Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity

Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin's lymphoma (NHL) may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP) as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP), not exceeding the total allowed dose of doxorubicin (500 mg/m2). Ten healthy controls were included in our study. Human heart-type fatty acid-binding protein (H-FABP) was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF) of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients

A probabilistic multi-objective approach for FACTS devices allocation with different levels of wind penetration under uncertainties and load correlation

This study presents a probabilistic multi-objective optimization approach to obtain the optimal locations and sizes of static var compensator (SVC) and thyristor-controlled series capacitor (TCSC) in a power transmission network with large level of wind generation. In this study, the uncertainties of the wind power generation and correlated load demand are considered. The uncertainties are modeled in this work using the points estimation method (PEM). The optimization problem is solved using the Multi-objective particle swarm optimization (MOPSO) algorithm to find the best position and rating of the flexible AC transmission system (FACTS) devices. The objective of the problem is to maximize the system loadability while minimizing the power losses and FACTS devices installation cost. Additionally, a technique based on fuzzy decision-making approach is employed to extract one of the Pareto optimal solutions as the best compromise one. The proposed approach is applied on the modified IEEE 30-bus system. The numerical results evince the effectiveness of the proposed approach and shows the economic benefits that can be achieved when considering the FACTS controller

Novel Li3ClO based glasses with superionic properties for lithium batteries

Three types of next generation batteries are currently being envisaged among the international community: metal-air batteries, multivalent cation batteries and all-solid-state batteries. These battery designs require high-performance, safe and cost effective electrolytes that are compatible with optimized electrode materials. Solid electrolytes have not yet been extensively employed in commercial batteries as they suffer from poor ionic conduction at acceptable temperatures and insufficient stability with respect to lithium-metal. Here we show a novel type of glasses, which evolve from an antiperovskite structure and that show the highest ionic conductivity ever reported for the Li-ion (25 mS cm-1 at 25 °C). These glassy electrolytes for lithium batteries are inexpensive, light, recyclable, non-flammable and non-toxic. Moreover, they present a wide electrochemical window (higher than 8 V) and thermal stability within the application range of temperatures

Tetralogy of Fallot: Imaging of common and uncommon associations by multidetector CT

AbstractPurposeTo demonstrate the superior role of multidetector computed tomography (MDCT) in delineation of the extracardiac vascular abnormalities including the pulmonary arterial tree, major aortopulmonary collateral arteries (MAPCAs), patent ductus arteriosus (PDA), and also the detection of the common and uncommon findings in Fallot Tetralogy cases for proper pre-surgical evaluation.Material and methodsA retrospective study of all multidetector CT images acquired to evaluate suspected cases of Tetralogy of Fallot sent by their respective referring physicians between April 2009 and August 2010. A total of 23 cases were included in this study. MDCT protocol, image analysis and calculations used in the diagnosis are explained in detail.ResultsDetailed explanation of the MDCT imaging findings in the 23 cases with Tetralogy of Fallot, as well as the common and uncommon associations of the disease, namely pulmonary atresia, MAPCAs, PDAs, atrial septal defects (ASDs), right sided aortic arch, and a few less common associations.ConclusionA customized approach to MDCT imaging improves the diagnostic accuracy and reduces unneeded prolongation of the study and sedation times. A careful preoperative perceptive of the complex cardiovascular anatomy in patients with Tetralogy of Fallot aids in exposing the patient to a directed and prepared surgical approach

Acacia senegal gum exudate offers protection against cyclophosphamide-induced urinary bladder cytotoxicity

Cylophosphamide (CYCL) is a strong anticancer and immunosuppressive agent but its urotoxicity presents one of the major toxic effects that limit its wide usage particularly in high dose regimens. Therefore, this study aimed to investigate Acacia Senegal gum exudate, Gum Arabic (GA), for its possible role as a natural, nontoxic agent against CYCL-induced urotoxicity. Male Swiss albino rats were exposed to CYCL (150 mg/kg BW, once i.p) with or without GA oral supplementation (7.5 g/kg/day for 6 days) through drinking water. Glutathione (GSH), Malondialdehyde (MDA) and Nitric oxide (NO) bladder contents were assessed. Responsiveness of the bladder rings to acetylcholine (ACh) in vitro, microscopic and macroscopic features are also investigated. CYCL produced pronounced harmful effects on bladder urothelial lining with significant increases in (MDA) and NO levels in the tissue homogenates. Bladder-GSH content is dropped by over 60% following CYCL injection. Bladder contractility, as measured by its responsiveness to ACh, recorded a marked reduction. The isolated bladders exhibited such macroscopic changes as severe edema, inflammation and extravasation. The bladder weight increased as well. Histological changes were evident in the form of severe congestion, petechial hemorrhage and chronic inflammatory reaction in the lamina propria accompanied with desquamated epithelia. GA, a potential protective agent, produced an almost complete reversal of NO induction, lipid peroxidation or cellular GSH bladder contents in the GA + CYCL-treated group. Likewise, bladder inflammation and edema were reduced. Bladder rings showed a remarkable recovery in their responsiveness to ACh. Bladder histological examination showed a near normal configuration and structural integrity, with a significant reduction in inflammation and disappearance of focal erosions. These remarkable effects of GA may be attributed to its ability to neutralize acrolein, the reactive metabolite of CYCL and/or the resultant reactive oxygen metabolites, through a scavenging action. GA may limit the cascading events of CYCL-induced damage, initiating a cytoprotective effect leading to structural and functional recovery of the bladder tissues

High-throughput sensing microtiter plate for determination of biogenic amines in seafood using fluorescence or eye-vision

A new optical sensing microplate was developed for rapid screening for the presence of biogenic amines (BAs) in seafood samples with high sensitivity. The deposition of a sensing spot (containing a chameleon dye (Py-1) in a polymeric cocktail) on the bottom of the wells of a standard microplate renders the plate a new sensing tool for a rapid and parallel detection of up to 96 (real) samples. This sensing microplate enables (1) a semi-quantitative readout of analyte concentration by eye-vision, (2) a rapid fluorescence readout of 96 samples with standard instrumentation in less than two minutes (unlike chromatographic and electrophoretic methods), (3) a statistically robust data evaluation (with 8–12 replicates) and (4) a rapid parallel sample preparation with standard 8 or 12-channel micropipettes. On reaction with biogenic amines, the dye shows a significant visible color change from blue over green to red color. The appearance of red color favorably coincides with the concentration of BAs that can induce symptoms of poisoning. The linear ranges of fluorescence calibration data for six biogenic amines cover the clinical toxicological relevant range of BAs that is too low to be detected by the human nose. The LODs range from 0.16 to 0.56 μg mL−1, with correlation coefficients (r2) between 0.985 and 0.999. Finally, the evolution of spoilage of four fish samples (monitored by determination of their BA status) and the increase of their total amine content were found to agree well with previous data on time-dependent evolution of BAs in fish

Development, validation, and proof-of-concept implementation of a two-year risk prediction model for undiagnosed atrial fibrillation using common electronic health data (UNAFIED)

Background: Many patients with atrial fibrillation (AF) remain undiagnosed despite availability of interventions to reduce stroke risk. Predictive models to date are limited by data requirements and theoretical usage. We aimed to develop a model for predicting the 2-year probability of AF diagnosis and implement it as proof-of-concept (POC) in a production electronic health record (EHR). Methods: We used a nested case-control design using data from the Indiana Network for Patient Care. The development cohort came from 2016 to 2017 (outcome period) and 2014 to 2015 (baseline). A separate validation cohort used outcome and baseline periods shifted 2 years before respective development cohort times. Machine learning approaches were used to build predictive model. Patients ≥ 18 years, later restricted to age ≥ 40 years, with at least two encounters and no AF during baseline, were included. In the 6-week EHR prospective pilot, the model was silently implemented in the production system at a large safety-net urban hospital. Three new and two previous logistic regression models were evaluated using receiver-operating characteristics. Number, characteristics, and CHA2DS2-VASc scores of patients identified by the model in the pilot are presented. Results: After restricting age to ≥ 40 years, 31,474 AF cases (mean age, 71.5 years; female 49%) and 22,078 controls (mean age, 59.5 years; female 61%) comprised the development cohort. A 10-variable model using age, acute heart disease, albumin, body mass index, chronic obstructive pulmonary disease, gender, heart failure, insurance, kidney disease, and shock yielded the best performance (C-statistic, 0.80 [95% CI 0.79-0.80]). The model performed well in the validation cohort (C-statistic, 0.81 [95% CI 0.8-0.81]). In the EHR pilot, 7916/22,272 (35.5%; mean age, 66 years; female 50%) were identified as higher risk for AF; 5582 (70%) had CHA2DS2-VASc score ≥ 2. Conclusions: Using variables commonly available in the EHR, we created a predictive model to identify 2-year risk of developing AF in those previously without diagnosed AF. Successful POC implementation of the model in an EHR provided a practical strategy to identify patients who may benefit from interventions to reduce their stroke risk