Comparative Bioactivities of Chemically Modified Fucoidan and λ-Carrageenan toward Cells Encapsulated in Covalently Cross-Linked Hydrogels.

The sulfated marine polysaccharides, fucoidan and λ-carrageenan, are known to possess anti-inflammatory, immunomodulatory, and cellular protective properties. Although they hold considerable promise for tissue engineering constructs, their covalent cross-linking in hydrogels and comparative bioactivities to cells are absent from the literature. Thus, fucoidan and λ-carrageenan were modified with methacrylate groups and were covalently cross-linked with the synthetic polymer poly(vinyl alcohol)-methacrylate (PVA-MA) to form 20 wt % biosynthetic hydrogels. Identical degrees of methacrylation were confirmed by 1H NMR, and covalent conjugation was determined by using a colorimetric 1,9-dimethyl-methylene blue (DMMB) assay. Pancreatic beta cells were encapsulated in the hydrogels, followed by culturing in the 3D environment for a prolonged period of 32 days and evaluation of the cellular functionality by live/dead, adenosine 5'-triphosphate (ATP) level, and insulin secretion. The results confirmed that fucoidan and λ-carrageenan exhibited ∼12% methacrylate substitution, which generated hydrogels with stable conjugation of the polysaccharides with PVA-MA. The cells encapsulated in the PVA-fucoidan hydrogels demonstrated consistently high ATP levels over the culture period. Furthermore, only cells in the PVA-fucoidan hydrogels retained glucose responsiveness, demonstrating comparatively higher insulin secretion in response to glucose. In contrast, cells in the PVA-λ-carrageenan and the PVA control hydrogels lost all glucose responsiveness. The present work confirms the superior effects of chemically modified fucoidan over λ-carrageenan on pancreatic beta cell survival and function in covalently cross-linked hydrogels, thereby illustrating the importance of differential polysaccharide structural features on their biological effects.

Simulating impaired left ventricular-arterial coupling in aging and disease: a systematic review.

Aortic stenosis, hypertension, and left ventricular hypertrophy often coexist in the elderly, causing a detrimental mismatch in coupling between the heart and vasculature known as ventricular-vascular (VA) coupling. Impaired left VA coupling, a critical aspect of cardiovascular dysfunction in aging and disease, poses significant challenges for optimal cardiovascular performance. This systematic review aims to assess the impact of simulating and studying this coupling through computational models. By conducting a comprehensive analysis of 34 relevant articles obtained from esteemed databases such as Web of Science, Scopus, and PubMed until July 14, 2022, we explore various modeling techniques and simulation approaches employed to unravel the complex mechanisms underlying this impairment. Our review highlights the essential role of computational models in providing detailed insights beyond clinical observations, enabling a deeper understanding of the cardiovascular system. By elucidating the existing models of the heart (3D, 2D, and 0D), cardiac valves, and blood vessels (3D, 1D, and 0D), as well as discussing mechanical boundary conditions, model parameterization and validation, coupling approaches, computer resources and diverse applications, we establish a comprehensive overview of the field. The descriptions as well as the pros and cons on the choices of different dimensionality in heart, valve, and circulation are provided. Crucially, we emphasize the significance of evaluating heart-vessel interaction in pathological conditions and propose future research directions, such as the development of fully coupled personalized multidimensional models, integration of deep learning techniques, and comprehensive assessment of confounding effects on biomarkers.

Electroconvulsive Therapy With Brain Cyst: A Simulation Study.

INTRODUCTION: Electroconvulsive therapy (ECT) is effective in treating severe depression and other neuropsychiatric disorders, but how the presence of an anatomical anomaly affects the electrical pathways between the electrodes remains unclear. We investigate the difference in electric field (E-field) distribution during ECT in the brain of a patient with an arachnoid cyst relative to hypothetical condition where the cyst was not present. METHODS: Magnetic resonance imaging scans of the head of a patient with a large left frontal cyst were segmented to construct a finite element model to study the E-field distribution during ECT. Five electrode configurations were investigated: right unilateral, left unilateral, bifrontal, and bitemporal and left anterior right temporal. The E-field distributions for all montages were compared with a hypothetical condition where brain tissue and electrical conductivity from the right frontal region was mirrored across the longitudinal fissure into the cyst. RESULTS: Differences in mean E-field and 90th percentile E-fields were mainly observed in brain regions closest to the cyst including the left inferior frontal gyrus and left middle frontal gyrus. This trend was most pronounced in montages where the electrodes were closest to the cyst such as left unilateral and bitemporal. CONCLUSION: The presence of a highly conductive cyst close to the ECT electrode tended to attract current into the cyst region, altering current pathways, with potential implications for therapeutic efficacy and safety. Placing electrodes farther away from the cyst is likely to minimize any effects on the E-field distribution and potentially clinical outcomes.

Slotted Monopole Patch Antenna for Microwave-Based Head Imaging Applications.

A modified monopole patch antenna for microwave-based hemorrhagic or ischemic stroke recognition is presented in this article. The designed antenna is fabricated on a cost-effective FR-4 lossy material with a 0.02 loss tangent and 4.4 dielectric constant. Its overall dimensions are 0.32 λ × 0.28 λ × 0.007 λ, where λ is the lower bandwidth 1.3 GHz frequency wavelength. An inset feeding approach is utilized to feed the antenna to reduce the input impedance (z = voltage/current). A total bandwidth (below -10 dB) of 2.4 GHz (1.3-3.7 GHz) is achieved with an effective peak gain of over 6 dBi and an efficiency of over 90%. A time-domain analysis confirms that the antenna produces minimal signal distortion. Simulated and experimental findings share a lot of similarities. Brain tissue is penetrated by the antenna to a satisfactory degree, while still exhibiting a safe specific absorption rate (SAR). The maximum SAR value measured for the head model is constrained to be equal to or below 0.1409 W/kg over the entire usable frequency band. Evaluation of theoretical and experimental evidence indicates the intended antenna is appropriate for Microwave Imaging (MWI) applications.

Differential effect of brief electrical stimulation on voltage-gated potassium channels.

Electrical stimulation of neuronal tissue is a promising strategy to treat a variety of neurological disorders. The mechanism of neuronal activation by external electrical stimulation is governed by voltage-gated ion channels. This stimulus, typically brief in nature, leads to membrane potential depolarization, which increases ion flow across the membrane by increasing the open probability of these voltage-gated channels. In spiking neurons, it is activation of voltage-gated sodium channels (NaV channels) that leads to action potential generation. However, several other types of voltage-gated channels are expressed that also respond to electrical stimulation. In this study, we examine the response of voltage-gated potassium channels (KV channels) to brief electrical stimulation by whole cell patch-clamp electrophysiology and computational modeling. We show that nonspiking amacrine neurons of the retina exhibit a large variety of responses to stimulation, driven by different KV-channel subtypes. Computational modeling reveals substantial differences in the response of specific KV-channel subtypes that is dependent on channel kinetics. This suggests that the expression levels of different KV-channel subtypes in retinal neurons are a crucial predictor of the response that can be obtained. These data expand our knowledge of the mechanisms of neuronal activation and suggest that KV-channel expression is an important determinant of the sensitivity of neurons to electrical stimulation.NEW & NOTEWORTHY This paper describes the response of various voltage-gated potassium channels (KV channels) to brief electrical stimulation, such as is applied during prosthetic electrical stimulation. We show that the pattern of response greatly varies between KV channel subtypes depending on activation and inactivation kinetics of each channel. Our data suggest that problems encountered when artificially stimulating neurons such as cessation in firing at high frequencies, or "fading," may be attributed to KV-channel activation.

Local Heterogeneous Electrical Restitution Properties of Rabbit Atria.

INTRODUCTION: This study aims to characterize the regional variability in rate-adaptation in the atria. METHODS AND RESULTS: Action potential (AP) responses to pulses with uniform as well as pseudo-random non-uniform pacing intervals were recorded from rabbit sino-atrial node, right and left atrial pectinate as well as pulmonary vein antrum tissue preparations using conventional intracellular glass microelectrodes. Steady-state restitution curves were reconstructed for various AP waveform metrics. We observed significant variability between the four regions under basal pacing representing the rabbit resting heart rate as well as regional variability in rate-adaptation to increased pacing frequencies. Right-left atrial restitution differences were further confirmed using the non-uniform pacing protocol, with significant differences in AP amplitude, duration (APD) as well as maximum phase 0 depolarization rate restitution curves in response to an identical sequence of non-uniform pacing intervals. In addition, we report regional differences in alternans of AP waveform metrics, over a wide range of pacing frequencies and not simply prior to 1:1 entrainment being lost. We also observed an increase in APD90 along the conduction pathway from the left atrium to pulmonary vein junction. CONCLUSIONS: Our results identified significant regional differences in electrical restitution in the rabbit atria and suggest their dependency on both baseline AP morphology and local intrinsic differences in rate-adaptation. We propose that the atrial heterogeneity in rate-adaptation could contribute to arrhythmogenesis and the greater susceptibility of pulmonary vein myocardial sleeves to ectopic foci and reentrant activity.

Focalised stimulation using high definition transcranial direct current stimulation (HD-tDCS) to investigate declarative verbal learning and memory functioning.

BACKGROUND: Declarative verbal learning and memory are known to be lateralised to the dominant hemisphere and to be subserved by a network of structures, including those located in frontal and temporal regions. These structures support critical components of verbal memory, including working memory, encoding, and retrieval. Their relative functional importance in facilitating declarative verbal learning and memory, however, remains unclear. OBJECTIVE: To investigate the different functional roles of these structures in subserving declarative verbal learning and memory performance by applying a more focal form of transcranial direct current stimulation, "High Definition tDCS" (HD-tDCS). Additionally, we sought to examine HD-tDCS effects and electrical field intensity distributions using computer modelling. METHODS: HD-tDCS was administered to the left dorsolateral prefrontal cortex (LDLPFC), planum temporale (PT), and left medial temporal lobe (LMTL) to stimulate the hippocampus, during learning on a declarative verbal memory task. Sixteen healthy participants completed a single blind, intra-individual cross-over, sham-controlled study which used a Latin Square experimental design. Cognitive effects on working memory and sustained attention were additionally examined. RESULTS: HD-tDCS to the LDLPFC significantly improved the rate of verbal learning (p=0.03, η(2)=0.29) and speed of responding during working memory performance (p=0.02, η(2)=0.35), but not accuracy (p=0.12, η(2)=0.16). No effect of tDCS on verbal learning, retention, or retrieval was found for stimulation targeted to the LMTL or the PT. Secondary analyses revealed that LMTL stimulation resulted in increased recency (p=0.02, η(2)=0.31) and reduced mid-list learning effects (p=0.01, η(2)=0.39), suggesting an inhibitory effect on learning. CONCLUSIONS: HD-tDCS to the LDLPFC facilitates the rate of verbal learning and improved efficiency of working memory may underlie performance effects. This focal method of administrating tDCS has potential for probing and enhancing cognitive functioning.

Revisiting frontoparietal montage in electroconvulsive therapy: clinical observations and computer modeling: a future treatment option for unilateral electroconvulsive therapy.

OBJECTIVES: The aim of this study was to compare the clinical effects of frontoparietal electrode placement, an alternative montage for right unilateral electroconvulsive therapy (ECT), with the commonly used temporoparietal montage. METHODS: In a single patient who received alternate treatments with the abovementioned right unilateral montages, within a treatment course of ECT, time-to-reorientation after each treatment and seizure expression were compared. Computer modeling was used to simulate and compare differences in electrical stimulation patterns in key cerebral regions, with the 2 montages. These simulations were done in an anatomically realistic head model recreated from magnetic resonance imaging scans of the patient's head. RESULTS: Time-to-reorientation was shorter after treatment with frontoparietal ECT (mean, 28.3 minutes; SD, 2.9 minutes) than after temporoparietal ECT (mean, 50.0 minutes; SD, 11.5 minutes), suggesting less retrograde memory impairment. Seizure duration and expression were similar for the 2 montages. Computer modeling demonstrated less hippocampal and right inferior frontal cortical stimulation but comparable anterior cingulate cortex stimulation with the frontoparietal montage. CONCLUSIONS: These results, although preliminary, suggest that the frontoparietal montage may result in less memory side effects, but comparable efficacy, to the temporoparietal montage.

Clinical Pilot Study and Computational Modeling of Bitemporal Transcranial Direct Current Stimulation, and Safety of Repeated Courses of Treatment, in Major Depression.

OBJECTIVES: This study aimed to examine a bitemporal (BT) transcranial direct current stimulation (tDCS) electrode montage for the treatment of depression through a clinical pilot study and computational modeling. The safety of repeated courses of stimulation was also examined. METHODS: Four participants with depression who had previously received multiple courses of tDCS received a 4-week course of BT tDCS. Mood and neuropsychological function were assessed. The results were compared with previous courses of tDCS given to the same participants using different electrode montages. Computational modeling examined the electric field maps produced by the different montages. RESULTS: Three participants showed clinical improvement with BT tDCS (mean [SD] improvement, 49.6% [33.7%]). There were no adverse neuropsychological effects. Computational modeling showed that the BT montage activates the anterior cingulate cortices and brainstem, which are deep brain regions that are important for depression. However, a fronto-extracephalic montage stimulated these areas more effectively. No adverse effects were found in participants receiving up to 6 courses of tDCS. CONCLUSIONS: Bitemporal tDCS was safe and led to clinically meaningful efficacy in 3 of 4 participants. However, computational modeling suggests that the BT montage may not activate key brain regions in depression more effectively than another novel montage--fronto-extracephalic tDCS. There is also preliminary evidence to support the safety of up to 6 repeated courses of tDCS.

A computational modelling study of transcranial direct current stimulation montages used in depression.

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which involves passing a mild electric current to the brain through electrodes placed on the scalp. Several clinical studies suggest that tDCS may have clinically meaningful efficacy in the treatment of depression. The objective of this study was to simulate and compare the effects of several tDCS montages either used in clinical trials or proposed, for the treatment of depression, in different high-resolution anatomically-accurate head models. Detailed segmented finite element head models of two subjects were presented, and a total of eleven tDCS electrode montages were simulated. Sensitivity analysis on the effects of changing the size of the anode, rotating both electrodes and displacing the anode was also conducted on selected montages. The F3-F8 and F3-F4 montages have been used in clinical trials reporting significant antidepressant effects and both result in relatively high electric fields in dorsolateral prefrontal cortices. Other montages using a fronto-extracephalic or fronto-occipital approach result in greater stimulation of central structures (e.g. anterior cingulate cortex) which may be advantageous in treating depression, but their efficacy has yet to be tested in randomised controlled trials. Results from sensitivity analysis suggest that electrode position and size may be adjusted slightly to accommodate other priorities, such as skin discomfort and damage.

Understanding the retina: a review of computational models of the retina from the single cell to the network level.

The vertebrate retina is a clearly organized signal-processing system. It contains more than 60 different types of neurons, arranged in three distinct neural layers. Each cell type is believed to serve unique role(s) in encoding visual information. While we now have a relatively good understanding of the constituent cell types in the retina and some general ideas of their connectivity, with few exceptions, how the retinal circuitry performs computation remains poorly understood. Computational modeling has been commonly used to study the retina from the single cell to the network level. In this article, we begin by reviewing retinal modeling strategies and existing models. We then discuss in detail the significance and limitations of these models, and finally, we provide suggestions for the future development of retinal neural modeling.

Hybrid soft computing systems for electromyographic signals analysis: a review.

Electromyographic (EMG) is a bio-signal collected on human skeletal muscle. Analysis of EMG signals has been widely used to detect human movement intent, control various human-machine interfaces, diagnose neuromuscular diseases, and model neuromusculoskeletal system. With the advances of artificial intelligence and soft computing, many sophisticated techniques have been proposed for such purpose. Hybrid soft computing system (HSCS), the integration of these different techniques, aims to further improve the effectiveness, efficiency, and accuracy of EMG analysis. This paper reviews and compares key combinations of neural network, support vector machine, fuzzy logic, evolutionary computing, and swarm intelligence for EMG analysis. Our suggestions on the possible future development of HSCS in EMG analysis are also given in terms of basic soft computing techniques, further combination of these techniques, and their other applications in EMG analysis.

Neural activity of retinal ganglion cells under continuous, dynamically-modulated high frequency electrical stimulation.

Objective.Current retinal prosthetics are limited in their ability to precisely control firing patterns of functionally distinct retinal ganglion cell (RGC) types. The aim of this study was to characterise RGC responses to continuous, kilohertz-frequency-varying stimulation to assess its utility in controlling RGC activity.Approach.We usedin vitropatch-clamp experiments to assess electrically-evoked ON and OFF RGC responses to frequency-varying pulse train sequences. In each sequence, the stimulation amplitude was kept constant while the stimulation frequency (0.5-10 kHz) was changed every 40 ms, in either a linearly increasing, linearly decreasing or randomised manner. The stimulation amplitude across sequences was increased from 10 to 300µA.Main results.We found that continuous stimulation without rest periods caused complex and irreproducible stimulus-response relationships, primarily due to strong stimulus-induced response adaptation and influence of the preceding stimulus frequency on the response to a subsequent stimulus. In addition, ON and OFF populations showed different sensitivities to continuous, frequency-varying pulse trains, with OFF cells generally exhibiting more dependency on frequency changes within a sequence. Finally, the ability to maintain spiking behaviour to continuous stimulation in RGCs significantly reduced over longer stimulation durations irrespective of the frequency order.Significance.This study represents an important step in advancing and understanding the utility of continuous frequency modulation in controlling functionally distinct RGCs. Our results indicate that continuous, kHz-frequency-varying stimulation sequences provide very limited control of RGC firing patterns due to inter-dependency between adjacent frequencies and generally, different RGC types do not display different frequency preferences under such stimulation conditions. For future stimulation strategies using kHz frequencies, careful consideration must be given to design appropriate pauses in stimulation, stimulation frequency order and the length of continuous stimulation duration.

A review of computational models of transcranial electrical stimulation.

Transcranial electrical stimulation (tES), which includes transcranial direct current stimulation (tDCS) and electroconvulsive therapy (ECT), has played an important role in the treatment of various psychiatric disorders. Decades of empirical research and clinical experience have led to new and improved brain stimulation techniques, but the mechanisms underlying treatment efficacy and side effects are poorly understood. As part of the ongoing research effort in tES, the value of computational models of transcranial electric current flow has been increasingly recognized, and a proliferation of modeling studies have been published. The complexity of these tES models ranges from simple sphere-based models of the head to high-resolution anatomical reconstructions based on head-image scans. This review provides an up-to-date description and comparison of existing computational models of tES (primarily tDCS and ECT), focusing on the modeling approaches adopted in previous studies and their significant finding.

Numerical investigation of the effect of cannula placement on thrombosis.

Despite the rapid advancement of left ventricular assist devices (LVADs), adverse events leading to deaths have been frequently reported in patients implanted with LVADs, including bleeding, infection, thromboembolism, neurological dysfunction and hemolysis. Cannulation forms an important component with regards to thrombus formation in assisted patients by varying the intraventricular flow distribution in the left ventricle (LV). To investigate the correlation between LVAD cannula placement and potential for thrombus formation, detailed analysis of the intraventricular flow field was carried out in the present study using a two way fluid structure interaction (FSI), axisymmetric model of a passive LV incorporating an inflow cannula. Three different cannula placements were simulated, with device insertion near the LV apex, penetrating one-fourth and mid-way into the LV long axis. The risk of thrombus formation is assessed by analyzing the intraventricular vorticity distribution and its associated vortex intensity, amount of stagnation flow in the ventricle as well as the level of wall shear stress. Our results show that the one-fourth placement of the cannula into the LV achieves the best performance in reducing the risk of thrombus formation. Compared to cannula placement near the apex, higher vortex intensity is achieved at the one-fourth placement, thus increasing wash out of platelets at the ventricular wall. One-fourth LV penetration produced negligible stagnation flow region near the apical wall region, helping to reduce platelet deposition on the surface of the cannula and the ventricular wall.

A hybrid symplectic principal component analysis and central tendency measure method for detection of determinism in noisy time series with application to mechanomyography.

We present a hybrid symplectic geometry and central tendency measure (CTM) method for detection of determinism in noisy time series. CTM is effective for detecting determinism in short time series and has been applied in many areas of nonlinear analysis. However, its performance significantly degrades in the presence of strong noise. In order to circumvent this difficulty, we propose to use symplectic principal component analysis (SPCA), a new chaotic signal de-noising method, as the first step to recover the system dynamics. CTM is then applied to determine whether the time series arises from a stochastic process or has a deterministic component. Results from numerical experiments, ranging from six benchmark deterministic models to 1/f noise, suggest that the hybrid method can significantly improve detection of determinism in noisy time series by about 20 dB when the data are contaminated by Gaussian noise. Furthermore, we apply our algorithm to study the mechanomyographic (MMG) signals arising from contraction of human skeletal muscle. Results obtained from the hybrid symplectic principal component analysis and central tendency measure demonstrate that the skeletal muscle motor unit dynamics can indeed be deterministic, in agreement with previous studies. However, the conventional CTM method was not able to definitely detect the underlying deterministic dynamics. This result on MMG signal analysis is helpful in understanding neuromuscular control mechanisms and developing MMG-based engineering control applications.

Cells-in-Touch: 3D Printing in Reconstruction and Modelling of Microscopic Biological Geometries for Education and Future Research Applications.

Additive manufacturing (3D printing) and computer-aided design (CAD) still have limited uptake in biomedical and bioengineering research and education, despite the significant potential of these technologies. The utility of organ-scale 3D-printed models of living structures is widely appreciated, while the workflows for microscopy data translation into tactile accessible replicas are not well developed yet. Here, we demonstrate an accessible and reproducible CAD-based methodology for generating 3D-printed scalable models of human cells cultured in vitro and imaged using conventional scanning confocal microscopy with fused deposition modeling (FDM) 3D printing. We termed this technology CiTo-3DP (Cells-in-Touch for 3D Printing). As a proof-of-concept, we created dismountable CiTo-3DP models of human epithelial, mesenchymal, and neural cells by using selectively stained nuclei and cytoskeletal components. We also provide educational and research context for the presented cellular models. In the future, the CiTo-3DP approach can be adapted to different imaging and 3D printing modalities and comprehensively present various cell types, subcellular structures, and extracellular matrices. The resulting CAD and 3D printed models could be used for a broad spectrum of education and research applications.

Repeatability of brain phase-based magnetic resonance electric properties tomography methods and effect of compressed SENSE and RF shimming.

Magnetic resonance electrical properties tomography (MREPT) is an emerging imaging modality to noninvasively measure tissue conductivity and permittivity. Implementation of MREPT in the clinic requires repeatable measurements at a short scan time and an appropriate protocol. The aim of this study was to investigate the repeatability of conductivity measurements using phase-based MREPT and the effects of compressed SENSE (CS), and RF shimming on the precision of conductivity measurements. Conductivity measurements using turbo spin echo (TSE) and three-dimensional balanced fast field echo (bFFE) with CS factors were repeatable. Conductivity measurement using bFFE phase showed smaller mean and variance that those measured by TSE. The conductivity measurements using bFFE showed minimal deviation with CS factors up to 8, with deviation increasing at CS factors > 8. Subcortical structures produced less consistent measurements than cortical parcellations at higher CS factors. RF shimming using full slice coverage 2D dual refocusing echo acquisition mode (DREAM) and full coverage 3D dual TR approaches further improved measurement precision. BFFE is a more optimal sequence than TSE for phase-based MREPT in brain. Depending on the area of the brain being measured, the scan can be safely accelerated with compressed SENSE without sacrifice of precision, offering the potential to employ MREPT in clinical research and applications. RF shimming with better field mapping further improves precision of the conductivity measures.

The direct influence of retinal degeneration on electrical stimulation efficacy: Significant implications for retinal prostheses.

Photoreceptor loss and inner retinal network remodeling severely impacts the ability of retinal prosthetic devices to create artificial vision. We developed a computational model of a degenerating retina based on rodent data and tested its response to retinal electrical stimulation. This model includes detailed network connectivity and diverse neural intrinsic properties, capable of exploring how the degenerated retina influences the performance of electrical stimulation during the degeneration process. Our model suggests the possibility of quantitatively modulating retinal ON and OFF pathways between phase II and III of retinal degeneration without requiring any differences between ON and OFF RGC intrinsic cellular properties. The model also provided insights about how remodeling events influence stage-dependent differential electrical responses of ON and OFF pathways.Clinical Relevance-This data-driven model can guide future development of retinal prostheses and stimulation strategies that may benefit patients at different stages of retinal disease progression, particularly in the early and mid-stages, thus increasing their global acceptance.