Numerical Simulation and Experimental Studies of a Ribbon Coil for Trans Spinal Magnetic Stimulation (TSMS) in Rats.

We propose a non-invasive Trans Spinal Magnetic Stimulation (TSMS) coil allowing for focal stimulation. The device is based on a new figure-8 ribbon design, ensuring low R0, and low heating. The two coils were designed and studied using the finite element method (FEM) coupled with NEURON and tested for efficacy on rats. The numerical simulations confirmed the generation of the observed action potentials when the coil was driven with 2.8kA.Clinical Relevance- Chronic neuropathic back and leg pain is one of the main indications for spinal cord stimulation in the United States. Chronic low back pain is one of the most common reasons patients seek medical care, and in 2013 resulted in 87.6 billion dollars in healthcare costs in the USA. Patients would most likely prefer a low-risk, non-invasive procedure, such as TSMS, to surgery with a significant rate of complications.

Systematic numerical assessment of occupational exposure to electromagnetic fields of transcranial magnetic stimulation.

PURPOSE: This study aims to perform a classification and rigorous numerical evaluation of the risks of occupational exposure in the health environment related to the administration of transcranial magnetic stimulation (TMS) treatment. The study investigates the numerically estimated induced electric field that occurs in the human tissues of an operator caused by exposure to the variable magnetic field produced by TMS during treatments. This could be a useful starting point for future risk assessment studies and safety indications in this context. METHODS: We performed a review of the actual positions assumed by clinicians during TMS treatments. Three different TMS coils (two circular and one figure-of-eight) were modeled and characterized numerically. Different orientations and positions of each coil with respect to the body of the operator were investigated to evaluate the induced electric (-E) field in the body tissues. The collected data were processed to allow comparison with the safety standards for occupational exposure, as suggested by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) 2010 guidelines. RESULTS: Under the investigated conditions, exposure to TMS shows some criticalities for the operator performing the treatment. Depending on the model of the TMS coil and its relative position with respect to the operator's body, the numerically estimated E-field could exceed the limits suggested by the ICNIRP 2010 guidelines. We established that the worst-case scenario for the three coils occurs when they are placed in correspondence of the abdomen, with the handle oriented parallel to the body (II orientation). Working at a maximum TMS stimulator output (MSO), the induced E-field is up to 7.32 V/m (circular coil) and up to 1.34 V/m (figure-of-eight coil). The induced E-field can be modulated by the TMS percentage of MSO (%MSO) and by the distance between the source and the operator. At %MSO equal to or below 80%, the figure-of-eight coil was compliant with the ICNIRP limit (1.13 V/m). Conversely, the circular coil causes an induced E-field above the limits, even when powered at a %MSO of 30%. Thus, in the investigated worst-case conditions, an operator working with a circular coil should keep a distance from its edge to be compliant with the guidelines limit, which depends on the selected %MSO: 38 cm at 100%, 32 cm at 80%, 26.8 cm at 50%, and 19.8 cm at 30%. Furthermore, attention should be paid to the induced E-field reached in the operator's hand as the operator typically holds the coil by hand. In fact in the hand, we estimated an induced E-field up to 10 times higher than the limits. CONCLUSIONS: Our numerical results indicate that coil positions, orientations, and distances with respect to the operator's body can determine the levels of induced E-field that exceed the ICNIRP limits. The induced E-field is also modulated by the choice of %MSO, which is related to the TMS application. Even under the best exposure conditions, attention should be paid to the exposure of the hand. These findings highlight the need for future risk assessment studies to provide more safety information for the correct and safe use of TMS devices.

An Artefactual Cluster of Mycobacterium abscessus Pneumonia among Cancer Patients Arising from Contamination.

The Mycobacteriumabscessus complex (MABC) is a group of rapidly growing, nontuberculous mycobacteria that are ubiquitous in soil, urban water pipes, swimming pools, and drinking water. Members of the MABC are considered opportunistic pathogens. The aim of this study was to investigate the origins of MABC detected in broncho-lavage (BL) samples from asymptomatic cancer patients. We turned our attention to washing and disinfection procedures for bronchoscopes; we also assessed water and disinfectant samples. Of 10 BL and 34 environmental samples tested, four BL samples (40%) and seven environmental samples (20.6%) tested positive for MABC. We hypothesized that contamination could arise from the prewashing machine and/or the water used because no patient had clinical or radiological signs consistent with MABC respiratory tract infection. Our study highlights the importance of evaluating cleaning and disinfection procedures for endoscope channels to reduce the potential spread of microorganisms and artefactual results arising from contamination.

Pulsed Electromagnetic Fields: A Novel Attractive Therapeutic Opportunity for Neuroprotection After Acute Cerebral Ischemia.

OBJECTIVES: Acute cerebral ischemia is characterized by several pathological processes evolving during time, which contribute to the final tissue damage. Secondary processes, such as prolonged inflammatory response, impaired mitochondrial function, and oxidative stress, are responsible for the progression of brain injury to the peri-infarct area, called "penumbra." Adenosine has been shown to play a crucial role in regulating the inflammatory cascade following brain ischemia. Pulsed electromagnetic fields (PEMFs) act as modulators of adenosine receptors, increasing the functionality of the endogenous adenosine. In particular, PEMF exposure induces a significant upregulation of A2A and A3 adenosine receptors in different neuronal cell types. Several lines of evidence suggest that PEMF exposure might play a neuroprotective role after ischemic damage. MATERIALS AND METHODS: This review summarizes the current knowledge on the mechanism of action of PEMFs and their biological effects on neuronal damage both in preclinical and clinical studies. RESULTS: PEMFs counteract hypoxia-induced apoptosis and ROS production in neuronal-like cells and exert a strong anti-inflammatory effect on microglial cells. Data from stroke animal models showed that PEMFs exposure is able to reduce the size of the infarct area and decrease the levels of pro-inflammatory mediators. In clinical studies, PEMFs stimulation proved to be safe and well tolerated. Preliminary results on acute ischemic stroke patients showed a dose-dependent reduction in the lesion size. CONCLUSIONS: Altogether, these data demonstrate the efficacy of PEMFs against several mechanisms underlying ischemic damage and suggest that PEMFs might represent a novel noninvasive adjunctive treatment for acute ischemic stroke, providing neuroprotection and reducing functional deficits following ischemia.

Microbiological and Chemical Assessment of Wastewater Discharged by Infiltration Trenches in Fractured and Karstified Limestone (SCA.Re.S. Project 2019-2020).

This study investigated the environmental contamination of groundwater as a consequence of the discharge of treated wastewater into the soil. The investigation focused on a wastewater treatment plant located in an area fractured by karst in the Salento peninsula (Apulia, Italy). Water samples were collected at four sites (raw wastewater, treated wastewater, infiltration trench, and monitoring well), monthly from May to December 2019 (with the exception of August), and were tested for (1) panel of bacteria; (2) enteric viruses; and (3) chemical substances. A gradual reduction in the concentration of bacteria, viruses and contaminants of emerging concern was observed across the profile of soil fissured by karst. All monitored bacteria were absent from the monitoring well, except for Pseudomonas aeruginosa. Pepper mild mottle virus and adenovirus were detected at all sampling sites. Personal care products and X-ray contrast media showed the greatest decrease in concentration from infiltration trench to the monitoring well, while the highest residual concentrations in the monitoring well were found for anticonvulsants (78.5%), antimicrobials (41.3%), and antipsychotic drugs (38.6%). Our results show that parameters provided by current law may not always be sufficient to evaluate the sanitary risk relating to the discharge of treated wastewater to the soil.

Evaluation of Air Contamination in Orthopaedic Operating Theatres in Hospitals in Southern Italy: The IMPACT Project.

Postoperative infections are a concern, especially in total knee and total hip arthroplasty. We evaluated the air quality in orthopaedic operating theatres in southeastern Italy to determine the level of bacterial contamination as a risk factor for postoperative infection. Thirty-five hospitals with operating theatres focused on total knee and total hip arthroplasty participated. We sampled the air passively and actively before surgeries began for the day (at rest) and 15 min after the surgical incision (in operation). We evaluated bacterial counts, particle size, mixed vs turbulent airflow systems, the number of doors, number of door openings during procedures and number of people in the operating theatre. We found no bacterial contamination at rest for all sampling methods, and significantly different contamination levels at rest vs in operation. We found no association between the number of people in the surgical team and bacteria counts for both mixed and turbulent airflow systems, and low bacterial loads, even when doors were always open. Overall, the air quality sampling method and type of ventilation system did not affect air quality.

Evidences of plasma membrane-mediated ROS generation upon ELF exposure in neuroblastoma cells supported by a computational multiscale approach.

BACKGROUND: Molecular mechanisms of interaction between cells and extremely low frequency magnetic fields (ELF-MFs) still represent a matter of scientific debate. In this paper, to identify the possible primary source of oxidative stress induced by ELF-MF in SH-SY5Y human neuroblastoma cells, we estimated the induced electric field and current density at the cell level. METHODS: We followed a computational multiscale approach, estimating the local electric field and current density from the whole sample down to the single cell level. The procedure takes into account morphological modeling of SH-SY5Y cells, arranged in different topologies. Experimental validation has been carried out: neuroblastoma cells have been treated with Diphenyleneiodonium (DPI) -an inhibitor of the plasma membrane enzyme NADPH oxidase (Nox)- administered 24 h before exposure to 50 Hz (1 mT) MF. RESULTS: Macroscopic and microscopic dosimetric evaluations suggest that increased current densities are induced at the plasma membrane/extra-cellular medium interface; identifying the plasma membrane as the main site of the ELF-neuroblastoma cell interaction. The in vitro results provide an experimental proof that plasma membrane Nox exerts a key role in the redox imbalance elicited by ELF, as DPI treatment reverts the generation of reactive oxygen species induced by ELF exposure. GENERAL SIGNIFICANCE: Microscopic current densities induced at the plasma membrane are likely to play an active physical role in eliciting ELF effects related to redox imbalance. Multiscale computational dosimetry, supported by an in vitro approach for validation, is proposed as the innovative and rigorous paradigm to unveil mechanisms underlying the complex ELF-MF interactions.

Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

Human Aquaporin 4 Gating Dynamics under Perpendicularly-Oriented Electric-Field Impulses: A Molecular Dynamics Study.

Human aquaporin 4 has been studied using molecular dynamics (MD) simulations in the absence and presence of pulses of external static electric fields. The pulses were 10 ns in duration and 0.012-0.065 V/Å in intensity acting along both directions perpendicular to the pores. Water permeability and the dipolar response of all residues of interest (including the selectivity filter) within the pores have been studied. Results showed decreased levels of water osmotic permeability within aquaporin channels during orthogonally-oriented field impulses, although care must be taken with regard to statistical certainty. This can be explained observing enhanced "dipolar flipping" of certain key residues, especially serine 211, histidine 201, arginine 216, histidine 95 and cysteine 178. These residues are placed at the extracellular end of the pore (serine 211, histidine 201, and arginine 216) and at the cytoplasm end (histidine 95 and cysteine 178), with the key role in gating mechanism, hence influencing water permeability.

A Microdosimetric Study of Electropulsation on Multiple Realistically Shaped Cells: Effect of Neighbours.

Over the past decades, the effects of ultrashort-pulsed electric fields have been used to investigate their action in many medical applications (e.g. cancer, gene electrotransfer, drug delivery, electrofusion). Promising aspects of these pulses has led to several in vitro and in vivo experiments to clarify their action. Since the basic mechanisms of these pulses have not yet been fully clarified, scientific interest has focused on the development of numerical models at different levels of complexity: atomic (molecular dynamic simulations), microscopic (microdosimetry) and macroscopic (dosimetry). The aim of this work is to demonstrate that, in order to predict results at the cellular level, an accurate microdosimetry model is needed using a realistic cell shape, and with their position and packaging (cell density) characterised inside the medium.

Assessing the Electromagnetic Fields Generated By a Radiofrequency MRI Body Coil at 64 MHz: Defeaturing Versus Accuracy.

GOAL: This study aims at a systematic assessment of five computational models of a birdcage coil for magnetic resonance imaging (MRI) with respect to accuracy and computational cost. METHODS: The models were implemented using the same geometrical model and numerical algorithm, but different driving methods (i.e., coil "defeaturing"). The defeatured models were labeled as: specific (S2), generic (G32, G16), and hybrid (H16, [Formula: see text]). The accuracy of the models was evaluated using the "symmetric mean absolute percentage error" ("SMAPE"), by comparison with measurements in terms of frequency response, as well as electric ( ||→E||) and magnetic ( || →B ||) field magnitude. RESULTS: All the models computed the || →B || within 35% of the measurements, only the S2, G32, and H16 were able to accurately model the ||→E|| inside the phantom with a maximum SMAPE of 16%. Outside the phantom, only the S2 showed a SMAPE lower than 11%. CONCLUSIONS: Results showed that assessing the accuracy of || →B || based only on comparison along the central longitudinal line of the coil can be misleading. Generic or hybrid coils - when properly modeling the currents along the rings/rungs - were sufficient to accurately reproduce the fields inside a phantom while a specific model was needed to accurately model ||→E|| in the space between coil and phantom. SIGNIFICANCE: Computational modeling of birdcage body coils is extensively used in the evaluation of radiofrequency-induced heating during MRI. Experimental validation of numerical models is needed to determine if a model is an accurate representation of a physical coil.

The CNP signal is able to silence a supra threshold neuronal model.

Several experimental results published in the literature showed that weak pulsed magnetic fields affected the response of the central nervous system. However, the specific biological mechanisms that regulate the observed behaviors are still unclear and further scientific investigation is required. In this work we performed simulations on a neuronal network model exposed to a specific pulsed magnetic field signal that seems to be very effective in modulating the brain activity: the Complex Neuroelectromagnetic Pulse (CNP). Results show that CNP can silence the neurons of a feed-forward network for signal intensities that depend on the strength of the bias current, the endogenous noise level and the specific waveforms of the pulses. Therefore, it is conceivable that a neuronal network model responds to the CNP signal with an inhibition of its activity. Further studies on more realistic neuronal networks are needed to clarify if such an inhibitory effect on neuronal tissue may be the basis of the induced analgesia seen in humans and the antinociceptive effects seen in animals when exposed to the CNP.

Microdosimetry for nanosecond pulsed electric field applications: a parametric study for a single cell.

A microdosimetric study of nanosecond pulsed electric fields, including dielectric dispersivity of cell compartments, is proposed in our paper. A quasi-static solution based on the Laplace equation was adapted to wideband signals and used to address the problem of electric field estimation at cellular level. The electric solution was coupled with an asymptotic electroporation model able to predict membrane pore density. An initial result of our paper is the relevance of the dielectric dispersivity, providing evidence that both the transmembrane potential and the pore density are strongly influenced by the choice of modeling used. We note the crucial role played by the dielectric properties of the membrane that can greatly impact on the poration of the cell. This can partly explain the selective action reported on cancerous cells in mixed populations, if one considers that tumor cells may present different dielectric responses. Moreover, these kinds of studies can be useful to determine the appropriate setting of nsPEF generators as well as for the design and optimization of new-generation devices.

Modeling electromagnetic fields detectability in a HH-like neuronal system: stochastic resonance and window behavior.

Noise has already been shown to play a constructive role in neuronal processing and reliability, according to stochastic resonance (SR). Here another issue is addressed, concerning noise role in the detectability of an exogenous signal, here representing an electromagnetic (EM) field. A Hodgkin-Huxley like neuronal model describing a myelinated nerve fiber is proposed and validated, excited with a suprathreshold stimulation. EM field is introduced as an additive voltage input and its detectability in neuronal response is evaluated in terms of the output signal-to-noise ratio. Noise intensities maximizing spiking activity coherence with the exogenous EM signal are clearly shown, indicating a stochastic resonant behavior, strictly connected to the model frequency sensitivity. In this study SR exhibits a window of occurrence in the values of field frequency and intensity, which is a kind of effect long reported in bioelectromagnetic experimental studies. The spatial distribution of the modeled structure also allows to investigate possible effects on action potentials saltatory propagation, which results to be reliable and robust over the presence of an exogenous EM field and biological noise. The proposed approach can be seen as assessing biophysical bases of medical applications funded on electric and magnetic stimulation where the role of noise as a cooperative factor has recently gained growing attention.

Dielectric spectroscopy of blood cells suspensions: study on geometrical structure of biological cells.

A promising procedure combining dielectric spectroscopy of red blood cells and an inverse application of an effective medium theory (EMT) has been realized to prove the plausibility to obtain cells morphological information. This theoretical-experimental methodology could be the basis for an accurate and simple tool in diagnosis and research activity, especially when cell morphological alterations are a prime indicator of illness as in all hematopoietic pathologies.