Real-time optical manipulation of cardiac conduction in intact hearts

Optogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all‐optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide‐field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free‐run mode with submillisecond temporal resolution or in a closed‐loop fashion: a tailored hardware and software platform allowed real‐time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real‐time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real‐time resynchronization therapy and cardiac defibrillation. Furthermore, the closed‐loop approach was applied to simulate a re‐entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof‐of‐concept that a real‐time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart

Coastal ocean forecasting with an unstructured grid model in the southern Adriatic and northern Ionian seas

SANIFS (Southern Adriatic Northern Ionian coastal Forecasting System) is a coastal-ocean operational system based on the unstructured grid finite-element three-dimensional hydrodynamic SHYFEM model, providing short-term forecasts. The operational chain is based on a downscaling approach starting from the large-scale system for the entire Mediterranean Basin (MFS, Mediterranean Forecasting System), which provides initial and boundary condition fields to the nested system. The model is configured to provide hydrodynamics and active tracer forecasts both in open ocean and coastal waters of southeastern Italy using a variable horizontal resolution from the open sea (3–4 km) to coastal areas (50–500 m). Given that the coastal fields are driven by a combination of both local (also known as coastal) and deep-ocean forcings propagating along the shelf, the performance of SANIFS was verified both in forecast and simulation mode, first (i) on the large and shelf-coastal scales by comparing with a large-scale survey CTD (conductivity–temperature–depth) in the Gulf of Taranto and then (ii) on the coastal-harbour scale (Mar Grande of Taranto) by comparison with CTD, ADCP (acoustic doppler current profiler) and tide gauge data. Sensitivity tests were performed on initialization conditions (mainly focused on spin-up procedures) and on surface boundary conditions by assessing the reliability of two alternative datasets at different horizontal resolution (12.5 and 6.5 km). The SANIFS forecasts at a lead time of 1 day were compared with the MFS forecasts, highlighting that SANIFS is able to retain the large-scale dynamics of MFS. The large-scale dynamics of MFS are correctly propagated to the shelf-coastal scale, improving the forecast accuracy (+17 % for temperature and +6 % for salinity compared to MFS). Moreover, the added value of SANIFS was assessed on the coastal-harbour scale, which is not covered by the coarse resolution of MFS, where the fields forecasted by SANIFS reproduced the observations well (temperature RMSE equal to 0.11 °C). Furthermore, SANIFS simulations were compared with hourly time series of temperature, sea level and velocity measured on the coastal-harbour scale, showing a good agreement. Simulations in the Gulf of Taranto described a circulation mainly characterized by an anticyclonic gyre with the presence of cyclonic vortexes in shelf-coastal areas. A surface water inflow from the open sea to Mar Grande characterizes the coastal-harbour scale

A new search-and-rescue service in the Mediterranean Sea: a demonstration of the operational capability and an evaluation of its performance using real case scenarios

Abstract. A new web-based and mobile decision support system (DSS) for search-and-rescue (SAR) at sea is presented, and its performance is evaluated using real case scenarios. The system, named OCEAN-SAR, is accessible via the website http://www.ocean-sar.com. In addition to the website, dedicated applications for iOS and Android have been created to optimise the user experience on mobile devices. OCEAN-SAR simulates drifting objects at sea, using as input ocean currents and wind data provided, respectively, by the CMEMS and ECMWF. The modelling of the drifting objects is based on the leeway model, which parameterises the wind drag of an object using a series of coefficients. These coefficients have been measured in field experiments for different types of objects, ranging from a person in the water to a coastal freighter adrift. OCEAN-SAR provides the user with an intuitive interface to run simulations and to visualise their results using Google Maps. The performance of the service is evaluated by comparing simulations to data from the Italian Coast Guard pertaining to actual incidents in the Mediterranean Sea

Histopathological comparison of intramural coronary artery remodeling and myocardial fibrosis in obstructive versus end-stage hypertrophic cardiomyopathy

Background: Although imaging techniques have demonstrated the existence of microvascular abnormalities in hypertrophic cardiomyopathy (HCM), a detailed histopathological assessment is lacking as well as a comparison between different phases of the disease. We aimed to compare microvasculopathy and myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) versus end-stage (ES) HCM. Methods: 27 myectomy specimens of HOCM patients and 30 ES-HCM explanted hearts were analyzed. Myocardial fibrosis was quantitatively determined with dedicated software and qualitatively classified as scar-like or interstitial. Intramural coronary arteries were evaluated separately according to lumen diameter: 100–500 μ versus <100 μ. Microvasculopathy assessment included the description of medial and intimal abnormalities and stenosis grading. The two subgroups were compared considering only the anterobasal septum of ES explanted hearts. Results: Median value of fibrosis in the anterobasal septum of explanted hearts was 34.6% as opposed to 10.3% of myectomy specimens (p < 0.001). Scar-like fibrosis was widely found in ES hearts while interstitial fibrosis was distinctive of HOCM (p < 0.001). All slides showed 100–500 μ microvasculopathy without any differences between subgroups in terms of lumen narrowing, extent of the disease and type of parietal involvement. Among ES hearts these lesions were associated with scar-like fibrosis (p = 0.034). <100-μ microvasculopathy was also frequent with no differences between subgroups. Conclusions: Microvasculopathy is an intrinsic feature of HCM with similar characteristics across the natural phases of the disease. Conversely, myocardial fibrosis changes over time with ES hearts showing a three-fold greater amount, mainly scar-like. ES showed a closer association between microvasculopathy and replacement fibrosis

Understanding the heart-brain axis response in COVID-19 patients: A suggestive perspective for therapeutic development

In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role of the deregulation of the heart-brain axis (HBA), a bidirectional flow of information, in leading to severe multiorgan disease syndrome (MODS) in patients with confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Noteworthy, HBA dysfunction may worsen the outcome of the COVID-19 patients. In this review, we discuss the critical role HBA plays in both promoting and limiting MODS in COVID-19. We also highlight the role of HBA as new target for novel therapeutic strategies in COVID-19 in order to open new translational frontiers of care. This is a translational perspective from the Italian Society of Cardiovascular Researches

Black sea observing system

The ultimate goal of modern operational oceanography are end user oriented products with high scientific quality. Beneficiaries are the governmental services, coast and offshore based enterprises and research institutions that make use of the products generated by operational oceanography. Direct users are coastal managers, shipping, search and rescue, oil spill combat, offshore industry, ports, fishing, tourism, and recreation industry. Indirect beneficiaries, through climate forecasting based on ocean observations, are food, energy, water and medical suppliers. Availability of updated information on the actual state as well as forecast of marine environment is essential for the success and safety of maritime operations in the offshore industry. Various systems for the collection and presentation of marine data for the needs of different users have been developed and put in operation in the Black Sea. The systems are located both along the coast and in the open sea and the information they provide is used by both the maritime industry and the widest range of users. The Black Sea Monitoring and Forecasting Center in the frame of the Copernicus Marine Service is providing regular and systematic information about the physical state of the ocean, marine ecosystem and wave conditions in the Black Sea area, assimilating observations, keeping efficient operations, advanced technology and high quality modeling products. Combining and optimizing in situ, remote sensing, modeling and forecasting into a Black Sea observing system is a task that has to be solved, and that will allow to get a more complete and comprehensive picture of the state of the marine environment as well as to forecast future changes of physical and biogeochemical state of the Black Sea and the Black Sea ecosystem

A relocatable ocean model in support of environmental emergencies

During the Costa Concordia emergency case, regional, subregional, and relocatable ocean models have been used together with the oil spill model, MEDSLIK-II, to provide ocean currents forecasts, possible oil spill scenarios, and drifters trajectories simulations. The models results together with the evaluation of their performances are presented in this paper. In particular, we focused this work on the implementation of the Interactive Relocatable Nested Ocean Model (IRENOM), based on the Harvard Ocean Prediction System (HOPS), for the Costa Concordia emergency and on its validation using drifters released in the area of the accident. It is shown that thanks to the capability of improving easily and quickly its configuration, the IRENOM results are of greater accuracy than the results achieved using regional or subregional model products. The model topography, and to the initialization procedures, and the horizontal resolution are the key model settings to be configured. Furthermore, the IRENOM currents and the MEDSLIK-II simulated trajectories showed to be sensitive to the spatial resolution of the meteorological fields used, providing higher prediction skills with higher resolution wind forcing.MEDESS4MS Project; TESSA Project; MyOcean2 Projectinfo:eu-repo/semantics/publishedVersio

Optical investigation of action potential and calcium handling maturation of hiPSC-cardiomyocytes on biomimetic substrates

Cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) are the most promising human source with preserved genetic background of healthy individuals or patients. This study aimed to establish a systematic procedure for exploring development of hiPSC-CM functional output to predict genetic cardiomyopathy outcomes and identify molecular targets for therapy. Biomimetic substrates with microtopography and physiological stiffness can overcome the immaturity of hiPSC-CM function. We have developed a custom-made apparatus for simultaneous optical measurements of hiPSC-CM action potential and calcium transients to correlate these parameters at specific time points (day 60, 75 and 90 post differentiation) and under inotropic interventions. In later-stages, single hiPSC-CMs revealed prolonged action potential duration, increased calcium transient amplitude and shorter duration that closely resembled those of human adult cardiomyocytes from fresh ventricular tissue of patients. Thus, the major contribution of sarcoplasmic reticulum and positive inotropic response to \u3b2-adrenergic stimulation are time-dependent events underlying excitation contraction coupling (ECC) maturation of hiPSC-CM; biomimetic substrates can promote calcium-handling regulation towards adult-like kinetics. Simultaneous optical recordings of long-term cultured hiPSC-CMs on biomimetic substrates favor high-throughput electrophysiological analysis aimed at testing (mechanistic hypothesis on) disease progression and pharmacological interventions in patient-derived hiPSC-CMs