Search results for: cardiac myosin binding protein-C

Authors: Jirapat Suriyachaisawat, Ekkit Surakarn

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Introduction: To improve early detection and mortality rate of in-hospital cardiac arrest, Emergency Response Team (ERT) system was planned and implemented since June 2009 to detect pre-arrest conditons and for any concerns. The ERT consisted of on duty physicians and nurses from emergency department. ERT calling criteria consisted of acute change of HR < 40 or > 130 beats per minute, systolic blood pressure < 90 mmHg, respiratory rate <8 or >28 breaths per minute, O2 saturation <90%, acute change in conscious state, acute chest pain or worry about the patients. From the data on ERT system implementation in our hospital in early phase (during June 2009-2011), there was no statistic significance in difference in in-hospital cardiac arrest incidence and overall hospital mortality rate. Since the introduction of the ERT service in our hospital, we have conducted continuous educational campaign to improve awareness in an attempt to increase use of the service. Methods: To investigate outcome of ERT system in in-hospital cardiac arrest and overall hospital mortality rate, we conducted a prospective, controlled before-and after examination of the long term effect of a ERT system on the incidence of cardiac arrest. We performed chi-square analysis to find statistic significance. Results: Of a total 623 ERT cases from June 2009 until December 2012, there were 72 calls in 2009, 196 calls in 2010, 139 calls in 2011 and 245 calls in 2012. The number of ERT calls per 1000 admissions in year 2009-10 was 7.69; 5.61 in 2011 and 9.38 in 2013. The number of code blue calls per 1000 admissions decreased significantly from 2.28 to 0.99 per 1000 admissions (P value < 0.001). The incidence of cardiac arrest decreased progressively from 1.19 to 0.34 per 1000 admissions and significant in difference in year 2012 (P value < 0.001 ). The overall hospital mortality rate decreased by 8 % from 15.43 to 14.43 per 1000 admissions (P value 0.095). Conclusions: ERT system implementation was associated with progressive reduction in cardiac arrests over three year period, especially statistic significant in difference in 4th year after implementation. We also found an inverse association between number of ERT use and the risk of occurrence of cardiac arrests, but we have not found difference in overall hospital mortality rate.

Keywords: cardiac arrest, outcome, in-hospital, ERT

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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Authors: Nicholas Bayfield, Liam Bibo, Charley Budgeon, Robert Larbalestier, Tom Briffa

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Introduction: Stress hyperglycaemia is common following cardiac surgery. Its optimal management is uncertain and may differ by diabetic status. This study assesses the in-hospital glycaemic management of cardiac surgery patients and associated postoperative outcomes. Methods: A retrospective cohort analysis of all patients undergoing cardiac surgery at Fiona Stanley Hospital from February 2015 to May 2019 was undertaken. Management and outcomes of hyperglycaemia following cardiac surgery were assessed. Follow-up was assessed to 1 year postoperatively. Multivariate regression modelling was utilised. Results: 1050 non-diabetic patients and 689 diabetic patients were included. In the non-diabetic cohort, patients with mild (peak blood sugar level [BSL] < 14.3), transient stress hyperglycaemia managed without insulin were not at an increased risk of wound-related morbidity (P=0.899) or mortality at 1 year (P=0.483). Insulin management was associated with wound-related readmission to hospital (P=0.004) and superficial sternal wound infection (P=0.047). Prolonged or severe stress hyperglycaemia was predictive of hospital re-admission (P=0.050) but not morbidity or mortality (P=0.546). Diabetes mellitus was an independent risk factor 1-year mortality (OR; 1.972 [1.041–3.736], P=0.037), graft harvest site wound infection (OR; 1.810 [1.134–2.889], P=0.013) and wound-related readmission (OR; 1.866 [1.076–3.236], P=0.026). In diabetics, postoperative peak BSL > 13.9mmol/L was predictive of graft harvest site infections (OR; 3.528 [1.724-7.217], P=0.001) and wound-related readmission OR; 3.462 [1.540-7.783], P=0.003) regardless of modality of management. A peak BSL of 10.0-13.9 did not increase the risk of morbidity/mortality compared to a peak BSL of < 10.0 (P=0.557). Diabetics with a peak BSL of 13.9 or less did not have significantly increased morbidity/mortality outcomes compared to non-diabetics (P=0.418). Conclusion: In non-diabetic patients, transient mild stress hyperglycaemia following cardiac surgery does not uniformly require treatment. In diabetic patients, postoperative hyperglycaemia with peak BSL exceeding 13.9mmol/L was associated with wound-related morbidity and hospital readmission following cardiac surgery.

Keywords: cardiac surgery, pulmonary embolism, pulmonary embolectomy, cardiopulmonary bypass

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Authors: Gary Young, David Zepeda, Gilbert Nyaga

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This study investigated whether vertical integration of hospitals and physicians is associated with better care for patients with cardiac conditions. A dramatic change in the U.S. hospital industry is the integration of hospital and physicians through hospital acquisition of physician practices. Yet, there is little evidence regarding whether this form of vertical integration leads to better operational performance of hospitals. The study was conducted as an observational investigation based on a pooled, cross-sectional database. The study sample comprised over hospitals in the State of California. The time frame for the study was 2010 to 2012. The key performance measure was hospitals’ degree of compliance with performance criteria set out by the federal government for managing patients with cardiac conditions. These criteria relate to the types of clinical tests and medications that hospitals should follow for cardiac patients but hospital compliance requires the cooperation of a hospital’s physicians. Data for this measure was obtained from a federal website that presents performance scores for U.S. hospitals. The key independent variable was the percentage of cardiologists that a hospital employs (versus cardiologists who are affiliated but not employed by the hospital). Data for this measure was obtained from the State of California which requires hospitals to report financial and operation data each year including numbers of employed physicians. Other characteristics of hospitals (e.g., information technology for cardiac care, volume of cardiac patients) were also evaluated as possible complements or substitutes for physician employment by hospitals. Additional sources of data included the American Hospital Association and the U.S. Census. Empirical models were estimated with generalized estimating equations (GEE). Findings suggest that physician employment is positively associated with better hospital performance for cardiac care. However, findings also suggest that information technology is a substitute for physician employment.

Keywords: physician employment, hospitals, verical integration, cardiac care

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Authors: Vignesh Ratnaraj, Jaewon Chang

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Background: Frailty is associated with poorer outcomes in cardiac surgery, but the heterogeneity in frailty assessment tools makes it difficult to ascertain its true impact in cardiac surgery. Slow gait speed is a simple, validated, and reliable marker of frailty. We performed a systematic review and meta-analysis to examine the effect of slow gait speed on postoperative cardiac surgical patients. Methods: PubMED, MEDLINE, and EMBASE databases were searched from January 2000 to August 2021 for studies comparing slow gait speed and “normal” gait speed. The primary outcome was in-hospital mortality. Secondary outcomes were composite mortality and major morbidity, AKI, stroke, deep sternal wound infection, prolonged ventilation, discharge to a healthcare facility, and ICU length of stay. Results: There were seven eligible studies with 36,697 patients. Slow gait speed was associated with an increased likelihood of in-hospital mortality (risk ratio [RR]: 2.32; 95% confidence interval [CI]: 1.87–2.87). Additionally, they were more likely to suffer from composite mortality and major morbidity (RR: 1.52; 95% CI: 1.38–1.66), AKI (RR: 2.81; 95% CI: 1.44–5.49), deep sternal wound infection (RR: 1.77; 95% CI: 1.59–1.98), prolonged ventilation >24 h (RR: 1.97; 95% CI: 1.48–2.63), reoperation (RR: 1.38; 95% CI: 1.05–1.82), institutional discharge (RR: 2.08; 95% CI: 1.61–2.69), and longer ICU length of stay (MD: 21.69; 95% CI: 17.32–26.05). Conclusion: Slow gait speed is associated with poorer outcomes in cardiac surgery. Frail patients are twofold more likely to die during hospital admission than non-frail counterparts and are at an increased risk of developing various perioperative complications.

Keywords: cardiac surgery, gait speed, recovery, frailty

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Authors: Rashid Azeem

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Introduction: Eosinophilia, which can be categorized as mild, moderate, and severe form on the basis of increasing eosinophil counts, might be responsible for a wide range of cardiac manifestations, varying from a simple myocarditis to a severe state like endomyocardial fibrosis. Eosinophils are involved in the pathogenesis of a variety of cardiovascular disorder like Loffler endocarditis, eosinophilic granulomatosis with polyangitis (EGPH), and hyper eosinophilic (HES). Among them HES carries and incidence rate b/w 48% and 75% and is the main causes of cardiac motility and mobility due to eosinophilia involvement. Aims and objectives: The aim of this study is to determine the frequency of eosinophilia in cardiac patients and to ascertain the evidence of endomyocardial diseases in eosinophilic patients in a cardiology institution Material and Methods: This cross sectional analytical study was conducted in hematology Department of Peshawar institute of Cardiology after approval from hospital ethical and research committee. All 70 patients were subjected to detailed history and clinical examination. Investigation like CBC, Chest X-ray, ECG, Echo, Angiography findings were used to monitor patient’s clinical status. Data is analyzed using SPSS version 25 and MS Excel. Results: Out of 70 patients in our study, a total of 66 patients(94 %) shows evidence of cardiac manifestations. In our study, we have observed a number of abnormal ECG patterns in cardiac patients presenting with eosinophilia, like T wave changes, loss of R wave, sinus bradycardia with LVH strain, and ST wave abnormality. abnormal echocardiographic findings were observed in our patients, like valvular abnormalities (in 45.7%), RWMA abnormalities (in 2.8%), isolated ventricular dysfunction (in 21.4%), and in 10% patients, normal echocardiography. We further noted abnormal coronary angiography findings in cardiac patients with eosinophilia ranging from single vessel to multi vessel occlusions. Conclusions: Eosinophils are involved in the pathogenesis of a variety of cardiovascular disorders which can be detected by various diagnostic means, and the severity of the disease increases with time and with increasing eosinophil count ranging from simple myocarditis to a fatal condition like endomyocardial fibrosis. Thus, increased eosinophilic count as a laboratory parameter in cardiac patients may be a sign of endomyocardial damage which will further help cardiologist to intervene more aggressively then routine approach to a cardiac patient.

Keywords: eosinophilia, endomyocardial fibrosis, cardiac, hypereosinophilic syndrome

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Authors: Ravshan A. Ibadov, Sardor Kh. Ibragimov

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Objective. The aim of the study was to optimize the protocol of cardiopulmonary resuscitation (CPR) after cardiovascular surgical interventions. Methods. The experience of CPR conducted on patients after cardiovascular surgical interventions in the Department of Intensive Care and Resuscitation (DIR) of the Republican Specialized Scientific-Practical Medical Center of Surgery named after Academician V. Vakhidov is presented. The key to the new approach is the rapid elimination of reversible causes of cardiac arrest, followed by either defibrillation or electrical cardioversion (depending on the situation) before external heart compression, which may damage sternotomy. Careful use of adrenaline is emphasized due to the potential recurrence of hypertension, and timely resternotomy (within 5 minutes) is performed to ensure optimal cerebral perfusion through direct massage. Out of 32 patients, cardiac arrest in the form of asystole was observed in 16 (50%), with hypoxemia as the cause, while the remaining 16 (50%) experienced ventricular fibrillation caused by arrhythmogenic reactions. The age of the patients ranged from 6 to 60 years. All patients were evaluated before the operation using the ASA and EuroSCORE scales, falling into the moderate-risk group (3-5 points). CPR was conducted for cardiac activity restoration according to the American Heart Association and European Resuscitation Council guidelines (Ley SJ. Standards for Resuscitation After Cardiac Surgery. Critical Care Nurse. 2015;35(2):30-38). The duration of CPR ranged from 8 to 50 minutes. The ARASNE II scale was used to assess the severity of patients' conditions after CPR, and the Glasgow Coma Scale was employed to evaluate patients' consciousness after the restoration of cardiac activity and sedation withdrawal. Results. In all patients, immediate chest compressions of the necessary depth (4-5 cm) at a frequency of 100-120 compressions per minute were initiated upon detection of cardiac arrest. Regardless of the type of cardiac arrest, defibrillation with a manual defibrillator was performed 3-5 minutes later, and adrenaline was administered in doses ranging from 100 to 300 mcg. Persistent ventricular fibrillation was also treated with antiarrhythmic therapy (amiodarone, lidocaine). If necessary, infusion of inotropes and vasopressors was used, and for the prevention of brain edema and the restoration of adequate neurostatus within 1-3 days, sedation, a magnesium-lidocaine mixture, mechanical intranasal cooling of the brain stem, and neuroprotective drugs were employed. A coordinated effort by the resuscitation team and proper role allocation within the team were essential for effective cardiopulmonary resuscitation (CPR). All these measures contributed to the improvement of CPR outcomes. Conclusion. Successful CPR following cardiac surgical interventions involves interdisciplinary collaboration. The application of an optimized CPR standard leads to a reduction in mortality rates and favorable neurological outcomes.

Keywords: cardiac surgery, cardiac arrest, resuscitation, critically ill patients

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Authors: Angelis P. Barlampas

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The purpose of this study is to inform the reader, about the various applications of artificial intelligence (AI), in cardiac imaging. AI grows fast and its role is crucial in medical specialties, which use large amounts of digital data, that are very difficult or even impossible to be managed by human beings and especially doctors.Artificial intelligence (AI) refers to the ability of computers to mimic human cognitive function, performing tasks such as learning, problem-solving, and autonomous decision making based on digital data. Whereas AI describes the concept of using computers to mimic human cognitive tasks, machine learning (ML) describes the category of algorithms that enable most current applications described as AI. Some of the current applications of AI in cardiac imaging are the follows: Ultrasound: Automated segmentation of cardiac chambers across five common views and consequently quantify chamber volumes/mass, ascertain ejection fraction and determine longitudinal strain through speckle tracking. Determine the severity of mitral regurgitation (accuracy > 99% for every degree of severity). Identify myocardial infarction. Distinguish between Athlete’s heart and hypertrophic cardiomyopathy, as well as restrictive cardiomyopathy and constrictive pericarditis. Predict all-cause mortality. CT Reduce radiation doses. Calculate the calcium score. Diagnose coronary artery disease (CAD). Predict all-cause 5-year mortality. Predict major cardiovascular events in patients with suspected CAD. MRI Segment of cardiac structures and infarct tissue. Calculate cardiac mass and function parameters. Distinguish between patients with myocardial infarction and control subjects. It could potentially reduce costs since it would preclude the need for gadolinium-enhanced CMR. Predict 4-year survival in patients with pulmonary hypertension. Nuclear Imaging Classify normal and abnormal myocardium in CAD. Detect locations with abnormal myocardium. Predict cardiac death. ML was comparable to or better than two experienced readers in predicting the need for revascularization. AI emerge as a helpful tool in cardiac imaging and for the doctors who can not manage the overall increasing demand, in examinations such as ultrasound, computed tomography, MRI, or nuclear imaging studies.

Keywords: artificial intelligence, cardiac imaging, ultrasound, MRI, CT, nuclear medicine

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Authors: Arunima Verma, Padmabati Mondal

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Serotonin-receptor binding plays a key role in several neurological and biological processes, including mood, sleep, hunger, cognition, learning, and memory. In this article, we performed molecular dynamics simulation to examine the key residues that play an essential role in the binding of serotonin to the G-protein-coupled 5-HT₁ᴮ receptor (5-HT₁ᴮ R) via electrostatic interactions. An end-point free energy calculation method (MM-PBSA) determines the stability of the 5-HT1B R due to serotonin binding. The single-point mutation of the polar or charged amino acid residues (Asp129, Thr134) on the binding sites and the calculation of binding free energy validate the importance of these residues in the stability of the serotonin-receptor complex. Principal component analysis indicates the serotonin-bound 5-HT1BR is more stabilized than the apo-receptor in terms of dynamical changes. The difference dynamic cross-correlations map shows the correlation between the transmembrane and mini-Go, which indicates signal transduction happening between mini-Go and the receptor. Allosteric communication reveals the key nodes for signal transduction in 5-HT1BR. These results provide useful insights into the signal transduction pathways and mutagenesis study to regulate the functionality of the complex. The developed protocols can be applied to study local non-covalent interactions and long-range allosteric communications in any protein-ligand system for computer-aided drug design.

Keywords: allostery, CADD, MD simulations, MM-PBSA

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Authors: Gehan A. Hegazy, Hesham N. Mustafa, Sally A. El Awdan, Marawan AbdelBaset

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Doxorubicin (DOX) is a chemotherapeutic agent used for the treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on the heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy-two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10 mg/kg); CoQ10 group (200 mg/kg); L-carnitine group (100 mg/kg); DOX + CoQ10 group; DOX + L-carnitine group. CoQ10 and L-carnitine treatment orally started five days before a single dose of 10 mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for ten days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF-), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With visible improvements in -SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.

Keywords: CoQ10, doxorubicin, L-Carnitine, cardiotoxicity

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Authors: Hoa Thi Hoang, Stephan Sass, Michael U. Kumke

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Concanavalin A (conA) is a protein has been widely used in sensor system based on its specific binding to α-D-Glucose or α-D-Manose. For glucose sensor using conA, either fluoresence based techniques with intensity based or lifetime based are used. In this research, liposomes made from phospholipids were used as a biomimetic membrane system. In a first step, novel building blocks containing perylene labeled glucose units were added to the system and used to decorate the surface of the liposomes. Upon the binding between rhodamine labeled con A to the glucose units at the biomimetic membrane surface, a Förster resonance energy transfer system can be formed which combines unique fluorescence properties of perylene (e.g., high fluorescence quantum yield, no triplet formation) and its high hydrophobicity for efficient anchoring in membranes to form a novel probe for the investigation of sugar-driven binding reactions at biomimetic surfaces. Two glucose-labeled perylene derivatives were synthesized with different spacer length between the perylene and glucose unit in order to probe the binding of conA. The binding interaction was fully characterized by using high-end fluorescence techniques. Steady-state and time-resolved fluorescence techniques (e.g., fluorescence depolarization) in combination with single-molecule fluorescence spectroscopy techniques (fluorescence correlation spectroscopy, FCS) were used to monitor the interaction with conA. Base on the fluorescence depolarization, the rotational correlation times and the alteration in the diffusion coefficient (determined by FCS) the binding of the conA to the liposomes carrying the probe was studied. Moreover, single pair FRET experiments using pulsed interleaved excitation are used to characterize in detail the binding of conA to the liposome on a single molecule level avoiding averaging out effects.

Keywords: concanavalin A, FRET, sensor, biomimetic membrane

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Authors: Leena Korpinen, Rauno Pääkkönen, Fabriziomaria Gobba, Vesa Virtanen

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The number of persons with implanted cardiac pacemakers (PM) has increased in Western countries. The aim of this paper is to investigate the possible situations where persons with a PM may be exposed to extremely low frequency (ELF) electric (EF) and magnetic fields (MF) that may disturb their PM. Based on our earlier studies, it is possible to find such high public exposure to EFs only in some places near 400 kV power lines, where an EF may disturb a PM in unipolar mode. Such EFs cannot be found near 110 kV power lines. Disturbing MFs can be found near welding machines. However, we do not have measurement data from welding. Based on literature and earlier studies at Tampere University of Technology, it is difficult to find public EF or MF exposure that is high enough to interfere with PMs.

Keywords: cardiac pacemaker, electric field, magnetic field, electrical engineering

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Authors: Abraham J. Rizkalla, Tristan D. Yan

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Atrial myxoma is the most common primary cardiac tumor, and can result in cardiac failure secondary to obstruction, or systemic embolism due to fragmentation. Traditionally, excision of atrial an myxoma has been performed through median sternotomy, however the robotic approach offers several advantages including less pain, improved cosmesis, and faster recovery. Here, we highlight the less well recognized advantages and technical aspects to robotic myxoma resection. This video-presentation demonstrates the resection of a papillary subtype left atrial myxoma using the DaVinci© Xi surgical robot. The 10x magnification and 3D vision allows for the interface between the tumor and the interatrial septum to be accurately dissected, without the need to patch the interatrial septum. Several techniques to avoid tumor fragmentation and embolization are demonstrated throughout the procedure. The tumor was completely excised with clear margins. There was no atrial septal defect or mitral valve injury on post operative transesophageal echocardiography. The patient was discharged home on the fourth post-operative day. This video-presentation highlights the advantages of the robotic approach in atrial myxoma resection compared with sternotomy, as well as emphasizing several technical considerations to avoid potential complications.

Keywords: cardiac surgery, left atrial myxoma, cardiac tumour, robotic resection

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Authors: Santosh Sharma Parajuli, Diwas Manandhar

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Background: Perioperative pain management plays an integral part in patients undergoing cardiac surgery. We studied the effect of Erector Spinae Plane block on acute postoperative pain reduction and 24 hours opioid consumption in adult cardiac surgical patients. Methods: Twenty-five adult cardiac surgical patients who underwent cardiac surgery with sternotomy in whom ESP catheters were placed preoperatively were kept in group E, and the other 25 patients who had undergone cardiac surgery without ESP catheter and pain management done with conventional opioid injection were placed in group C. Fentanyl was used for pain management. The primary study endpoint was to compare the consumption of fentanyl and to assess the numeric rating scale in the postoperative period in the first 24 hours in both groups. Results: The 24 hours fentanyl consumption was 43.00±51.29 micrograms in the Erector Spinae Plane catheter group and 147.00±60.94 micrograms in the control group postoperatively which was statistically significant (p <0.001). The numeric rating scale was also significantly reduced in the Erector Spinae Plane group compared to the control group in the first 24 hours postoperatively. Conclusion: Erector Spinae Plane block is superior to the conventional opioid injection method for postoperative pain management in CABG patients. Erector Spinae Plane block not only decreases the overall opioid consumption but also the NRS score in these patients.

Keywords: erector, spinae, plane, numerical rating scale

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Authors: Elena Ivany, Leanne Aitken

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Little is known about the delivery of end-of-life care in cardiac intensive care unit (CICU) settings. The aims of this study were to highlight the nurse-identified barriers and facilitators to delivering end-of-life care in the CICU, and to identify whether any of the barriers and/or facilitators are specific to the CICU setting. This was an exploratory qualitative study utilizing semi-structured individual interviews as the data collection method and inductive thematic analysis to structure the data. Six CICU nurses took part in the study. Five key themes were identified, each theme including both barriers and facilitators. The five key themes are as follows: patient-centered care, emotional challenges, reaching concordance, nursing contribution and the surgical intensive care unit.

Keywords: end-of-life, cardiovascular disease, cardiac surgery, critical care

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Authors: Sadiya S. Silvee

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Generally, the decision of the higher court is binding on its subordinate courts. As provided in Article 111 of the Constitution, 'the law declared by the Appellate Division (AD) shall be binding on the High Court Division (HCD) and the law declared by either division of the Supreme Court shall be binding on all courts subordinate to it.' This means the judicial discipline requires the HCD to follow the decision of the AD and that it is necessary for the lower tiers of courts to accept the decision of the higher tiers as a binding precedent. Analyzing the application of Article 111 of the Constitution in the criminal justice system as a sentencing guideline, the paper, by examining whether there is any consistency in decision between one HC Bench and another HC Bench, explores whether HCD can per incuriam its previous decision. In doing so, the Death Reference (DR) Cases are contemplated. Furthermore, the paper shall examine whether the Court of Session follows the decision of the HCD while using their discretion to make the choice between death and imprisonment for life under section 302 of PC. The paper argues due to the absence of any specific direction for sentencing and inconsistency in jurisprudence among the HCD; the subordinate courts are in a dilemma.

Keywords: death reference, sentencing factor, sentencing guideline, criminal justice system and constitution

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Authors: Sakina Fatima, Joseph-Patrick W. E. Clarke, Patricia A. Thibault, Subha Kalyaanamoorthy, Michael Levin, Aravindhan Ganesan

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Heteronuclear ribonucleoprotein (hnRNPA1 or A1) is associated with the pathology of different diseases, including neurological disorders and cancers. In particular, the aggregation and dysfunction of A1 have been identified as a critical driver for neurodegeneration (NDG) in Multiple Sclerosis (MS). Structurally, A1 includes a low-complexity domain (LCD) and two RNA-recognition motifs (RRMs), and their interdomain coordination may play a crucial role in A1 aggregation. Previous studies propose that RNA-inhibitors or nucleoside analogs that bind to RRMs can potentially prevent A1 self-association. Therefore, molecular-level understanding of the structures, dynamics, and nucleotide interactions with A1 RRMs can be useful for developing therapeutics for NDG in MS. In this work, a combination of computational modelling and biochemical experiments were employed to analyze a set of RNA-A1 RRM complexes. Initially, the atomistic models of RNA-RRM complexes were constructed by modifying known crystal structures (e.g., PDBs: 4YOE and 5MPG), and through molecular docking calculations. The complexes were optimized using molecular dynamics simulations (200-400 ns), and their binding free energies were computed. The binding affinities of the selected complexes were validated using a thermal shift assay. Further, the most important molecular interactions that contributed to the overall stability of the RNA-A1 RRM complexes were deduced. The results highlight that adenine and guanine are the most suitable nucleotides for high-affinity binding with A1. These insights will be useful in the rational design of nucleotide-analogs for targeting A1 RRMs.

Keywords: hnRNPA1, molecular docking, molecular dynamics, RNA-binding proteins

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Authors: Birgit Rasmussen, Thomas Maribo, Bente S. Toft

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BACKGROUND: Cardiac rehabilitation is the standard treatment for ischemic heart disease. Cardiac rehabilitation improves quality of life, reduces mortality and the risk of readmission, and provides patients with valuable knowledge and encouragement from peers and staff. Still, less than half of eligible patients enroll. Face-to-face interventions have the potential to support patients' decision-making and increase enrolment in cardiac rehabilitation. However, we lack knowledge of the content and characteristics of interventions. AIM: The aim was to outline and evaluate the content and characteristics of studies that have reported on face-to-face interventions to encourage enrolment in cardiac rehabilitation in patients with ischemic heart disease. METHOD: This scoping review followed the Joanne Briggs Institute methodology. Based on an a-priori protocol that defined the systematic search criteria, six databases were searched for studies published between 2001 and 2023. Two reviewers independently screened and selected studies. All authors discussed the summarized data prior to the narrative presentation. RESULTS: After screening and full text review of 5583 records, 20 studies of heterogeneous design and content were included. Four studies described the key contents in face-to-face interventions to be education, support of autonomy, addressing reasons for change, and emotional and cognitive support while showing understanding. Two studies used motivational interviewing to target patients' experiences and address worries and anticipated difficulties. Four quantitative studies found associations between enrolment and intention to attend, cardiac rehabilitation barriers, exercise self-efficacy, and perceived control. When patients asked questions, enrolment rates were higher, while providing reassurance and optimism could lead to non-attendance if patients had a high degree of worry. In qualitative studies, support to overcome barriers and knowledge about health benefits from participation in cardiac rehabilitation facilitated enrolment. Feeling reassured that the cardiac condition was good could lead to non-attendance. DISCUSSION AND CONCLUSION: To support patients' enrolment in cardiac rehabilitation, it is recommended that interventions integrate a person-centered dialogue. Individual worries and barriers to cardiac rehabilitation should be jointly explored. When talking with patients for whom worries predominate, the recommendation is to focus on the patients' perspectives and avoid too much focus on reassurance and problem-solving. The patients' perspectives, the mechanisms of change, and the process evaluation of the intervention including person-centeredness are relevant to include in future studies.

Keywords: ischemic heart disease, cardiac rehabilitation, enrolment, person-centered, in-hospital interventions

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Authors: Heru Al Amin

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Sarcoidosis is a granulomatous inflammatory disorder of unclear etiology that can affect multiple different organ systems. Isolated cardiac sarcoidosis is a very rare condition that causes lethal arrhythmia and heart failure. A definite diagnosis of cardiac sarcoidosis remains challenging. The use of multimodality imaging plays a pivotal role in the diagnosis of this entity. Case summary: In this report, we discuss a case of a 50-year-old woman who presented with recurrent palpitation, dizziness, vertigo and presyncope. Electrocardiogram revealed variable heart blocks, including first-degree AV block, second-degree AV block, high-degree AV block, complete AV block, trifascicular block and sometimes supraventricular arrhythmia. Twenty-four hours of Holter monitoring show atrial bigeminy, first-degree AV block and trifascicular block. Transthoracic echocardiography showed Thinning of basal anteroseptal and inferred septum with LV dilatation with reduction of Global Longitudinal Strain. A dual-chamber pacemaker was implanted. CT Coronary angiogram showed no coronary artery disease. Cardiac magnetic resonance revealed basal anteroseptal and inferior septum thinning with focal edema with LGE suggestive of sarcoidosis. Computed tomography of the chest showed no lymphadenopathy or pulmonary infiltration. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) of the whole body showed. We started steroids and followed up with the patient. Conclusion: This case serves to highlight the challenges in identifying and managing isolated CS in a young patient with recurrent syncope with variable heart block. Early, even late initiation of steroids can improve arrhythmia as well as left ventricular function.

Keywords: cardiac sarcoidosis, conduction abnormality, syncope, cardiac MRI

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Authors: Ashrafosadat Mousavi Laer, Elaheh Moravej

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The art of binding was simple and elementary at the beginning of Islam. This art thrived gradually and continued its development as an independent art. Identification of the binding techniques and used materials in covers and investigation of the arrays give us indexes for the better identification of different doctrines and methods of that time. The catalogers of the manuscripts usually pay attention to four items: gender, color, art elegances, injury, and exquisiteness of the cover. The criterion for classification of the covers is their art nature and gender. 15th century AD (9th century AH) was the period of the binding art development in which the most beautiful covers were produced by the so-called method of ‘burning’. At 16th century AD (10th century AH), in Safavid era, art changed completely and a fundamental evolution occurred in the technique and method of binding. The greatest change in this art was the extensive use of stamp that was made mostly of steel and copper. Theses stamps were presses against leather. These covers were called ‘beat’. In this paper, writing and bookbinding of about 32 Shahnamehs of Safavid era available in the Iranian libraries and museums are studied. An analytical-statistical study shows that four methods have been used including beat, burning, mosaic, and oily. 69 percent of the covers of these copies are cardboards with a leathery coating (goatskin) and have been produced by burning and beat methods. Its reasons are that these two methods have been common methods in Safavid era and performing them was only feasible on leather and the most desirable and commonly used leather of that time was goatskin which was the best option for cover legend durability and preserving the book and it was more durable because it had been made of goat skin. In addition, it had prepared a suitable opportunity for the binding artist’s creativity and innovation.

Keywords: Shahnameh, Safavid era, bookbinding, beat cover, burning cover

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Authors: Sonam Kumari

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Tuberculosis is the deadliest disease worldwide. Millions of people lose their lives every year due to this disease. It has turned lethal due to the erratic nature of its causative organism, Mycobacterium tuberculosis (Mtb). Mtb tends to enter into an inactive, dormant state and emerge to replicating state upon encountering favorable conditions. The mechanism by which Mtb switches from the dormant state to the replicative form is still poorly characterized. Proteome studies have given us an insight into the role of certain proteins in giving stupendous virulence to Mtb, but numerous dotsremain unconnected and unaccounted. The WhiB family of proteins is one such protein that is associated with developmental processes in actinomycetes. Mtb has seven such proteins (WhiB1 to WhiB7). WhiB proteins are transcriptional regulators; they regulate various essential genes of Mtbby binding to their promoter DNA. Biophysical parameters of the effect of DNA binding on WhiB proteins has not yet been appropriately characterized. Interaction with DNA induces conformational changes in the WhiB proteins, confirmed by steady-state fluorescence and circular dichroism spectroscopy. ITC has deduced thermodynamic parameters and the binding affinity of the interaction. Since these transcription factors are highly unstable in vitro, their stability and solubility were enhanced by the co-expression of molecular chaperones. The present study findings help determine the conditions under which the WhiB proteins interact with their interacting partner and the factors that influence their binding affinity. This is crucial in understanding their role in regulating gene expression in Mtbandin targeting WhiB proteins as a drug target to cure TB.

Keywords: mycobacterium tuberculosis, TB, whiB proteins, ITC

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Authors: Ioannis Panagiotopoulos, Efstathios Kastritis, Anastasia Katinioti, Georgios Efthymiadis, Argyrios Doumas, Maria Koutelou

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Introduction: Transthyretin amyloidosis (ATTR) is a rare but serious infiltrative disease. Myocardial scintigraphy with DPD has emerged as the most effective, non-invasive, highly sensitive, and highly specific diagnostic method for cardiac ATTR amyloidosis. However, there are cases in which additional laboratory investigations reveal AL amyloidosis or other diseases despite a positive DPD scintigraphy. We describe the experience from the Onassis Cardiac Surgery Center and the monitoring center for infiltrative myocardial diseases of the cardiology clinic at AHEPA. Materials and Methods: All patients with clinical suspicion of cardiac or extracardiac amyloidosis undergo a myocardial scintigraphy scan with Tc-99m DPD. In this way, over 500 patients have been examined. Further diagnostic approach based on clinical and imaging findings includes laboratory investigation and invasive techniques (e.g., biopsy). Results: Out of 76 patients in total with positive myocardial scintigraphy Grade 2 or 3 according to the Perugini scale, 8 were proven to suffer from AL Amyloidosis during the investigation of paraproteinemia. Among these patients, 3 showed Grade 3 uptake, while the rest were graded as Grade 2, or 2 to 3. Additionally, one patient presented diffuse and unusual radiopharmaceutical uptake in soft tissues throughout the body without cardiac involvement. These findings raised suspicions, leading to the analysis of κ and λ light chains in the serum, as well as immunostaining of proteins in the serum and urine of these specific patients. The final diagnosis was AL amyloidosis. Conclusion: The value of DPD scintigraphy in the diagnosis of cardiac amyloidosis from transthyretin is undisputed. However, positive myocardial scintigraphy with DPD should not automatically lead to the diagnosis of ATTR amyloidosis. Laboratory differentiation between ATTR and AL amyloidosis is crucial, as both prognosis and therapeutic strategy are dramatically altered. Laboratory exclusion of paraproteinemia is a necessary and essential step in the diagnostic algorithm of ATTR amyloidosis for all positive myocardial scintigraphy with diphosphonate tracers since >20% of patients with Grade 3 and 2 uptake may conceal AL amyloidosis.

Keywords: AL amyloidosis, amyloidosis, ATTR, myocardial scintigraphy, Tc-99m DPD

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Authors: Sandipika Gupta

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Objective: Due to admirably low 30-day mortality rates for paediatric cardiac surgery, it is now pertinent to turn towards more intermediate-length outcomes such as morbidities closely associated with these surgeries. One such morbidity, major adverse events (MAE) comprises a group of adverse outcomes associated with paediatric cardiac surgery (e.g. cardiac arrest, major haemorrhage). Methods: This is a retrospective study that analysed the incidence and impact of MAE which was the primary outcome in the UK population. The data was collected in 5 centres between October 2015 and June 2017, amassing 3090 surgical episodes. The incidence and risk factors for MAE, were assessed through descriptive statistical analyses and multivariate logistic regression. The secondary outcomes of life status at 6 months and the length of hospital stay were also evaluated to understand the impact of MAE on patients. Results: Out of 3090 episodes, 134 (4.3%) had a postoperative MAE. The majority of the episodes were in: neonates (47%, P<0.001), high-risk cardiac diagnosis groups (20.1%, P<0.001), episodes with longer 5mes on the bypass (72.4%, P<0.001) and urgent surgeries (57.9%, P<0.001). Episodes reporting MAE also reported longer lengths of stay in hospital (29 days vs 9 days, P<0.001). Furthermore, patients experiencing MAE were at a higher risk of mortality at the 6-month life status check (mortality rates: 29.2% vs 2%, P<0.001).Conclusions: Key risk factors were identified. An important negative impact of MAE was found for patients. The identified risk factors could be used to profile and flag at-risk patients. Monitoring of MAE rates and closer investigation into the care pathway before and after individual MAEs in children’s heart units may lead to a reduction in these terrible events.

Keywords:

Procedia PDF Downloads 232

Authors: Prasanna Ramachandran, Kareem Graham, Helena Kiefel, Sunit Jain, Todd DeSantis

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Microbes that reside inside the mammalian GI tract, commonly referred to as the gut microbiome, have been shown to have therapeutic effects in animal models of disease. We hypothesize that specific proteins produced by these microbes are responsible for this activity and may be used directly as therapeutics. To speed up the discovery of these key proteins from the big-data metagenomics, we have applied machine learning techniques. Using amino acid sequences of known epitopes and their corresponding binding partners, protein interaction descriptors (PID) were calculated, making a positive interaction set. A negative interaction dataset was calculated using sequences of proteins known not to interact with these same binding partners. Using Random Forest and positive and negative PID, a machine learning model was trained and used to predict interacting versus non-interacting proteins. Furthermore, the continuous variable, cosine similarity in the interaction descriptors was used to rank bacterial therapeutic candidates. Laboratory binding assays were conducted to test the candidates for their potential as therapeutics. Results from binding assays reveal the accuracy of the machine learning prediction and are subsequently used to further improve the model.

Keywords: protein-interactions, machine-learning, metagenomics, microbiome

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Authors: Kakali Bhadra

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Binding of small molecules to DNA and recently to RNA, continues to attract considerable attention for developing effective therapeutic agents for control of gene expression. This work focuses towards understanding interaction of harmalol, a dihydro beta-carboline alkaloid, with different nucleic acid motifs viz. double stranded CT DNA, single stranded A-form poly(A), double-stranded A-form of poly(C)·poly(G) and clover leaf tRNAphe by different spectroscopic, calorimetric and molecular modeling techniques. Results of this study converge to suggest that (i) binding constant varied in the order of CT DNA > poly(C)·poly(G) > tRNAphe > poly(A), (ii) non-cooperative binding of harmalol to poly(C)·poly(G) and poly(A) and cooperative binding with CT DNA and tRNAphe, (iii) significant structural changes of CT DNA, poly(C)·poly(G) and tRNAphe with concomitant induction of optical activity in the bound achiral alkaloid molecules, while with poly(A) no intrinsic CD perturbation was observed, (iv) the binding was predominantly exothermic, enthalpy driven, entropy favoured with CT DNA and poly(C)·poly(G) while it was entropy driven with tRNAphe and poly(A), (v) a hydrophobic contribution and comparatively large role of non-polyelectrolytic forces to Gibbs energy changes with CT DNA, poly(C)·poly(G) and tRNAphe, and (vi) intercalated state of harmalol with CT DNA and poly(C)·poly(G) structure as revealed from molecular docking and supported by the viscometric data. Furthermore, with competition dialysis assay it was shown that harmalol prefers hetero GC sequences. All these findings unequivocally pointed out that harmalol prefers binding with ds CT DNA followed by ds poly(C)·poly(G), clover leaf tRNAphe and least with ss poly(A). The results highlight the importance of structural elements in these natural beta-carboline alkaloids in stabilizing different DNA and RNA of various motifs for developing nucleic acid based better therapeutic agents.

Keywords: calorimetry, docking, DNA/RNA-alkaloid interaction, harmalol, spectroscopy

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Authors: L. Bikulciene, E. Venskaityte, G. Jarusevicius

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Non-stationary and nonlinear signals generated by living complex systems defy traditional mechanistic approaches, which are based on homeostasis. Previous our studies have shown that the evaluation of the interactions of physiological signals by using special analysis methods is suitable for observation of physiological processes. It is demonstrated the possibility of using deep physiological model, based interpretation of the changes of the human body’s functional states combined with an application of the analytical method based on matrix theory for the physiological signals analysis, which was applied on high risk cardiac patients. It is shown that evaluation of cardiac signals interactions show peculiar for each individual functional changes at the onset of hemodynamic restoration procedure. Therefore we suggest that the alterations of functional state of the body, after patients overcome surgery can be complemented by the data received from the suggested approach of the evaluation of functional variables interactions.

Keywords: cardiac diseases, complex systems theory, ECG analysis, matrix analysis

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Authors: Fahad Almehmadi, Abdullah Alrajhi, Bader K. Alaslab, Abdullah A. Al Qurashi, Hattan A. Hassani

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Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is an uncommon, inheritable cardiac disorder characterized by the progressive substitution of cardiac myocytes by fibro-fatty tissues. This pathologic substitution predisposes patients to ventricular arrhythmias and right ventricular failure. The underlying genetic defect predominantly involves genes encoding for desmosome proteins, particularly plakophilin-2 (PKP2). These aberrations lead to impaired cell adhesion, heightening the susceptibility to fibrofatty scarring under conditions of mechanical stress. Primarily, ARVD/C affects the right ventricle, but it can also compromise the left ventricle, potentially leading to biventricular heart failure. Clinical presentations can vary, spanning from asymptomatic individuals to those experiencing palpitations, syncopal episodes, and, in severe instances, sudden cardiac death. The establishment of a diagnostic criterion specifically tailored for ARVD/C significantly aids in its accurate diagnosis. Nevertheless, the task of early diagnosis is complicated by the disease's frequently asymptomatic initial stages, and the overall rarity of ARVD/C cases reported globally. In some cases, as exemplified by the adult female patient in this report, the disease may advance to terminal stages, rendering therapies like Ventricular Tachycardia (VT) ablation ineffective. This case underlines the necessity for increased awareness and understanding of ARVD/C to aid in its early detection and management. Through such efforts, we aim to decrease morbidity and mortality associated with this challenging cardiac disorder.

Keywords: ARVD/C, cardiology, interventional cardiology, cardiac electrophysiology

Procedia PDF Downloads 63

Authors: Nidhi Chadha, A. K. Tiwari, Marilyn D. Milton, Anil K. Mishra

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Translocator protein (18 kDa) TSPO is highly expressed during microglia activation in neuroinflammation. Although a number of PET ligands have been developed for the visualization of activated microglia, one of the advantageous approaches is to develop potential optical imaging (OI) probe. Our study involves computational screening, synthesis and evaluation of TSPO ligand through various imaging modalities namely PET/SPECT/Optical. The initial computational screening involves pharmacophore modeling from the library designing having oxo-benzooxazol-3-yl-N-phenyl-acetamide groups and synthesis for visualization of efficacy of these compounds as multimodal imaging probes. Structure modeling of monomer, Ala147Thr mutated, parallel and anti-parallel TSPO dimers was performed and docking analysis was performed for distinct binding sites. Computational analysis showed pattern of variable binding profile of known diagnostic ligands and NBMP via interactions with conserved residues along with TSPO’s natural polymorphism of Ala147→Thr, which showed alteration in the binding affinity due to considerable changes in tertiary structure. Preliminary in vitro binding studies shows binding affinity in the range of 1-5 nm and selectivity was also certified by blocking studies. In summary, this skeleton was found to be potential probe for TSPO imaging due to ease in synthesis, appropriate lipophilicity and reach to specific region of brain.

Keywords: TSPO, molecular modeling, imaging, docking

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Authors: Ratna Farida Soenarto, Anas Alatas, Made Ryan Kharmayani

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Background: Conventional ultrafiltration (CUF) system was shown to be helpful in reducing anti-inflammatory mediators for patients who underwent open heart surgery. Additionally, modified ultrafiltration (MUF) has been shown to reduce anti-inflammatory mediators further while reducing interstitial fluid volume at the same time. However, there has been minimal data concerning the efficacy of combining both ultrafiltration methods. This study aims to compare inflammation marker, vascular resistance, and cardiac index on CUF+MUF patients with CUF only patients undergoing open heart surgery. Method: This is a single blind randomized controlled trial on patients undergoing open heart surgery between June 2021 - October 2021 in CiptoMangunkusumo National Referral Hospital and Jakarta Heart Hospital. Patients wererandomized using block randomization into modified ultrafiltration following conventional ultrafiltration (CUF+MUF) and conventional ultrafiltration (CUF) only. Outcome assessed in this study were 24-hoursinterleukin-6 levels, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), and cardiac index. Results: A total of 38patients were included (19 CUF+MUF and 19 CUF subjects). There was no difference in postoperative IL-6 level between groups (p > 0.05).No difference in PVR was observed between groups.Higher difference in SVR was observed in CUF+MUF group (-646 vs. -261dyn/s/cm-5, p < 0.05). Higher cardiac index was observed on CUF+MUF group (0.93 vs. 0.48, p < 0.05). Conclusion: Patients undergoing open heart surgery with modified ultrafiltration following conventional ultrafiltration had similar systemic inflammatory response and better cardiac response than those having conventional ultrafiltration.

Keywords: open-heart, CUF, MUF, SVR, PVR, IL-6

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Authors: Kh. Dehkordi, R. Sharifi Gholam, S. Arshadi

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Objective: Oxidative stress is produced under diabetic conditions and possibly causes various forms of tissue damage inpatients with diabetes. Antioxidants defend against the harmful effect of free radicals, which are associated with heart disease, cancer, arthritis, aging and many other diseases1). Antioxidants are very stable molecules capable of neutralizing free radicals by donating an electron to them.The aim of this study was to examine the effect of swimming training, fenugreek seed extract and glibenclamide on plasma glucose and cardiac antioxidants activity in diabetic rats. Design: For this purpose, fifty male wistar rats were divided into five groups, two groups of control rats (diabetic control [DC] and healthy control [HC]), one group of endurance swimming training (EST), one group of fenugreek seed extract highdose (F1, 1.74 g/kg b.w), one group of fenugreek seed extract middle dose (F2, 0.87 g/kg b.w), one group of glibenclamide (G, 0.5 mg/kg b.w). Materials and Methods: Diabetes induced by streptozotocine (STZ), data was analyzed using the one-way ANOVA followed by a Tukey test. Significance level was 0.05. Results: All of the groups' exception of HC showed significant decrease in body weight (P < 0.05), but the diabetic control and swimming training group exhibited a more decrease. All of the groups have shown a significant decrease in plasma glucose than DC group (P < 0.05) but this reduction was more in G group than DC no HC group. S, G and HC groups have shown significant increase in cardiac antioxidant than DC group (P < 0.05) but there wasn't significant difference in other groups (P > 0.05). Conclusion: The present results indicate that regular swimming training lead to decrease in plasma glucose and enhanced cardiac antioxidants in diabetic rats.

Keywords: swimming, glucose, cardiac, antioxidants

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