Sinus node disease in subjects with type 1 ECG pattern of Brugada syndrome

AbstractBackgroundThe spectrum of phenotypes related to mutations of the SCN5A gene include Brugada syndrome (BS), long QT syndrome, progressive cardiac conduction defect, and sinus node disease (SND). The present study investigated the incidence of SND in subjects with type 1 electrocardiogram (ECG) pattern of BS.Methods and resultsThe study population consisted of 68 individuals (55 males, mean age 44.8±12.8 years) with spontaneous (n=27) or drug-induced (n=41) type 1 ECG pattern of BS. Twenty-eight subjects were symptomatic with a history of syncope (41.2%). SND was observed in 6 symptomatic subjects (8.8%), and was mainly attributed to sino-atrial block with sinus pauses. Two patients were initially diagnosed with SND, and received a pacemaker. Patients with SND displayed an increased P-wave duration in leads II and V2, PR interval in leads II and V2, QRS duration in leads II and V2, and increased QTc interval in lead V2 (p<0.05). AH and HV intervals as well as corrected sinus node recovery time (cSNRT) were significantly prolonged in subjects with SND (p<0.05). During a mean follow-up period of 5.0±3.6 years, five subjects with a history of syncope suffered appropriate implantable cardioverter defibrillator (ICD) discharges due to ventricular arrhythmias (7.4%). None of those diagnosed with SND suffered syncope or ICD therapies.ConclusionSND is not an uncommon finding in subjects with type 1 ECG pattern of BS. The occurrence of SND in relatively young patients may deserve meticulous investigation including sodium channel blocking test

miRNA-Based Technologies in Cancer Therapy

The discovery of therapeutic miRNAs is one of the most exciting challenges for pharmaceutical companies. Since the first miRNA was discovered in 1993, our knowledge of miRNA biology has grown considerably. Many studies have demonstrated that miRNA expression is dysregulated in many diseases, making them appealing tools for novel therapeutic approaches. This review aims to discuss miRNA biogenesis and function, as well as highlight strategies for delivering miRNA agents, presenting viral, non-viral, and exosomic delivery as therapeutic approaches for different cancer types. We also consider the therapeutic role of microRNA-mediated drug repurposing in cancer therapy

FIR, IIR and Wavelet Algorithms for the Rigorous Filtering of GOCE SGG Data to the GOCE MBW

Gravity field and steady-state Ocean Circulation Explorer (GOCE) data are strongly affected by noise and long-wavelength errors outside the satellite measurement bandwidth (MBW). One of the main goals in utilizing GOCE data for gravity field modeling is the application of filtering techniques that can remove gross errors and reduce low-frequency errors and high-frequency noise while preserving the original signal. This paper aims to present and analyze three filtering strategies used to de-noise the GOCE Level 2 data from long-wavelength correlated errors and noise. These strategies are Finite Impulse Response (FIR), Infinite Impulse Response (IIR), and Wavelet Multi-resolution Analysis (WL), which have been applied to GOCE residual second order derivatives of the gravity potential. Several experiments were performed for each filtering scheme in order to identify the ideal filtering parameters. The outcomes indicate that all the suggested filtering strategies proved to be effective in removing low-frequency errors while preserving the signals in the GOCE MBW, with FIR filtering providing the overall best results

Wave reflections and systemic vascular resistance are stronger determinants of pulse pressure amplification than aortic stiffness in drug-naïve hypertensives

Background: Aortic-to-brachial pulse pressure (PP) amplification is a novel biomarker that prognosticates the cardiovascular risk above and beyond central aortic and brachial blood pressure. This phenomenon is modulated by left ventricular contractility and chronotrophy, large-artery stiffness and reflecting properties of microcirculation. However, the relative importance of these parameters as hemodynamic determinant of PP amplification remains elusive. Methods: A total of 88 consecutive drug-naïve hypertensives underwent a non-invasive assessment of central and peripheral hemodynamics via impedance cardiography and pulse wave analysis. Participants were classified into tertiles according to the magnitude of PP amplification. Hemodynamic determinants of low PP amplification were explored in univariate and multivariate regression analysis. Results: Compared with the high tertile, patients within the low PP amplification tertile were older and more commonly female and had lower height, weight and heart rate. Augmentation index (AIx) and systemic vascular resistance index (SVRI) were higher among patients within the low PP amplification tertile, whereas aortic pulse wave velocity (PWV) did not differ among groups. In multivariate analysis, higher AIx (OR: 1.27; 95% CI: 1.09–1.48) and higher SVRI were independently associated with higher odds for low PP amplification, whereas higher heart rate was the only parameter related to lower odds for low PP amplification (OR: 0.84; 95% CI: 0.71–0.99). Conclusion: This study shows that among newly-diagnosed drug-naïve hypertensives, elevated wave reflections and systemic vascular resistance are stronger determinants of PP amplification than aortic stiffness

Developing an International Combined Applied Surgical Science and Wet Lab Simulation Course as an Undergraduate Teaching Model

Background. Essential Skills in the Management of Surgical Cases (ESMSC) is an international, animal model-based course. It combines interactive lectures with basic ex vivo stations and more advanced wet lab modules, that is, in vivo dissections and Heart Transplant Surgery on a swine model. Materials and Methods. Forty-nine medical students (male, N=27, female N=22, and mean age = 23.7 years) from King’s College London (KCL) and Greek Medical Schools attended the course. Participants were assessed with Direct Observation of Procedural Skills (DOPS), as well as Multiple Choice Questions (MCQs). Paired t-test associations were used to evaluate whether there was statistically significant improvement in their performance. Aim. To evaluate the effectiveness of a combined applied surgical science and wet lab simulation course as a teaching model for surgical skills at the undergraduate level. Results. The mean MCQ score was improved by 2.33/32 (P<0.005). Surgical skills competences, as defined by DOPS scores, were improved in a statically significant manner (P<0.005 for all paired t-test correlations). Conclusions. ESMSC seems to be an effective teaching model, which improves the understanding of the surgical approach and the basic surgical skills. In vivo models could be used potentially as a step further in the Undergraduate Surgical Education

ABC of Surgical Teaching: Time to Consider a Global Blueprint for Holistic Education

Background Educating and equipping students and trainees into clinicians capable of meeting healthcare demands and service provision needs is essential. Unprecedented events like COVID-19 pandemic, highlight urgent need for reformation of training to ensure high quality education is maintained. To this end, we describe an innovative and globally adaptable blueprint for establishing a surgical curriculum, aiming to optimize preparation of future surgeons. Methods We used a structured protocol to synthesize evidence from previous systematic reviews focused on surgical education alongside a series of focused original educational studies. This approach allowed incorporation of prospectively applied novel ideas into the existing landscape of published evidence. All material used for this proof of concept derives from the outputs of a dedicated research network for surgical education (eMERG). Results We propose the foundation blueprint framework called “Omnigon iG4” as a globally applicable model. It allows adaptation to individual local educational environments for designing, appraising and/or refining surgical curricula. We also describe the “Omnigon iG4 Hexagon Pragmatic Model,” a novel perspective model which assesses the performance of our blueprint in a multi-layer fashion. This “Hexagon” model is the first to introduce pragmatic outcomes in curricula performance assessment. Conclusions This proof of concept, “Omnigon iG4,” proposes an adaptable version of a curriculum blueprint. The framework allows educators to establish a surgical curriculum with the ability to map out competencies, permitting full control over their intended learning outcomes. This can form the basis for developing globally adaptable multifaceted Simulation-Based learning (SBL) courses or even surgical curricula for undergraduates

The role of late gadolinium enhancement in predicting arrhythmic events in cardiac sarcoidosis patients – a mini-review

Sarcoidosis is a multisystem inflammatory disorder with an unknown origin. Symptomatic cardiac involvement is rare and occurs in about 5% of patients with sarcoidosis. Fatal ventricular arrhythmias are the most severe clinical presentation of the disease. Cardiac magnetic resonance (CMR) is a useful non-invasive tool for the risk stratification of ventricular arrhythmias and sudden cardiac death (SCD) in patients with cardiac sarcoidosis (CS). More specifically, late gadolinium enhancement (LGE), a CMR tool for scar detection, has been found to be significantly associated with arrhythmic events in CS patients. This review aims to present the existing evidence regarding the association of LGE with adverse events and especially with fatal ventricular arrhythmias

The role of late gadolinium enhancement in predicting arrhythmic events in cardiac sarcoidosis patients – A mini-review

Sarcoidosis is a multisystem inflammatory disorder with an unknown origin. Symptomatic cardiac involvement is rare and occurs in about 5% of patients with sarcoidosis. Fatal ventricular arrhythmias are the most severe clinical presentation of the disease. Cardiac magnetic resonance (CMR) is a useful non-invasive tool for the risk stratification of ventricular arrhythmias and sudden cardiac death (SCD) in patients with cardiac sarcoidosis (CS). More specifically, late gadolinium enhancement (LGE), a CMR tool for scar detection, has been found to be significantly associated with arrhythmic events in CS patients. This review aims to present the existing evidence regarding the association of LGE with adverse events and especially with fatal ventricular arrhythmias

Noninvasive risk factors for the prediction of inducibility on programmed ventricular stimulation in post-myocardial infarction patients with an ejection fraction &gt;= 40% at risk for sudden cardiac arrest: Insights from the PRESERVE-EF study

Background In the PRESERVE-EF study, a two-step sudden cardiac death (SCD) risk stratification approach to detect post-myocardial infarction (MI) patients with left ventricle ejection fraction (LVEF) &gt;= 40% at risk for major arrhythmic events (MAEs) was used. Seven noninvasive risk factors (NIRFs) were extracted from a 24-h ambulatory electrocardiography (AECG) and a 45-min resting recording. Patients with at least one NIRF present were referred for invasive programmed ventricular stimulation (PVS) and inducible patients received an Implantable Cardioverter - Defibrillator (ICD). Methods In the present study, we evaluated the performance of the NIRFs, as they were described in the PRESERVE-EF study protocol, in predicting a positive PVS. In the PRESERVE-EF study, 152 out of 575 patients underwent PVS and 41 of them were inducible. For the present analysis, data from these 152 patients were analyzed. Results Among the NIRFs examined, the presence of signal averaged ECG-late potentials (SAECG-LPs) &gt;= 2/3 and non-sustained ventricular tachycardia (NSVT) &gt;= 1 eposode/24 h cutoff points were important predictors of a positive PVS study, demonstrating in the logistic regression analysis odds ratios 2.285 (p = .027) and 2.867 (p = .006), respectively. A simple risk score based on the above cutoff points in combination with LVEF &lt; 50% presented high sensitivity but low specificity for a positive PVS. Conclusion Cutoff points of NSVT &gt;= 1 episode/24 h and SAECG-LPs &gt;= 2/3 in combination with a LVEF &lt; 50% were important predictors of inducibility. However, the final decision for an ICD implantation should be based on a positive PVS, which is irreplaceable in risk stratification

Cadmium effects on brain acetylcholinesterase activity and antioxidant status of adult rats: modulation by zinc, calcium and L-cysteine co-administration

We have previously reported that cadmium (Cd) as 3CdSO4 · 8H2O decreases rat brain total antioxidant status and L-cysteine (Cys) has a protective effect against it. The aim of the present study was to investigate the effects of subacute Cd administration, either alone or (almost simultaneously) with zinc (Zn), calcium (Ca) and Cys, on brain acetylcholinesterase (AChE) activity and brain total antioxidant status in male adult rats. All substances were administered intraperitoneally. Cadmium (1 mg/kg/day for 14 days) increased AChE activity (+46%; P&lt;0.001) and decreased total antioxidant status (−29%; P&lt;0.001). Zinc and Ca (both 1 mg/kg/day for 14 days) increased AChE activity (+18%; P&lt;0.01 and +53%; P&lt;0.001) and caused no changes on rat brain total antioxidant status. L-Cysteine (7 mg/kg/day for 14 days) impressively increased AChE activity (+185%; P&lt;0.001) and augmented total antioxidant status (+26%; P&lt;0.001). In the groups of Zn+Cd, Ca+Cd and Cys+Cd co-administration, AChE activity remained high (+42%; P&lt;0.001, +41%; P&lt;0.001 and +141%; P&lt;0.001 respectively), while total antioxidant status returned to the saline control levels. L-Cysteine given before a toxic dose of Cd (5 mg/kg) resulted in high AChE activity (+85%; P&lt;0.001), a total antioxidant status similar to the control values, and survival of the treated rats. In conclusion, Cd increased brain AChE activity and decreased brain total antioxidant status of adult male rats. Zinc, Ca and Cys, given just before Cd administration, modified the Cd-induced effects and restored rat brain total antioxidant status to the control levels