Amphetamine (AMPH) exposure induces behavioural and neurochemical sensitization observed in rodents as hyperlocomotion and increased dopamine release in response to a subsequent dose. Brain ...Angiotensin II modulates dopaminergic neurotransmission through its AT1 receptors (AT1‐R), positively regulating striatal dopamine synthesis and release. This work aims to evaluate the AT1‐R role in the development and maintenance of AMPH‐induced sensitization. Also, the AT1‐R involvement in striatal dopamine reuptake was analysed. The sensitization protocol consisted of daily AMPH administration for 5 days and tested 21 days after withdrawal. An AT1‐R antagonist, candesartan, was administered before or after AMPH exposure to evaluate the participation of AT1‐R in the development and maintenance of sensitization, respectively. Sensitization was evaluated by locomotor activity and c‐Fos immunostaining. Changes in dopamine reuptake kinetics were evaluated 1 day after AT1‐R blockade withdrawal treatment, with or without the addition of AMPH in vitro. The social interaction test was performed as another behavioural output. Repeated AMPH exposure induced behavioural and neurochemical sensitization, which was prevented and reversed by candesartan. The AT1‐R blockade increased the dopamine reuptake kinetics. Neither the AMPH administration nor the AT1‐R blockade altered the performance of social interaction. Our results highlight the AT1‐R's crucial role in AMPH sensitization. The enhancement of dopamine reuptake kinetics induced by the AT1‐R blockade might attenuate the neuroadaptive changes that lead to AMPH sensitization and its self‐perpetuation. Therefore, AT1‐R is a prominent candidate as a target for pharmacological treatment of pathologies related to dopamine imbalance, including drug addiction and schizophrenia.
Effects of AT1‐R blockade over amphetamine‐induced sensitization. AT1‐R blockade prevents and reverses amphetamine sensitization in part due to the increased dopamine reuptake kinetics induced by AT1‐R blockade. The scheme is a representation of the basal conditions (a), the prevention (b) and the reversion (c) induced by AT1‐R blockade.
This article explores the application of chemometric tools including multivariate curve resolution with alternating least squares for the simultaneous determination of gallic and caffeic acids on the ...surface of a glassy carbon electrode without additional modification. Gallic and caffeic acids are primary polyphenols, the most abundant in red wines produced in Argentina, and are often used as quality markers for them. These polyphenols significantly contribute to the organoleptic properties of wines from this origin, but their electrochemical signals overlap significantly, making simultaneous quantification challenging without additional experiments such as electrode modification or alternative analytical techniques beyond differential pulse voltammetry. This study successfully quantified these compounds in complex mixtures by generating second-order data from differential pulse voltammetry experiments conducted at various potential steps and subsequently applying multivariate curve resolution with alternating least squares. The use of constraints during optimization prevented rotational ambiguities common in this modeling, leading to unique results in validation samples. The limits of detection (LOD) found for gallic and caffeic acids were 1.6 and 7.6 mg L
−1
, which are in excellent agreement with the expected concentrations of these compounds in red wines. The concentration ranges analyzed showed a linear dependency (between the LOD and 300 mg L
−1
) with the signals estimated by the model for both analytes. Advantages such as simplicity, low cost, and high speed, as well as not requiring electrode modification, combined with excellent results obtained for real samples, make it a promising alternative for polyphenol analysis in the wine industry.
This work presents an eco-friendly electroanalytical method without electrode modifications assisted by chemometrics, for the simultaneous determination of gallic and caffeic acids in red wines, even in the presence of uncalibrated interference.
•Electrochemical biosensors demonstrated to be an excellent analytical tool to quantify miRNAs.•Amplification strategies have allowed to obtain ultrasensitive electrochemical miRNA ...biosensing.•Non-amplified biosensors present competitive analytical performance in shorter times.
MicroRNAs (miRNAs) are non-coding regulatory RNAs that play an important role in RNA silencing and post-transcriptional gene expression regulation. Since their dysregulation has been associated with Alzheimer disease, cardiovascular diseases and different types of cancer, among others, miRNAs can be used as biomarkers for early diagnosis and prognosis of these diseases. The methods commonly used to quantify miRNAs are, in general, complex, costly, with limited application for point-of-care devices or resource-limited facilities. Electrochemical biosensors, mainly those based on nanomaterials, have emerged as a promising alternative to the conventional miRNA detection methods and have paved the way to the development of sensitive, fast, and low-cost detection systems. This review is focused on the most relevant contributions performed in the field of electrochemical miRNAs biosensors between 2017 and the beginning of 2020. The main contribution of this article is the critical discussion of the different amplification strategies and the comparative analysis between amplified and non-amplified miRNA electrochemical biosensing and between the different amplification schemes. Particular emphasis was given to the importance of the nanostructures, enzymes, labelling molecules, and special sequences of nucleic acids or analogues on the organization of the different bioanalytical platforms, the transduction of the hybridization event and the generation the analytical signal.
Abstract
Background
Pulmonary vein isolation (PVI) with endoscopic laser balloon systems (ELBS) is an innovative option for catheter ablation of atrial fibrillation (AF). The third-generation ELBS ...has several structural improvements, including a novel feature (RAPID mode), potentially allowing a high-speed and precise circumferential PVI. Nevertheless, there is a need for large, multicentre studies on its use.
Objective
To assess the safety, efficiency, and efficacy of the third-generation ELBS in a multicentric, international cohort of patients.
Methods
We analyzed the data of all consecutive patients who underwent PVI using the third-generation ELBS between June 2019 and December 2022 in eight Italian and one German Hospital. For each pulmonary vein (PV), the maximum amount of laser delivery with the RAPID mode was attempted. When RAPID mode was not feasible, the operator used point-by-point laser delivery.
Results
We enrolled 429 patients (mean age 61.1±10.7 years, persistent atrial fibrillation 27.7%, female patients 27.7%). The operators isolated 1654 pulmonary veins. 93 (21.7%) patients had an anatomical variation of the left atrium, 60 of them had either a left or a right common trunk, and 33 had a middle PV. Mean total procedural and fluoroscopic times were 115.4±58.2 min and 19.3±12.8 min, respectively. Information on the use of RAPID mode was available for 336 patients: mean use of this feature was possible for 86±18.2 % of the PVs circumference. The operators could use the RAPID mode for at least 90% of all PVs circumference in 148 of 336 patients (44%), and ablation using only RAPID mode was possible in 79 of them (23%). 12 (2.8%) periprocedural complications occurred. There were 6 (1.4%) episodes of phrenic nerve palsy, of which only 1 (0.2%) did not completely resolve during follow up. 3 (0.7%) pericardial tamponades occurred, with a subsequent need for pericardiocentesis. Finally, there were 3 (0.7%) periprocedural transient ischaemic attacks (TIA), which resolved without sequelae. 219 patients were followed up for at least six months (mean follow-up 12.3 ± 6 months). Among these, 63 (28.8%) presented a clinical and/or subclinical recurrence after the blanking period.
Conclusion
This is the largest multicentre cohort of patients treated with the third-generation ELBS. In this multicentric international experience, the system proved to be safe, efficient and effective and the RAPID mode showed optimal applicability.
Abstract
Background
Laser balloon ablation is a promising option for performing pulmonary vein isolation (PVI) which is the cornerstone of invasive atrial fibrillation (AF) treatment.
Purpose
We ...aimed to investigate the acute efficacy and safety of the novel third-generation of the laser balloon system in an initial multicenter experience.
Methods
First and consecutive patients who underwent PVI with LB3 for drug-resistant paroxysmal or persistent AF at 7 Italian sites were included in this analysis. Study endpoints were acute procedural efficacy, defined as successful isolation of all identified PVs without radiofrequency touch-up, total and fluoroscopy times, and periprocedural complications.
Results
Our population included 86 patients (81% males, mean age 60.6±9.5 years) who underwent a procedure of PVI using LB3 between June 2020 and March 2021.
Most patients had paroxysmal AF (74%) and were in sinus rhythm at the beginning of the procedure. The mean procedure time was 138±60 min; fluoroscopy time was 22±17 min and the mean ablation time was 44±40 min. Of the 313 targeted PVs, 311 (99.4%) could be isolated with first-pass LB3 application, while 2 (0.6%) required radiofrequency touchup. At the end of the procedure, all patients were in sinus rhythm and 26 (32%) received electrical cardioversion to achieve stable sinus rhythm.
The total rate of major compilations was 1.2% (1/82 patients): one pericardial tamponade requiring epicardial puncture. No surgical intervention was necessary, and the patient recovered without any sequalae. There were no vascular access complications or phrenic nervy palsy. Three pinhole balloon raptures (3.5%) were observed during energy applications that required replacement of the whole system but had no effect on patient safety.
Conclusions
In a first multicenter experience, the LB3 system for PVI was safe with excellent acute efficacy.
Funding Acknowledgement
Type of funding sources: None.
Abstract Background Pulmonary vein isolation (PVI) with the use of an endoscopic laser balloon (ELB) is an alternative option for catheter ablation of atrial fibrillation (AF). The third-generation ...system has several improvements, including the novel RAPID mode (RM), potentially allowing a one-shot, continuous, circumferential laser lesion for PVI. Objective In an international, multicentric cohort, we assessed the third-generation ELB’s safety, efficacy, and long-term effectiveness. We also focused on the learning curve (LC) and the use of RM. Methods Between June 2019 and December 2022, we prospectively obtained data on all the patients who consecutively underwent ablation of AF using the third-generation ELB in eight Italian and one German hospital. Each operator attempted to use the RM to the maximum extent in every procedure. Follow-up (FU) visits were scheduled at 3, 6, 12 and 24 months and included a Holter-ECG of 24 hours or, if the patient was a carrier, a device interrogation (implantable loop recorder or two-chamber/three-chamber pacemaker/defibrillator). For FU analysis, we included patients with data available after the blanking period (the first 90 days after the procedure). We analysed the LC, comparing the outcomes of the first fifteen patients of each centre with the remaining patients. In addition, we investigated the impact of an extensive use of the RM (at least 90% of all PV circumferences) on the procedural and FU outcomes. Results we enrolled 427 patients. Of these, 328 had a FU >90 days. The mean total procedural and fluoroscopic times were 105 (66-150) and 17 (10-28) minutes, respectively. Serious adverse procedural events occurred in 11 patients (2.6 %) as follows: 3 periprocedural transient ischaemic attacks, 4 pericardial tamponades, 1 persistent phrenic nerve palsy and 3 severe vascular complications. The mean FU period was of 365 days (194-533). AF recurrence-free rate was 76.7% (95% CI, 70.8%-81.5%) at 12 months. Median RM use was 94% (81-100) of the PVs circumference. RM could be used for at least 90% of all PV circumferences in 188 (55.8%) patients, and the operators could perform an RM-only procedure in 82 (24.3%) patients. Patients treated after the LC or with extensive use of RM showed significantly reduced procedural times and rates of AF recurrence. In a multivariate analysis, the use of the RM was not an independent predictor of a lower recurrence rate at FU, demonstrating only a tendency toward significance (86.0% 77.3-91.6 vs 71.3% 61.3-79.2, HR 0.52, CI 0.26-1.07, p 0.075). Conclusion In this prospective, multicentre, international registry of patients treated with the third-generation ELB, the system proved efficient, safe, and effective. Completing the LC and using the RM reduced procedural time and arrhythmia recurrence. However, using RM was not an independent predictor of a lower recurrence rate.
Outcome comparisons among subcutaneous implantable cardioverter-defibrillator (S-ICD) recipients with nonischemic cardiomyopathies are scarce.
The aim of this study was to evaluate differences in ...device-related outcomes among S-ICD recipients with different structural substrates.
Patients enrolled in the i-SUSI (International SUbcutaneouS Implantable cardioverter defibrillator registry) project were grouped according to the underlying substrate (ischemic vs nonischemic) and subgrouped into dilated cardiomyopathy, hypertrophic cardiomyopathy, Brugada syndrome (BrS), arrhythmogenic right ventricular cardiomyopathy (ARVC). The main outcome of our study was to compare the rates of appropriate and inappropriate shocks and device-related complications.
Among 1698 patients, the most common underlying substrate was ischemic (31.7%), followed by dilated cardiomyopathy (20.5%), BrS (10.8%), hypertrophic cardiomyopathy (8.5%), and ARVC (4.4%). S-ICD for primary prevention was more common in the nonischemic cohort (70.9% vs 65.4%; P = .037). Over a median (interquartile range) follow-up of 26.5 (12.6-42.8) months, no differences were observed in appropriate shocks between ischemic and nonischemic patients (4.8%/y vs 3.9%/y; log-rank, P = .282). ARVC (9.0%/y; hazard ratio HR 2.492; P = .001) and BrS (1.8%/y; HR 0.396; P = .008) constituted the groups with the highest and lowest rates of appropriate shocks, respectively. Device-related complications did not differ between groups (ischemic: 6.4%/y vs nonischemic: 6.1%/y; log-rank, P = .666), nor among underlying substrates (log-rank, P = .089). Nonischemic patients experienced higher rates of inappropriate shocks than did ischemic S-ICD recipients (4.4%/y vs 3.0%/y; log-rank, P = .043), with patients with ARVC (9.9%/y; P = .001) having the highest risk, even after controlling for confounders (adjusted HR 2.243; confidence interval 1.338-4.267; P = .002).
Most S-ICD recipients were primary prevention nonischemic cardiomyopathy patients. Among those, patients with ARVC tend to receive the most frequent appropriate and inappropriate shocks and patients with BrS the least frequent appropriate shocks.
Background
Arterial stiffness and cardiac hypertrophy are independent cardiovascular risk factors. Aim of this study was to describe the relationship between these organ damages in a large cohort of ...essential hypertensive (EH) treated patients.
Methods
We performed standard trans-thoracic echocardiography to measure anatomical (left ventricular mass indexed by body surface area LVMI and relative wall thickness RWT) and functional (ejection fraction, diastolic function E/A and deceleration time) cardiac parameters on 827 treated EH patients. Carotid-femoral pulse wave velocity (PWV) was used to estimate arterial stiffness. Data were analyzed by linear regressions or ANOVA and post-hoc Bonferroni test.
Results
Patients were 53±14 years old (Mean ± SD)and 50% were male. Their mean blood pressure values were 142.3±18.6/86.7±10.6 mmHg; cardiac structural and functional parameters were in the normal range, PWV was 10.7m/sec. Geometry of left ventricle, as defined by LVMI and RWT (ESC guidelines), was normal in 336 (43%) patients, while in 163 (21%) we found concentric remodelling, concentric hypertrophy in 173 (22%) and eccentric hypertrophy in 109 (14%) patients. PWV was significantly different between the 4 subgroups (p = 0.001), with concentric and eccentric hypertrophy patients having significantly higher PWV values (11.5±2.7 and 11.4±3 m/sec respectively) than patients with normal heart geometry (10.2±2.6m/sec) (p ≤ 0.001 for both).
Conclusions
In EH patients arterial stiffness is associated with the degree of cardiac damage. This may reflect a common pathway leading to these alterations caused by hypertension in different but tightly related organs such as heart and arteries.
Women have been historically underrepresented in implantable cardioverter-defibrillator (ICD) trials. No data on sex differences regarding subcutaneous ICDs (S-ICD) carriers have been described. Aim ...of our study was to investigate sex-related differences among unselected S-ICD recipients.
Consecutive patients enrolled in the multicentre, international i-SUSI registry were analysed. Comparisons between sexes were performed using a 1:1 propensity matching adjusted analysis for age, body mass index (BMI), left ventricular function, and substrate. The primary outcome was the rate of appropriate shocks during follow-up. Inappropriate shocks and other device-related complications were deemed secondary outcomes. A total of 1698 patients were extracted from the i-SUSI registry; 399 (23.5%) were females. After propensity matching, two cohorts of 374 patients presenting similar baseline characteristics were analysed. Despite similar periprocedural characteristics and a matched BMI, women resulted at lower risk of conversion failure as per PRAETORIAN score (73.4% vs. 81.3%, P = 0.049). Over a median follow-up time of 26.5 12.7-42.5 months, appropriate shocks were more common in the male cohort (rate/year 3.4% vs. 1.7%; log-rank P = 0.049), while no significant differences in device-related complications (rate/year: 6.3% vs. 5.8%; log-rank P = 0.595) and inappropriate shocks (rate/year: 4.3% vs. 3.1%; log-rank P = 0.375) were observed. After controlling for confounders, sex remained significantly associated with the primary outcome (aHR 1.648; CI 0.999-2.655, P = 0.048), while not resulting predictor of inappropriate shocks and device-related complications.
In a propensity-matched cohort of S-ICD recipients, women are less likely to experience appropriate ICD therapy, while not showing higher risk of device-related complications.
ClinicalTrials.gov Identifier: NCT0473876.
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