lifex-ep: a robust and efficient software for cardiac electrophysiology simulations.

BACKGROUND: Simulating the cardiac function requires the numerical solution of multi-physics and multi-scale mathematical models. This underscores the need for streamlined, accurate, and high-performance computational tools. Despite the dedicated endeavors of various research teams, comprehensive and user-friendly software programs for cardiac simulations, capable of accurately replicating both normal and pathological conditions, are still in the process of achieving full maturity within the scientific community. RESULTS: This work introduces [Formula: see text]-ep, a publicly available software for numerical simulations of the electrophysiology activity of the cardiac muscle, under both normal and pathological conditions. [Formula: see text]-ep employs the monodomain equation to model the heart's electrical activity. It incorporates both phenomenological and second-generation ionic models. These models are discretized using the Finite Element method on tetrahedral or hexahedral meshes. Additionally, [Formula: see text]-ep integrates the generation of myocardial fibers based on Laplace-Dirichlet Rule-Based Methods, previously released in Africa et al., 2023, within [Formula: see text]-fiber. As an alternative, users can also choose to import myofibers from a file. This paper provides a concise overview of the mathematical models and numerical methods underlying [Formula: see text]-ep, along with comprehensive implementation details and instructions for users. [Formula: see text]-ep features exceptional parallel speedup, scaling efficiently when using up to thousands of cores, and its implementation has been verified against an established benchmark problem for computational electrophysiology. We showcase the key features of [Formula: see text]-ep through various idealized and realistic simulations conducted in both normal and pathological scenarios. Furthermore, the software offers a user-friendly and flexible interface, simplifying the setup of simulations using self-documenting parameter files. CONCLUSIONS: [Formula: see text]-ep provides easy access to cardiac electrophysiology simulations for a wide user community. It offers a computational tool that integrates models and accurate methods for simulating cardiac electrophysiology within a high-performance framework, while maintaining a user-friendly interface. [Formula: see text]-ep represents a valuable tool for conducting in silico patient-specific simulations.

A mathematical model that integrates cardiac electrophysiology, mechanics, and fluid dynamics: Application to the human left heart.

We propose a mathematical and numerical model for the simulation of the heart function that couples cardiac electrophysiology, active and passive mechanics and hemodynamics, and includes reduced models for cardiac valves and the circulatory system. Our model accounts for the major feedback effects among the different processes that characterize the heart function, including electro-mechanical and mechano-electrical feedback as well as force-strain and force-velocity relationships. Moreover, it provides a three-dimensional representation of both the cardiac muscle and the hemodynamics, coupled in a fluid-structure interaction (FSI) model. By leveraging the multiphysics nature of the problem, we discretize it in time with a segregated electrophysiology-force generation-FSI approach, allowing for efficiency and flexibility in the numerical solution. We employ a monolithic approach for the numerical discretization of the FSI problem. We use finite elements for the spatial discretization of partial differential equations. We carry out a numerical simulation on a realistic human left heart model, obtaining results that are qualitatively and quantitatively in agreement with physiological ranges and medical images.

Steering the multipotent mesenchymal cells towards an anti-inflammatory and osteogenic bias via photobiomodulation therapy: How to kill two birds with one stone.

The bone marrow-derived multipotent mesenchymal cells (MSCs) have captured scientific interest due to their multi-purpose features and clinical applications. The operational dimension of MSCs is not limited to the bone marrow reservoir, which exerts bone-building and niche anabolic tasks; they also meet the needs of quenching inflammation and restoring inflamed tissues. Thus, the range of MSC activities extends to conditions such as neurodegenerative diseases, immune disorders and various forms of osteopenia. Steering these cells towards becoming an effective therapeutic tool has become mandatory. Many laboratories have employed distinct strategies to improve the plasticity and secretome of MSCs. We aimed to present how photobiomodulation therapy (PBM-t) can manipulate MSCs to render them an extraordinary anti-inflammatory and osteogenic instrument. Moreover, we discuss the outcomes of different PBM-t protocols on MSCs, concluding with some perplexities and complexities of PBM-t in vivo but encouraging and feasible in vitro solutions.

Impact on Glucose Homeostasis: Is Food Biofortified with Molybdenum a Workable Solution? A Two-Arm Study.

Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to changes in gastrointestinal hormone levels and specifically Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), Glucagon-Like Peptide 2 (GLP-2), and Gastric Inhibitory Polypeptide (GIP). A cohort of 24 people was supplemented with biofortified lettuce for 12 days. Blood and urine samples were obtained at baseline (T0) and after 12 days (T2) of supplementation. Blood was analyzed for glucose, insulin, insulin resistance, ß-cell function, and insulin sensitivity, PYY, GLP-1, GLP-2 and GIP. Urine samples were tested for molybdenum concentration. The results showed that consumption of lettuce biofortified with molybdenum for 12 days did not affect beta cell function but significantly reduced fasting glucose, insulin, insulin resistance and increased insulin sensitivity in healthy people. Consumption of biofortified lettuce did not show any modification in urine concentration of molybdenum among the groups. These data suggest that consumption of lettuce biofortified with molybdenum improves glucose homeostasis and PYY and GIP are involved in the action mechanism.

Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study.

It is estimated that one-third of the world's population lives in areas where iodine (I) is scarce and its deficiency is responsible for many related disorders, such as goiter, reproductive failure, hearing loss, growth impairment, congenital I deficiency syndrome, and numerous kinds of brain injury. Mineral deficiencies can be overcome via dietary diversification and mineral supplementation. An alternative or even complementary way is represented by the intake of biofortified foods, which can tackle this lack of micronutrients. In this short-term double-arm nutritional intervention study, a cohort of ten people was supplemented with curly endive leaf biofortified with I and ten people with curly endive without biofortification (Intervention Study on Iodine Biofortification Vegetables (Nutri-I-Food - Full-Text View - ClinicalTrials.gov). The effects on whole-body homeostasis and specifically on I, glucose, lipid, and hepatic, iron metabolism was investigated. Blood samples were obtained at baseline and after 12 days of supplementation with curly endive and compared with controls. Hematochemical and urinary parameters were analyzed at baseline and after 12 days. The results showed that short-term I curly endive intervention did not affect the whole body homeostasis in healthy people and revealed an increase in I concentration in urine samples and an increase in vitamin D, calcium, and potassium concentration in blood samples only in the biofortified cohort respect to controls. This study suggests that short-term consumption of I curly endive crops is safe and could positively impact body health.

A Narrative Review on Oral and Periodontal Bacteria Microbiota Photobiomodulation, through Visible and Near-Infrared Light: From the Origins to Modern Therapies.

Photobiomodulation (PBM) consists of a photon energy transfer to the cell, employing non-ionizing light sources belonging to the visible and infrared spectrum. PBM acts on some intrinsic properties of molecules, energizing them through specific light wavelengths. During the evolution of life, semiconducting minerals were energized by sun radiation. The molecules that followed became photoacceptors and were expressed into the first proto-cells and prokaryote membranes. Afterward, the components of the mitochondria electron transport chain influenced the eukaryotic cell physiology. Therefore, although many organisms have not utilized light as an energy source, many of the molecules involved in their physiology have retained their primordial photoacceptive properties. Thus, in this review, we discuss how PBM can affect the oral microbiota through photo-energization and the non-thermal effect of light on photoacceptors (i.e., cytochromes, flavins, and iron-proteins). Sometimes, the interaction of photons with pigments of an endogenous nature is followed by thermal or photodynamic-like effects. However, the preliminary data do not allow determining reliable therapies but stress the need for further knowledge on light-bacteria interactions and microbiota management in the health and illness of patients through PBM.

Near-Infrared 810 nm Light Affects Porifera Chondrosia reniformis (Nardo, 1847) Regeneration: Molecular Implications and Evolutionary Considerations of Photobiomodulation-Animal Cell Interaction.

Chemotrophic choice as a metabolic source of energy has characterised animal cell evolution. However, light interactions with animal cell photoacceptors that are able to increase energetic metabolism (photo-biomodulation (PBM)) have been previously described. In the present study, we cut three specimens of Chondrosia reniformis into four equal parts (12 fragments), and we irradiated the regenerating edge of six fragments with the previously characterised 810 nm near-infrared light, delivered at 1 W, 60 J/cm2, 1 W/cm2, and 60 J in a continuous-wave mode for 60 s through a flat-top hand-piece with a rounded spot-size area of 1 cm2. Six fragments were irradiated with 0 W for 60 s as the controls. We performed irradiation at the time 0 h and every 24 h for a total of five administrations. We monitored the regeneration process for five days (120 h) in aquaria by examining the macroscopic and histological changes. We analysed the gene expression profile of the inflammatory processes, apoptosis, heat stress, growth factors, and collagen production and determined oxidative stress enzyme activity and the total prokaryotic symbiont content. PBM sped up C. reniformis regeneration when compared to the controls. Particularly, transforming growth factor TGF3 and TGF6 upregulation during the early phase of regeneration and TGF5 upregulation 120 h postinjury in the irradiated samples supports the positive effect of PBM in sponge tissue recovery. Conversely, the expression of TGF4, a sponge fibroblast growth factor homologue, was not affected by irradiation, indicating that multiple, independent pathways regulate the TGF genes. The results are consistent with our previous data on a wide range of organisms and humans, suggesting that PBM interaction with primary and secondary cell targets has been conserved through the evolution of life forms.

808-nm Photobiomodulation Affects the Viability of a Head and Neck Squamous Carcinoma Cellular Model, Acting on Energy Metabolism and Oxidative Stress Production.

Photobiomodulation (PBM) is a form of low-dose light therapy that acts through energy delivery from non-ionizing sources. During the recent two decades, there has been tremendous progress with PBM acceptance in medicine. However, PBM effects on potential stimulation of existing malignant or pre-malignant cells remain unknown. Thus, the primary endpoint was to assess the safety of PBM treatment parameters on head and neck squamous cell carcinoma (HNSCC) proliferation or survival. The secondary endpoint was to assess any putative anti-cancer effects of PBM treatments. Cell viability, energy metabolism, oxidative stress, and pro- and anti-apoptotic markers expression were investigated on a Human Head and Neck Squamous Cell Carcinoma cellular model (OHSU-974 FAcorr cell line). PBM therapy was administered through the 810 nm diode laser (GaAlAs) device (Garda Laser, 7024 Negrar, Verona, Italy) at the powers of 0, 0.25, 0.50, 0.75, 1.00, or 1.25 W in continuous wave (CW) mode for an exposure time of 60 s with a spot-size of 1 cm2 and with a distance of 1.86 cm from the cells. Results showed that 810-nm PBM affected oxidative phosphorylation in OHSU-971 FAcorr, causing a metabolic switch to anaerobic glycolysis. In addition, PBM reduced the catalase activity, determining an unbalance between oxidative stress production and the antioxidant defenses, which could stimulate the pro-apoptotic cellular pathways. Our data, at the parameters investigated, suggest the safeness of PBM as a supportive cancer therapy. Pre-clinical and clinical studies are necessary to confirm the in vitro evidence.

Improving Consistency of Photobiomodulation Therapy: A Novel Flat-Top Beam Hand-Piece versus Standard Gaussian Probes on Mitochondrial Activity.

The tremendous therapeutic potential of photobiomodulation therapy in different branches of medicine has been described in the literature. One of the molecular mechanisms for this treatment implicates the mitochondrial enzyme, cytochrome C oxidase. However, the efficacy and consistency of clinical outcomes with photobiomodulation treatments has been fiercely debated. This work was motivated by this need to improve photobiomodulation devices and delivery approaches. We designed a novel hand-piece with a flat-top beam profile of irradiation. We compared the beam profile versus a standard hand-piece and a fibre probe. We utilized isolated mitochondria and performed treatments at various spots within the beam, namely, the centre, left and right edge. We examined mitochondrial activity by assessing ATP synthesis with the luciferin/luciferase chemiluminescent method as a primary endpoint, while mitochondrial damage was assessed as the secondary endpoint. We observed a uniform distribution of the power density with the flat-top prototype compared to a wide Gaussian beam profile with the standard fibre and standard hand-piece. We noted increased production of ATP in the centre of all three beams with respect to the non-treated controls (p < 0.05). Both the fibre and standard hand-piece demonstrated less increase in ATP synthesis at the edges than the centre (p < 0.05). In contrast, ATP synthesis was increased homogenously in the flat-top handpiece, both in the centre and the edges of the beam. Fibre, standard hand-piece and the flat-top hand-piece prototype have discrete beam distribution characteristics. This significantly affected the mitochondrial activity with respect to their position within the treated areas. Flat-top hand-piece enhances the uniformity of photobiomodulation treatments and can improve the rigour and reproducibility of PBM clinical outcomes.

Mitochondrial Bioenergetic, Photobiomodulation and Trigeminal Branches Nerve Damage, What's the Connection? A Review.

BACKGROUND: Injury of the trigeminal nerve in oral and maxillofacial surgery can occur. Schwann cell mitochondria are regulators in the development, maintenance and regeneration of peripheral nerve axons. Evidence shows that after the nerve injury, mitochondrial bioenergetic dysfunction occurs and is associated with pain, neuropathy and nerve regeneration deficit. A challenge for research is to individuate new therapies able to normalise mitochondrial and energetic metabolism to aid nerve recovery after damage. Photobiomodulation therapy can be an interesting candidate, because it is a technique involving cell manipulation through the photonic energy of a non-ionising light source (visible and NIR light), which produces a nonthermal therapeutic effect on the stressed tissue. METHODS: The review was based on the following questions: (1) Can photo-biomodulation by red and NIR light affect mitochondrial bioenergetics? (2) Can photobiomodulation support damage to the trigeminal nerve branches? (preclinical and clinical studies), and, if yes, (3) What is the best photobiomodulatory therapy for the recovery of the trigeminal nerve branches? The papers were searched using the PubMed, Scopus and Cochrane databases. This review followed the ARRIVE-2.0, PRISMA and Cochrane RoB-2 guidelines. RESULTS AND CONCLUSIONS: The reliability of photobiomodulatory event strongly bases on biological and physical-chemical evidence. Its principal player is the mitochondrion, whether its cytochromes are directly involved as a photoacceptor or indirectly through a vibrational and energetic variation of bound water: water as the photoacceptor. The 808-nm and 100 J/cm2 (0.07 W; 2.5 W/cm2; pulsed 50 Hz; 27 J per point; 80 s) on rats and 800-nm and 0.2 W/cm2 (0.2 W; 12 J/cm2; 12 J per point; 60 s, CW) on humans resulted as trustworthy therapies, which could be supported by extensive studies.

Photobiomodulation and Oxidative Stress: 980 nm Diode Laser Light Regulates Mitochondrial Activity and Reactive Oxygen Species Production.

Photobiomodulation with 808 nm laser light electively stimulates Complexes III and IV of the mitochondrial respiratory chain, while Complexes I and II are not affected. At the wavelength of 1064 nm, Complexes I, III, and IV are excited, while Complex II and some mitochondrial matrix enzymes seem to be not receptive to photons at that wavelength. Complex IV was also activated by 633 nm. The mechanism of action of wavelengths in the range 900-1000 nm on mitochondria is less understood or not described. Oxidative stress from reactive oxygen species (ROS) generated by mitochondrial activity is an inescapable consequence of aerobic metabolism. The antioxidant enzyme system for ROS scavenging can keep them under control. However, alterations in mitochondrial activity can cause an increment of ROS production. ROS and ATP can play a role in cell death, cell proliferation, and cell cycle arrest. In our work, bovine liver isolated mitochondria were irradiated for 60 sec, in continuous wave mode with 980 nm and powers from 0.1 to 1.4 W (0.1 W increment at every step) to generate energies from 6 to 84 J, fluences from 7.7 to 107.7 J/cm2, power densities from 0.13 to 1.79 W/cm2, and spot size 0.78 cm2. The control was equal to 0 W. The activity of the mitochondria's complexes, Krebs cycle enzymes, ATP production, oxygen consumption, generation of ROS, and oxidative stress were detected. Lower powers (0.1-0.2 W) showed an inhibitory effect; those that were intermediate (0.3-0.7 W) did not display an effect, and the higher powers (0.8-1.1 W) induced an increment of ATP synthesis. Increasing the power (1.2-1.4 W) recovered the ATP production to the control level. The interaction occurred on Complexes III and IV, as well as ATP production and oxygen consumption. Results showed that 0.1 W uncoupled the respiratory chain and induced higher oxidative stress and drastic inhibition of ATP production. Conversely, 0.8 W kept mitochondria coupled and induced an increase of ATP production by increments of Complex III and IV activities. An augmentation of oxidative stress was also observed, probably as a consequence of the increased oxygen consumption and mitochondrial isolation experimental conditions. No effect was observed using 0.5 W, and no effect was observed on the enzymes of the Krebs cycle.

Integration of activation maps of epicardial veins in computational cardiac electrophysiology.

In this work we address the issue of validating the monodomain equation used in combination with the Bueno-Orovio ionic model for the prediction of the activation times in cardiac electro-physiology of the left ventricle. To this aim, we consider four patients who suffered from Left Bundle Branch Block (LBBB). We use activation maps performed at the septum as input data for the model and maps at the epicardial veins for the validation. In particular, a first set (half) of the latter are used to estimate the conductivities of the patient and a second set (the remaining half) to compute the errors of the numerical simulations. We find an excellent agreement between measures and numerical results. Our validated computational tool could be used to accurately predict activation times at the epicardial veins with a short mapping, i.e. by using only a part (the most proximal) of the standard acquisition points, thus reducing the invasive procedure and exposure to radiation.

Dynamics of pistachio oils by proton nuclear magnetic resonance relaxation dispersion.

A number of pistachio oils were selected in order to test the efficacy of nuclear magnetic resonance relaxation dispersion (NMRD) technique in the evaluation of differences among oils (1) obtained from seeds subjected to different thermal desiccation processes, (2) retrieved from seeds belonging to the same cultivar grown in different geographical areas and (3) produced by using seed cultivars sampled in the same geographical region. NMRD measures relaxation rate values which are related to the dynamics of the chemical components of complex food systems. Results not only allowed to relate kinematic viscosity to relaxometry parameters but also were successful in the differentiation among the aforementioned oils. In fact, from the one hand, the larger the kinematic viscosity, the faster the rotational motions appeared as compared to the translational ones. On the other hand, relaxation rate curves (NMRD) varied according to the oxidative stresses and chemical composition of each sample. The present study showed for the first time that NMRD is a very promising technique for quick evaluations of pistachio oil quality without the need for time-consuming chemical manipulations.