Oscillatory phenomena in electrophysiological networks: The coupling between cell bioelectricity and transcription.

Morphogenetic regulation during embryogenesis and regeneration rely on information transfer and coordination between different regions. Here, we explore theoretically the coupling between bioelectrical and transcriptional oscillations at the individual cell and multicellular levels. The simulations, based on a set of ion channels and intercellular gap junctions, show that bioelectrical and transcriptional waves can electrophysiologically couple distant regions of a model network in phase and antiphase oscillatory states that include synchronization phenomena. In this way, different multicellular regionalizations can be encoded by cell potentials that oscillate between depolarized and polarized states, thus allowing a spatio-temporal coding. Because the electric potential patterns characteristic of development and regeneration are correlated with the spatial distributions of signaling ions and molecules, bioelectricity can act as a template for slow biochemical signals following a hierarchy of experimental times. In particular, bioelectrical gradients that couple cell potentials to transcription rates give to each single cell a rough idea of its location in the multicellular ensemble, thus controlling local differentiation processes that switch on and off crucial parts of the genome.

pH-Dependent Effects in Nanofluidic Memristors.

Multipore membranes with nanofluidic diodes show memristive and current rectifying effects that can be controlled by the nanostructure asymmetry and ionic solution characteristics in addition to the frequency and amplitude of the electrical driving signal. Here, we show that the electrical conduction phenomena, which are modulated by the interaction between the pore surface charges and the solution mobile ions, allow for a pH-dependent neuromorphic-like potentiation of the membrane conductance by voltage pulses. Also, we demonstrate that arrangements of memristors can be employed in the design of electrochemical circuits for implementing logic functions and information processing in iontronics.

Implementation of Society for Cardiovascular Angiography and Interventions classification in patients with cardiogenic shock secondary to acute myocardial infarction in a spanish university hospital.

BACKGROUND: Killip-Kimball classification has been used for estimating death risk in patients suffering acute myocardial infarction (AMI). Killip-Kimball stage IV corresponds to cardiogenic shock. However, the Society for Cardiovascular Angiography and Interventions (SCAI) classification provides a more precise tool to classify patients according to shock severity. The aim of this study was to apply this classification to a cohort of Killip IV patients and to analyze the differences in death risk estimation between the two classifications. METHODS: A single-center retrospective cohort study of 100 consecutive patients hospitalized for "Killip IV AMI" between 2016 and 2023 was performed to reclassify patients according to SCAI stage. RESULTS: Distribution of patients according to SCAI stages was B=4%, C=53%, D=27%, E=16%. Thirty-day mortality increased progressively according to these stages (B=0%, C=11.88%, D=55.56%, E=87.50%; P<0.001). The exclusive use of Killip IV stage overestimated death risk compared to SCAI C (35% vs. 11.88%, P=0.002) and underestimated it compared to SCAI D and E stages (35% vs. 55.56% and 87.50%, P=0.03 and P<0.001, respectively). Age >69 years, creatinine >1.15 mg/dl and advanced SCAI stages (SCAI D and E) were independent predictors of 30-day mortality. Mechanical circulatory support use showed an almost significant benefit in advanced SCAI stages (D and E hazard ratio, 0.45; 95% confidence interval, 0.19-1.06; P=0.058). CONCLUSIONS: SCAI classification showed superior death risk estimation compared to Killip IV. Age, creatinine levels and advanced SCAI stages were independent predictors of 30-day mortality. Mechanical circulatory support could play a beneficial role in advanced SCAI stages.

Memristive arrangements of nanofluidic pores.

We demonstrate that nanofluidic diodes in multipore membranes show a memristive behavior that can be controlled not only by the amplitude and frequency of the external signal but also by series and parallel arrangements of the membranes. Each memristor consists of a polymeric membrane with conical nanopores that allow current rectification due to the electrical interaction between the ionic solution and the pore surface charges. This surface charge-regulated ionic transport shows a rich nonlinear physics, including memory and inductive effects, which are characterized here by the current-voltage curves and electrical impedance spectroscopy. Also, neuromorphiclike potentiation of the membrane conductance following voltage pulses (spikes) is observed. The multipore membrane with nanofluidic diodes shows physical concepts that should have application for information processing and signal conversion in iontronics hybrid devices.

Diagnostic accuracy of virtual non-contrast CT for aortic valve stenosis severity evaluation.

BACKGROUND: Computed tomography aortic valve calcium (AVC) score has accepted value for diagnosing and predicting outcomes in aortic stenosis (AS). Multi-energy CT (MECT) allows virtual non-contrast (VNC) reconstructions from contrast scans. We aim to compare the VNC-AVC score to the true non-contrast (TNC)-AVC score for assessing AS severity. METHODS: We prospectively included patients undergoing a MECT for transcatheter aortic valve replacement (TAVR) planning. TNC-AVC was acquired before contrast, and VNC-AVC was derived from a retrospectively gated contrast-enhanced scan. The Agatston scoring method was used for quantification, and linear regression analysis to derive adjusted-VNC values. RESULTS: Among 109 patients (55% female) included, 43% had concordant severe and 14% concordant moderate AS. TNC scan median dose-length product was 116 â€‹mGy∗cm. The median TNC-AVC was 2,107 AU (1,093-3,372), while VNC-AVC was 1,835 AU (1293-2,972) after applying the coefficient (1.46) and constant (743) terms. A strong correlation was demonstrated between methods (r â€‹= â€‹0.93; p â€‹< â€‹0.001). Using accepted thresholds (>1,300 AU for women and >2,000 AU for men), 65% (n â€‹= â€‹71) of patients had severe AS by TNC-AVC and 67% (n â€‹= â€‹73) by adjusted-VNC-AVC. After estimating thresholds for adjusted-VNC (>1,564 AU for women and >2,375 AU for men), 56% (n â€‹= â€‹61) had severe AS, demonstrating substantial agreement with TNC-AVC (κ â€‹= â€‹0.77). CONCLUSIONS: MECT-derived VNC-AVC showed a strong correlation with TNC-AVC. After adjustment, VNC-AVC demonstrated substantial agreement with TNC-AVC, potentially eliminating the requirement for an additional scan and enabling reductions in both radiation exposure and acquisition time.

Neuromorphic responses of nanofluidic memristors in symmetric and asymmetric ionic solutions.

We show that ionic conduction properties of a multipore nanofluidic memristor can be controlled not only by the amplitude and frequency of an external driving signal but also by chemical gating based on the electrolyte concentration, presence of divalent and trivalent cations, and multi-ionic systems in single and mixed electrolytes. In addition, we describe the modulation of current rectification and hysteresis phenomena, together with neuromorphic conductance responses to voltage pulses, in symmetric and asymmetric external solutions. In our case, memristor conical pores act as nanofluidic diodes modulated by ionic solution characteristics due to the surface charge-regulated ionic transport. The above facts suggest potential sensing and actuating applications based on the conversion between ionic and electronic signals in bioelectrochemical hybrid circuits.

Synaptical Tunability of Multipore Nanofluidic Memristors.

We demonstrate a multipore nanofluidic memristor with conical pores showcasing a wide range of hysteresis and memristor properties that provide functionalities for brainlike computation in neuromorphic applications. Leveraging the interplay between the charged functional groups on the pore surfaces and the confined ionic solution, the memristor characteristics are modulated through the electrolyte type, ionic concentrations, and pH levels of the aqueous solution. The multipore membrane mimics the functional characteristics of biological ion channels and displays synaptical potentiation and depression. Furthermore, this property can be inverted in polarity by chemically varying the pH level. The ability to modulate memory effects by ionic conductivity holds promise for enhancing signal information processing capabilities.

Correcting instructive electric potential patterns in multicellular systems: External actions and endogenous processes.

BACKGROUND: Transmembrane electrical potential differences in cells modulate the spatio-temporal distribution of signaling ions and molecules that are instructive for downstream signaling pathways in multicellular systems. The local coupling between bioelectricity and protein transcription patterns allows dynamic subsystems (modules) of cells that share the same bioelectrical state to show similar biochemical downstream processes. METHODS: We simulate theoretically how the integration-segregation pattern formed by the different multicellular modules that define a biosystem can be controlled by multicellular potentials. To this end, we couple together the model equations of the bioelectrical network to those of the genetic network. RESULTS: The coupling provided by the intercellular junctions and the external microenvironment allows the restoration of the target bioelectrical pattern by changing the transcription rate of specific ion channels, the post-translational blocking of these channels, and changes in the environmental ionic concentrations. CONCLUSIONS: The simulations show that the single-cell feedback between bioelectrical and transcriptional processes, together with the coupling provided by the intercellular junctions and the environment, can correct large-scale patterns by means of suitable external actions. GENERAL SIGNIFICANCE: This study provides a theoretical advancement in the understanding of how the multicellular bioelectric coupling may guide repolarizing interventions for regenerating a tissue, with potential implications in biomedicine.

Cation pumping against a concentration gradient in conical nanopores characterized by load capacitors.

We study the cation transport against an external concentration gradient (cation pumping) that occurs in conical nanopores when zero-average oscillatory and white noise potentials are externally applied. This pumping, based on the electrically asymmetric nanostructure, is characterized here by a load capacitor arrangement. In the case of white noise signals, the conical nanopore acts as an electrical valve that allows extraction of order from chaos. No molecular carriers, specific ion pumps, and competitive ion-binding phenomena are required. The nanopore conductance on/off states mimic those of the voltage-gated ion channels in the cell membrane. These channels allow modulating membrane potentials and ionic concentration gradients along oscillatory pulses in circadian rhythms and the cell cycle. We show that the combination of asymmetric nanostructures with load capacitors can be useful for the understanding of nanofluidic processes based on bioelectrochemical gradients.

Biphasic concentration patterns in ionic transport under nanoconfinement revealed in steady-state and time-dependent properties.

Ion permeation across nanoscopic structures differs considerably from microfluidics because of strong steric constraints, transformed solvent properties, and charge-regulation effects revealed mostly in diluted solutions. However, little is known about nanofluidics in moderately concentrated solutions, which are critically important for industrial applications and living systems. Here, we show that nanoconfinement triggers general biphasic concentration patterns in a myriad of ion transport properties by using two contrasting systems: a biological ion channel and a much larger synthetic nanopore. Our findings show a low-concentration regime ruled by classical Debye screening and another one where ion-ion correlations and enhanced ion-surface interactions contribute differently to each electrophysiological property. Thus, different quantities (e.g., conductance vs noise) measured under the same conditions may appear contradictory because they belong to different concentration regimes. In addition, non-linear effects that are barely visible in bulk conductivity only in extremely concentrated solutions become apparent in nanochannels around physiological conditions.

Transplantation of fragments from different planaria: A bioelectrical model for head regeneration.

Head-tail planaria morphologies are influenced by the electric potential differences across the animal's primary axis, as evidenced e.g. by voltage-sensitive dyes and functional experiments that create permanent lines of 2-headed but genetically wild-type animals. However, bioelectrical and biochemical models that make predictions on what would happen in the case of spatial chimeras made by tissue transplantation from different planaria (different species and head shapes) are lacking. Here, we use a bioelectrical model to qualitatively describe the effects of tissue transplantation on the shape of the regenerated head. To this end, we assume that the cells may have distinct sets of ion channels and ascribe the system outcome to the axial distributions of average cell potentials over morphologically relevant regions. Our rationale is that the distributions of signaling ions and molecules are spatially coupled with multicellular electric potentials. Thus, long-time downstream transcriptional events should be triggered by short-time bioelectrical processes. We show that relatively small differences between the ion channel characteristics of the cells could eventually give noticeable changes in the electric potential profiles and the expected morphological deviations, which suggests that small but timely bioelectrical actions may have significant morphological effects. Our approach is based on the observed relationships between bioelectrical regionalization and biochemical gradients in body-plan studies. Such models are relevant to regenerative, developmental, and cancer biology in which cells with distinct properties and morphogenetic target states confront each other in the same tissue.

Influence of BMI on virtual coronary artery calcium scoring.

PURPOSE: Virtual non-contrast (VNC) coronary artery calcium scoring (CAC) may obviate the need for traditional non-contrast (TNC) CAC. There is no data on the influence of body mass index (BMI) on VNC reliability. We aimed to evaluate the influence of BMI on VNC CAC agreement with TNC. MATERIALS AND METHODS: All patients who underwent sequential CAC and coronary CT angiography (CCTA) using spectral CT with TNC CAC > 0 between August 2020 and December 2021 were included. Agatston CAC scores were calculated manually by 2 blinded readers from VNC scans. A correction factor was calculated from the slope of the linear regression using the method of least squares and applied to the VNC scores. Bland-Altman plots and Cohen's weighted Kappa were utilized. RESULTS: We included 174 patients (57.5% female). Mean BMI was 32.6 ± 7.02 kg/m2 [BMI < 30 (39.7%); BMI 30-40 (45.4%); and BMI > 40 kg/m2 (14.9%)]. Mean TNC CAC was 177.8 ± 316.86 and mean VNC CAC after applying the correction factor 149.34 ± 296.73. The TNC value strongly correlated with VNC (r = 0.94; p < 0.0001). As BMI increased there was a progressive reduction in signal-to-noise ratio, contrast-to-noise ratio and coronary enhancement (p < 0.05). The degree of agreement between VNC and TNC CAC decreased as BMI increased (agreement = 91.79 (weighted Kappa = 0.72), 91.14 (weighted Kappa = 0.58) and 88.46% (weighted Kappa = 0.48) (all P values < 0.001) for BMI < 30; 30-40 and > 40 kg/m2, respectively). CONCLUSION: BMI has a significant influence on the accuracy of VNC CAC. VNC CAC shows substantial agreement in non-obese patients but performs poorly in BMI > 40 kg/m2. This is the first study to evaluate the influence of body mass index (BMI) on virtual non-contrast (VNC) coronary artery calcium scoring (CAC) as compared to traditional non-contrast (TNC). We retrospectively evaluated 174 patients with TNC CAC and two blinded reviewers manually calculated the VNC CAC. All cases were included without specific selection for quality. The ratio between the two directly proportional values was determined using the slope from the linear regression through the method of least squares. This correction factor of 2.65 was applied to the calcium scores obtained from VNC images. We found that VNC CAC shows substantial risk-class agreement with TNC in non-obese patients (agreement = 91.79 and weighted Kappa = 0.72) but performs poorly in BMI > 40 kg/m2 (agreement: 88.46% and weighted Kappa = 0.48). These findings show the potential use of VNC CAC to avoid additional radiation in non-obese patients. However, further research on potential improvement strategies for VNC CAC in obese patients is needed.

Electrical conductance of conical nanopores: Symmetric and asymmetric salts and their mixtures.

We have studied experimentally the electrical conductance-voltage curves of negatively and positively charged conical nanopores bathed in ionic solutions with monovalent, divalent, and trivalent cations at electrochemically and biologically relevant ionic concentrations. To better understand the interaction between the pore surface charge and the mobile ions, both single salts and salt mixtures have been considered. We have paid attention to the effects on the conductance of the cation valency, the pore charge asymmetry, and the pore charge inversion phenomena due to trivalent ions, both in single salts and salt mixtures. In addition, we have described how small concentrations of multivalent ions can tune the nanopore conductance due to monovalent majority ions, together with the effect of these charges on the additivity of ionic conductance and fluoride-induced negative differential conductance phenomena. This compilation and discussion of previously presented experimental data offers significant insights on the interaction between fixed and mobile charges confined in nanoscale volumes and should be useful in establishing and checking new models for describing ionic transport in the vicinity of charged surfaces.

Tromboembolia pulmonar e infarto de miocardio embólico en paciente con trombo en tránsito a través de foramen oval permeable / Pulmonary embolism and embolic myocardial infarction in a patient with thrombi in transit through a patent foramen ovale

Resumen Se presenta el caso de una paciente ingresada por cuadro clínico de infarto agudo de miocardio con elevación del segmento ST. Tras la realización de una coronariografía emergente en la que se evidencia un trombo en la arteria coronaria derecha, sin objetivar lesiones ateroscleróticas, es diagnosticada de infarto de probable origen embólico. Tras realizar un ecocardiograma transtorácico, se detecta la presencia de trombos en las cavidades derechas e izquierdas del corazón. Por ello se realiza angiografía por tomografía computarizada con protocolo de embolia pulmonar, que confirma la presencia de embolia pulmonar bilateral masiva. Tras esto, se repitió el ecocardiograma transtorácico, hallándose un aneurisma del septo interauricular, con aparente protrusión de una masa trombótica a través de él. Se inició terapia anticoagulante con buena evolución por parte de la paciente, habiendo desaparecido los trombos en el ecocardiograma con test de burbujas que se realizó días después, en el que se demostró la presencia de un foramen oval permeable. Con la presentación de este caso se pretende, en primer lugar, ilustrar una afección que en contadas ocasiones se puede objetivar mediante prueba de imagen, y en segundo lugar, hacer una breve revisión del diagnóstico y el manejo del foramen oval permeable como parte del estudio de fuente embólica.

Abstract The authors describe a case of a patient admitted with ST elevation myocardial infarction. An emergent coronariography was done, showing a thrombus in the right coronary artery, without evidence of atherosclerotic lesions in the coronary bed. Due to this, she is diagnosed with probable embolic myocardial infarction. When she was performed a transthoracic echocardiography, the presence of free thrombi was detected in right and left chambers of the heart. Due to this, a CT angiography with pulmonary embolism protocol was done, confirming the presence of a massive bilateral pulmonary embolism. After that, a new trans-thoracic echocardiography was done, finding an aneurism at interatrial septum, with an apparent protrusion of thrombotic mass through it. The decision taken was initiating therapeutic anticoagulation, having the patient a positive evolution with disappearance of thrombi in the bubble test performed days later, and showing the presence of a patent foramen ovale. The purpose of the presentation of this case report is, firstly, illustrating an entity which in very few occasions can be demonstrated by imaging tests, and secondly, making a brief review of the diagnosis and management of the patent foramen ovale as a part of the study of embolic sources.

Fluoride-Induced Negative Differential Resistance in Nanopores: Experimental and Theoretical Characterization.

We describe experimentally and theoretically the fluoride-induced negative differential resistance (NDR) phenomena observed in conical nanopores operating in aqueous electrolyte solutions. The threshold voltage switching occurs around 1 V and leads to sharp current drops in the nA range with a peak-to-valley ratio close to 10. The experimental characterization of the NDR effect with single pore and multipore samples concern different pore radii, charge concentrations, scan rates, salt concentrations, solvents, and cations. The experimental fact that the effective radius of the pore tip zone is of the same order of magnitude as the Debye length for the low salt concentrations used here is suggestive of a mixed pore surface and bulk conduction regime. Thus, we propose a two-region conductance model where the mobile cations in the vicinity of the negative pore charges are responsible for the surface conductance, while the bulk solution conductance is assumed for the pore center region.

Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate.

Electric potential distributions can act as instructive pre-patterns for development, regeneration, and tumorigenesis in cell systems. The biophysical states influence transcription, proliferation, cell shape, migration, and differentiation through biochemical and biomechanical downstream transduction processes. A major knowledge gap is the origin of spatial patterns in vivo, and their relationship to the ion channels and the electrical synapses known as gap junctions. Understanding this is critical for basic evolutionary developmental biology as well as for regenerative medicine. We computationally show that cells may express connexin proteins with different voltage-gated gap junction conductances as a way to maintain multicellular regions at distinct membrane potentials. We show that increasing the multicellular connectivity via enhanced junction function does not always contribute to the bioelectrical normalization of abnormally depolarized multicellular patches. From a purely electrical junction view, this result suggests that the reduction rather than the increase of specific connexin levels can also be a suitable bioelectrical approach in some cases and time stages. We offer a minimum model that incorporates effective conductances ultimately related to specific ion channel and junction proteins that are amenable to external regulation. We suggest that the bioelectrical patterns and their encoded instructive information can be externally modulated by acting on the mean fields of cell systems, a complementary approach to that of acting on the molecular characteristics of individual cells. We believe that despite the limitations of a biophysically focused model, our approach can offer useful qualitative insights into the collective dynamics of cell system bioelectricity.

Morphology changes induced by intercellular gap junction blocking: A reaction-diffusion mechanism.

Complex anatomical form is regulated in part by endogenous physiological communication between cells; however, the dynamics by which gap junctional (GJ) states across tissues regulate morphology are still poorly understood. We employed a biophysical modeling approach combining different signaling molecules (morphogens) to qualitatively describe the anteroposterior and lateral morphology changes in model multicellular systems due to intercellular GJ blockade. The model is based on two assumptions for blocking-induced patterning: (i) the local concentrations of two small antagonistic morphogens diffusing through the GJs along the axial direction, together with that of an independent, uncoupled morphogen concentration along an orthogonal direction, constitute the instructive patterns that modulate the morphological outcomes, and (ii) the addition of an external agent partially blocks the intercellular GJs between neighboring cells and modifies thus the establishment of these patterns. As an illustrative example, we study how the different connectivity and morphogen patterns obtained in presence of a GJ blocker can give rise to novel head morphologies in regenerating planaria. We note that the ability of GJs to regulate the permeability of morphogens post-translationally suggests a mechanism by which different anatomies can be produced from the same genome without the modification of gene-regulatory networks. Conceptually, our model biosystem constitutes a reaction-diffusion information processing mechanism that allows reprogramming of biological morphologies through the external manipulation of the intercellular GJs and the resulting changes in instructive biochemical signals.

Cardiac tamponade secondary to leptospirosis. A rare association: A case report.

Herein is described the case of a 39-year-old female agronomist who was admitted to hospital after a syncopal episode. She had had fever, abdominal pain, nausea, and vomiting for the previous month. The patient showed signs of hypoperfusion, so a trans-thoracic echocardiography was done, demonstrating the presence of a cardiac tamponade. An emergency pericardiocentesis was performed, draining 500 ml of hematic content. Thoracic-abdominal computed tomography showed bilateral pleural effusion and also peritoneal effusion. Laboratory tests were compatible with an inflammatory situation with neutrophilic leukocytosis, alteration of hepatic function, and a plateau elevation of high-sensitivity troponin T. Colchicine was initiated but the evolution of the patient was torpid, making necessary the performance of a pericardial window due to an abrupt increase of pericardial effusion and echocardiographic signs of impending cardiac tamponade. Two chest tubes were inserted due to an increasing bilateral pleural effusion. Serology was positive for Leptospira spp. so doxycycline was initiated. She reported that she had inspected a rice-field the previous month. The patient presented a good response to the treatment, being discharged from hospital completely asymptomatic, with no pericardial effusion and practically resolved pleural effusions. She was evaluated again one month later, with no trace of effusions or symptoms. .