Organ Neuroprosthetics: Connecting Transplanted and Artificial Organs with the Nervous System.

Implantable neural interfaces with the central and peripheral nervous systems are currently used to restore sensory, motor, and cognitive functions in disabled people with very promising results. They have also been used to modulate autonomic activities to treat diseases such as diabetes or hypertension. Here, this study proposes to extend the use of these technologies to (re-)establish the connection between new (transplanted or artificial) organs and the nervous system in order to increase the long-term efficacy and the effective biointegration of these solutions. In this perspective paper, some clinically relevant applications of this approach are briefly described. Then, the choices that neural engineers must implement about the type, implantation location, and closed-loop control algorithms to successfully realize this approach are highlighted. It is believed that these new "organ neuroprostheses" are going to become more and more valuable and very effective solutions in the years to come.

Expanding the Frontiers of Guardian Antioxidant Selenoproteins in Cardiovascular Pathophysiology.

Significance: Physiological levels of reactive oxygen and nitrogen species (ROS/RNS) function as fundamental messengers for many cellular and developmental processes in the cardiovascular system. ROS/RNS involved in cardiac redox-signaling originate from diverse sources, and their levels are tightly controlled by key endogenous antioxidant systems that counteract their accumulation. However, dysregulated redox-stress resulting from inefficient removal of ROS/RNS leads to inflammation, mitochondrial dysfunction, and cell death, contributing to the development and progression of cardiovascular disease (CVD). Recent Advances: Basic and clinical studies demonstrate the critical role of selenium (Se) and selenoproteins (unique proteins that incorporate Se into their active site in the form of the 21st proteinogenic amino acid selenocysteine [Sec]), including glutathione peroxidase and thioredoxin reductase, in cardiovascular redox homeostasis, representing a first-line enzymatic antioxidant defense of the heart. Increasing attention has been paid to emerging selenoproteins in the endoplasmic reticulum (ER) (i.e., a multifunctional intracellular organelle whose disruption triggers cardiac inflammation and oxidative stress, leading to multiple CVD), which are crucially involved in redox balance, antioxidant activity, and calcium and ER homeostasis. Critical Issues: This review focuses on endogenous antioxidant strategies with therapeutic potential, particularly selenoproteins, which are very promising but deserve more detailed and clinical studies. Future Directions: The importance of selective selenoproteins in embryonic development and the consequences of their mutations and inborn errors highlight the need to improve knowledge of their biological function in myocardial redox signaling. This could facilitate the development of personalized approaches for the diagnosis, prevention, and treatment of CVD. Antioxid. Redox Signal. 40, 369-432.

Pull the fuzes: Processing protein precursors to generate apoplastic danger signals for triggering plant immunity.

The apoplast is one of the first cellular compartments outside the plasma membrane encountered by phytopathogenic microbes in the early stages of plant tissue invasion. Plants have developed sophisticated surveillance mechanisms to sense danger events at the cell surface and promptly activate immunity. However, a fine tuning of the activation of immune pathways is necessary to mount a robust and effective defense response. Several endogenous proteins and enzymes are synthesized as inactive precursors, and their post-translational processing has emerged as a critical mechanism for triggering alarms in the apoplast. In this review, we focus on the precursors of phytocytokines, cell wall remodeling enzymes, and proteases. The physiological events that convert inactive precursors into immunomodulatory active peptides or enzymes are described. This review also explores the functional synergies among phytocytokines, cell wall damage-associated molecular patterns, and remodeling, highlighting their roles in boosting extracellular immunity and reinforcing defenses against pests.

A multi-channel stimulator with an active electrode array implant for vagal-cardiac neuromodulation studies.

BACKGROUND: Implantable vagus nerve stimulation is a promising approach for restoring autonomic cardiovascular functions after heart transplantation. For successful treatment a system should have multiple electrodes to deliver precise stimulation and complex neuromodulation patterns. METHODS: This paper presents an implantable multi-channel stimulation system for vagal-cardiac neuromodulation studies in swine species. The system comprises an active electrode array implant percutaneously connected to an external wearable controller. The active electrode array implant has an integrated stimulator ASIC mounted on a ceramic substrate connected to an intraneural electrode array via micro-rivet bonding. The implant is silicone encapsulated for biocompatibility and implanted lifetime. The stimulation parameters are remotely transmitted via a Bluetooth telemetry link. RESULTS: The size of the encapsulated active electrode array implant is 8 mm × 10 mm × 3 mm. The stimulator ASIC has 10-bit current amplitude resolution and 16 independent output channels, each capable of delivering up to 550 µA stimulus current and a maximum voltage of 20 V. The active electrode array implant was subjected to in vitro accelerated lifetime testing at 70 °C for 7 days with no degradation in performance. After over 2 h continuous stimulation, the surface temperature change of the implant was less than 0.5 °C. In addition, in vivo testing on the sciatic nerve of a male Göttingen minipig demonstrated that the implant could effectively elicit an EMG response that grew progressively stronger on increasing the amplitude of the stimulation. CONCLUSIONS: The multi-channel stimulator is suitable for long term implantation. It shows potential as a useful tool in vagal-cardiac neuromodulation studies in animal models for restoring autonomic cardiovascular functions after heart transplantation.

A proposed index of myocardial staining for vein of Marshall ethanol infusion: an Italian single-center experience.

BACKGROUND: Mitral isthmus (MI) conduction block is a fundamental step in anatomical approach treatment for persistent atrial fibrillation (PeAF). However, MI block is hardly achievable with endocardial ablation only. Retrograde ethanol infusion (EI) into the vein of Marshall (VOM) facilitates MI block. Fluorographic myocardial staining (MS) during VOM-EI could be helpful in predicting procedural alcoholization outcome even if its role is qualitatively assessed in the routine. The aim was to quantitatively assess MS during VOM-EI and to evaluate its association with MI block achievement. METHODS: Consecutive patients undergoing catheter ablation for PeAF at Fondazione Toscana Gabriele Monasterio (Pisa, Italy) from February 2022 to May 2023 were considered. Patients with identifiable VOM were included. A proposed index of MS (MSI) was retrospectively calculated in each included patient. Correlation of MSI with low-voltage zones (LVZ) extension after VOM-EI and its association with MI block achievement were assessed. RESULTS: In total, 42 patients out of 49 (85.8%) had an identifiable VOM. MI block was successfully achieved in 35 patients out of 42 (83.3%). MSI was significantly associated with the occurrence of MI block (OR 1.24 (1.03-1.48); p = 0.022). A higher MSI resulted in reduced ablation time (p = 0.014) and reduced radiofrequency applications (p = 0.002) to obtain MI block. MSI was also associated with MI block obtained by endocardial ablation only (OR 1.07 (1.02-1.13); p = 0.002). MSI was highly correlated with newly formed LVZ extension (r = 0.776; p = 0.001). CONCLUSIONS: In our study cohort, optimal MSI predicts MI block and facilitates its achievement with endocardial ablation only.