• Hypercholesterolemia causes endothelial and myocardial dysfunction, as well as aggravates ischemia/reperfusion (I/R)-induced myocardial injury. (nih.gov)
  • ischemia/reperfusion injury (I/R injury). (nih.gov)
  • Cardiac ischemia-reperfusion injury (IRI) occurs intra-operatively during heart transplantation (HTx), underpinning graft survival. (uwo.ca)
  • Cardiac ischemia-reperfusion injury (IRI) occurs when transplanting a heart from donor to recipient. (uwo.ca)
  • Despite the complexpathophysiology of ischemia, hypoxia alone is a sufficient stimulus to induce a variety of adaptive responsesthat protect against ischemia-reperfusion injury. (grantome.com)
  • Aim 1 will investigate the mechanisms by which EPO protects the heart from injury following ischemiaand reperfusion. (grantome.com)
  • Exercise protects cardiac mitochondria against ischemia-reperfusion injury. (musc.edu)
  • While PCAS has a unique cause and consequences, it can ultimately be thought of as type of global ischemia-reperfusion injury. (wikipedia.org)
  • This reperfusion results in inflammatory injury through three overlapping mechanisms. (wikipedia.org)
  • Unlike other causes of ischemia-reperfusion injury, such as organ transplants, PCAS results from global ischemia-reperfusion and subsequently has global organ damage. (wikipedia.org)
  • The symptoms of PCAS are related to the effect of ischemia-reperfusion injury on individual systems, though there is significant co-morbidity between all organs' responses. (wikipedia.org)
  • As a result, any amount of brain ischemia, especially when it is prolonged in cases of cardiac arrest, typically results in brain injury. (wikipedia.org)
  • For out-of-hospital cardiac arrest, brain injury is the cause of death in most patients who undergo ROSC but ultimately die. (wikipedia.org)
  • Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion injury remains incomplete. (elifesciences.org)
  • Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodelling without influencing infarct size. (elifesciences.org)
  • In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodelling, while recruited macrophages determine infarct size after I/R injury. (elifesciences.org)
  • Preconditioning with sevoflurane (SEV) may drive back ischemia-reperfusion injury in a number of organs, however, the advantages of SEV against acute lung injury (ALI), induced by intestinal ischemia-reperfusion (IIR), as well as the root mechanisms remain to become elucidated. (researchdataservice.com)
  • Preconditioning with SEV continues to be demonstrated to drive back ischemia-reperfusion injury in a variety of organs, especially in the lungs and mind (19,20). (researchdataservice.com)
  • Stem cell-derived cardiac myocytes are potential sources for testing cardiocytoprotective molecules against ischemia/reperfusion injury in vitro. (nih.gov)
  • Cell viability in simulated ischemia/reperfusion (SI/R)-induced injury and a known cardiocytoprotective NO-donor, S-nitroso-n-acetylpenicillamine (SNAP) was tested. (nih.gov)
  • After analysis of full embryoid bodies (EBs) and cardiac marker (VCAM and cardiac troponin I) positive cells of three lines at 6 conditions (32 different conditions altogether), we found significant SI/R injury-induced cell death in both full EBs and VCAM+ cardiac cells at later stage of their differentiation. (nih.gov)
  • Numerous therapies to protect cardiac tissue from reperfusion-induced injury have been explored, and ample pre-clinical research has attempted to identify drugs or techniques to mitigate cardiac damage. (unab.cl)
  • This review provides a current summary of the principal molecules, pathways, and mechanisms underlying cardiomyocyte and cardiac fibroblast crosstalk during ischemia/reperfusion injury. (unab.cl)
  • Hydrogel delivery of purinergic enzymes improves cardiac ischemia/reperfusion injury. (amedeo.com)
  • Aims: The FDA-approved histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA, Vorinostat) has been shown to induce cardiomyocyte autophagy and blunt ischemia/reperfusion (I/R) injury when administered at the time of reperfusion. (wustl.edu)
  • We suggest PTP might efficiently diminish cardiac ischemia/reperfusion-induced apoptosis and autophagy injury. (ntnu.edu.tw)
  • Cardiac function and injury were determined by microcirculation, electrocardiography, and infarct size. (ntnu.edu.tw)
  • Cardiac injury activated ER stress-78-kDa glucose-regulated protein expression, increased the Bax/Bcl-2 ratio, cleaved caspase 3 expression and poly-(ADP-ribose)-polymerase fragments, leading to apoptosis formation, and promoted LC3-II expression, resulting in autophagy formation. (ntnu.edu.tw)
  • Conclusions PTP significantly reduced cardiac ischemia/reperfusion injury by upregulating antioxidant, antiapoptotic, and antiautophagic mechanisms. (ntnu.edu.tw)
  • Chien, CY , Chien, CT & Wang, SS 2014, ' Progressive thermopreconditioning attenuates rat cardiac ischemia/reperfusion injury by mitochondria-mediated antioxidant and antiapoptotic mechanisms ', Journal of Thoracic and Cardiovascular Surgery , 卷 148, 編號 2, 頁 705-713. (ntnu.edu.tw)
  • Whereas mitochondrial ATP synthesis was minimally decreased by Txnip deletion, cellular ATP content and lactate formation were higher in Txnip-KO hearts after ischemia-reperfusion injury. (jci.org)
  • Partial kidney ischemia-reperfusion (IR) injury is the principal cause of acute kidney injury. (hindawi.com)
  • Kidney partial ischemia-reperfusion (IR) injury is defined as a reduction of the renal blood flow (RBF) followed by the recovery of RBF and reoxygenation [ 1 ]. (hindawi.com)
  • IPC is described as short, transient, and nonlethal ischemia periods and subsequent reperfusion which is performed before IR injury and can protect the kidney against long-term ischemia [ 6 - 8 ]. (hindawi.com)
  • Reperfusion injury refers to the tissue damage inflicted when blood flow is restored after an ischemic period of more than about ten minutes. (benbest.com)
  • Cryonics patients frequently experience ischemic & reperfusion injury between the time when the heart stops and cryostorage begins. (benbest.com)
  • In this article I attempt to evaluate the nature & extent of ischemic & reperfusion injury -- primarily focused on the impact for cryonics (although certainly relevant to stroke and cardiac arrest). (benbest.com)
  • I focus my attention on ischemic/reperfusion injury to the brain. (benbest.com)
  • Cardiopulmonary bypass (CPB) causes systemic inflammatory response and ischemia-reperfusion (IR) injury. (hindawi.com)
  • To investigate the effect and mechanism of simvastatin on myocardial injury in cardiac valve surgery with CPB. (hindawi.com)
  • However, CPB inevitably causes systemic inflammatory response and ischemia-reperfusion (IR) injury, which can negatively affect postoperative cardiac function and a patient's long-term prognosis [ 1 ]. (hindawi.com)
  • Recent clinical studies have reported that using statins during the perioperative period can limit inflammation and oxidation, reduce cardiac muscle injury, and improve the patient's prognosis [ 2 - 4 ], but the dosage, duration, effects, and mechanisms associated with these outcomes are not clear. (hindawi.com)
  • IR injury and inflammatory response can substantially activate cell autophagy [ 6 ], and autophagy has been demonstrated to play an important role in the pathologic process of cardiac muscle injury [ 7 ]. (hindawi.com)
  • In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients' survival rate. (researchsquare.com)
  • Previous studies have shown that ischemia/reperfusion (I/R) injury acts as a significant role in PGD(4), contributing to adverse short- and long-term clinical outcomes in the recipients. (researchsquare.com)
  • Honors spotlight star, Luca Walborn under the mentorship of Dr. Kolwicz studying "the Effects of the Ketogenic Diet on Cardiac Ischemia-Reperfusion Injury in Mice. (ursinus.edu)
  • The Effects of the Ketogenic Diet on Cardiac Ischemia-Reperfusion Injury in Mice. (ursinus.edu)
  • Once baseline function is achieved, we then we expose the heart to an ischemia-reperfusion injury and study how it performs. (ursinus.edu)
  • The neuroprotective effects of remifentanil preconditioning against cerebral ischemia/reperfusion injury have been recently reported. (springer.com)
  • Here we investigated whether remifentanil postconditioning exerts neuroprotective effects against global cerebral ischemia/reperfusion injury in rats and its potential mechanisms. (springer.com)
  • We found remifentanil postconditioning markedly improved the spatial learning and memory as well as attenuated neuronal apoptosis in hippocampus caused by cerebral ischemia/reperfusion injury. (springer.com)
  • The results suggest that remifentanil postconditioning exhibits neuroprotective effects against global cerebral ischemia/reperfusion injury in rats, and its mechanisms might involve inhibition of neuronal apoptosis through the PI3K pathway. (springer.com)
  • Wang JY, Shen J, Gao Q et al (2008) Ischemic postconditioning protects against global cerebral ischemia/reperfusion-induced injury in rats. (springer.com)
  • Yuan Y, Guo Q, Ye Z et al (2011) Ischemic postconditioning protects brain from ischemia/reperfusion injury by attenuating endoplasmic reticulum stress-induced apoptosis through PI3K-Akt pathway. (springer.com)
  • Abstract Compound Danshen Dripping Pills (CDDPs) have been used in clinical treatment to protect the heart from ischemia / reperfusion (IR) injury for many years. (bvsalud.org)
  • Our findings suggest that empagliflozin enters cardiac mitochondria and directly causes these effects by increasing mitochondrial ATP via inhibition of NHE1 and Nav1.5 or their common downstream sites. (nature.com)
  • Given the central role that mitochondria play during hypoxia, we hypothesized that Txnip deletion would enhance ischemia-reperfusion damage. (jci.org)
  • In humans, 615 distinct teeps o protein hae been identifee'd frae cardiac mitochondria, [16] whauras in rats , 940 proteins hae been reportit. (wikipedia.org)
  • This case shows that potentially lethal arrhythmias can arise during reperfusion and that ventricular fibrillation during reperfusion may be self-terminating. (bmj.com)
  • In conclusion, decreased or increased protein expression of several TRPM4 variants linked to cardiac conduction disorders or ventricular arrhythmias were found to be caused by altered TRPM4 half-life compared to the WT form. (frontiersin.org)
  • The clinician must be aware of these arrhythmias, in addition to reperfusion strategies, and must treat those that require intervention to avoid exacerbation of ischemia and subsequent hemodynamic compromise. (medscape.com)
  • Viability of hiChol adult cardiac myocytes was significantly decreased and superoxide level was increased in normoxia and these changes were further aggravated by SI/R. HiChol combined with hyperglycemia further aggravated cell death, however level of oxidative stress increased only in normoxic condition. (nih.gov)
  • HiChol rat cardiac myocytes showed reduction of cell viability and increased oxidative stress, which were further aggravated by SI/R and with additional hyperglycemia. (nih.gov)
  • However, harmful stimuli (such as ischemia-reperfusion, oxidative stress, and toxic chemicals) can change the direction and efficiency of intercellular mitochondrial transfer. (frontiersin.org)
  • Cardiac myocytes isolated from neonatal or adult rat hearts were cultured in control or in three different hypercholesterolemic media with increasing cholesterol content (hiChol) or hiChol + hyperglycemic medium, respectively. (nih.gov)
  • Cholesterol uptake was tested by Filipin staining in neonatal cardiac myocytes. (nih.gov)
  • Neonatal cardiac myocytes took up cholesterol from the different hiChol media at a concentration-dependent manner. (nih.gov)
  • In normoxia, viability of hiChol neonatal cardiac myocytes was not significantly changed, however, superoxide levels were increased as compared to vehicle. (nih.gov)
  • After SI/R, the viability of hiChol neonatal cardiac myocytes was decreased and total ROS level was increased as compared to vehicle. (nih.gov)
  • This is the first demonstration that the combination of the current hypercholesterolemic medium and SI/R in cardiac myocytes mimics the cardiac pathology of the comorbid heart with I/R and hypercholesterolemia. (nih.gov)
  • Here we performed a systematic analysis of two different induced pluripotent stem cell lines (iPSC 3.4 and 4.1) and an embryonic stem cell (ESC) line-derived cardiac myocytes at two different developmental stages. (nih.gov)
  • management of ST-segment-elevation myocardial infarction (STEMI) patients, and primary percutaneous coronary intervention (PCI) is the preferred reperfusion therapy when first-medical-contact-to-balloon time is within 90 minutes for patients admitted directly to a PCI-capable hospital and 2 hours for patients transferred to a PCI-capable hospital. (cdc.gov)
  • The advent of coronary care units and early reperfusion therapy (lytic or percutaneous coronary intervention) has substantially decreased in-hospital mortality rates and has improved the outcome in survivors of the acute phase of MI. (medscape.com)
  • To estimate the group size, a pilot study was conducted for measuring the serum cardiac troponin T (cTnT) at 6 h after surgery in 10 patients who received statin and placebo treatment (ratio 1 : 1). (hindawi.com)
  • These protective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of serum proinflammatory cytokines (Interleukin-1β, Interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CM group compared with the vehicle group. (researchsquare.com)
  • An integrated cardiac support network incorporating standardised risk stratification, point-of-care troponin testing and cardiologist-supported decision making was progressively implemented in non-metropolitan areas of South Australia from 2001 to 2008. (mja.com.au)
  • the most common one is via an effect on diuresis/natriuresis, but the mechanisms involved in these impressive cardiac benefits are incompletely understood. (nature.com)
  • Despite recent findings regarding the functional implications of TRPM4 in cardiac diseases, the molecular and cellular mechanisms leading to altered conduction are poorly understood. (frontiersin.org)
  • Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. (researchgate.net)
  • We tested the hypothesis that 8-Br is also protective under clinically relevant conditions (regional ischaemia) when applied either before ischemia or at the beginning of reperfusion, and this effect is associated with the mitochondrial permeability transition pore (MPTP). (mdpi.com)
  • Results: No difference in baseline cardiac function was evident until 6 months onwards, where Gunn rats demonstrated aortic dilatation and reduced peak ejection velocities. (edu.au)
  • Results Coronary arterial ischemia/reperfusion depressed cardiac microcirculation, induced ST-segment elevation and increased infarct size in non-PTP and PTP rats. (ntnu.edu.tw)
  • The rats in the IR group underwent 45 min partial kidney ischemia, and the animals in the IPC + IR group underwent two 5 min cycles of partial kidney ischemia followed by 10 min reperfusion and partial kidney ischemia for 45 min. (hindawi.com)
  • This myocardial dysfunction may present as prolonged cardiogenic shock, highly variable blood pressures, reduced cardiac output and/or dysrhythmias. (wikipedia.org)
  • Post-cardiac arrest syndrome (PCAS) is an inflammatory state of pathophysiology that can occur after a patient is resuscitated from a cardiac arrest. (wikipedia.org)
  • While in a state of cardiac arrest, the body experiences a unique state of global ischemia. (wikipedia.org)
  • Before cardiac arrest, the body is in a state of homeostasis. (wikipedia.org)
  • However, during cardiac arrest, the body is in circulatory and pulmonary arrest. (wikipedia.org)
  • If the cause of the cardiac arrest was fundamentally a coronary pathology, then the consequences to the heart may include myocardial infarction complications. (wikipedia.org)
  • A cardiac arrest is the abrupt cessation of normal blood flow circulation due to the failure of the heart to contract effectively during systole . (wikidoc.org)
  • Cardiac arrest is a life-threatening condition and must be treated as such irrespective of the underlying cause. (wikidoc.org)
  • Excessive glutamate release resulting in excessive Ca +2 entry into cells is the excitotoxicity which initiates the brain ischemic damage seen in stroke and cardiac arrest. (benbest.com)
  • MAs may be manifested either in hemodynamic collapse or in cardiac arrest: The sudden loss of effective blood flow due to atrial fibrillation (AF) with rapid VT leads to hemodynamic collapse, and VT and VF result in cardiac arrest necessitating CPR or electric defibrillation. (medscape.com)
  • Cardiac Arrest Cardiac arrest is the cessation of cardiac mechanical activity resulting in the absence of circulating blood flow. (msdmanuals.com)
  • Cardiac arrest stops blood from flowing to vital organs, depriving them of. (msdmanuals.com)
  • Several studies have suggested that empagliflozin improves the cardiac energy state which is a partial cause of its potency. (nature.com)
  • Since PCI can be administered only at PCI-capable hospitals, geographic factors may affect the choice of reperfusion therapy for STEMI patients. (cdc.gov)
  • PCI access site bleeding was the reperfusion strategy for STEMI patients. (cdc.gov)
  • The aim of this study was to test if terminal T-wave inversion (TTWI) at admission ECG (before reperfusion) can serve as a predictor of ventricular fibrillation during reperfusion (rVF) in patients with anterior STEMI undergoing primary PCI. (lu.se)
  • Reperfusion was thought to be responsible for the ventricular fibrillation because the arrhythmia started while the ST segment was returning to the baseline during an episode of silent ischaemia that was probably caused by coronary spasm. (bmj.com)
  • 2] About 90% of patients who have an acute myocardial infarction (AMI) develop some form of cardiac arrhythmia during or immediately after the event. (medscape.com)
  • Electrolyte imbalances (eg, hypokalemia and hypomagnesemia) and hypoxia further contribute to the development of cardiac arrhythmia. (medscape.com)
  • Previous experimental/simulation study suggested a terminal T-wave inversion (TTWI) in ischemia-related ECG leads corresponding to anterior infarct localization as an independent predictor of reperfusion VF (rVF). (lu.se)
  • This augmented adverse remodelling after I/R and led to an increased infarct size and deterioration of cardiac function. (elifesciences.org)
  • For other discussions on myocardial infarction, see Myocardial Infarction, Right Ventricular Infarction, Acute Myocardial Infarct Imaging, and Cardiac Markers. (medscape.com)
  • Apoptosis evaluation showed that CDDPs significantly ameliorated the cardiac apoptosis level after IR. (bvsalud.org)
  • In the heart, cardiomyocytes, fibroblasts, and endothelial cells interact to form the cardiac tissue. (unab.cl)
  • Pathological variants in TRPM4 gene have been linked to several cardiac phenotypes such as complete heart block (CHB), ventricular tachycardia, and Brugada syndrome (BrS). (frontiersin.org)
  • Empagliflozin also enhanced cardiac robustness by maintaining intracellular ATP levels and the recovery capacity in the infarcted area during ischemic-reperfusion. (nature.com)
  • In addition, several studies have demonstrated the beneficial effects of empagliflozin on myocardial infarction (MI) in diabetic animal models 10 , 11 , prompting us to investigate the real-time ATP change in cardiac energy production in an ischemic-reperfusion model of MI. (nature.com)
  • However, few studies have revealed the effects of perioperative oral simvastatin on post-CPB changes in cardiac muscle autophagy or the influence of the degree of autophagy on postoperative cardiac function and prognosis [ 8 , 9 ]. (hindawi.com)
  • The present clinical randomized controlled trial explored the protective effect of perioperative simvastatin on cardiac muscle after CPB and the relationship of such effects to cardiomyocyte autophagy. (hindawi.com)
  • In summary, available evidence from the present meta-analysis suggests that perioperative administration of dexmedetomidine in adult cardiac surgery might reduce the incidence of AKI. (medscape.com)
  • Furthermore, as cardiac IRI results in poor outcomes for the patient, we may be able to use research in this field to help future recipients. (uwo.ca)
  • Pre-hospital transport times and outcomes after different reperfusion strategies for ST-elevation myocardial infarction. (cdc.gov)
  • Third, reperfusion initiates an immune, inflammatory response resulting in the circulation of pro-inflammatory cytokines such as TNFα, IL-6 and IL-8 as well as complement activation (such as TCC and C3bc). (wikipedia.org)
  • The "ischemia" phase of cardiac IRI occurs when the donor heart is being collected and blood/oxygen is not going to the heart. (uwo.ca)
  • The cAMP analogue 8-Br-cAMP-AM (8-Br) confers marked protection against global ischaemia/reperfusion of isolated perfused heart. (mdpi.com)
  • Changes in cardiac energy production play a critical role in the pathophysiology of heart failure. (nature.com)
  • 50% loss of mtDNA content in the border zones of mouse hearts, but SAHA pretreatment and reperfusion treatment alone reverted mtDNA content and mitochondrial mass to control levels. (wustl.edu)
  • Cardiac dysrhythmias can be induced by various triggers. (medscape.com)
  • Identifying the molecules and cellular signal pathways implicated in these processes will be crucial for creating effective tissue-preserving treatments during or after reperfusion. (unab.cl)
  • Taken together, CITED4 expression is necessary for exercise-induced regional remodeling of the heart's microstructural helicity revealing how a key molecular regulator of cardiac remodeling manifests into downstream local tissue-level changes. (researchgate.net)
  • Expression of transcription factor CITED4 is necessary for exercise-induced regional remodeling of the heart's microstructural helicity, revealing how a key molecular regulator of cardiac remodeling mediates local tissue-level changes. (researchgate.net)
  • For patients outside the recommended time frame for PCI, reperfusion strategy includes pharmacoinvasive therapy with fibrinolysis, followed by either rescue PCI or routine early PCI. (cdc.gov)
  • As the prevalence of the metabolic syndrome is increasing, better understanding of cardiac metabolism is needed to identify potential new targets for therapeutic intervention. (jci.org)
  • For non-ST-segment-elevation myocardial infarction, reperfusion is via percutaneous intervention or coronary artery bypass graft surgery. (msdmanuals.com)
  • Aim 2 will investigate the role of HIF-1 in mediating adaptive responses to cardiac ischemiaand reperfusion. (grantome.com)
  • Little is known regarding myocardial stress resistance in hyperbilirubinaemic conditions or whether life-long exposure modifies cardiac function, which might contribute to protection from cardiovascular disease. (edu.au)
  • However, the physiological role for this channel in cardiac function remains unclear. (frontiersin.org)
  • The gold standard method for measuring direct, real-time complete cardiac function, particularly myocardial contractility measurements, PV loops can be generated by plotting real-time left or right ventricular pressure against ventricular volume during a complete cardiac cycle. (adinstruments.com)
  • Providing instant cardiovascular function feedback based on morphology, position and timing of the loop, ventricular pressure volume is the only research technique that provides you full diastolic analysis and allows you to vary the load and measure beat-to-beat response of that changing load in cardiac performance. (adinstruments.com)
  • The Ventri-Cath PV Loop catheters are multi-segment pressure-volume (PV) catheters for complete cardiac function assessment in continuously beating, intact hearts of large animals (including dog, pig and sheep). (adinstruments.com)
  • Surprisingly, Txnip-KO hearts had greater recovery of cardiac function after an ischemia-reperfusion insult. (jci.org)
  • Cardiac function in vivo was assessed by echocardiography . (bvsalud.org)
  • In the present study, we crossed cytoATP-Tg or mitoATP-Tg mice with a mouse model of T2D and assessed the effects of empagliflozin on the cardiac energy status of those mice. (nature.com)
  • C and D ) Respiration control ratio was obtained from permeabilized cardiac fibers incubated with indicated substrates in 11 WT and 7 Txnip-KO mice. (jci.org)
  • To investigate the mechanism underlying the improvement in cardiac energy status with empagliflozin, real-time and accurate monitoring of the pathways and amount of energy production in vivo is needed. (nature.com)
  • We intend to investigate the effect of GTN in patients undergoing cardiac surgery being subjected to RIPC in its role as a Nitric Oxide (NO) donor. (druglib.com)
  • Deletion of Tbc1d4/As160 abrogates cardiac glucose uptake and increases myocardial damage after ischemia/reperfusion. (mpg.de)
  • Global cerebral ischemia followed by reperfusion, which leads to extensive neuronal damage, particularly the neurons in the hippocampal CA1 region. (springer.com)
  • Others(smartphone application) : In this study, the investigators will provide smartphone application based 12-week pulmonary or cardiac rehabilitation program to patients with chronic respiratory, cardiac, or geriatric diseases. (who.int)
  • If return of spontaneous circulation (ROSC) is achieved after CPR, then circulation resumes, resulting in global reperfusion and the subsequent distribution of the ischemia products throughout the body. (wikipedia.org)
  • Included were 130 patients with valvulopathy who underwent surgery with CPB in the department of cardiac surgery at our hospital from February 2013 to December 2014. (hindawi.com)