Search Results (141)

We conducted ultrasonic (1-MHz) laboratory measurements on 210 samples from the Vaca Muerta Formation (Neuquén Basin, Argentina) to determine the factors influencing acoustic velocities in siliciclastic–carbonate mudstone. We quantitatively assessed the calcium carbonate and total organic carbon (TOC) content and qualitatively identified the quartz and clay mineralogy. For brine-saturated samples, P-wave velocities ranged from 2826 to 6816 m/s, S-wave velocities ranged from 1474 to 3643 m/s, and porosity values ranged from 0.01 to 19.4%. Carbonate content percentages, found to be critically important, vary widely from 0.08 to 98.0%, while TOC ranged from 0 to 5.3%. Velocity was primarily controlled by carbonate content and, to a lesser extent, by the non-carbonate mineralogy of the rock (e.g., quartz, clay minerals). TOC content had little effect on the acoustic properties. Due to the low porosity of most samples, mineral composition had a stronger influence on velocity than porosity or pore geometry. The V_p/V_s ratio of dry samples ranged from 1.38 to 1.97 and decreased as porosity increased. In saturated samples, the V_p/V_s ratio ranged from 1.46 to 2.06 and appeared independent of porosity. A clear distinction between carbonate and mixed lithofacies under both saturated and dry conditions was observed in all samples. Full article

Spiral wave dynamics in cardiac tissue are critically implicated in the pathogenesis of arrhythmias. This study investigates the effects of modulating calcium and potassium currents on spiral wave stability in a two-dimensional cardiac model. The gate variable that dynamically regulates the opening probability of ion channels also plays a significant role in the control of the spiral wave dynamics. We demonstrate that reducing gate variables accelerates wave propagation, thins spiral arms, and shortens action potential duration, ultimately inducing dynamic instability. Irregular electrocardiogram (ECG) patterns and altered action potential morphology further suggest an enhanced arrhythmogenic potential. These findings elucidate the ionic mechanisms underlying spiral wave breakup, providing both theoretical insights and practical implications for the development of targeted arrhythmia treatments. Full article

The neurological basis of consciousness remains unknown despite innumerable theories proposed for over a century. The major obstacle is that empirical studies demonstrate that all sensory information is subdivided and parcellated as it is processed within the brain. A central region where such diverse information combines to form conscious expression has not been identified. A novel hypothesis was introduced over two decades ago that proposed astrocytes, with their ability to interconnect to form a global syncytium within the neocortex, are the locus of consciousness based on their ability to integrate synaptic signals. However, it was criticized because intercellular calcium waves, which are initiated by synaptic activity, are too slow to contribute to consciousness but ideal for memory formation. Although astrocytes are known to exhibit rapid electrical responses in active sensory pathways (e.g., vision), it was technically impossible to determine electrical activity within the astroglia syncytium because of the challenge of separating syncytial electrical responses from simultaneous neuronal electrical activity. Therefore, research on astroglia syncytial electrical activity lagged for over sixty years, until recently, when an ingenuous technique was developed to eliminate neuronal electrical interference. These technical advances have demonstrated that the astroglia syncytium, although massive and occupying the entire neocortex, is isoelectric with minimal impedance. Most importantly, the speed of electrical conductance within the syncytium is as rapid as that of neural networks. Therefore, the astroglia syncytium is theoretically capable of transmitting integrated local synaptic signaling globally throughout the entire neocortex to bind all functional areas of the brain in a timeframe required for consciousness. Full article

Erosion poses significant threats to infrastructures and ecosystems, exacerbated by climate change-driven sea-level rise and intensified wave actions. Microbially induced calcium carbonate precipitation (MICP) has emerged as a promising, sustainable, and eco-friendly solution for erosion mitigation. This review synthesizes recent advancements in optimizing biomineralization efficiency, multi-scale erosion control, and field-scale MICP implementations in marine dynamic conditions. Key findings include the following: (1) Kinetic analysis of Ca²⁺ conversion confirmed complete ion utilization within 24 h under optimized PA concentration (3%), resulting in a compressive strength of 2.76 MPa after five treatment cycles in ISO-standard sand. (2) Field validations in Ahoskie and Sanya demonstrated the efficacy of MICP in coastal erosion control through tailored delivery systems and environmental adaptations. Sanya’s studies highlighted seawater-compatible MICP solutions, achieving maximum 1743 kPa penetration resistance in the atmospheric zone and layered “M-shaped” CaCO₃ precipitation in tidal regions. (3) Experimental studies revealed that MICP treatments (2–4 cycles) reduced maximum scour depth by 84–100% under unidirectional currents (0.3 m/s) with the maximum surface CaCO₃ content reaching 3.8%. (4) Numerical simulations revealed MICP enhanced seabed stability by increasing vertical effective stress and reducing pore pressure. Comparative analysis demonstrates that while the destabilization depth of untreated seabed exhibits a linear correlation with wave height increments, MICP-treated seabed formations maintain exceptional stability through cohesion-enhancing properties, even when subjected to progressively intensified wave forces. This review supports the use of biomineralization as a sustainable alternative for shoreline protection, seabed stabilization, and offshore foundation integrity. Full article

Long-range intercellular communication is essential for multicellular biological systems to regulate multiscale cell–cell interactions and maintain life. Growing evidence suggests that intercellular calcium waves (ICWs) act as a class of long-range signals that influence a broad spectrum of cellular functions and behaviors. Importantly, mechanical signals, ranging from single-molecule-scale to tissue-scale in vivo, can initiate and modulate ICWs in addition to relatively well-appreciated biochemical and bioelectrical signals. Despite these recent conceptual and experimental advances, the full nature of underpinning mechanotransduction mechanisms by which cells convert mechanical signals into ICW dynamics remains poorly understood. This review provides a systematic analysis of quantitative ICW dynamics around three main stages: initiation, propagation, and regeneration/relay. We highlight the landscape of upstream molecules and organelles that sense and respond to mechanical stimuli, including mechanosensitive membrane proteins and cytoskeletal machinery. We clarify the roles of downstream molecular networks that mediate signal release, spread, and amplification, including adenosine triphosphate (ATP) release, purinergic receptor activation, and gap junction (GJ) communication. Furthermore, we discuss the broad pathophysiological implications of ICWs, covering pathophysiological processes such as cancer metastasis, tissue repair, and developmental patterning. Finally, we summarize recent advances in optical imaging and artificial intelligence (AI)/machine learning (ML) technologies that reveal the precise spatial-temporal-functional dynamics of ICWs and ATP waves. By synthesizing these insights, we offer a comprehensive framework of ICW mechanobiology and propose new directions for mechano-therapeutic strategies in disease diagnosis, cancer immunotherapies, and drug discovery. Full article

Background/Objectives: Calcific tendinopathy of the shoulder is a degenerative condition characterized by calcium deposits within the rotator cuff tendons, particularly the supraspinatus. It is a frequent cause of chronic shoulder pain and functional limitation, adversely affecting quality of life. While conservative treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs), physiotherapy, and corticosteroid injections are commonly used, extracorporeal shock wave therapy (ESWT) has emerged as a promising non-invasive alternative. This interventional clinical trial compared the efficacy of ultrasound-guided versus landmark-based ESWT in treating calcific tendinopathy. Methods: Eighty-four patients with ultrasound-confirmed calcific tendinopathy were randomized into two groups. Group 1 received ultrasound-guided ESWT with real-time targeting of the deposit; Group 2 received landmark-based ESWT based on anatomical palpation. Both groups underwent three sessions (2000 impulses at 2.2 bars, energy level 5, 8 Hz). Clinical outcomes were assessed using the Constant–Murley score (CMS) at baseline, 12 weeks, and 6 months. Calcific deposit resorption was evaluated via ultrasound imaging. Results: The ultrasound-guided group showed a significant improvement in CMS from a median of 50 (range: 30–75) at baseline to 97 (52–100) at 6 months. The landmark-based group also improved, from 48 (32–74) to 79 (40–96). At 6 months post-treatment, 90.9% of patients in the ultrasound-guided group achieved successful outcomes (CMS ≥ 86), compared to 50% in the landmark-based group. Complete calcific resorption occurred in 65.9% of patients in Group 1, compared to 50% in Group 2; 15% of patients in Group 2 showed no resorption. Conclusions: Ultrasound-guided ESWT was significantly more effective than landmark-based ESWT in improving shoulder function, reducing pain, and promoting calcific deposit resorption. These findings support ultrasound guidance as a preferred approach for optimizing ESWT outcomes in patients with calcific tendinopathy of the shoulder. Full article

Background and Objectives: Cardiovascular diseases are prevalent entities, especially in emergency patients. Arterial stiffness is a known predictor of cardiovascular risk and mortality and is quantified by carotid-femoral pulse wave velocity (cfPWV). It is caused in part by vascular calcification, but exact details of the underlying mechanisms are yet to be elucidated, and current data suggest endocrine influences. This study thus aimed to assess the associations of endocrine parameters, particularly thyroid and parathyroid hormones, calcium, inorganic phosphate, and vitamin D, with cfPWV as a surrogate for arterial stiffness. Materials and Methods: Adults presenting to a single tertiary care emergency department in Vienna between 2018 and 2023 were prospectively enrolled. CfPWV was measured non-invasively, and levels of thyroid and parathyroid hormones and 25-hydroxyvitamin D, calcium, and inorganic phosphate were assessed. Results: In total, data from 827 patients, predominantly male (57%) and around 60 (47–72) years of age, were assessed. We observed a significant worsening of cfPWV with increasing parathyroid hormone levels (p < 0.001) and TSH levels (p = 0.03). No significant influences of calcium, inorganic phosphate, or 25-hydroxyvitamin D were observed. Conclusions: Thyroid and parathyroid hormone levels are associated with arterial stiffness in emergency department patients, suggesting a need for a comprehensive workup in patients at risk because of comorbidities and age. Additional prospective studies are needed to further elucidate the role of endocrinology in arterial stiffness and the subsequent relevance in emergency medicine. Full article

The article investigates the characteristics of the phase composition and structure of supersulfated cement (SSC) during hardening using X-ray, electron microscopy, and ultrasonic analysis methods. The influence of different types of activators, hardening accelerators, and superplasticizers on the type and morphology of the newly formed phases during SSC hardening was studied. The effect of a polycarboxylate-type superplasticizer and calcium chloride on the standard consistency and setting times of SSC was experimentally determined. It was established that the introduction of the superplasticizer reduces the standard consistency by 10–16%. Experimental data showed higher effectiveness of phosphogypsum as a sulfate activator compared to gypsum stone. The strength increase of SSC at 7 days reached up to 35%, and at 28 days, up to 15%. Based on the kinetics of ultrasonic wave propagation during SSC hardening, the main stages of structure formation and the influence of cement composition on these stages were determined. The experimental results demonstrate the effect of SSC composition on its standard consistency, setting time, and mechanical properties. The impact of the type of activator and admixtures on the change in SSC strength during storage was investigated. It was found that the addition of a polycarboxylate-type superplasticizer significantly reduces the strength loss of SSC during long-term storage. Using mathematical modeling, experimentally obtained statistical models of strength were developed, which allow for the quantitative evaluation of individual and combined effects, as well as the determination of optimal SSC compositions. Full article

Background: Terahertz (THz) waves, lying between millimeter waves and infrared light, may interact with biomolecules due to their unique energy characteristics. However, whether THz waves are neurally regulated remains controversial, and the underlying mechanism is elusive. Methods: Mouse brain slices were exposed to 1.94 THz waves for 1 h. Synaptic plasticity was evaluated via transmission electron microscopy (TEM), long-term potentiation (LTP), and neuronal class III β-tubulin (Tuj1) and synaptophysin (SYN) expression. Immunofluorescence (IF) and electrophysiology were used to identify neurons sensitive to THz waves. The calcium activity of excitatory neurons, glutamate receptor currents, and glutamate neuron marker expression was also assessed using calcium imaging, a patch clamp, and Western blotting (WB). Optogenetics and chemogenetics were used to determine the role of excitatory neurons in synaptic plasticity impairment after THz wave exposure. NMDA receptor 2B (GluN2B) was overexpressed in the ventral hippocampal CA1 (vCA1) by a lentivirus to clarify the role of GluN2B in THz wave-induced synaptic plasticity impairment. Results: Exposure to 1.94 THz waves increased postsynaptic density (PSD) thickness and reduced the field excitatory postsynaptic potential (fEPSP) slope and Tuj1 and SYN expression. THz waves diminished vCA1 glutamatergic neuron activity and excitability, neural electrical activity, and glutamate transporter function. THz waves reduced N-methyl-D-aspartate receptor (NMDAR) current amplitudes and NMDAR subunit expression. Activating vCA1 glutamatergic neurons through optogenetics and chemogenetics mitigated THz wave-induced synaptic plasticity impairment. GluN2B subunit overexpression improved synaptic plasticity marker expression, synaptic ultrastructure, and the fEPSP slope. Conclusions: Exposure to 1.94 THz waves decreased synaptic plasticity, glutamatergic neuron excitability, and glutamatergic synaptic transmission in the vCA1. Glutamatergic neuron activation and GluN2B overexpression alleviated THz wave-induced synaptic plasticity impairment; thus, neuromodulation could be a promising therapeutic strategy to mitigate the adverse effects of THz radiation. Full article

The role of calcium, an essential secondary messenger, in cell division remains an outstanding question in cell biology despite several significant findings over the past few decades. Among them is the landmark discovery of intracellular calcium waves during cytokinesis, the last stage of cell division, in fish cells. Nevertheless, subsequent studies have been largely unable to determine the underlying molecular mechanism of these cytokinetic transients. At the center of this stalemate stands two challenging questions, how these calcium transients rise and what they do during cytokinesis. Yeast, despite its proven prowess as a model organism to study cell cycle, has not drawn much interest in addressing these questions. However, the recent discovery of cytokinetic calcium spikes in the fission yeast Schizosaccharomyces pombe has provided novel insights into how calcium regulates cytokinesis. In this review, I will primarily focus on our current understanding of the molecular mechanism of cytokinetic calcium transients in yeast cells. First, I will briefly recount the discovery of cytokinetic calcium transients in animal cells. This will be followed by an introduction to the intracellular calcium homeostasis. Next, I will discuss yeast cytokinetic calcium spikes, the ion channel Pkd2 that promotes these spikes, and the potential molecular targets of these spikes. I will also compare the calcium regulation of cytokinesis between yeast and animal cells. I will conclude by presenting a few critical questions in our continued quest to understand how calcium regulates cytokinesis. Full article

Medulloblastoma (MB) groups 3 and 4 lack targeted therapies despite their dismal prognoses. Ion channels and pumps have been implicated in promoting MB metastasis and growth; however, their roles remain poorly understood. In this study, we repurposed FDA-approved channel blockers and modulators to investigate their potential anti-tumor effects in MB cell lines (DAOY and D283) and primary cell cultures derived from a patient with MB. For the first time, we report spontaneous calcium signaling in MB cells. Spontaneous calcium signals were significantly reduced by mibefradil (calcium channel blocker), paxilline (calcium-activated potassium channel blocker), and thioridazine (potassium channel blocker). These drugs induced dose-dependent cytotoxicity in both the DAOY and D283 cell lines, as well as in primary cell cultures of a patient with group 3 or 4 MB. In contrast, digoxin and ouabain, inhibitors of the Na/K pump, reduced the calcium signaling by over 90% in DAOY cells and induced approximately 90% cell death in DAOY cells and 80% cell death in D283 cells. However, these effects were significantly diminished in the cells derived from a patient with MB, highlighting the variability in drug sensitivity among MB models. These findings demonstrate that calcium signaling is critical for MB cell survival and that the targeted inhibition of calcium pathways suppresses tumor cell growth across multiple MB models. Full article

Rotavirus is an enteric virus that leads to 200,000 deaths worldwide every year. The live-cell imaging evaluating rotavirus infection of MA104 cells revealed that rotavirus replication and spread occurs in a spatially controlled manner. Specifically, following initial rotavirus infection, the infected cells die, and the second round of infection occurs in the restricted area surrounding the initially infected cell. Interestingly, we found that the time required to establish the secondary infection is shorter compared to the time required for the initial infection. To determine if this increase in the kinetic of secondary infection was due to the early release of viruses or priming of the cells that are infected during the secondary infection, we used a combination of live-cell microscopy, trypsin neutralization assays, and the pharmacological inhibition of calcium signaling. Together, our results show that the second round of infection required rotavirus to be released and accessible to extracellular proteases. In addition, we found that the calcium wave induced upon rotavirus infection was critical for initial infection but did not play a role in the establishment of a secondary infection. Finally, we uncovered that high viral titers released from the initial infection were sufficient to accelerate the rate of the secondary infection. Full article

Background: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) and exposing patients to higher risk of early cardiovascular (CV) atherosclerotic diseases. Though the estimated prevalence of heterozygous FH (HeFH) is about 1 in 200, FH is still underdiagnosed and undertreated. Coronary artery calcification (CAC) assessment and arterial stiffness measured as pulse wave velocity (PWV) have demonstrated their accuracy in CV risk assessment, but data on HeFH are lacking. This study aims to evaluate CAC and PWV in a population of HeFH patients to improve risk stratification and therapy timing and setting. Methods: One hundred genetically characterized HeFH patients, regularly followed up since diagnosis, were recruited at our outpatient clinic. In all patients, CAC, PWV measurement, and LDL-C burden calculation were assessed. Results: The mean age was 45 ± 16 years. A total of 25% of patients had hypertension, and 15% were in secondary prevention. Through univariate analysis, we found strong positive correlations between CAC and both PWV (r = 0.52 p > 0.0001) and total LDL-C burden (r = 0.52 p < 0.0001). No other associations with lipid parameters were found. Multivariate analysis showed that CAC was independently associated with PWV adjusted for sex, total LDL-C burden, systolic blood pressure, smoking, LDL-C, HDL-C, and statin treatment. Conclusions: Arterial stiffness is strongly associated with CAC in HeFH patients with similar total LDL-C burden and CV risk profiles. Personalized risk assessment based on arterial stiffness and CAC evaluation enhances the stratification and management of cardiovascular risk in FH patients, supporting individualized therapeutic approaches. Full article

Migraine with aura (MwA) is a common and severely disabling neurological disorder, characterised by transient yet recurrent visual disturbances, including scintillating scotomas, flickering photopsias, and complex geometric patterns. These episodic visual phenomena significantly compromise daily functioning, productivity, and overall quality of life. Despite extensive research, the underlying pathophysiological mechanisms remain only partially understood. Cortical spreading depression (CSD), a propagating wave of neuronal and glial depolarisation, has been identified as a central process in MwA. This phenomenon is triggered by ion channel dysfunction, leading to elevated intracellular calcium levels and excessive glutamate release, which contribute to widespread cortical hyperexcitability. Genetic studies, particularly involving the CACNA gene family, further implicate dysregulation of calcium channels in the pathogenesis of MwA. Recent advances in neuroimaging, particularly functional magnetic resonance imaging (fMRI), have provided critical insights into the neurophysiology of MwA. These results support the central role of CSD as a basic mechanism behind MwA and imply that cortical dysfunction endures beyond brief episodes, possibly due to chronic neuronal dysregulation or hyperexcitability. The visual cortex of MwA patients exhibits activation patterns in comparison to other neuroimaging studies, supporting the possibility that it is a disease-specific biomarker. Its distinctive sensory and cognitive characteristics are influenced by a complex interplay of cortical, vascular, and genetic factors, demonstrating the multifactorial nature of MwA. We now know much more about the pathophysiology of MwA thanks to the combination of molecular and genetic research with sophisticated neuroimaging techniques like arterial spin labelling (ASL) and fMRI. This review aims to synthesize current knowledge and analyse molecular and neurophysiological targets, providing a foundation for developing targeted therapies to modulate cortical excitability, restore neural network stability, and alleviate the burden of migraine with aura. The most important and impactful research in our field has been the focus of this review, which highlights important developments and their contributions to the knowledge and treatment of migraine with aura. Full article

Background: Adhesion within endodontic obturation material and root canal walls improves the efficacy of the endodontic treatment by establishing a barrier that inhibits reinfection and entombs residual bacteria. This study evaluates the push-out bond strength (POBS) of calcium silicate sealers compared to an epoxy-resin-based sealer. Methods: A total of 36 extracted mono-radicular teeth were prepared with Pro Taper Ultimate and irrigated with 5.25% sodium hypochlorite and 17% EDTA. The specimens were randomly split into three groups (n = 12) according to the endodontic sealer and filling technique used as follows: Ah Plus with the continuous wave condensation technique (CWC), Ah Bioceramic (Ah Bio) with the single-cone technique, and Total Fill Hi-Flow (FKG Hi-Flow) with the CWC technique. The material was allowed to set for 4 weeks, and afterwards, the roots were placed in acrylic resin and sectioned into 1 mm transverse slices. A POBS test was conducted using a universal testing machine, and the mode of bond failure was assessed at 4× magnification using a stereomicroscope. Six specimens from each group were selected for SEM-EDX examination to evaluate dentinal tubule penetration. The data were analysed using analysis of variance and Tukey and Bonferroni post hoc tests. Results: The POBS tests revealed higher values for Ah Plus in comparison to both calcium silicate sealers (p < 0.001), while FKG Hi-Flow showed superior results to Ah Bio (p < 0.001). The cohesive mode of failure was prevalent in all three groups. Conclusions: In conclusion, the resin-based sealer showed higher bond strength and better dentinal tubule penetration than the two calcium silicate sealers tested, while FKG Hi-Flow outperformed AH Bio. Full article