Long-term in vitro recording of cardiac action potentials on microelectrode arrays for chronic cardiotoxicity assessment.

The reliable identification of chronic cardiotoxic effects in in vitro screenings is fundamental for filtering out toxic molecular entities before in vivo animal experimentation and clinical trials. Present techniques such as patch-clamp, voltage indicators, and standard microelectrode arrays do not offer at the same time high sensitivity for measuring transmembrane ion currents and low-invasiveness for monitoring cells over long time. Here, we show that optoporation applied to microelectrode arrays enables measuring action potentials from human-derived cardiac syncytia for more than 1 continuous month and provides reliable data on chronic cardiotoxic effects caused by known compounds such as pentamidine. The technique has high potential for detecting chronic cardiotoxicity in the early phases of drug development.

Telematics pre-operative psychological and nutritional assessment in candidates for bariatric surgery during COVID-19 phase 2: a pilot prospective observational study.

BACKGROUND: Obesity represents a risk factor for COVID-19 infection. Therefore, in order to reduce COVID-19 related comorbidities in obese population a continuation of obesity treatment is needed. However, bariatric procedures were postponed because of COVID-19 restrictions, delaying treatment for obese patients seeking for surgery. This study aimed to test the feasibility of a telematics pre-operative psychological and nutritional assessment as an alternative tool during COVID-19 outbreak. METHODS: Twenty-six patients were contacted. The pre-operative assessment consisted in 3-weekly one-to-one online sessions and a final in-person multidisciplinary session. The protocol feasibility has been evaluated on the following outcome: rejection rate (%), dropout rate (%), compliance and satisfaction's degree. RESULTS: Eighteen participants completed the whole protocol and 10% dropped-out. Seventy-two percent of participants obtained an excess weight loss ≥5%. All participants were satisfied of the telematics assessment. CONCLUSIONS: COVID-19 emergency has changed standard hospital procedures and this study could represent a landmark for an online pre-operative assessment method to adopt in case of new restrictions.

Improving reliability and reducing costs of cardiotoxicity assessments using laser-induced cell poration on microelectrode arrays.

Drug-induced cardiotoxicity is a major barrier to drug development and a main cause of withdrawal of marketed drugs. Drugs can strongly alter the spontaneous functioning of the heart by interacting with the cardiac membrane ion channels. If these effects only surface during in vivo preclinical tests, clinical trials or worse after commercialization, the societal and economic burden will be significant and seriously hinder the efficient drug development process. Hence, cardiac safety pharmacology requires in vitro electrophysiological screening assays of all drug candidates to predict cardiotoxic effects before clinical trials. In the past 10 years, microelectrode array (MEA) technology began to be considered a valuable approach in pharmaceutical applications. However, an effective tool for high-throughput intracellular measurements, compatible with pharmaceutical standards, is not yet available. Here, we propose laser-induced optoacoustic poration combined with CMOS-MEA technology as a reliable and effective platform to detect cardiotoxicity. This approach enables the acquisition of high-quality action potential recordings from large numbers of cardiomyocytes within the same culture well, providing reliable data using single-well MEA devices and single cardiac syncytia per each drug. Thus, this technology could be applied in drug safety screening platforms reducing times and costs of cardiotoxicity assessments, while simultaneously improving the data reliability.

Cost-effective and multifunctional acquisition system for in vitro electrophysiological investigations with multi-electrode arrays.

In vitro multi-electrode array (MEA) technology is nowadays involved in a wide range of applications beyond neuroscience, such as cardiac electrophysiology and bio-interface studies. However, the cost of commercially available acquisition systems severely limits its adoption outside specialized laboratories with high budget capabilities. Thus, the availability of low-cost methods to acquire signals from MEAs is important to allow research labs worldwide to exploit this technology for an ever-expanding pool of experiments independently from their economic possibilities. Here, we provide a comprehensive toolset to assemble a multifunctional in vitro MEA acquisition system with a total cost 80% lower than standard commercial solutions. We demonstrate the capabilities of this acquisition system by employing it to i) characterize commercial MEA devices by means of electrical impedance measurements ii) record activity from cultures of HL-1 cells extracellularly, and iii) electroporate HL-1 cells through nanostructured MEAs and record intracellular signals.

Chemical Functionalization of Plasmonic Surface Biosensors: A Tutorial Review on Issues, Strategies, and Costs.

In an ideal plasmonic surface sensor, the bioactive area, where analytes are recognized by specific biomolecules, is surrounded by an area that is generally composed of a different material. The latter, often the surface of the supporting chip, is generally hard to be selectively functionalized, with respect to the active area. As a result, cross talks between the active area and the surrounding one may occur. In designing a plasmonic sensor, various issues must be addressed: the specificity of analyte recognition, the orientation of the immobilized biomolecule that acts as the analyte receptor, and the selectivity of surface coverage. The objective of this tutorial review is to introduce the main rational tools required for a correct and complete approach to chemically functionalize plasmonic surface biosensors. After a short introduction, the review discusses, in detail, the most common strategies for achieving effective surface functionalization. The most important issues, such as the orientation of active molecules and spatial and chemical selectivity, are considered. A list of well-defined protocols is suggested for the most common practical situations. Importantly, for the reported protocols, we also present direct comparisons in term of costs, labor demand, and risk vs benefit balance. In addition, a survey of the most used characterization techniques necessary to validate the chemical protocols is reported.

Prevalence of adenoma of gallbladder, ultrasonographic and histological assessment in a retrospective series of 450 cholecystectomy.

BACKGROUND: Adenomyomas of the gallbladder are difficult to examine during standard ultrasound examination of the abdomen. They sometimes undergo malignant transformation and their optimal management still remains a problem. The authors have aimed to investigate the ultrasonographic and histopathological prevalence of gallbladder adenomyomas focusing on the diagnostic performance of ultrasound examination. MATERIALS AND METHODS: A retrospective series of 450 consecutive patients who underwent cholecystectomy is reported. Data regarding characteristics of the patients, US and histology examination of the gallbladder were collected. Sensitivity, specificity, positive and negative predictive values of ultrasound scan were calculated with respect to histological examination of the gallbladder. RESULTS: The study group consisted of 261 female and 189 male. Ultrasound scan detected adenomyomas in 22 patients, confirmed by histopathology in 13 and found to be not present in 9. Incidental adenomyomas were found in 16 patients of 428 who underwent cholecystectomy for gallstones. Prevalence was 4.9% and 6.4% for ultrasound scan and histopathology respectively. Ultrasound scan showed sensitivity of 43.3% (c.i.:25.4%-62.5%), specificity of 97.8% (c.i.:95.9%-99%) with a positive predictive value of 59% (c.i.:36.3%-79.2%) and with a negative predictive value of 96.2% (c.i.:93.7%- 97.6%). On histopathology, adenomyomas localized in the fundus were predominant. Two female patients with adenomyomas of the fundus (diameter 5 mm) and single stone showed intestinal metaplasia with high-grade dysplasia. CONCLUSIONS: The diagnosis of gallbladder adenomyomas by ultrasound scan still remains a problem because of its low sensitivity, which is mainly due to the association with gallstones. Histopathological findings in the perilesional mucosa confirm the hypothesis of a metaplasia-dysplasia-carcinoma sequence already shown in the colon-rectum. At present, the selection of patients requiring cholecystectomy is still controversial.