetics of fludarabine in patients with aplastic anemia and Fanconi anemia undergoing allogeneic hematopoietic stem cell transplantation.

Although hematopoietic stem cell transplantation (HSCT) with a conditioning regimen consisting of fludarabine (F-araA) and cyclophosphamide (Cy) is associated with improved outcome in young patients with aplastic anemia (AA) and Fanconi anemia (FA), several factors limit the success of the procedure. We evaluated the population pharmacokinetics (POPPK) of F-araA and its influence on HSCT outcome in patients (n=53) with AA and FA undergoing HSCT. Patients carrying a 5'-UTR polymorphism in NT5E gene (rs2295890 G>C) exhibited significantly lower plasma F-araA clearance compared to those with wild-type genotype (7.12 vs 5.03 L/h/m2 (29%) P<0.05). F-araA clearance was significantly higher in patients with AA compared to FA (2.46 ×, P<1e-6). Of all the outcome parameters evaluated (engraftment, rejection/graft failure, GvHD, TRM, OS), high F-araA AUC (>29.4 µm*h) was the only significant factor associated with the development of aGvHD by both univariate and multivariate analysis (P=0.02). The influence of plasma F-araA levels need to be evaluated in a larger cohort of patients to propose the need for therapeutic drug monitoring.

Attenuation of arsenic trioxide induced cardiotoxicity through flaxseed oil in experimental rats.

OBJECTIVES: Arsenic trioxide (As2O3) is a potent drug for acute promyelocytic leukaemia, but its clinical trials are allied with some serious adverse events mainly cardiac functional abnormalities. So the objective of our investigation is to identify the cardioprotective action of flaxseed oil (FSO), a natural compound against As2O3 induced cardiotoxicity. METHODS: Male wistar rats were treated with As2O3 (4 mg/kg) to induce cardiotoxicity. FSO (250 and 500 mg/kg) was given in combination with As2O3 for evaluating its cardioprotective efficacy. RESULTS: Treatment with As2O3 resulted in deposition of arsenic in heart tissue, increased cardiac marker enzymes release, lipid peroxidation (LPO), oxidative insults and pathological damages in the heart. Co-treatment with FSO (500 mg/kg) significantly reduced the arsenic accumulation, cardiac marker enzymes, LPO and cardiac structural alterations. FSO treatment significantly improved cardiac glutathione content, antioxidant enzymes and reduced the pathological damages in cardiac tissue. Gas chromatographic-mass spectrometry analysis revealed that the major fatty acid content in the FSO is alpha-linolenic acid, which has a strong milieu in cardiac health. CONCLUSION: The results of the current investigation suggested that FSO is an effective agent in reducing arsenic-induced cardiac toxicity and can be used as an adjunct/dietary supplement for the cancer patients on As2O3 therapy.

Polyphenol rich ethanolic extract from Boerhavia diffusa L. mitigates angiotensin II induced cardiac hypertrophy and fibrosis in rats.

Boerhavia diffusa is a renowned edible medicinal plant extensively used against different ailments including heart diseases in the traditional system of medicine in several countries. The present study aims to evaluate the therapeutic efficacy of ethanolic extract of Boerhavia diffusa (BDE) on cardiac hypertrophy and fibrosis induced by angiotensin II (Ang II) in male wistar rats and to identify the active components present in it. A substantial increase of hypertrophy markers such as cardiac mass index, concentration of ANP and BNP, cardiac injury markers like CK-MB, LDH and SGOT, has been observed in hypertrophied groups whereas BDE treatment attenuated these changes when compared to hypertrophied rats. Moreover, Ang II induced myocardial oxidative stress was reduced by BDE which was apparent from diminished level of lipid and protein oxidation products, increased activities of membrane bound ATPases and endogenous antioxidant enzymes along with enhanced translocation of Nrf2 from the cytosol to nucleus. It appears that BDE evokes its antioxidant effects by attenuating lipid peroxidation, enhancing the translocation of Nrf2 from the cytoplasm to nucleus as well as by regulating the metabolism of glutathione. The extent of fibrosis during cardiac hypertrophy was determined by histopathology analysis and the results revealed that BDE treatment considerably reduced the fibrosis in the heart. HPLC analysis of BDE leads to the identification of four compounds viz., quercetin, kaempferol, boeravinone B and caffeic acid. The study substantiate the effect of B. diffusa in protecting the heart from pathological hypertrophy and the attenuation of cardiac abnormalities may be partly attributed through the reduction of oxidative stress and cardiac fibrosis. Since the plant is widely used as a green leafy vegetable, incorporation of this plant in diet may be an alternative way for the prevention and better management of heart diseases and associated complications.

Omega-3 Fatty Acid Protects Against Arsenic Trioxide-Induced Cardiotoxicity In Vitro and In Vivo.

Arsenic trioxide (As2O3) is a highly effective therapeutic against acute promyelocytic leukaemia, but its clinical efficacy is burdened by serious cardiac toxicity. The present study was performed to evaluate the effect of omega (ω)-3 fatty acid on As2O3-induced cardiac toxicity in in vivo and in vitro settings. In in vivo experiments, male Wistar rats were orally administered with As2O3 4 mg/kg body weight for a period of 45 days and cardiotoxicity was assessed. As2O3 significantly increased the tissue arsenic deposition, micronuclei frequency and creatine kinase (CK)-MB activity. There were a rise in lipid peroxidation and a decline in reduced glutathione, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase in heart tissue of arsenic-administered rats. The cardioprotective role of ω-3 fatty acid was assessed by combination treatment with As2O3. ω-3 fatty acid co-administration with As2O3 significantly alleviated these changes. In in vitro study using H9c2 cardiomyocytes, As2O3 treatment induced alterations in cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, cellular calcium levels and mitochondrial membrane potential (∆Ψm). ω-3 fatty acid co-treatment significantly increased cardiomyocyte viability, reduced LDH release, lipid peroxidation and intracellular calcium concentration and improved the ∆Ψm. These findings suggested that the ω-3 fatty acid has the potential to protect against As2O3-induced cardiotoxicity.