Search Results (48)

Background: Antibiotic-resistant Pseudomonas aeruginosa (P. aeruginosa) strains are an increasing cause of morbidity and mortality. Pulsed blue light (PBL) enhances porphyrin-induced reactive oxygen species and has been clinically shown to be harmless to the skin at low doses. Bacteriophages, viruses that infect bacteria, offer a promising non-antibiotic bactericidal approach. This study investigates the potential synergism between low-dose PBL and phage therapy against P. aeruginosa in planktonic cultures and preformed biofilms. Methods: We conducted a factorial dose–response in vitro study combining P. aeruginosa-specific phages with PBL (457 nm, 33 kHz) on both PA14 and multidrug-resistant PATZ2 strains. After excluding direct PBL effects on phage titer or activity, we assessed effectiveness on planktonic cultures using growth curve analysis (via growth_curve_outcomes, a newly developed, Python-based tool available on GitHub) , CFU, and PFU. Biofilm efficacy was evaluated using CFU post-sonication, crystal violet staining, and live/dead staining with confocal microscopy. Finally, we assessed reactive oxygen species (ROS) as a potential mechanism using the nitro blue tetrazolium reduction assay. ANOVA or Kruskal–Wallis tests with post hoc Tukey or Conover–Iman tests were used for comparisons (n = 5 biological replicates and technical triplicates). Results: The bacterial growth lag phase was significantly extended for phage alone or PBL alone, with a synergistic effect of up to 144% (p < 0.001 for all), achieving a 9 log CFU/mL reduction at 24 h (p < 0.001). In preformed biofilms, synergistic combinations significantly reduced biofilm biomass and bacterial viability (% Live, median (IQR): Control 80%; Phage 40%; PBL 25%; PBL&Phage 15%, p < 0.001). Mechanistically, PBL triggered transient ROS in planktonic cultures, amplified by phage co-treatment, while a biphasic ROS pattern in biofilms reflected time-dependent synergy. Conclusions: Phage therapy combined with PBL demonstrates a synergistic bactericidal effect against P. aeruginosa in both planktonic cultures and biofilms. Given the strong safety profile of PBL and phages, this approach may lead to a novel, antibiotic-complementary, safe treatment modality for patients suffering from difficult-to-treat antibiotic-resistant infections and biofilm-associated infections. Full article

Low-Energy High-Current Electron Beam (LEHCEB) is an innovative vacuum technology employed for the surface modification of conductive materials. Surface treatments by means of LEHCEB allow the melting and rapid solidification of a thin layer (up to ~10 μm) of material. The short duration of each pulse (2.5 μs) allows for the generation of high thermal rates, up to 10⁹ K/s. Due to the peculiar features of LEHCEB source, in situ temperature monitoring inside the vacuum chamber is unfeasible, even with the most rapid IR pyrometers available on the market. Therefore, multiphysics simulations serve as a tool for predicting and assessing the thermal effects induced by electron beam irradiation. COMSOL Multiphysics was employed to study the thermal behaviour of metals and alloys at the sub-microsecond time scale by implementing both experimental power time profiles and semi-empirical electron penetration functions. Three case studies were considered: (a) 17-4 PH steel produced by Binder Jetting, (b) biphasic Al-Si13 alloy, and (c) Magnetron Sputtering Nb films on Ti substrate. The influence on the thermal effects of electron accelerating voltage and number of pulses was investigated, as well as the role of the physicochemical properties of the materials. Full article

Background/Objectives: Electrode impedance is crucial for optimizing cochlear implant (CI) stimulation and hearing outcomes. While typically stable, some patients experience unexplained impedance fluctuations. This study used electrode impedance subcomponent analysis to identify the subcomponents contributing to these impedance fluctuations. Methods: This study analyzed clinical electrode impedances and transimpedance matrix (TIM) measurements in 10 CI patients with Nucleus devices (CI422, CI522, or CI622 electrode arrays) who exhibited fluctuating or rising electrode impedances. TIM measurements used a cathodic-leading biphasic pulse (110 CLs, 75 µs/phase, 7 µs interphase interval). Electrode impedances were determined at 6, 12, 18, 24, and 75 µs, and subcomponents (access resistance [near-field/far-field] and polarization impedance [Warburg capacitance/Faraday resistance]) were calculated. Results: Both access resistance and polarization impedance changes contributed to impedance fluctuations. Large changes in near-field resistance compared to far-field resistance were associated with increased resistance to current flow closer to the surface of the electrode. The decreased double-layer capacitance and slightly increased Faraday resistance further suggested increased resistance to charge transfer at the electrode–electrolyte interface. Conclusions: Electrode impedance subcomponent analysis reveals changes in the electrochemical reaction at the electrode surface that cause fluctuating or rising CI electrode impedances. Full article

Recent advances in micro-retinal implant technologies have shown promise in vision restoration, yet challenges remain regarding pixel resolution, reliability, power leakage, cost-effectiveness, and device lifespan. Existing devices often face difficulties meeting the long-term safety and reliability requirements set by regulatory bodies such as the FDA and the European Union, making them impractical for widespread use. This research introduces a 256-pixel hexagonal subretinal device with an advanced digital controller designed to overcome these limitations. The proposed system offers solutions to issues of resolution, compactness, economic constraints, and control over biphasic pulse parameters. It was specifically designed to deliver flicker-free vision while increasing resolution and light sensitivity. A prototype was developed using field-programmable gate arrays (FPGAs) and amplitude-shift keying (ASK) modulators for wireless data transmission. The system was fabricated on a microchip and tested against various performance parameters, demonstrating its potential for future commercial viability. Full article

The cultivation of excitable cells typically profits from continuous electrical stimulation, but electrochemical consequences are mostly harmful and must be minimized. The properties of the electrode materials and stimulation impulses are key. Here, we developed an easy method to analyze the electrochemical impact of biphasic, current-controlled impulses, applied via graphite electrodes, using phenol red as the redox indicator. We also tested the stimulation conditions for the long-term cultivation of myocardial tissue. The colorimetric assay was able to detect ±0.2% deviations in typical positive and negative pulse charges. Phenol red was best preserved (20% degradation over 24 h) by impulses of equivalent positive and negative charges (full charge balance), generated with either manual calibration, capacitive electrode coupling, or feedback regulation of electrode polarization. Feedback regulation established full charge balance at pre-pulse voltages of about 300 mV, but also provided the option to selectively compensate irreversible electrode reactions. Modifications to shape and timing did not affect the electrochemical effects of symmetric impulses. Charge-balanced stimulation maintained more than 80% of the contractility of porcine left ventricular myocardium after 10 days of culture, whereas disbalances of 2–4% provoked weakening and discoloration of the tissues. Active polarization regulation, in contrast to capacitive electrode coupling, reproduced the biological advantages of full charge balance. Full article

Gene electrotransfer (GET) has gained significant momentum as a non-viral gene delivery method for various clinical applications, primarily in the cancer immunotherapy and vaccine development space. Preclinical studies have demonstrated exogenous gene delivery and expression in various tissues, including the liver, skin, cardiac muscle, and skeletal muscle. However, protein replacement applications of this technology have yet to be fully actuated. Plasmid DNA skeletal muscle delivery has been shown to maintain expression for up to 18 months. In the current study, we evaluated localized skeletal muscle delivery for protein replacement applications. We developed localized in vivo electro gene therapy (liveGT) protocols utilizing mono- and biphasic pulse sequences for localized pulse delivery directly to skeletal muscle with a custom monopolar platinum electrode. Plasmid DNA encoding human insulin and human glucokinase were chosen for this study to evaluate the liveGT platform for protein replacement potential. Initial in vitro GET was performed in mouse myoblasts to evaluate human insulin and glucokinase co-delivery. This was followed by liveGT-mediated reporter gene delivery in the skeletal muscle of Sprague–Dawley rats for pulse sequence selection. Protein replacement potential was evaluated in healthy (non-diabetic) rats with liveGT-mediated human insulin and glucokinase co-delivery to skeletal muscle. Human and rat insulin levels were measured via ELISA over the course of 3 months. Fed-state blood glucose measurements were monitored in correlation with serum human insulin levels. LiveGT-mediated skeletal muscle reprogramming successfully produced physiological levels of human insulin in serum over the course of 3 months. Hypo- and hyperglycemic events were not observed. Therefore, liveGT is a safe and viable platform for potential protein replacement therapies. Full article

Electrical stimulation can be used in several applications such as fatigue reduction, muscle rehabilitation, neurorehabilitation, neuro-prosthesis and pain relief. Moreover, electrical stimulation can be used for drug delivery applications or body fluids extraction (e.g., sweat and interstitial fluid) to successively monitor several parameters, such as glucose, lactate, etc. All these applications are performed using electrical stimulator devices capable of applying constant voltage pulses or constant current pulses via electrodes to human tissues. Usually, constant current stimulators are most widely used because of their safety, stability, and repeatability. Thus, the aim of this work was to design, realize and test a mixed-signal electronic interface capable of producing current pulses with custom amplitude, duration, frequency, polarity and symmetry with extended voltage compliance. To achieve this result, we developed a high-voltage current stimulator suitable for iontophoresis applications. Current stimuli can be applied setting the intensity, frequency and duty cycle of the stimulation patterns through a µC. A custom electronic interface was designed to allow the control of the injected current in real time and to prevent electrical injuries to the patient by avoiding potential unwanted short circuits. Moreover, the system was tested in a simulated environment demonstrating its effectiveness and applicability for transdermal monitoring applications. The obtained results show that the device is able to apply monophasic and biphasic pulses, ranging from 0.1 to 10 mA, with a maximum error of about 10% at the minimum intensity; in addition, current stimuli can be applied up to a maximum frequency of 100 kHz with a voltage compliance of 120 V. Full article

The phenomenon known as bipolar cancellation is observed when biphasic nanosecond electric field pulses are used, which results in reduced electroporation efficiency when compared to unipolar pulses of the same parameters. Basically, the negative phase of the bipolar pulse diminishes the effect of the positive phase. Our study aimed to investigate how bipolar cancellation affects Ca²⁺ electrochemotherapy and cellular response under varying electric field intensities and pulse durations (3–7 kV/cm, 100, 300, and 500 ns bipolar 1 MHz repetition frequency pulse bursts, n = 100). As a reference, standard microsecond range parametric protocols were used (100 µs × 8 pulses). We have shown that the cancellation effect is extremely strong when the pulses are closely spaced (1 MHz frequency), which results in a lack of cell membrane permeabilization and consequent failure of electrochemotherapy in vitro. To validate the observations, we have performed a pilot in vivo study where we compared the efficacy of monophasic (5 kV/cm × ↑500 ns × 100) and biphasic sequences (5 kV/cm × ↑500 ns + ↓500 ns × 100) delivered at 1 MHz frequency in the context of Ca²⁺ electrochemotherapy (B16-F10 cell line, C57BL/6 mice, n = 24). Mice treated with bipolar pulses did not exhibit prolonged survival when compared to the untreated control (tumor-bearing mice); therefore, the bipolar cancellation phenomenon was also occurrent in vivo, significantly impairing electrochemotherapy. At the same time, the efficacy of monophasic nanosecond pulses was comparable to 1.4 kV/cm × 100 µs × 8 pulses sequence, resulting in tumor reduction following the treatment and prolonged survival of the animals. Full article

Electroactive microfiber-based scaffolds aid neural tissue repair. Carbon microfibers (CMFs) coated with the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)] (PEDOT:PSS-co-MA) provide efficient support and guidance to regrowing axons across spinal cord lesions in rodents and pigs. We investigated the electrical and structural performance of PEDOT:PSS-co-MA-coated carbon MFs (PCMFs) for long-term, biphasic electrical stimulation (ES). Chronopotentiometry and electrochemical impedance spectroscopy (EIS) allowed the characterization of charge transfer in PCMFs during ES in vitro, and morphological changes were assessed by scanning electron microscopy (SEM). PCMFs that were 4 mm long withstood two-million-biphasic pulses without reaching cytotoxic voltages, with a 6 mm length producing optimal results. Although EIS and SEM unveiled some polymer deterioration in the 6 mm PCMFs, no significant changes in voltage excursions appeared. For the preliminary testing of the electrical performance of PCMFs in vivo, we used 12 mm long, 20-microfiber assemblies interconnected by metallic microwires. PCMFs-assemblies were implanted in two spinal cord-injured pigs and submitted to ES for 10 days. A cobalt–alloy interconnected assembly showed safe voltages for about 1.5 million-pulses and was electrically functional at 1-month post-implantation, suggesting its suitability for sub-chronic ES, as likely required for spinal cord repair. However, improving polymer adhesion to the carbon substrate is still needed to use PCMFs for prolonged ES. Full article

Alginate is a natural polymer with good biocompatible properties and is a potential polymeric material for the sustainable development and replacement of petroleum derivatives. However, the non-spinnability of pure alginate solutions has hindered the expansion of alginate applications. With the continuous development of electrospinning technology, synthetic polymers, such as PEO and PVA, are used as co-spinning agents to increase the spinnability of alginate. Moreover, the coaxial, parallel Janus, tertiary and other diverse and novel electrospun fiber structures prepared by multi-fluid electrospinning have found a new breakthrough for the problem of poor spinning of natural polymers. Meanwhile, the diverse electrospun fiber structures effectively achieve multiple release modes of drugs. The powerful combination of alginate and electrostatic spinning is widely used in many biomedical fields, such as tissue engineering, regenerative engineering, bioscaffolds, and drug delivery, and the research fever continues to climb. This is particularly true for the controlled delivery aspect of drugs. This review provides a brief overview of alginate, introduces new advances in electrostatic spinning, and highlights the research progress of alginate-based electrospun nanofibers in achieving various controlled release modes, such as pulsed release, sustained release, biphasic release, responsive release, and targeted release. Full article

Background/Objectives: The aim of this study was to investigate the feasibility and safety of neuromuscular electrical stimulation (NMES) in patients on extracorporeal membrane oxygenation (ECMO) and thoroughly assess any potential adverse events. Methods: We conducted a prospective observational study assessing safety and feasibility, including 16 ICU patients on ECMO support who were admitted to the cardiac surgery ICU from January 2022 to December 2023. The majority of patients were females (63%) on veno-arterial (VA)-ECMO (81%), while the main cause was cardiogenic shock (81%) compared to respiratory failure. Patients underwent a 45 min NMES session while on ECMO support that included a warm-up phase of 5 min, a main phase of 35 min, and a recovery phase of 5 min. NMES was implemented on vastus lateralis, vastus medialis, gastrocnemius, and peroneus longus muscles of both lower extremities. Two stimulators delivered biphasic, symmetric impulses of 75 Hz, with a 400 μsec pulse duration, 5 sec on (1.6 sec ramp up and 0.8 sec ramp down) and 21 sec off. The intensity levels aimed to cause visible contractions and be well tolerated. Primary outcomes of this study were feasibility and safety, evaluated by whether NMES sessions were successfully achieved, and by any adverse events and complications. Secondary outcomes included indices of rhabdomyolysis from biochemical blood tests 24 h after the application of NMES. Results: All patients successfully completed their NMES session, with no adverse events or complications. The majority of patients achieved type 4 and 5 qualities of muscle contraction. Conclusions: NMES is a safe and feasible exercise methodology for patients supported with ECMO. Full article

This paper presents a novel, cost-effective technique for estimating the Doppler effect in the time domain using a single pulse and subsequently leveraging the precise Doppler value to recover the radar waveform. The proposed system offers several key advantages over existing techniques, including the ability to calculate the target speed without any frequency ambiguity and the ability to detect a wide range of target speeds. These two features are not available in any existing techniques, including the conventional moving target detection (MTD) processor. To ensure improved accuracy and robust estimation, the system employs ensemble and iterative techniques by recursively and efficiently reducing the Doppler residues from the signal. Furthermore, the proposed system demonstrates effective signal recovery of a well-known bi-phase code shape at low signal-to-noise ratios in just a few iterations. The performance evaluation of the new algorithm demonstrates its practicability and its superiority over traditional radar systems. Implementation on software-defined radio (SDR) reveals that the proposed system excels in Doppler estimation and signal recovery at low SNRs, demonstrating promising results. Full article

As a noninvasive neuromodulation technique, transcranial magnetic stimulation (TMS) has important applications both in the exploration of mental disorder causes and the treatment of mental disorders. During the stimulation, the TMS system generates the intracranial time-varying induced E-field (E-field), which alters the membrane potential of neurons and subsequently exerts neural regulatory effects. The temporal waveform of the induced E-fields is directly related to the stimulation effect. To meet the needs of scientific research on diversified stimulation waveforms and flexible adjustable stimulation parameters, a novel efficient pulse magnetic stimulation circuit (the EPMS circuit) design based on asymmetric cascaded multilevel technology is proposed in this paper. Based on the transient analysis of the discharge circuit, this circuit makes it possible to convert the physical quantity (the intracranial induced E-field) that needs to be measured after magnetic stimulation into easily analyzable electrical signals (the discharge voltage at both ends of the stimulation coil in the TMS circuit). This EPMS circuit can not only realize monophasic and biphasic cosine-shaped intracranial induced E-fields, which are widely used in the market, but also realize three types of new intracranial induced E-field stimulation waveform with optional amplitude and adjustable pulse width, including monophasic near-rectangular, biphasic near-rectangular and monophasic/biphasic ladder-shaped stimulation waveform, which breaks through the limitation of the stimulation waveform of traditional TMS systems. Among the new waveforms produced by the EPMS circuit, further research was conducted on the dynamic response characteristics of neurons under the stimulation of the biphasic four-level waveform (the BFL waveform) with controllable parameters. The relationship between TMS circuit parameters (discharge voltage level and duration) and corresponding neural response characteristics (neuron membrane potential change and neuronal polarizability ratio) was explained from a microscopic perspective. Accordingly, the biological physical quantities (neuronal membrane potential) that are difficult to measure can be transformed into easily analyzable electrical signals (the discharge voltage level and duration). Results showed that compared with monophasic and biphasic cosine induced E-fields with the same energy loss, the neuron polarization ratio is decreased by 54.5% and 87.5%, respectively, under the stimulation of BFL waveform, which could effectively enhance the neuromodulation effect and improve the stimulation selectivity. Full article

We aimed to investigate the acute effects of blood flow restriction (BFR) combined with neuromuscular electrical stimulation (NMES) on muscle strength, thigh circumference, and knee joint reposition sense in female amateur football players, as well as to determine whether this procedure is safe. Methods: This was a pilot trial. Twenty female amateur football players were randomized into two groups: group 1 (n = 10) received a single NMES session; group 2 (n = 10) received NMES + BFR. The measured variables included maximal voluntary eccentric contraction (MVEC) and maximal voluntary concentric contraction (MVCC), thigh circumference, and knee joint reposition sense test. The type of electrical current used was TENS (symmetrical biphasic rectangular pulse, 350 μs, and 50 Hz), combined simultaneously with active knee extension (75 repetitions in 4 sets, 20% MVCC, 30 s rest between sets), for both groups. Group 2 had BFR added (80% of arterial occlusion pressure). Results: Statistically significant differences (p ≤ 0.05) were obtained for thigh circumference in both groups. The comparison between groups did not show statistically significant differences (p ≤ 0.05) in MVEC, MVCC, thigh circumference, or the knee joint reposition sense test. Conclusions: Both the isolated NMES intervention and its combination with BFR induced immediate changes in thigh circumference without impairing the muscle strength or proprioceptive ability of the football players. However, these results should be interpreted with caution, and future studies including a control group and isolated BFR application are needed. Full article

Electroporation is used in medicine for drug and gene delivery, and as a nonthermal ablation method in tumor treatment and cardiac ablation. Electroporation involves delivering high-voltage electric pulses to target tissue; however, this can cause effects beyond the intended target tissue like nerve stimulation, muscle contractions and pain, requiring use of sedatives or anesthetics. It was previously shown that adjusting pulse parameters may mitigate some of these effects, but not how these adjustments would affect electroporation’s efficacy. We investigated the effect of varying pulse parameters such as interphase and interpulse delay while keeping the duration and number of pulses constant on nerve stimulation, muscle contraction and assessing pain and electroporation efficacy, conducting experiments on human volunteers, tissue samples and cell lines in vitro. Our results show that using specific pulse parameters, particularly short high-frequency biphasic pulses with short interphase and long interpulse delays, reduces muscle contractions and pain sensations in healthy individuals. Higher stimulation thresholds were also observed in experiments on isolated swine phrenic nerves and human esophagus tissues. However, changes in the interphase and interpulse delays did not affect the cell permeability and survival, suggesting that modifying the pulse parameters could minimize adverse effects while preserving therapeutic goals in electroporation. Full article