Search results for: reperfusion arrhythmia

Authors: Niyada Naksuk, Thoetchai Peeraphatdit, Vitaly Herasevich, Peter A. Brady, Suraj Kapa, Samuel J. Asirvatham

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Introduction: Little is known about the safety of antipsychotic therapy for delirium in the coronary care unit (CCU). Our aim was to examine the effect of delirium and antipsychotic therapy among CCU patients. Methods: Pre-study Confusion Assessment Method-Intensive Care Unit (CAM–ICU) criteria were implemented in screening consecutive patients admitted to Mayo Clinic, Rochester, the USA from 2004 through 2013. Death status was prospectively ascertained. Results: Of 11,079 study patients, the incidence of delirium was 8.3% (n=925). Delirium was associated with an increased risk of in-hospital mortality (adjusted OR 1.49; 95% CI, 1.08-2.08; P=.02) and one-year mortality among patients who survived from CCU admission (adjusted HR 1.46; 95% CI, 1.12-1.87; P=.005). A total of 792 doses of haloperidol (5 IQR [3-10] mg/day) or quetiapine (25 IQR [13-50] mg/day) were given to 244 patients with delirium. The clinical characteristics of patients with delirium who did and did not receive antipsychotic therapy were not different (baseline corrected QT [QTc] interval 460±61 ms vs. 457±58 ms, respectively; P = 0.57). In comparison to baseline, mean QTc intervals after the first and third doses of the antipsychotics were not significantly prolonged in haloperidol (448±56, 458±57, and 450±50 ms, respectively) or quetiapine groups (459±54, 467±68, and 462±46 ms, respectively) (P > 0.05 for all). Additionally, in-hospital mortality (adjusted OR 0.67; 95% CI, 0.42-1.04; P=.07), ventricular arrhythmia (adjusted OR 0.87; 95% CI, 0.17-3.62; P=.85) and one-year mortality among the hospital survivors (adjusted HR 0.86; 95% CI 0.62-1.17; P = 0.34) were not different in patients with delirium irrespective of whether or not they received antipsychotics. Conclusions: In patients admitted to the CCU, delirium was associated with an increase in both in-hospital and one-year mortality. Low doses of haloperidol and quetiapine appeared to be safe, without an increase in risk of sudden cardiac death, in-hospital mortality, or one-year mortality in carefully monitored patients.

Keywords: arrhythmias, haloperidol, mortality, qtc interval, quetiapine

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Authors: Huawei Bai, Jianguo Yao, Fellow, IEEE

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Atrial fibrillation (AF) is the most common form of heart arrhythmia and is closely associated with mortality and morbidity in heart failure, stroke, and coronary artery disease. The development of single spot optical sensors enables widespread photoplethysmography (PPG) screening, especially for AF, since it represents a more convenient and noninvasive approach. To our knowledge, most existing studies based on public and unbalanced datasets can barely handle the multiple noises sources in the real world and, also, lack interpretability. In this paper, we construct a large- scale PPG dataset using measurements collected from PPG wrist- watch devices worn by volunteers and propose an attention-based two-stream heterogeneous neural network (TSHNN). The first stream is a hybrid neural network consisting of a three-layer one-dimensional convolutional neural network (1D-CNN) and two-layer attention- based bidirectional long short-term memory (Bi-LSTM) network to learn representations from temporally sampled signals. The second stream extracts latent representations from the PPG time-frequency spectrogram using a five-layer CNN. The outputs from both streams are fed into a fusion layer for the outcome. Visualization of the attention weights learned demonstrates the effectiveness of the attention mechanism against noise. The experimental results show that the TSHNN outperforms all the competitive baseline approaches and with 98.09% accuracy, achieves state-of-the-art performance.

Keywords: PPG wearables, atrial fibrillation, feature fusion, attention mechanism, hyber network

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Authors: Ibrahim Ahmed, Richard Amoateng, Akhil Jain, Mohamed Ahmed

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Alcoholic cardiomyopathy (ACM) is a type of acquired cardiomyopathy caused by chronic alcohol consumption. Frequently ACM is associated with arrhythmias such as atrial flutter. Our aim was to characterize the patient demographics and investigate the effect of atrial flutter (AF) on ACM. This was a retrospective cohort study using the Nationwide Inpatient Sample database to identify admissions in adults with principal and secondary diagnoses of alcoholic cardiomyopathy and atrial flutter from 2019. Multivariate linear and logistic regression models were adjusted for age, gender, race, household income, insurance status, Elixhauser comorbidity score, hospital location, bed size, and teaching status. The primary outcome was all-cause mortality, and secondary outcomes were the length of stay (LOS) and total charge in USD. There was a total of 21,855 admissions with alcoholic cardiomyopathy, of which 1,635 had atrial flutter (AF-ACM). Compared to Non-AF-ACM cohort, AF-ACM cohort had fewer females (4.89% vs 14.54%, p<0.001), were older (58.66 vs 56.13 years, p<0.001), fewer Native Americans (0.61% vs2.67%, p<0.01), had fewer smaller (19.27% vs 22.45%, p<0.01) & medium-sized hospitals (23.24% vs28.98%, p<0.01), but more large-sized hospitals (57.49% vs 48.57%, p<0.01), more Medicare (40.37% vs 34.08%, p<0.05) and fewer Medicaid insured (23.55% vs 33.70%, p=<0.001), fewer hypertension (10.7% vs 15.01%, p<0.05), and more obesity (24.77% vs 16.35%, p<0.001). Compared to Non-AF-ACM cohort, there was no difference in AF-ACM cohort mortality rate (6.13% vs 4.20%, p=0.0998), unadjusted mortality OR 1.49 (95% CI 0.92-2.40, p=0.102), adjusted mortality OR 1.36 (95% CI 0.83-2.24, p=0.221), but there was a difference in LOS 1.23 days (95% CI 0.34-2.13, p<0.01), total charge $28,860.30 (95% CI 11,883.96-45,836.60, p<0.01). In patients admitted with ACM, the presence of AF was not associated with a higher all-cause mortality rate or odds of all-cause mortality; however, it was associated with 1.23 days increase in LOS and a $28,860.30 increase in total hospitalization charge. Native Americans, older age and obesity were risk factors for the presence of AF in ACM.

Keywords: alcoholic cardiomyopathy, atrial flutter, cardiomyopathy, arrhythmia

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Authors: A. Kherraf, S. Ouarrak, L. Azzouzi, R. Habbal

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Introduction: Preserved LVEF heart failure is an important cause of mortality and morbidity in hypertensive patients. A strong correlation between impaired diastolic function and longitudinal systolic dysfunction. could have several explanations, first, the diastole is an energy dependent process, especially during its first phase, it also includes active systolic components during the phase of iso volumetric relaxation, in addition, the impairment of the intrinsic myocytic function is part of hypertensive pathology as evidenced by recent studies. METHODS AND MATERIALS: This work consists of performing in a series of 333 hypertensive patients (aged 25 to 75 years) a complete echocardiographic study, including LVEF by Simpson biplane method, the calculation of the indexed left ventricular mass, the analysis of the diastolic function, and finally, the study of the longitudinal deformation of the LV by the technique of speckletracking (calculation of the GLS). Patients with secondary hypertension, leaky or stenosing valve disease, arrhythmia, and a history of coronary insufficiency were excluded from this study. RESULTS: Of the 333 hypertensive patients, 225 patients (67.5%) had impaired diastolic function, of which 60 patients (18%) had high filling pressures. 49.39% had echocardigraphic HVG, Almost all of these patients (60 patients) had low GLS. There is a statistically very significant relationship between lower GLS and increased left ventricular filling pressures in hypertensive patients. These results suggest that increased filling pressures are closely associated with atrioventricular interaction in patients with hypertension, with a strong correlation with impairment of longitudinal systolic function and diastolic function CONCLUSION: Overall, a linear relationship is established between increased left ventricular mass, diastolic dysfunction, and longitudinal LV systolic dysfunction

Keywords: hypertension, diastolic function, left ventricle, heart failure

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Authors: Omar bin Mihat

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The number of sudden deaths is increasing over the past years. These deaths occur not during physical activities but upon cessation. Post-mortem confirms these deaths as cardiac arrest non-specifically. Congenital heart disease is a condition undiagnosed whereby only surface upon physical exertion leading to sudden death is unavoidable. Channelopathy, a condition that refers to any disease from the defect in iron-channel function, particularly the sodium-potassium pump, during the cessation of the exercise can be controlled. The derivation of heart rate return (HRrtn) is a procedure of a control cooling down process according to the heart rate (HR). Empirically, potassium rises linearly with intensity and falls sharply upon abrupt cessation of exertion, resulting in fatal arrhythmia due to hypokalaemia. It is vital that the flux of potassium should be maintained within the normal range during physical activities. To achieve this, the dosage of physical exertion (exercise) should be identified. Various percentages of the intensity of maximum heart rate (MHR) will precipitate different adaptations and remodeling of various organs. 70% of MHR will surface physiological adaptations, including enhancement of endurance, fitness level, and general health, and there was no significant rise of serum potassium (K+) during the entire phase of the treadmill brisk walk at a different rate of perceived exertion (RPE) from the subject of various fitness background. There was also no significant rise in blood pressure (BP) during the entire phase of the treadmill brisk walk, substantiating 70% MHR is the safe dosage across different parameters of health and fitness level.

Keywords: potassium, maximal heart rate, exercise dosage, fitness level

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Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

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Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

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Authors: Zouhair Haddi, Stephane Delliaux, Jean-Francois Pons, Ismail Kechaf, Jean-Claude De Haro, Mustapha Ouladsine

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Atrial fibrillation (AF) has been considered as the most common cardiac arrhythmia, and a major public health burden associated with significant morbidity and mortality. Nowadays, telemedical approaches targeting cardiac outpatients situate AF among the most challenged medical issues. The automatic, early, and fast AF detection is still a major concern for the healthcare professional. Several algorithms based on univariate analysis have been developed to detect atrial fibrillation. However, the published results do not show satisfactory classification accuracy. This work was aimed at resolving this shortcoming by proposing multivariate data analysis methods for automatic AF detection. Four publicly-accessible sets of clinical data (AF Termination Challenge Database, MIT-BIH AF, Normal Sinus Rhythm RR Interval Database, and MIT-BIH Normal Sinus Rhythm Databases) were used for assessment. All time series were segmented in 1 min RR intervals window and then four specific features were calculated. Two pattern recognition methods, i.e., Principal Component Analysis (PCA) and Learning Vector Quantization (LVQ) neural network were used to develop classification models. PCA, as a feature reduction method, was employed to find important features to discriminate between AF and Normal Sinus Rhythm. Despite its very simple structure, the results show that the LVQ model performs better on the analyzed databases than do existing algorithms, with high sensitivity and specificity (99.19% and 99.39%, respectively). The proposed AF detection holds several interesting properties, and can be implemented with just a few arithmetical operations which make it a suitable choice for telecare applications.

Keywords: atrial fibrillation, multivariate data analysis, automatic detection, telemedicine

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Authors: Fae Princess Bermudez

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Background: One of the least significant leads on a 12-lead electrocardiogram is the augmented right lead (aVR), as it is not as specific compared to the other leads. In this case series, the value of lead aVR, which is more often than not ignored, is highlighted. Three cases of aVR ST segment elevation on 12-lead electrocardiogram are described, with the end outcome of demise of all three patients. The importance of immediate revascularization is described to improve prognosis in this group of patients. Objectives: This case series aims to primarily present under-reported cases of isolated aVR ST-segrment elevation myocardial infarction (STEMI), their course and outcome. More specific aims are to identify the criteria in determination of isolated aVR STEMI, know its clinical significance, and determine appropriate management for patients with this ECG finding. Method: A short review of previous studies, case reports, articles and guidelines from 2011-2016 was done. The author reviewed available literature, sorted out those that proved to be significant for the presented cases, and described them in conjunction with the aforementioned cases. Findings: Based on the limited information on these rare or under-reported cases, it was found that isolated aVR STEMI had a poorer prognosis that led to significant mortality and morbidity of patients. The significance of aVR ST-elevation was that of an occlusion of the left coronary artery or a severe three-vessel disease in the presence of an Acute Coronary Syndrome. Guidelines from American Heart Association/American College of Cardiology Foundation in 2013 already recognized ST-elevation of lead aVR in isolation as a STEMI; hence, recommended that patients with this particular ECG finding should undergo reperfusion strategies to improve prognosis. Conclusion: The indispensability of isolated aVR ST-segment elevation on ECG should alert physicians, especially Emergency physicians, to the high probability of Acute Coronary Syndrome with a very poor prognosis. If this group of patients is not promptly managed, demise may ensue, with cardiogenic shock as the most probable cause. With this electrocardiogram finding, physicians must be quick to make clinical decisions to increase chances of survival of this group of patients.

Keywords: AVR ST-elevation, diffuse ST-segment depression, left coronary artery infarction, myocardial infarction

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Authors: Richa Shri, Varinder Singh, Kundan Singh Bora, Abhishek Bhanot, Rahul Kumar, Amit Kumar, Ravinder Kaur

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The term ‘neuroprotection’ means preserving/salvaging function and structure of neurons. Neuroprotection is an adjunctive treatment option for neurodegenerative disorders. Oxidative stress is considered a major culprit in neurodegenerative disorders; hence, management strategies include use of antioxidants. Our search for a neuroprotective agent began with Allium cepa L. or onions, (family Amaryllidaceae) - a potent antioxidant. We have investigated the neuroprotective potential of onions in experimental models of ischemic stroke, diabetic neuropathy, neuropathic pain, and dementia. In pre and post-ischemic stroke model, the methanol extract of outer scales of onion bulbs (MEOS) prevented memory loss and motor in-coordination; reduced oxidative stress and cerebral infarct size. This also prevented and ameliorated diabetic neuropathy in mice. The MEOS was fractionated to yield a flavonoid rich fraction (FRF) that successfully reversed ischemia-reperfusion induced neuronal damage, thereby demonstrating that the flavonoids are responsible for the activity. The FRF effectively ameliorated chronic constriction induced neuropathic pain in rats. The FRF was subjected to bioactivity-guided fractionated. It was seen that FRF is more effective as compared to the isolated components probably due to synergism among the constituents (i.e., quercetin and quercetin glucosides) in the FRF. The outer scales of onion bulbs have great potential for prevention as well as for treatment of neuronal disorders. Red onions, with higher amounts of flavonoids as compared to the white onions, produced more significant neuroprotection. Thus, the standardized FRF from the waste material of a commonly used vegetable, especially the red variety, may be developed as a valuable neuroprotective agent.

Keywords: Allium cepa, antioxidant activity, flavonoid rich fraction, neuroprotection

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Authors: Athicha Cherdpunt, Patompong Satapornpong

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The medical cannabis is made up of components also known as cannabinoids, which consists of two ingredients which are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Interestingly, the Cannabinoid can be used for many treatments such as chemotherapy, including nausea and vomiting, cachexia, anorexia nervosa, spinal cord injury and disease, epilepsy, pain, and many others. However, the adverse drug reactions (ADRs) of THC can cause sedation, anxiety, dizziness, appetite stimulation and impairments in driving and cognitive function. Furthermore, genetic polymorphisms of CYP2C9, CYP2C19 and CYP3A4 influenced the THC metabolism and might be a cause of ADRs. Particularly, CYP2C19*17 allele increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (UM). The aim of this study, is to investigate the frequency of CYP2C19*17 alleles in Thai patients who have been treated with medical cannabis. We prospectively enrolled 60 Thai patients who were treated with medical cannabis and clinical data from College of Pharmacy, Rangsit University. DNA of each patient was isolated from EDTA blood, using the Genomic DNA Mini Kit. CYP2C19*17 genotyping was conducted using the real time-PCR ViiA7 (ABI, Foster City, CA, USA). 30 patients with medical cannabis-induced ADRs group, 20 (67%) were female, and 10 (33%) were male, with an age range of 30-69 years. On the other hand, 30 patients without medical cannabis-induced ADRs (control group) consist of 17 (57%) female and 13 (43%) male. The most ADRs for medical cannabis treatment in the case group were dry mouth and dry throat (77%), tachycardia (70%), nausea (30%) and arrhythmia(10%). Accordingly, the case group carried CYP2C19*1/*1 (normal metabolizer) approximately 93%, while 7% patients carrying CYP2C19*1/*17 (ultra rapid metabolizers) exhibited in this group. Meanwhile, we found 90% of CYP2C19*1/*1 and 10% of CYP2C19*1/*17 in control group. In this study, we identified the frequency of CYP2C19*17 allele in Thai population which will support the pharmacogenetics biomarkers for screening and avoid ADRs of medical cannabis treatment.

Keywords: CYP2C19, allele frequency, ultra rapid metabolizer, medical cannabis

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Authors: Kenichi Yamahara, Makiko Ohshima, Shunsuke Ohnishi, Hidetoshi Tsuda, Akihiko Taguchi, Toshihiro Soma, Hiroyasu Ogawa, Jun Yoshimatsu, Tomoaki Ikeda

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We have previously reported the therapeutic potential of rat fetal membrane(FM)-derived mesenchymal stem cells (MSCs) using various rat models including hindlimb ischemia, autoimmune myocarditis, glomerulonephritis, renal ischemia-reperfusion injury, and myocardial infarction. In this study, 1) we isolated and characterized MSCs from human amnion and chorion; 2) we examined their differences in the expression profile of growth factors and cytokines; and 3) we investigated the therapeutic potential and difference of these MSCs using murine hindlimb ischemia and acute graft-versus-host disease (GVHD) models. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of GVHD disease. Our results highlight that human amnionand chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.

Keywords: amnion, chorion, fetal membrane, mesenchymal stem cells

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Authors: Naso Isaiah Thanavisuth

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Introduction: Medical cannabis can be used for treatment, including anorexia, pain, inflammation, multiple sclerosis, Parkinson's disease, epilepsy, cancer, and metabolic syndrome-related disorders. However, medical cannabis leads to adverse effects (AEs), which is delta-9-tetrahydrocannabinol (THC). In previous studies, the major of THC metabolism enzymes are CYP2C9. Especially, the variation of CYP2C9 gene consist of CYP2C9*2 on exon 3 (C430T) (Arg144Cys) and CYP2C9*3 on exon 7 (A1075C) (Ile359Leu) to decrease enzyme activity. Notwithstanding, there is no data describing whether the variant of CYP2C9 genes are a pharmacogenetics marker for prediction of THC-induced AEs in Thai patients. Objective: We want to investigate the association between CYP2C9 gene and THC-induced AEs in Thai patients. Method: We enrolled 39 Thai patients with medical cannabis treatment consisting of men and women who were classified by clinical data. The quality of DNA extraction was assessed by using NanoDrop ND-1000. The CYP2C9*2 and *3 genotyping were conducted using the TaqMan real time PCR assay (ABI, Foster City, CA, USA). Results: All Thai patients who received the medical cannabis consist of twenty four (61.54%) patients who were female and fifteen (38.46%) were male, with age range 27- 87 years. Moreover, the most AEs in Thai patients who were treated with medical cannabis between cases and controls were tachycardia, arrhythmia, dry mouth, and nausea. Particularly, thirteen (72.22%) medical cannabis-induced AEs were female and age range 33 – 69 years. In this study, none of the medical cannabis groups carried CYP2C9*2 variants in Thai patients. The CYP2C9*3 variants (*1/*3, intermediate metabolizer, IM) and (*3/*3, poor metabolizer, PM) were found, three of thirty nine (7.69%) and one of thirty nine (2.56%) , respectively. Conclusion: This is the first study to confirm the genetic polymorphism of CYP2C9 and medical cannabis-induced AEs in the Thai population. Although, our results indicates that there is no found the CYP2C9*2. However, the variation of CYP2C9 allele might serve as a pharmacogenetics marker for screening before initiating the therapy with medical cannabis for prevention of medical cannabis-induced AEs.

Keywords: CYP2C9, medical cannabis, adverse effects, THC, P450

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Authors: Beatriz Lafuente Alcázar, Yash Wani, Amit J. Nimunkar

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Cardiovascular Diseases (CVDs) are the leading cause of death globally, and around 80% of sudden cardiac deaths are due to arrhythmias or irregular heartbeats. The majority of these pathologies are revealed by either short-term or long-term alterations in the electrocardiogram (ECG) morphology. The ECG is the main diagnostic tool in cardiology. It is a non-invasive, pain free procedure that measures the heart’s electrical activity and that allows the detecting of abnormal rhythms and underlying conditions. A cardiologist can diagnose a wide range of pathologies based on ECG’s form alterations, but the human interpretation is subjective and it is contingent to error. Moreover, ECG records can be quite prolonged in time, which can further complicate visual diagnosis, and deeply retard disease detection. In this context, deep learning methods have risen as a promising strategy to extract relevant features and eliminate individual subjectivity in ECG analysis. They facilitate the computation of large sets of data and can provide early and precise diagnoses. Therefore, the cardiology field is one of the areas that can most benefit from the implementation of deep learning algorithms. In the present study, a deep learning algorithm is trained following a novel approach, using a combination of different databases as the training set. The goal of the algorithm is to achieve the detection of R-peaks in ECG signals. Its performance is further evaluated in ECG signals with different origins and features to test the model’s ability to generalize its outcomes. Performance of the model for detection of R-peaks for clean and noisy ECGs is presented. The model is able to detect R-peaks in the presence of various types of noise, and when presented with data, it has not been trained. It is expected that this approach will increase the effectiveness and capacity of cardiologists to detect divergences in the normal cardiac activity of their patients.

Keywords: arrhythmia, deep learning, electrocardiogram, machine learning, R-peaks

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Authors: Tanakrit Doltanakarn

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Introduction: These days, cannabis is being accepted in many countries due to the fact that cannabis could be use in medical. The medical cannabis is used to treat and reduce the pain many diseases. For example, neuropathic pain, Parkinson, autism disorders, cancer pain reduce the adverse effect of chemotherapy, diabetes, and migraine. Active ingredients in cannabis that modulate patients' perceptions of their conditions include Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), flavonoids, and terpenes. However, there is an adverse effect of cannabis, cardiovascular effects, psychosis, schizophrenia, mood disorder, and cognitive alternation. These effects are from the THC and CBD ingredients in the cannabis. The metabolize processes of delta-9 THC to 11-OH-delta 9 -THC (inactive form), THC were cause of adverse effects. Interestingly, the distributions of CYP2C9 gene (CYP2C9*2 and CYP2C9*3, poor metabolizer) that might affect incidences of adverse effects in patients who treated with medical cannabis. Objective: The aim of this study we want to investigate the association between genetic polymorphism of CYP2C9 frequency and Thai patients who treated with medical cannabis. Materials and Methods:We recruited sixty-five unrelated Thai patients from the College of Pharmacy, Rangsit University. DNA were extracted using Genomic DNA Mini Kit. Genotyping of CYP2C9*2 (430C>T, rs1799853) and CYP2C9*3 (1075A>C, rs1057910) were genotyped by the TaqMan Real-time PCR assay. Results: Among these 31 medicals cannabis-induced ADRs patients, they were diagnosed with 22 (33.85%) tachycardia and 3 (4.62%) arrhythmia. There were 34 (52.31%) medical cannabis-tolerant controls who were included in this study.40 (61.53%) Thai patients were female, and 25 (38.46%) were male, with median age of 57 (range 27 – 87) years. In this study, we found none of the medical cannabis-induced ADRs carried CYP2C9*2 variant along with medical cannabis-tolerant control group. CYP2C9*3 variant (intermediate metabolizer, IM) was found just only one of thirty-one (3.23%) in the medical cannabis-induced ADRs and two of thirty-fourth (5.88%) in the tolerant controls. Conclusions: Thus, the distribution of CYP2C9 alleles offer a comprehensive view of pharmacogenomics marker in Thai population that could be used as a reference for worldwide to investigate the pharmacogenomics application.

Keywords: medical cannabis, adverse effect, CYP2C9, thai patients

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Authors: Firouz Amani, Adalat Hoseinian, Sajjad Hakimian

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Background: The mortality due to Myocardial Infarction (MI) is often occur during the first hours after onset of symptom. So, for taking the necessary treatment and decreasing the mortality rate, timely visited of the hospital could be effective in this regard. The aim of this study was to investigate the impact of effective factors in mortality of MI patients by using Linear Logistic Regression. Materials and Methods: In this case-control study, all patients with Acute MI who referred to the Ardabil city hospital were studied. All of died patients were considered as the case group (n=27) and we select 27 matched patients without Acute MI as a control group. Data collected for all patients in two groups by a same checklist and then analyzed by SPSS version 24 software using statistical methods. We used the linear logistic regression model to determine the effective factors on mortality of MI patients. Results: The mean age of patients in case group was significantly higher than control group (75.1±11.7 vs. 63.1±11.6, p=0.001).The history of non-cardinal diseases in case group with 44.4% significantly higher than control group with 7.4% (p=0.002).The number of performed PCIs in case group with 40.7% significantly lower than control group with 74.1% (P=0.013). The time distance between hospital admission and performed PCI in case group with 110.9 min was significantly upper than control group with 56 min (P=0.001). The mean of delay time from Onset of symptom to hospital admission (patient delay) and the mean of delay time from hospital admissions to receive treatment (system delay) was similar between two groups. By using logistic regression model we revealed that history of non-cardinal diseases (OR=283) and the number of performed PCIs (OR=24.5) had significant impact on mortality of MI patients in compare to other factors. Conclusion: Results of this study showed that of all studied factors, the number of performed PCIs, history of non-cardinal illness and the interval between onset of symptoms and performed PCI have significant relation with morality of MI patients and other factors were not meaningful. So, doing more studies with a large sample and investigated other involved factors such as smoking, weather and etc. is recommended in future.

Keywords: acute MI, mortality, heart failure, arrhythmia

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Authors: Jhiamluka Zservando Solano Velasquez, Raul Palma, Alejandro Calderon, Servio Paguada, Erick Marin, Kellyn Funes, Hana Sandoval, Oscar Hernandez

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Background: Screening cardiac conditions in primary care in developing countries can be challenging, and Honduras is not the exception. One of the main limitations is the underfunding of the Healthcare System in general, causing conventional ECG acquisition to become a secondary priority. Objective: Development of a low-cost ECG to improve screening of arrhythmias in primary care and communication with a specialist in secondary and tertiary care. Methods: Design a portable, pocket-size low-cost 3 lead ECG (Handy EKG). The device is autonomous and has Wi-Fi/Bluetooth connectivity options. A mobile app was designed which can access online servers with machine learning, a subset of artificial intelligence to learn from the data and aid clinicians in their interpretation of readings. Additionally, the device would use the online servers to transfer patient’s data and readings to a specialist in secondary and tertiary care. 50 randomized patients volunteer to participate to test the device. The patients had no previous cardiac-related conditions, and readings were taken. One reading was performed with the conventional ECG and 3 readings with the Handy EKG using different lead positions. This project was possible thanks to the funding provided by the National Autonomous University of Honduras. Results: Preliminary results show that the Handy EKG performs readings of the cardiac activity similar to those of a conventional electrocardiograph in lead I, II, and III depending on the position of the leads at a lower cost. The wave and segment duration, amplitude, and morphology of the readings were similar to the conventional ECG, and interpretation was possible to conclude whether there was an arrhythmia or not. Two cases of prolonged PR segment were found in both ECG device readings. Conclusion: Using a Frugal innovation approach can allow lower income countries to develop innovative medical devices such as the Handy EKG to fulfill unmet needs at lower prices without compromising effectiveness, safety, and quality. The Handy EKG provides a solution for primary care screening at a much lower cost and allows for convenient storage of the readings in online servers where clinical data of patients can then be accessed remotely by Cardiology specialists.

Keywords: low-cost hardware, portable electrocardiograph, prototype, remote healthcare

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Authors: Bharat Rawat, Shekhar Rajbhandari, Yadav Bhatta, Jay Prakash Jaiswal, Shivaji Bikram Silwal, Rajiv Shrestha, Shova Sunuwar

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Introduction: The honey produced by the bees fed on Rhobdodendron species containing grayanotoxin is known as mad honey. Grayanotoxin is found in honey obtained from the nectar of Rhododendron species growing on the mountains of the Black Sea region of Turkey and also in Japan, Nepal, Brazil, parts of North America, and Europe. Although the incidence of grayanotoxin poisoning is rare, there is concern that the number of cases per year will rise with the increasing demand for organic products. Mad honey intoxication might present with mild symptoms of cardiovascular, gastrointestinal and neurological systems or might also present with a life-threatening form with AV block and cardiovascular collapse. In this article, we describe the summary of five cases, which came to our hospital with mad honey related cardiac complications. Findings: In last one year, five cases presented in the emergency department with sudden onset of Loss of consciousness, dizziness, shortness of breath. They felt difficulty after the consumption of 1-3 teaspoonful of wild honey. The honey was brought from most of the rural parts of Nepal like khotang. Some of them also came with vomiting, dizziness, and loose stool. On examination, most of them had severe bradycardia and low blood pressure. No abnormalities were detected on systemic examinations. In one patient, ECG and cardiac enzymes showed features of the acute coronary syndrome, but his treadmill test done few days later was normal. All patients were managed with inj. Atropine, I/V normal saline, and other supportive measures and discharged in a stable condition within one or two days. Conclusions: Rhododendrons is the national flower of Nepal. The specific species of rhododendron found in Nepal which contains the toxin is not known. Bees feeding on these rhododendrons are known to transfer the grayanotoxin to the honey they produce. Most symptoms are mild and resolve themselves without medical intervention. Signs and symptoms of grayanotoxin poisoning rarely last more than 24 hours and are usually not fatal. Some signs of mad honey poisoning include Bradycardia, Cardiac arrhythmia, Hypotension, Nausea and Vomiting. They respond to close monitoring and appropriate supportive treatment. Normally, patients recover completely with no residual damage to the heart or its conduction system.

Keywords: rhobdodendron, honey, grayanotoxin, bradycardia

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Authors: Yongrong Liu, Xin Tang

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Background: Persistent atrial fibrillation is a common arrhythmia closely related to heart failure. Heart rate control is an essential strategy for treating persistent atrial fibrillation. Still, the understanding of the relationship between different heart rate control levels and the risk of heart failure rehospitalization is limited. Objective: The objective of the study is to determine the relationship between different levels of heart rate control in patients with persistent atrial fibrillation and the risk of readmission for heart failure. Methods: We conducted a retrospective dual-centre cohort study, collecting data from patients with persistent atrial fibrillation who received outpatient treatment at two tertiary hospitals in central and western China from March 2019 to March 2020. The collected data included age, gender, body mass index (BMI), medical history, and hospitalization frequency due to heart failure. Patients were divided into three groups based on their heart rate control levels: Group I with a resting heart rate of less than 80 beats per minute, Group II with a resting heart rate between 80 and 100 beats per minute, and Group III with a resting heart rate greater than 100 beats per minute. The readmission rates due to heart failure within one year after discharge were statistically analyzed using propensity score matching in a 1:1 ratio. Differences in readmission rates among the different groups were compared using one-way ANOVA. The impact of varying levels of heart rate control on the risk of readmission for heart failure was assessed using the Cox proportional hazards model. Binary logistic regression analysis was employed to control for potential confounding factors. Results: We enrolled a total of 1136 patients with persistent atrial fibrillation. The results of the one-way ANOVA showed that there were differences in readmission rates among groups exposed to different levels of heart rate control. The readmission rates due to heart failure for each group were as follows: Group I (n=432): 31 (7.17%); Group II (n=387): 11.11%; Group III (n=317): 90 (28.50%) (F=54.3, P<0.001). After performing 1:1 propensity score matching for the different groups, 223 pairs were obtained. Analysis using the Cox proportional hazards model showed that compared to Group I, the risk of readmission for Group II was 1.372 (95% CI: 1.125-1.682, P<0.001), and for Group III was 2.053 (95% CI: 1.006-5.437, P<0.001). Furthermore, binary logistic regression analysis, including variables such as digoxin, hypertension, smoking, coronary heart disease, and chronic obstructive pulmonary disease as independent variables, revealed that coronary heart disease and COPD also had a significant impact on readmission due to heart failure (p<0.001). Conclusion: The correlation between the heart rate control level of patients with persistent atrial fibrillation and the risk of heart failure rehospitalization is positive. Reasonable heart rate control may significantly reduce the risk of heart failure rehospitalization.

Keywords: heart rate control levels, heart failure rehospitalization, persistent atrial fibrillation, retrospective cohort study

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Authors: Anna Mirczak

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Introduction: In connection with the aging of the population and the increase in the number of people with chronic illnesses, the priority objective for public health has become not only lengthening life, but also improving quality of life in older persons, as well as maintenance of their relative independence and active participation in social life. The most important determinant of a person’s quality of life is health. According to the literature, older people with chronic illness who live in rural settings are at greater risk for poor outcomes than their urban counterparts. Furthermore research characterizes the rural elderly as having a higher incidence of sickness, dysfunction, disability, restricted mobility, and acute and chronic conditions than their urban citizens. It is dictated by the overlapping certain specific socio-economic factors typical for rural areas which include: social and geography exclusion, limited access to health care centers, and low socioeconomic status. Aim of the study: The objective of this study was to recognize health status and needs of older people living in selected rural areas in Poland and evaluate the impacts of working in the farm on their health status. Material and methods: The study was performed personally, using interviews based on the structural questionnaires, during the period from March 2011 to October 2012. The group of respondents consisted 203 people aged 65 years and over living in selected rural areas in Poland. The analysis of collected research material was performed using the statistical package SPSS 19 for Windows. The level of significance for the tested the hypotheses assumed value of 0.05. Results: The mean age of participants was 75,5 years (SD=5,7) range from 65 to 94 years. Most of the interviewees had children (89.2%) and grandchildren (83.7) and lived mainly with family members (75.9%) mostly in double (46.8%) and triple (20.8%) household. The majority of respondents (71,9%) were physical working on the farm. At the time of interview, each of the respondents reported that they had been diagnosed with at least one chronic diseases by their GP. The most common were: hypertension (67,5%), osteoarthritis (44,8%), atherosclerosis (43,3%), cataract (40,4%), arrhythmia (28,6%), diabetes mellitus (19,7%) and stomach or duodenum ulcer diseases (17,2%).The number of diseases occurring of the sample was dependent on gender and age. Significant associations were observed between working on the farm and frequency of occurrence cardiovascular diseases, the gastrointestinal tract dysfunction and sensory disorders. Conclusions: The most common causes of disability among older citizens were: chronic diseases, malnutrition and complaints about access to health services (especially to cardiologist and an ophthalmologist). Health care access and health status are a particular concern in rural areas where the population is older, has lower education and income levels, and is more likely to be living in medically underserved areas than is the case in urban areas.

Keywords: ageing, health status, older people, rural

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Authors: R. P. Hewawasam, A. F. Dulhunty

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The ryanodine receptor (RyR) is an intracellular ion channel that releases Ca2+ from the sarcoplasmic reticulum and is essential for the excitation-contraction coupling and contraction in striated muscle. Human muscle specific glutathione transferase M2-2 (GSTM2-2) is a highly specific inhibitor of cardiac ryanodine receptor (RyR2) activity. Single channel-lipid bilayer studies and Ca2+ release assays performed using the C-terminal half of the GSTM2-2 and its mutants F157A and Y160A confirmed the ability of the C terminal domain of GSTM2-2 to specifically inhibit the cardiac ryanodine receptor activity. Objective of the present study is to determine the effect of C terminal domain of GSTM2-2 (GSTM2-2C) and the mutants, F157A and Y160A on the Ca2+ transients of neonatal ventricular cardiomyocytes. Primary cardiomyocytes were cultured from neonatal rats. They were treated with GSTM2-2C and the two mutants F157A and Y160A at 15µM and incubated for 2 hours. Then the cells were led with Fluo-4AM, fluorescent Ca2+ indicator, and the field stimulated (1 Hz, 3V and 2ms) cells were excited using the 488 nm argon laser. Contractility of the cells were measured and the Ca2+ transients in the stained cells were imaged using Leica SP5 confocal microscope. Peak amplitude of the Ca2+ transient, rise time and decay time from the peak were measured for each transient. In contrast to GSTM2C which significantly reduced the % shortening (42.8%) in the field stimulated cells, F157A and Y160A failed to reduce the % shortening.Analysis revealed that the average amplitude of the Ca2+ transient was significantly reduced (P<0.001) in cells treated with the wild type GSTM2-2C compared to that of untreated cells. Cells treated with the mutants F157A and Y160A didn’t change the Ca2+ transient significantly compared to the control. A significant increase in the rise time (P< 0.001) and a significant reduction in the decay time (P< 0.001) were observed in cardiomyocytes treated with GSTM2-2C compared to the control but not with F157A and Y160A. These results are consistent with the observation that GSTM2-2C reduced the Ca2+ release from the cardiac SR significantly whereas the mutants, F157A and Y160A didn’t show any effect compared to the control. GSTM2-2C has an isoform-specific effect on the cardiac ryanodine receptor activity and also it inhibits RyR2 channel activity only during diastole. Selective inhibition of RyR2 by GSTM2-2C has significant clinical potential in the treatment of cardiac arrhythmias and heart failure. Since GSTM2-2C-terminal construct has no GST enzyme activity, its introduction to the cardiomyocyte would not exert any unwanted side effects that may alter its enzymatic action. The present study further confirms that GSTM2-2C is capable of decreasing the Ca2+ release from the cardiac SR during diastole. These results raise the future possibility of using GSTM2-2C as a template for therapeutics that can depress RyR2 function when the channel is hyperactive in cardiac arrhythmias and heart failure.

Keywords: arrhythmia, cardiac muscle, cardiac ryanodine receptor, GSTM2-2

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Authors: Ayse Gul Bilen

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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).

Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI

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Authors: Elizabeth M. Annoni, Elena G. Tolkacheva

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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that is a known prognostic marker for stroke, heart failure and death. Reentrant mechanisms of rotor formation, which are stable electrical sources of cardiac excitation, are believed to cause AF. No existing commercial mapping systems have been demonstrated to consistently and accurately predict rotor locations outside of the pulmonary veins in patients with persistent AF. There is a clear need for robust spatio-temporal techniques that can consistently identify rotors using unique characteristics of the electrical recordings at the pivot point that can be applied to clinical intracardiac mapping. Recently, we have developed four new signal analysis approaches – Shannon entropy (SE), Kurtosis (Kt), multi-scale frequency (MSF), and multi-scale entropy (MSE) – to identify the pivot points of rotors. These proposed techniques utilize different cardiac signal characteristics (other than local activation) to uncover the intrinsic complexity of the electrical activity in the rotors, which are not taken into account in current mapping methods. We validated these techniques using high-resolution optical mapping experiments in which direct visualization and identification of rotors in ex-vivo Langendorff-perfused hearts were possible. Episodes of ventricular tachycardia (VT) were induced using burst pacing, and two examples of rotors were used showing 3-sec episodes of a single stationary rotor and figure-8 reentry with one rotor being stationary and one meandering. Movies were captured at a rate of 600 frames per second for 3 sec. with 64x64 pixel resolution. These optical mapping movies were used to evaluate the performance and robustness of SE, Kt, MSF and MSE techniques with respect to the following clinical limitations: different time of recordings, different spatial resolution, and the presence of meandering rotors. To quantitatively compare the results, SE, Kt, MSF and MSE techniques were compared to the “true” rotor(s) identified using the phase map. Accuracy was calculated for each approach as the duration of the time series and spatial resolution were reduced. The time series duration was decreased from its original length of 3 sec, down to 2, 1, and 0.5 sec. The spatial resolution of the original VT episodes was decreased from 64x64 pixels to 32x32, 16x16, and 8x8 pixels by uniformly removing pixels from the optical mapping video.. Our results demonstrate that Kt, MSF and MSE were able to accurately identify the pivot point of the rotor under all three clinical limitations. The MSE approach demonstrated the best overall performance, but Kt was the best in identifying the pivot point of the meandering rotor. Artifacts mildly affect the performance of Kt, MSF and MSE techniques, but had a strong negative impact of the performance of SE. The results of our study motivate further validation of SE, Kt, MSF and MSE techniques using intra-atrial electrograms from paroxysmal and persistent AF patients to see if these approaches can identify pivot points in a clinical setting. More accurate rotor localization could significantly increase the efficacy of catheter ablation to treat AF, resulting in a higher success rate for single procedures.

Keywords: Atrial Fibrillation, Optical Mapping, Signal Processing, Rotors

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Authors: Mariia A. Parfenenko, Ilya S. Dantsev, Sergei V. Bochenkov, Natalia V. Vinogradova, Olga S. Groznova, Victoria Yu. Voinova

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Introduction: Autism is the most common neurodevelopmental disorder. Autism is characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns and frequently co-occurs with epilepsy, intellectual disabilities, connective tissue disorders, and other conditions. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and neurodevelopment in embryogenesis. CHD8 is one of the genes most frequently involved in autism. Patients and methods: 2 unrelated male patients, P3 and P12, aged 3 and 12 years old, underwent whole genome sequencing, which determined that they both had different likely pathogenic variants, both previously undescribed in literature. Sanger sequencing later determined that P12 inherited the variant from his affected mother. Results: P3 and P12 presented with autism, a developmental delay, ataxia, sleep disorders, overgrowth, and macrocephaly, as well as other clinical features typically present in patients with causative variants in CHD8. The mother of P12 also has autistic traits, as well as ataxia, hypotonia, sleep disorders, and other symptoms. However, P3 and P12 also have different cardiac abnormalities. P3 had signs of a repolarization disorder: a flattened T wave in the III and aVF derivations and a negative T wave in the V1-V2 derivations. He also had structural valve anomalies with associated regurgitation, local contractility impairment of the left ventricular, and diastolic dysfunction of the right ventricle. Meanwhile, P12 had Wolff-Parkinson-White syndrome and underwent radiofrequency ablation at the age of 2 years. At the time of observation, P12 had mild sinus arrhythmia and an incomplete right bundle branch block, as well as arterial hypertension. Discussion: Cardiac abnormalities were not previously reported in patients with causative variants in CHD8. The underlying mechanism for the formation of those abnormalities is currently unknown. However, the two hypotheses are either a disordered interaction with CHD7 – another chromodomain remodeler known to be directly involved in the cardiophenotype of CHARGE syndrome – a rare condition characterized by coloboma, heart defects and growth abnormalities, or the disrupted functioning of CHD8 as an A-Kinase Anchoring Protein, which are known to modulate cardiac function. Conclusion: We observed 2 unrelated autistic males with likely pathogenic variants in CHD8 that presented with typical symptoms of CHD8-related neurodevelopmental disorder, as well as cardiac abnormalities. Cardiac abnormalities have, until now, been considered uncharacteristic for patients with causative variants in CHD8. Further accumulation of data, including experimental evidence of the involvement of CHD8 in heart formation, will elucidate the mechanism underlying the cardiophenotype of those patients. Acknowledgements: Molecular genetic testing of the patients was made possible by the Charity Fund for medical and social genetic aid projects «Life Genome.»

Keywords: autism spectrum disorders, chromodomain-helicase-DNA-binding protein 8, neurodevelopmental disorder, cardio phenotype

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Authors: Michael Brave, Mark Kroll, Steven Karch, Charles Wetli, Michael Graham, Sebastian Kunz, Dorin Panescu

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Background: Conducted electrical weapons (CEW) are now used in 107 countries and are a common law enforcement less-lethal force practice in the United Kingdom (UK), United States of America (USA), Canada, Australia, New Zealand, and others. Use of these devices is rarely temporally associated with the occurrence of sudden arrest-related deaths (ARD). Because such deaths are uncommon, few Medical Examiners (MEs) ever encounter one, and even fewer offices have established comprehensive investigative protocols. Without sufficient scientific data, the role, if any, played by a CEW in a given case is largely supplanted by conjecture often defaulting to a CEW-induced fatal cardiac arrhythmia. In addition to the difficulty in investigating individual deaths, the lack of information also detrimentally affects being able to define and evaluate the ARD cohort generally. More comprehensive, better information leads to better interpretation in individual cases and also to better research. The purpose of this presentation is to provide MEs with a comprehensive evidence-based checklist to assist in the assessment of CEW-ARD cases. Methods: PUBMED and Sociology/Criminology data bases were queried to find all medical, scientific, electrical, modeling, engineering, and sociology/criminology peer-reviewed literature for mentions of CEW or synonymous terms. Each paper was then individually reviewed to identify those that discussed possible bioelectrical mechanisms relating CEW to ARD. A Naranjo-type pharmacovigilance algorithm was also employed, when relevant, to identify and quantify possible direct CEW electrical myocardial stimulation. Additionally, CEW operational manuals and training materials were reviewed to allow incorporation of CEW-specific technical parameters. Results: Total relevant PUBMED citations of CEWs were less than 250, and reports of death extremely rare. Much relevant information was available from Sociology/Criminology data bases. Once the relevant published papers were identified, and reviewed, we compiled an annotated checklist of data that we consider critical to a thorough CEW-involved ARD investigation. Conclusion: We have developed an evidenced-based checklist that can be used by MEs and their staffs to assist them in identifying, collecting, documenting, maintaining, and objectively analyzing the role, if any, played by a CEW in any specific case of sudden death temporally associated with the use of a CEW. Even in cases where the collected information is deemed by the ME as insufficient for formulating an opinion or diagnosis to a reasonable degree of medical certainty, information collected as per the checklist will often be adequate for other stakeholders to use as a basis for informed decisions. Having reviewed the appropriate materials in a significant number of cases careful examination of the heart and brain is likely adequate. Channelopathy testing should be considered in some cases, however it may be considered cost prohibitive (aprox $3000). Law enforcement agencies may want to consider establishing a reserve fund to help manage such rare cases. The expense may stay the enormous costs associated with incident-precipitated litigation.

Keywords: ARD, CEW, police, TASER

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Authors: Ibrahim Abdulla Labib, Medhat Mohamed Morsy, Gamal Hosny, Hanan Dawood Yassa, Gaber Hassan

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Amiodarone is a very effective drug, widely used for arrhythmia. Unfortunately it has many side effects involving many organs especially thyroid gland. The current work was conducted to elucidate the effect of amiodarone on the thyroid gland and the possible protective role of vitamin E. Fifty adult male albino rats weighed 200 – 250 grams were divided into five groups; ten rats each. Group I (Control): Five rats were sacrificed after three weeks and five rats were sacrificed after six weeks. Group II (Sham control): Each rat received sunflower oil orally; the solvent of vitamin E for three weeks. Group III (Amiodarone-treated): each rat received an oral dose of amiodarone; 150 mg/kg/day for three weeks. Group IV (Recovery): Each rat received amiodarone as group III then the drug was stopped for three weeks to evaluate recovery. Group V (Amiodarone + Vitamin E-treated): Each rat received amiodarone as group III followed by 100 mg/kg/day vitamin E orally for three weeks. Thyroid gland of the sacrificed animals were dissected out and prepared for light and electron microscopic studies. Amiodarone administration resulted in loss of normal follicular architecture as many follicles appeared either shrunken, empty or contained scanty pale colloid. Some follicles appeared lined by more than one layer of cells while others showed interruption of their membrane. Masson's Trichrome stained sections showed increased collagen fibers in between the thyroid follicles. Ultrastructurally, the apical border of the follicular cells showed few irregular detached microvilli. The nuclei of the follicular cells were almost irregular with chromatin condensation. The cytoplasm of most follicular cells revealed numerous dilated rough endoplasmic reticulum with numerous lysosomes. After three weeks of stopping amiodarone, the follicles were nearly regular in outline. Some follicles were filled with homogenous eosinophilic colloid and others had shrunken pale colloid or were empty. Some few follicles showed exfoliated cells in their lumina and others were still lined by more than one layer of follicular cells. Moderate amounts of collagen fibers were observed in-between thyroid follicles. Ultrastructurally, many follicular cells had rounded euchromatic nucleui, moderate number of lysosomes and moderately dilated rough endoplasmic reticulum. However, few follicular cells still showing irregular nucleui, dilated rough endoplasmic reticulum and many cytoplasmic vacuoles. Administration of vitamin E with amiodarone for three weeks resulted in obvious structural improvement. Most of the follicles were lined by a single layer of cuboidal cells and the lumina were filled with homogenous eosinophilic colloid with very few vacuolations. The majority of follicular cells had rounded nuclei with occasional detection of ballooned cells and dark nuclei. Scanty collagen fibers were detected among thyroid follicles. Ultrastructurally, most follicular cells exhibited rounded euchromatic nuclei with few short microvilli were projecting into the colloid. Few lysosomes were also noticed. It was concluded that amiodarone administration leads to many adverse histological changes in the thyroid gland. Some of these changes are reversible during the recovery period however concomitant vitamin E administration with amiodarone has a major protective role in preventing many of these changes.

Keywords: amiodarone, recovery, ultrastructure, vitamin E.

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Authors: Dina Farran, Mark Ashworth, Fiona Gaughran

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Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is associated with an increased risk of stroke, contributing to heart failure and death. In this project, we aim to improve patient safety by screening for stroke risk among people with AF and co-morbid mental illness. To do so, we started by conducting a systematic review and meta-analysis on prevalence, management, and outcomes of AF in people with Serious Mental Illness (SMI) versus the general population. We then evaluated oral anticoagulation (OAC) prescription trends in people with AF and co-morbid SMI in King’s College Hospital. We also evaluated the association between mental illness severity and OAC prescription in eligible patients in South London and Maudsley (SLaM) NHS Foundation Trust. Next, we implemented an electronic clinical decision support system (eCDSS) consisting of a visual prompt on patient electronic Personal Health Records to screen for AF-related stroke risk in three Mental Health of Older Adults wards at SLaM. Finally, we assessed the feasibility and acceptability of the eCDSS by qualitatively investigating clinicians’ perspectives of the potential usefulness of the eCDSS (pre-intervention) and their experiences and their views regarding its impact on clinicians and patients (post-intervention). The systematic review showed that people with SMI had low reported rates of AF. AF patients with SMI were less likely to receive OAC than the general population. When receiving warfarin, people with SMI, particularly bipolar disorder, experienced poor anticoagulation control compared to the general population. Meta-analysis showed that SMI was not significantly associated with an increased risk of stroke or major bleeding when adjusting for underlying risk factors. The main findings of the first observational study were that among AF patients having a high stroke risk, those with co-morbid SMI were less likely than non-SMI to be prescribed any OAC, particularly warfarin. After 2019, there was no significant difference between the two groups. In the second observational study, patients with AF and co-morbid SMI were less likely to be prescribed any OAC compared to those with dementia, substance use disorders, or common mental disorders, adjusting for age, sex, stroke, and bleeding risk scores. Among AF patients with co-morbid SMI, warfarin was less likely to be prescribed to those having alcohol or substance dependency, serious self-injury, hallucinations or delusions, and activities of daily living impairment. In the intervention, clinicians were asked to confirm the presence of AF, clinically assess stroke and bleeding risks, record risk scores in clinical notes, and refer patients at high risk of stroke to OAC clinics. Clinicians reported many potential benefits for the eCDSS, including improving clinical effectiveness, better identification of patients at risk, safer and more comprehensive care, consistency in decision making and saving time. Identified potential risks included rigidity in decision-making, overreliance, reduced critical thinking, false positive recommendations, annoyance, and increased workload. This study presents a unique opportunity to quantify AF patients with mental illness who are at high risk of severe outcomes using electronic health records. This has the potential to improve health outcomes and, therefore patients' quality of life.

Keywords: atrial fibrillation, stroke, mental health conditions, electronic clinical decision support systems

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Authors: Michael Josef Schwerer

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Background: Analyzing any aircraft accident is mandatory based on the regulations of the International Civil Aviation Organization and the respective country’s criminal prosecution authorities. Legal medicine investigations are unavoidable when fatalities involve the flight crew or when doubts arise concerning the pilot’s aeromedical health status before the event. As a result of frequently tremendous blunt and sharp force trauma along with the impact of the aircraft to the ground, consecutive blast or fire exposition of the occupants or putrefaction of the dead bodies in cases of delayed recovery, relevant findings can be masked or destroyed and therefor being inaccessible in standard pathology practice comprising just forensic autopsy and histopathology. Such cases are of considerable risk of remaining unsolved without legal consequences for those responsible. Further, no lessons can be drawn from these scenarios to improve flight safety and prevent future mishaps. Aims and Methods: To learn from previously unsolved aircraft accidents, re-evaluations of the investigation files and modern molecular pathology studies were performed. Genetic testing involved predominantly PCR-based analysis of gene regulation, studying DNA promotor methylations, RNA transcription and posttranscriptional regulation. In addition, the presence or absence of infective agents, particularly DNA- and RNA-viruses, was studied. Technical adjustments of molecular genetic procedures when working with archived sample material were necessary. Standards for the proper interpretation of the respective findings had to be settled. Results and Discussion: Additional molecular genetic testing significantly contributes to the quality of forensic pathology assessment in aviation mishaps. Previously undetected cardiotropic viruses potentially explain e.g., a pilot’s sudden incapacitation resulting from cardiac failure or myocardial arrhythmia. In contrast, negative results for infective agents participate in ruling out concerns about an accident pilot’s fitness to fly and the aeromedical examiner’s precedent decision to issue him or her an aeromedical certificate. Care must be taken in the interpretation of genetic testing for pre-existing diseases such as hypertrophic cardiomyopathy or ischemic heart disease. Molecular markers such as mRNAs or miRNAs, which can establish these diagnoses in clinical patients, might be misleading in-flight crew members because of adaptive changes in their tissues resulting from repeated mild hypoxia during flight, for instance. Military pilots especially demonstrate significant physiological adjustments to their somatic burdens in flight, such as cardiocirculatory stress and air combat maneuvers. Their non-pathogenic alterations in gene regulation and expression will likely be misinterpreted for genuine disease by inexperienced investigators. Conclusions: The growing influence of molecular pathology on legal medicine practice has found its way into aircraft accident investigation. As appropriate quality standards for laboratory work and data interpretation are provided, forensic genetic testing supports the medico-legal analysis of aviation mishaps and potentially reduces the number of unsolved events in the future.

Keywords: aviation medicine, aircraft accident investigation, forensic pathology, molecular pathology

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