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In the past decade, scientific research in the area of Nephrology has focused on evaluating the clinical utility and performance of various biomarkers for diagnosis, risk stratification and prognosis. Before implementing a biomarker in everyday clinical practice for screening a specific disease context, specific statistic measures are necessary to evaluate the diagnostic accuracy and performance of this biomarker. Receiver Operating Characteristic (ROC) Curve analysis is an important statistical method used to estimate the discriminatory performance of a novel diagnostic test, identify the optimal cut-off value for a test that maximizes sensitivity and specificity, and evaluate the predictive value of a certain biomarker or risk, prediction score. Herein, through practical examples, we aim to present a simple methodological approach to explain in detail the principles and applications of ROC curve analysis in the field of nephrology pertaining diagnosis and prognosis., (© 2024. The Author(s).)

Introduction: Hospitalization for decompensated heart failure is a major public health issue., Methods: We performed a meta-analysis to summarize and analyze if there is a benefit in using ultrafiltration over diuretics in terms of reducing mortality or hospital readmissions, primarily and identified 10 randomized controlled trials (RCTs) including 941 patients., Results: Compared to diuretics, treatment with ultrafiltration was associated with a significant reduction in heart failure hospitalizations (risk ratio [RR]: 0.72; 95% confidence interval [CI]: 0.55-0.96, p = 0.02) and significant increase in weight and net fluid loss (mean difference [MD]: -1.55, CI: -2.36 to -0.74, p = 0.0002) and (MD: -2.10, CI: -3.32 to -0.89, p = 0.0007), respectively. There was no significant difference among treatments regarding the duration of hospitalization, the increase in serum creatinine levels, and mortality., Conclusion: Among patients with decompensated heart failure, compared to diuretics, ultrafiltration is associated with reduced rehospitalizations and increased weight/net fluid loss., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

The assessment of risk and effect size of a specific endpoint associated to the presence/absence of a certain exposure is a hallmark in clinical and epidemiological research. In fact, before recommending any treatment, it is mandatory to investigate the magnitude of the benefits and harms between the exposure under investigation (e.g. a given treatment) and a specific disease or event. To do this, clinicians and statisticians use absolute (risk differences, number needed to treat, likelihood to be helped or harmed) and relative (risk ratio, incidence rate ratio, hazard ratio and odds ratio) measures of effect. Herein, using a series of clinical examples, we aim to present a step by step methodologic approach of measures of effect in the area of nephrology and urology., (© 2023. The Author(s).)

Introduction: The self-expanding, resheathable, repositionable transcatheter aortic heart valve Portico is being used successfully for transcatheter aortic valve implantation procedures (TAVI) in patients with severe aortic stenosis. The aim of this study was to evaluate outcomes at 2 years after TAVI with the Portico valve., Methods: Multicenter registry of clinical, echocardiographic and survival data from consecutive patients treated with the Portico TAVI system (Abbott, Chicago, IL, USA) in three cath labs in Northern Greece and Epirus during 2017-2020. The primary end point was all-cause mortality at 24 months. Secondary end points included procedural outcomes (efficacy and safety) and echocardiographic measurements., Results: A total of 90 patients (81 ± 6 years, 50% females, mean age 81 ± 6 years) were included in the registry. The indication for implantation was severe, symptomatic aortic stenosis (NYHA III, IV) in eighty-two (91.1%) and degeneration of a prosthetic aortic valve in eight (8.9%) patients. All patients were categorized as high surgical risk (mean Logistic Euroscore 25.9 ± 10, Euroscore II 7.7 ± 4.4 and STS score 10.8 ± 8.9). The procedure was performed transfemorally in all patients, under general anesthesia in 95.6%, under TOE guidance in 21.1%, with native valve predilatation in 46.7%, and the "resheath" option was used in 31.1% of the cases. The implantation was successful in 97.8% and there was a need for a second valve in 2.2% of the cases. Complications included permanent pacemaker implantation (16.7%), access cite complications (15.6%), arrythmias (23.3%), paravalvular leak (moderate 7.8%, severe 1.1%), acute kidney injury (7.8%), no strokes and one death during the procedure. Aortic valve peak velocity, peak and mean pressure gradients, were significantly reduced after the procedure. All-cause mortality at 1, 12 and 24 months was 4.4%, 6.7% and 7.8%, respectively., Conclusions: TAVI with the Portico system comprises an effective and safe solution for the management of severe, symptomatic aortic stenosis in high-risk surgical patients.

During the COVID-19 pandemic, different SARS-CoV-2 variants of concern (VOC) with specific characteristics have emerged and spread worldwide. At the same time, clinicians routinely evaluate the results of certain blood tests upon patient admission as well as during hospitalization to assess disease severity and the overall patient status. In the present study, we searched for significant cell blood count and biomarker differences among patients affected with the Alpha, Delta and Omicron VOCs at admission. Data from 330 patients were retrieved regarding age, gender, VOC, cell blood count results (WBC, Neut%, Lymph%, Ig%, PLT), common biomarkers (D-dimers, urea, creatinine, SGOT, SGPT, CRP, IL-6, suPAR), ICU admission and death. Statistical analyses were performed using ANOVA, the Kruskal-Wallis test, two-way ANOVA, Chi-square, T-test, the Mann-Whitney test and logistic regression was performed where appropriate using SPSS v.28 and STATA 14. Age and VOC were significantly associated with hospitalization, whereas significant differences among VOC groups were found for WBC, PLT, Neut%, IL-6, creatinine, CRP, D-dimers and suPAR. Our analyses showed that throughout the current pandemic, not only the SARS-CoV-2 VOCs but also the laboratory parameters that are used to evaluate the patient's status at admission are subject to changes.

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) are recommended by guidelines as first-line antihypertensive therapies in the general population or in patients with earlier stages of kidney disease. However, the cardioprotective benefit of these agents among patients on dialysis remains uncertain., Methods: We searched the MEDLINE, PubMed and Cochrane databases from inception through February 2022 to identify randomized controlled trials (RCTs) comparing the efficacy of ACEIs/ARBs relative to placebo or no add-on treatment in patients receiving dialysis. RCTs were eligible if they assessed fatal or non-fatal cardiovascular events as a primary efficacy endpoint., Results: We identified five RCTs involving 1582 dialysis patients. Compared with placebo or no add-on treatment, the use of ACEIs/ARBs was not associated with a significantly lower risk of cardiovascular events {risk ratio [RR] 0.79 [95% confidence interval (CI) 0.57-1.11]}. Furthermore, there was no benefit in cardiovascular mortality [RR 0.82 (95% CI 0.59-1.14)] and all-cause mortality [RR 0.86 (95% CI 0.64-1.15)]. These results were consistent when the included RCTs were stratified by subgroups, including hypertension, ethnicity, sample size, duration of follow-up and quality., Conclusion: The present meta-analysis showed that among patients on dialysis, the use of ACEIs/ARBs is not associated with a significantly lower risk of cardiovascular events and all-cause mortality as compared with placebo or no add-on treatment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Whereas hypertension is an established cardiovascular risk factor in the general population, the contribution of increased blood pressure (BP) to the huge burden of cardiovascular morbidity and mortality in patients receiving dialysis continues to be debated. In a large part, this controversy is attributable to particular difficulties in the accurate diagnosis of hypertension. The reverse epidemiology of hypertension in dialysis patients is based on evidence from large cohort studies showing that routine predialysis or postdialysis BP measurements exhibit a U-shaped or J-shaped association with cardiovascular or all-cause mortality. However, substantial evidence supports the notion that home or ambulatory BP measurements are superior to dialysis-unit BP recordings in diagnosing hypertension, in detecting evidence of target-organ damage and in prognosticating the all-cause death risk. In the first part of this article, we explore the accuracy of different methods of BP measurement in diagnosing hypertension among patients on dialysis. In the second part, we describe how the epidemiology of hypertension is modified when the assessment of BP is based on dialysis-unit versus home or ambulatory recordings.

Objective: In epilepsy patients, Transcranial Magnetic Stimulation (TMS) may result in the induction and modulation of epileptiform discharges (EDs). We hereby investigate the modulatory effects of TMS on brain connectivity in Genetic Generalized Epilepsy (GGE) and explore their potential as a diagnostic biomarker in GGE., Methods: Patients with GGE (n=18) and healthy controls (n=11) were investigated with a paired-pulse TMS-EEG protocol. The brain network was studied at local and at global levels using Coherence as an EEG connectivity measure. Comparison of patients vs controls was performed in a time-resolved manner by analyzing comparatively pre- vs post-TMS brain networks., Results: There was statistically significant TMS-induced modulation of connectivity at specific frequency bands within groups and difference in TMS-induced modulation between the two groups. The most significant difference between patients and controls related to connectivity modulation in the γ band at 1-3 sec post-TMS (p=0.004)., Conclusions: TMS modulates the healthy and epileptic brain connectivity in different ways. Our results indicate that TMS-EEG connectivity analysis can be a basis for a diagnostic biomarker of GGE., Significance: The analysis identifies specific time periods and frequency bands of interest of TMS-induced connectivity modulation and elucidates the effect of TMS on the healthy and epileptic brain connectivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Valvular heart disease (VHD) in non-valvular atrial fibrillation (AF) is a puzzling clinical entity. The aim of this study was to evaluate the prognostic effect of significant VHD (sVHD) among patients with non-valvular AF., Methods: This is a post-hoc analysis of the MISOAC-AF trial (NCT02941978). Consecutive inpatients with non-valvular AF who underwent echocardiography were included. sVHD was defined as the presence of at least moderate aortic stenosis (AS) or aortic/mitral/tricuspid regurgitation (AR/MR/TR). Cox regression analyses with covariate adjustments were used for outcome prediction., Results: In total, 983 patients with non-valvular AF (median age 76 [14] years) were analyzed over a median follow-up period of 32 [20] months. sVHD was diagnosed in 575 (58.5%) AF patients. sVHD was associated with all-cause mortality (21.6%/yr vs. 6.5%/yr; adjusted HR [aHR] 1.55, 95% confidence interval [CI] 1.17-2.06; p = 0.02), cardiovascular mortality (16%/yr vs. 4%/yr; aHR 1.70, 95% CI 1.09-2.66; p = 0.02) and heart failure-hospitalization (5.8%/yr vs. 1.8%/yr; aHR 2.53, 95% CI 1.35-4.63; p = 0.02). The prognostic effect of sVHD was particularly evident in patients aged < 80 years and in those without history of heart failure (p for interaction < 0.05, in both subgroups). After multivariable adjustment, moderate/severe AS and TR were associated with mortality, while AS and MR with heart failure-hospitalization., Conclusion: Among patients with non-valvular AF, sVHD was highly prevalent and beared high prognostic value across a wide spectrum of clinical outcomes, especially in patients aged < 80 years or in the absence of heart failure. Predominantly AS, as well as MR and TR, were associated with worse prognosis., (© 2021. The Author(s).)

Early identification of patients at risk for paroxysmal atrial fibrillation (PAF) is essential to attain optimal treatment and a favorable prognosis. We compared the performance of a beat-to-beat (B2B) P-wave analysis with that of standard P-wave indices (SPWIs) in identifying patients prone to PAF. To this end, 12-lead ECG and 10 min vectorcardiogram (VCG) recordings were obtained from 33 consecutive, antiarrhythmic therapy naïve patients, with a short history of low burden PAF, and from 56 age- and sex-matched individuals with no AF history. For both groups, SPWIs were calculated, while the VCG recordings were analyzed on a B2B basis, and the P-waves were classified to a primary or secondary morphology. Wavelet transform was used to further analyze P-wave signals of main morphology. Univariate analysis revealed that none of the SPWIs performed acceptably in PAF detection, while five B2B features reached an AUC above 0.7. Moreover, multivariate logistic regression analysis was used to develop two classifiers-one based on B2B analysis derived features and one using only SPWIs. The B2B classifier was found to be superior to SPWIs classifier; B2B AUC: 0.849 (0.754-0.917) vs. SPWIs AUC: 0.721 (0.613-0.813), p value: 0.041. Therefore, in the studied population, the proposed B2B P-wave analysis outperforms SPWIs in detecting patients with PAF while in sinus rhythm. This can be used in further clinical trials regarding the prognosis of such patients.

The pathophysiology of human immunodeficiency virus (HIV)-associated bone loss is complex and to date largely unknown. In this study, we investigated serum expression of microRNAS (miRNAs) linked to bone metabolism in HIV-associated bone loss. This was a case-control study. Thirty male individuals with HIV infection (HIV+) and osteoporosis/osteopenia (HIV+/OP+) (cases) and 30 age-matched male HIV+ individuals with normal bone mass (HIV+/OP-) (controls) were included in the analysis. Thirty male individuals matched for age without HIV infection (HIV-), were also included as second controls. The selected panel of miRNAs was as follows: hsa-miRNA-21-5p; hsa-miRNA-23a-3p; hsa-miRNA-24-2-5p; hsa-miRNA-26a-5p; hsa-miRNA-29a-3p; hsa-miRNA-124-3p; hsa-miRNA-33a-5p; and hsa-miRNA-133a-3p. Within the cohort of HIV+ individuals, relative serum expression of miRNA-21-5p and miRNA-23a-3p was significantly lower ( p < 0.001) while the expression of miRNA-24-2-5p was significantly higher ( p = 0.030) in HIV+/OP+ compared to HIV+/OP-. Expression of miRNA-21-5p demonstrated a sensitivity of 84.6% and a specificity of 66.7 in distinguishing HIV+/OP+ individuals. Expression of circulating miRNAs related to bone metabolism; miRNA-23a-3p, miRNA-24-2-5p, and miRNA-21-5p is significantly altered in HIV+OP+ individuals, in line with data on other causes of osteoporosis, suggesting a common pattern of circulating miRNAs independent of the underlying cause.

Alzheimer's Disease ( AD ) is a neurogenerative disorder and the most common type of dementia with a rapidly increasing world prevalence. In this paper, the ability of several statistical and spectral features to detect AD from electroencephalographic ( EEG ) recordings is evaluated. For this purpose, clinical EEG recordings from 14 patients with AD (8 with mild AD and 6 with moderate AD ) and 10 healthy, age-matched individuals are analyzed. The EEG signals are initially segmented in nonoverlapping epochs of different lengths ranging from 5 s to 12 s. Then, a group of statistical and spectral features calculated for each EEG rhythm (δ, θ, α, β, and γ) are extracted, forming the feature vector that trained and tested a Random Forests classifier. Six classification problems are addressed, including the discrimination from whole-brain dynamics and separately from specific brain regions in order to highlight any alterations of the cortical regions. The results indicated a high accuracy ranging from 88.79% to 96.78% for whole-brain classification. Also, the classification accuracy was higher at the posterior and central regions than at the frontal area and the right side of temporal lobe for all classification problems.

Background/aim: Exercise training usually complements pharmacological therapy of type 1 diabetes mellitus, however, little is known about its impact on cardiac autonomic neuropathy. Our aim was to evaluate the impact of exercise on electrocardiographic parameters and heart rate variability in diabetic rats., Materials and Methods: Wistar rats were randomly assigned to four groups (n=12): Sedentary control (SC), sedentary diabetic (SD), exercise control (EC), and exercise diabetic (ED). Diabetes was induced by a single intraperitoneal injection of streptozotocin (45 mg/kg). Exercise groups underwent 8 weeks of training on a treadmill. At the end of the study, echocardiography was performed and continuous electrocardiographic recording was obtained by intra-abdominally implanted telemetric devices. Diabetes induction significantly reduced the heart rate and increased the blood glucose level (p<0.001) and R-wave amplitude (p<0.05). Frequency-domain spectral variables were also analyzed. The SD group had a significantly lower absolute high-frequency component (p<0.05) and higher normalized low-frequency component, as well as low-frequency power divided by the high-frequency power ratio when compared to the SC and EC groups (p<0.05). All these diabetes-related adverse changes in heart rate variability parameters were significantly reversed by exercise training (p<0.05). Overall, our study shows that early initiation of systemic exercise training prevents the development of cardiac autonomic neuropathy in rats with type 1 diabetes mellitus, by favorable change in the balance between parasympathetic and sympathetic activity., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Circulating microRNAs (miRs) are currently being investigated as novel biomarkers for osteoporosis and osteoporotic fractures., Aim: The aim of this study was to investigate serum levels of specific microRNAs, known regulators of bone metabolism, in postmenopausal women with low bone mass and with or without vertebral fractures (VFs)., Methods: For the analysis, 14 miRs were isolated from the serum of 35 postmenopausal women with low bone mass and with at least one moderate VF and 35 postmenopausal women with low bone mass without fractures. Thirty postmenopausal women with normal BMD values and no history of fractures served as controls. Main outcome parameters were changes in the expression of selected miRs in the serum of patient population and compared with controls., Results: From the 14 miRs that were selected, we identified 5 miRs, namely miR-21-5p, miR-23a, miR-29a-3p, miR-124-3p and miR-2861 that were significantly deregulated in the serum of patients with low bone mass compared with controls. Serum miR-124 and miR-2861 were significantly higher, whereas miR-21, miR-23 and miR-29 were lower in patients compared with controls. In a sub-group analysis of the patient population, the expression of miR-21-5p was significantly lower among osteoporotic/osteopenic women with VFs, showing 66% sensitivity and 77% specificity in distinguishing women with a vertebral fracture., Conclusion: This study identifies a differential expression pattern of miR-21-5p in the serum of women with low BMD and VFs., (© 2017 European Society of Endocrinology.)

Diabetes mellitus has been described in chronic hemolytic anemias, but data are scarce regarding glucose metabolism in normoglycemic patients. To address this issue, we evaluated insulin sensitivity and secretion in patients with sickle cell disease (SCD) and normal oral glucose tolerance test (OGTT). Forty-five adult patients with homozygous sickle cell disease and Hb S/β-thalassemia (β-thal) (mean age 42.5 ± 9.5 years) and 45 healthy individuals matched for age and body mass index (BMI) were included in the study. All participants underwent an oral glucose tolerance test (OGTT) after an overnight fast. All patients had normal OGTT. Fasting glucose values did not differ significantly between groups, however, fasting insulin levels were significantly lower in the patient group compared to the control group (5.1 ± 2.7 μUI/mL vs. 11.3 ± 6.6 μUI/mL, p <0.005, respectively). Pancreatic β-cell insulin secretion index in the fasting state was significantly lower in patients with sickle cell disease compared with controls as assessed by calculations of the homeostatic model assessment for β-cell function (HOMA β%) (77.0 vs. 106.0%, respectively, p <0.001), while HOMA insulin resistance (HOMA IR), was lower in the sickle cell disease patients, albeit not statistically significant (0.8 vs. 1.1, respectively, p = 0.054). The HOMA β% was significantly correlated with ferritin levels (r = -526, p <0.001) (negative correlation) and with 25-hydroxy (OH)-vitamin D levels (r = 0.479, p <0.001) (positive correlation), even when adjusted for serum ferritin levels. Normoglycemic patients with sickle cell disease demonstrated impaired β-cell function with reduced insulin secretion even before OGTT was impaired.

Aims: We investigated the role of endothelin-B receptors on sympathetic activation originating from the adrenal gland or from the myocardium and its impact on arrhythmogenesis during acute myocardial infarction., Main Methods: We studied two groups of rats (n=120, 284±2 g), namely wild-type and ETB-deficient. Myocardial infarction was induced by permanent ligation of the left coronary artery and ventricular tachyarrhythmias were evaluated from continuous electrocardiographic recordings. Sympathetic activation, measured by indices of heart rate variability, was evaluated after adrenalectomy or catecholamine depletion induced by reserpine. Acute left ventricular failure was assessed by total animal activity., Key Findings: Adrenalectomy decreased the total duration of tachyarrhythmias in ETB-deficient rats, but their incidence remained higher, compared to wild-type rats. After reserpine, heart rate variability indices and tachyarrhythmias were similar in the two groups during the initial, ischaemic phase. During evolving infarction, tachyarrhythmia duration was longer in ETB-deficient rats, despite lower sympathetic activation. Heart rate was lower in ETB-deficient rats throughout the 24-hour observation period, whereas activity was comparable in the two groups., Significance: Endothelin-B receptors modulate sympathetic activation during acute myocardial infarction not only in the ventricular myocardium, but also in the adrenal gland. Sympathetic activation markedly increases early-phase ventricular tachyarrhythmias, but other mechanisms involving the endothelin system underlie delayed arrhythmogenesis., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

In this paper, we describe the PERFORM system for the continuous remote monitoring and management of Parkinson's disease (PD) patients. The PERFORM system is an intelligent closed-loop system that seamlessly integrates a wide range of wearable sensors constantly monitoring several motor signals of the PD patients. Data acquired are pre-processed by advanced knowledge processing methods, integrated by fusion algorithms to allow health professionals to remotely monitor the overall status of the patients, adjust medication schedules and personalize treatment. The information collected by the sensors (accelerometers and gyroscopes) is processed by several classifiers. As a result, it is possible to evaluate and quantify the PD motor symptoms related to end of dose deterioration (tremor, bradykinesia, freezing of gait (FoG)) as well as those related to over-dose concentration (Levodopa-induced dyskinesia (LID)). Based on this information, together with information derived from tests performed with a virtual reality glove and information about the medication and food intake, a patient specific profile can be built. In addition, the patient specific profile with his evaluation during the last week and last month, is compared to understand whether his status is stable, improving or worsening. Based on that, the system analyses whether a medication change is needed--always under medical supervision--and in this case, information about the medication change proposal is sent to the patient. The performance of the system has been evaluated in real life conditions, the accuracy and acceptability of the system by the PD patients and healthcare professionals has been tested, and a comparison with the standard routine clinical evaluation done by the PD patients' physician has been carried out. The PERFORM system is used by the PD patients and in a simple and safe non-invasive way for long-term record of their motor status, thus offering to the clinician a precise, long-term and objective view of patient's motor status and drug/food intake. Thus, with the PERFORM system the clinician can remotely receive precise information for the PD patient's status on previous days and define the optimal therapeutical treatment.

The antiarrhythmic potential of postconditioning in in vivo models remains poorly defined. We compared the effects of pre- and postconditioning on ventricular arrhythmogenesis against controls with and without reperfusion. Wistar rats (n = 40, 269 ± 3 g) subjected to ischemia (30 minutes)--reperfusion (24 hours) were assigned to the following groups: (1) preconditioning (2 cycles), (2) postconditioning (6 cycles), or (3) no intervention and were compared with (4) nonreperfused infarcts and (5) sham-operated animals. Infarct size was measured, and arrhythmogenesis was evaluated with continuous telemetric electrocardiographic recording, heart rate variability indices, and monophasic action potentials (MAPs). During a 24-hour observation period, no differences in mortality were observed. Reperfusion decreased infarct size and ameliorated sympathetic activation during the late reperfusion phase. Preconditioning decreased infarct size by a further 35% (P = .0017), but only a marginal decrease (by 18%, P = .075) was noted after postconditioning. Preconditioning decreased arrhythmias during ischemia and early reperfusion, whereas postconditioning almost abolished them during the entire reperfusion period. No differences were noted in MAPs or in the magnitude of sympathetic activation between the 2 interventions. Compared to postconditioning, preconditioning affords more powerful cytoprotection, but both interventions exert antiarrhythmic actions. In the latter, these are mainly evident during the ischemic phase and continue during early reperfusion. Postconditioning markedly decreases reperfusion arrhythmias during a prolonged observation period. The mechanisms underlying the antiarrhythmic effects of pre- and postconditioning are likely different but remain elusive.

Electrooculographic (EOG) artefacts are one of the most common causes of Electroencephalogram (EEG) distortion. In this paper, we propose a method for EOG Blinking Artefacts (BAs) detection and removal from EEG. Normalized Correlation Coefficient (NCC), based on a predetermined BA template library was used for detecting the BA. Ensemble Empirical Mode Decomposition (EEMD) was applied to the contaminated region and a statistical algorithm determined which Intrinsic Mode Functions (IMFs) correspond to the BA. The proposed method was applied in simulated EEG signals, which were contaminated with artificially created EOG BAs, increasing the Signal-to-Error Ratio (SER) of the EEG Contaminated Region (CR) by 35 dB on average.

Background: Chronic hind-limb ischemia confers cytoprotection after coronary occlusion, but it is unclear whether it ameliorates substrate formation for ventricular tachyarrhythmias (VTs)., Materials and Methods: Chronic hind-limb ischemia was generated by femoral artery excision in 50 rats, while 25 animals were sham-operated. Left coronary artery ligation was performed after 3 weeks and infarct size was measured 24 hours thereafter. The inducibility of VTs was assessed by programmed electrical stimulation (PES) 4 weeks post-ligation. A score was assigned, based on protocol stage and tachyarrhythmia duration. Monophasic action potentials (MAP) were recorded prior to and 4 weeks after ligation., Results: The infarct size was smaller (p=0.000079) in the ischemic rats (25.7±2.1%) than in the controls (41.7±2.2%), accompanied by a lower (p=0.029) arrhythmia score (1.05±0.38 versus 2.70±0.68, respectively). The action potential duration (APD) was shorter (p<0.05) in the ischemic rats prior to ligation and remained stable after 4 weeks., Conclusion: Chronic hind limb ischemia limits infarct size and decreases inducible ventricular tachyarrhythmias.

The arrhythmogenic effects of endothelin-1 (ET-1) are mediated via ETA-receptors, but the role of ETB-receptors is unclear. We examined the pathophysiologic role of ETB-receptors on ventricular tachyarrhythmias (VT/VF) during myocardial infarction (MI). MI was induced by coronary ligation in two animal groups, namely in wild-type (n = 63) and in ETB-receptor-deficient (n = 61) rats. Using a telemetry recorder, VT/VF episodes were evaluated during phase I (the 1st hour) and phase II (2-24 h) post-MI, with and without prior beta-blockade. Action potential duration at 90% repolarization (APD90) was measured from monophasic epicardial recordings and indices of sympathetic activation were assessed using fast-Fourier analysis of heart rate variability. Serum epinephrine and norepinephrine were measured with radioimmunoassay. MI size was similar in the two groups. There was a marked temporal variation in VT/VF duration; during phase I, it was higher (p = 0.0087) in ETB-deficient (1,519 +/- 421 s) than in wild-type (190 +/- 34 s) rats, but tended (p = 0.086) to be lower in ETB-deficient (4.2 +/- 2.0 s) than in wild-type (27.7 +/- 8.0 s) rats during phase II. Overall, the severity of VT/VF was greater in ETB-deficient rats, evidenced by higher (p = 0.0058) mortality (72.0% vs. 32.1%). There was a temporal variation in heart rate and in the ratio of low- to high-frequency spectra, being higher (<0.001) during phase I, but lower (p < 0.05) during phase II in ETB-deficient rats. Likewise, 1 h post-MI, serum epinephrine (p = 0.025) and norepinephrine (p < 0.0001) were higher in ETB-deficient (4.20 +/- 0.54, 14.24 +/- 1.39 ng/ml) than in wild-type (2.30 +/- 0.59, 5.26 +/- 0.67 ng/ml) rats, respectively. After beta-blockade, VT/VF episodes and mortality were similar in the two groups. The ETB-receptor decreases sympathetic activation and arrhythmogenesis during the early phase of MI, but these effects diminish during evolving MI.

Objectives: This paper describes a methodology for the monitoring of the fetal cardiac health status during pregnancy, through the effective and non-invasive monitoring of the abdominal ECG signals (abdECG) of the mother., Methods: For this purpose, a three-stage methodology has been developed. In the first stage, the fetal heart rate (fHR) is extracted from the abdECG signals, using nonlinear analysis. Also, the eliminated ECG (eECG) is calculated, which is the abdECG after the maternal QRSs elimination. In the second stage, a blind source separation technique is applied to the eECG signals and the fetal ECG (fECG) is obtained. Finally, monitoring of the fetus is implemented using features extracted from the fHR and fECG, such as the T/QRS ratio and the characterization of the fetal ST waveforms., Results: The methodology is evaluated using a dataset of simulated multichannel abdECG signals: 94.79% accuracy for fHR extraction, 92.49% accuracy in T/QRS ratio calculation and 79.87% in ST waveform classification., Conclusions: The novel non-invasive proposed methodology is advantageous since it offers automated identification of fHR and fECG and automated ST waveform analysis, exhibiting a high diagnostic accuracy.

Multichannel chromosome image acquisition is used for cancer diagnosis and research on genetic disorders. This type of imaging, apart from aiding the cytogeneticist in several ways, facilitates the visual detection of chromosome abnormalities. However, chromosome misclassification errors result from different factors, such as uneven hybridization, spectral overlap among fluors, and biochemical noise. In this paper, we enhance the chromosome classification accuracy by making use of a region Bayes classifier that increases the classification accuracy when compared to the already developed pixel-by-pixel classifier and by incorporating the vector median filtering approach for filtering of the image. The method is evaluated using a publicly available database that contains 183 six-channel chromosome sets of images. The overall improvement on the chromosome classification accuracy is 9.99%, compared to the pixel-by-pixel classifier without filtering. This improvement in the chromosome classification accuracy would allow subtle deoxyribonucleic acid abnormalities to be identified easily. The efficiency of the method might further improve by using features extracted from each region and a more sophisticated classifier.

Resting tremor (RT) is one of the most frequent signs of the Parkinson's disease (PD), occurring with various severities in about 75% of the patients. Current diagnosis is based on subjective clinical assessment, which is not always easy to capture subtle, mild and intermittent tremors. The aim of the present study is to assess the suitability and clinical value of a computer based real-time system as an aid to diagnosis of PD, in particular the presence of RT. Five healthy subjects were asked to simulate several severities of RT in hands and feet in three static activities. The behaviour of the subjects is measured using tri-axial accelerometers, which are placed at four different positions on the body. Frequency-domain features, strongly correlated with the RT activity, are extracted from the accelerometer data. The classification of RT severity based on those features, provided accuracy 76%. The real-time system designed for efficient extraction of those features and the provision of a continuous RT severity measure is described.

The effects of dual (ETA and ETB) endothelin receptor blockade on ventricular arrhythmogenesis during acute myocardial infarction are not well defined. We randomly allocated Wistar rats to bosentan (100 mg/kg daily, n=24), a dual endothelin receptor antagonist, or vehicle (n=23). After 7 days of treatment, myocardial infarction was induced by permanent coronary ligation. Ventricular tachyarrhythmias were evaluated for 24 h following ligation, using a miniature telemetry electrocardiogram recorder. Action potential duration was measured from monophasic epicardial recordings and sympathetic activation was assessed by heart rate variability and catecholamine serum level measurements. Compared to controls (1012+/-185 s), bosentan (59+/-24 s) markedly decreased (P<0.00001) the total duration of ventricular tachyarrhythmias during the delayed (1-24 h) phase post-ligation, with a modest effect during the early (0-1 h) phase (132+/-38 s, versus 43+/-18 s, respectively, P=0.053). Treatment did not affect infarct size or total mortality. Action potential duration at 90% repolarization prolonged in controls (from 93.1+/-4.7 ms to 117.6+/-6.9 ms), displaying increased temporal dispersion (from 4.14+/-0.45 ms to 10.42+/-2.51 ms, both P<0.001), but was preserved in treated animals. Bosentan decreased norepinephrine, but increased epinephrine levels 24 h post-ligation. Low frequency spectra of heart rate variability, an index of net sympathetic tone, were lower in bosentan-treated rats. Dual endothelin-1 receptor blockade decreases ventricular tachyarrhythmias during myocardial infarction without reperfusion, by preventing repolarization inhomogeneity. Diverse treatment effects on sympathetic activation may ameliorate the antiarrhythmic action.

In this paper, we use a one-dimensional model of the rabbit sinoatrial node (SAN), and we investigate the response of the model to hyperpolarizing and depolarizing stimulus. Depending on the stimulus timing, either a delay or an advance in the occurrence of next action potential is produced. This resetting behavior of the model is quantified in terms of phase transition curves (PTCs) for short electrical current pulses of varying amplitude which span the whole period. The main focus of this paper is to compare the dynamic properties of the spatially extended system and the single cell model. The detailed analysis of the results provides new insights in the understanding of the transition from the theoretical single cell models to the spatially extended systems.

The effects of dronedarone, a non-iodinated derivative of amiodarone, on ventricular tachycardia and ventricular fibrillation post-myocardial infarction are not well established. Fifty-five Wistar rats were randomly allocated to a 2-week oral treatment with either vehicle (n=18), amiodarone (30 mg/kg, n=20), or dronedarone (30 mg/kg, n=17). After acute coronary artery ligation, a single-lead electrocardiogram was continuously recorded for 24 h and episodes of ventricular tachycardia/fibrillation as well as mortality rates were analysed. Monophasic action potential recordings were obtained from the left ventricular epicardium at baseline and 24 h post-myocardial infarction. Thyroid hormones and catecholamines were measured using radioimmunoassay. Thyroid function was similar in the 3 groups. Compared to controls, amiodarone and dronedarone equally decreased the number of ventricular tachycardia/fibrillation episodes by approximately 75%. Both agents prevented the increase in monophasic action potential duration and in beat-to-beat variation. Norepinephrine levels were lower only after amiodarone treatment. Despite the observed antiarrhythmic effect, total mortality did not differ between groups (38.8% in controls, 30.0% in the amiodarone group and 58.8% in the dronedarone group), because of excess bradyarrhythmic mortality in both drug groups that reached significance in the dronedarone group. Dronedarone and amiodarone display similar antiarrhythmic efficacy post-myocardial infarction, partly by preventing repolarization inhomogeneity. However, dronedarone increases bradyarrhythmic mortality possibly secondary to its negative inotropic effects.

GH (growth hormone) administration during acute MI (myocardial infarction) ameliorates subsequent LV (left ventricular) dysfunction. In the present study, we examined the effects of such treatment on arrhythmogenesis. A total of 53 Wistar rats (218+/-17 g) were randomized into two groups receiving two intraperitoneal injections of either GH (2 international units/kg of body weight; n=26) or normal saline (n=27), given at 24 h and 30 min respectively, prior to MI, which was generated by left coronary artery ligation. A single-lead ECG was recorded for 24 h post-MI, using an implanted telemetry system. Episodes of VT (ventricular tachyarrhythmia) and VF (ventricular fibrillation) during the first hour (phase I) and the hours following (phase II) MI were analysed. Monophasic action potential was recorded from the lateral LV epicardium at baseline and 24 h post-MI, and APD90 (action duration at 90% of repolarization) was measured. Infarct size was calculated 24 h post-MI. Infarct size and phase I VT+VF did not differ significantly between groups, but phase II hourly duration of VT+VF episodes was 82.8+/-116.6 s/h in the control group and 18.3+/-41.2 s/h in the GH group (P=0.0027), resulting in a lower arrhythmic (P=0.016) and total (P=0.0018) mortality in GH-treated animals. Compared with baseline, APD90 was prolonged significantly 24 h post-MI in the control group, displaying an increased beat-to-beat variation, but remained unchanged in the GH group. We conclude that GH decreases phase II VTs during MI in the rat. This finding may have implications in cardiac repair strategies.

In this work, the dynamic response of the sinoatrial node (SAN), the natural pacemaker of the heart, to short external stimuli is investigated using the Zhang et al. model. The model equations are solved twice for the central cell and for the peripheral cell. A short current pulse is applied to reset the spontaneous rhythmic activity of the single sinoatrial node cell. Depending on the stimulus timing either a delay or an advance in the occurrence of next action potential is produced. This resetting behavior is quantified in terms of phase transition curves (PTCs) for short electrical current pulses of varying amplitude which span the whole period. For low stimulus amplitudes the transition from advance to delay is smooth, while at higher amplitudes abrupt changes and discontinuities are observed in PTCs. Such discontinuities reveal critical stimuli, the application of which can result in annihilation of activity in central SAN cells. The detailed analysis of the ionic mechanisms involved in its resetting behavior of sinoatrial node cell models provides new insight into the dynamics and physiology of excitation of the sinoatrial node of the heart.

Objective: Ventricular remodeling is a common corollary of myocardial infarction. We hypothesized that this process may be attenuated by growth hormone, administered as a single high-dose, selectively in the infarct zone, early postmyocardial infarction., Design: In 35 pigs (29+/-4 kg), myocardial infarction was generated by inflation of an over-the-wire angioplasty balloon in the circumflex artery for 60 min and 5 further pigs were sham-operated. Ten minutes after reperfusion, the pigs were randomized (2:1) to either growth hormone (1 IU/kg) (n=23) or normal saline (n=12), delivered via the balloon catheter. All survivors were treated with captopril and were sacrificed 4 weeks after myocardial infarction., Results: Compared to controls, growth hormone-treated animals displayed lower heart weight (4.1+/-0.5 g/kg body weight, versus 3.4+/-0.4 g/kg, respectively, p=0.003) and dimensions (left ventricular short axis diameter 46+/-7 mm versus 37+/-6 mm, p=0.01; right ventricular short axis diameter 38+/-7 mm versus 30+/-5 mm p=0.001). Growth hormone increased wall thickness in the infarct (6.0+/-1.8 in controls versus 9.9+/-3.7 in treated animals, p=0.004) and non-infarct zones (10.6+/-1.8 in controls versus 15.5+/-3.8 in treated animals, p=0.0006) and produced higher (p<0.05) microvascular density in both zones., Conclusion: Intracoronary administration of growth hormone attenuates left and right ventricular remodeling by inducing hypertrophy and by enhancing angiogenesis.

When a brief current pulse is incident on excitable cells in cardiac and other nervous tissue, a change in phase of the cell's response is usually observed. In cardiac tissue, the cells are bared to external stimulation of generally positive currents, which depolarize the cells. In this paper an overview of the application of the phase resetting technique (PRT) in several cardiac models is presented. We discuss the effects of external stimuli in several cardiac cell models and we provide the phase transition curves (PTCs) resulted from the application of PRT with the Zhang et al. sinoatrial node model.

Objective: Endothelin-1 (ET-1) production increases during acute myocardial infarction (MI) and may contribute to the genesis of ventricular tachycardia (VT) and ventricular fibrillation (VF). However, the antiarrhythmic effects of ET-1 receptor blockade, examined shortly after MI, have been debated. In the present study, we examined the effects of such treatment on VT/VF during the first 24 h post-MI., Methods: Thirty-five Wistar rats (223+/-22 g) were randomly allocated to either the ET-1 receptor-A (ETA) antagonist BQ-123 (0.4 mg/kg, BQ-123 group, n=17), or normal saline (control group, n=18) and were subjected to coronary artery ligation. A single-lead electrocardiogram was continuously recorded for 24 h post-MI, using an implanted telemetry system, and episodes of VT/VF were analyzed. Monophasic action potential (MAP) recordings were obtained from the left (LV) and right (RV) ventricular epicardium at baseline, 5 min after treatment and 24 h post-MI., Results: There were 15.94+/-19.35 episodes/h/rat of VT/VF in the control group and 1.66+/-2.22 in the BQ-123 group (p=0.010), resulting in a lower (p=0.030) arrhythmic mortality in treated animals. The mean episode duration was 7.40+/-7.16 s for the control group and 2.30+/-1.37 s for the BQ-123 group (p=0.011). The maximum decrease in VT/VF was observed during the 1st, 5th and 6th hours post-MI. In the control group, LV MAP duration increased 24 h post-MI, displaying an increased beat-to-beat variation, but remained unchanged in the BQ-123 group., Conclusion: Acute ETA blockade reduces the incidence of VT/V F during the first 24-h post-MI in the rat, through a decrease in the dispersion of repolarization.