Environment Constrains Fitness Advantages of Division of Labor in Microbial Consortia Engineered for Metabolite Push or Pull Interactions.

Fitness benefits from division of labor are well documented in microbial consortia, but the dependency of the benefits on environmental context is poorly understood. Two synthetic Escherichia coli consortia were built to test the relationships between exchanged organic acid, local environment, and opportunity costs of different metabolic strategies. Opportunity costs quantify benefits not realized due to selecting one phenotype over another. The consortia catabolized glucose and exchanged either acetic or lactic acid to create producer-consumer food webs. The organic acids had different inhibitory properties and different opportunity costs associated with their positions in central metabolism. The exchanged metabolites modulated different consortial dynamics. The acetic acid-exchanging (AAE) consortium had a "push" interaction motif where acetic acid was secreted faster by the producer than the consumer imported it, while the lactic acid-exchanging (LAE) consortium had a "pull" interaction motif where the consumer imported lactic acid at a comparable rate to its production. The LAE consortium outperformed wild-type (WT) batch cultures under the environmental context of weakly buffered conditions, achieving a 55% increase in biomass titer, a 51% increase in biomass per proton yield, an 86% increase in substrate conversion, and the complete elimination of by-product accumulation all relative to the WT. However, the LAE consortium had the trade-off of a 42% lower specific growth rate. The AAE consortium did not outperform the WT in any considered performance metric. Performance advantages of the LAE consortium were sensitive to environment; increasing the medium buffering capacity negated the performance advantages compared to WT. IMPORTANCE Most naturally occurring microorganisms persist in consortia where metabolic interactions are common and often essential to ecosystem function. This study uses synthetic ecology to test how different cellular interaction motifs influence performance properties of consortia. Environmental context ultimately controlled the division of labor performance as shifts from weakly buffered to highly buffered conditions negated the benefits of the strategy. Understanding the limits of division of labor advances our understanding of natural community functioning, which is central to nutrient cycling and provides design rules for assembling consortia used in applied bioprocessing.

Quantitative analysis of macroscopic solute transport in the murine brain.

BACKGROUND: Understanding molecular transport in the brain is critical to care and prevention of neurological disease and injury. A key question is whether transport occurs primarily by diffusion, or also by convection or dispersion. Dynamic contrast-enhanced (DCE-MRI) experiments have long reported solute transport in the brain that appears to be faster than diffusion alone, but this transport rate has not been quantified to a physically relevant value that can be compared to known diffusive rates of tracers. METHODS: In this work, DCE-MRI experimental data is analyzed using subject-specific finite-element models to quantify transport in different anatomical regions across the whole mouse brain. The set of regional effective diffusivities ([Formula: see text]), a transport parameter combining all mechanisms of transport, that best represent the experimental data are determined and compared to apparent diffusivity ([Formula: see text]), the known rate of diffusion through brain tissue, to draw conclusions about dominant transport mechanisms in each region. RESULTS: In the perivascular regions of major arteries, [Formula: see text] for gadoteridol (550 Da) was over 10,000 times greater than [Formula: see text]. In the brain tissue, constituting interstitial space and the perivascular space of smaller blood vessels, [Formula: see text] was 10-25 times greater than [Formula: see text]. CONCLUSIONS: The analysis concludes that convection is present throughout the brain. Convection is dominant in the perivascular space of major surface and branching arteries (Pe > 1000) and significant to large molecules (> 1 kDa) in the combined interstitial space and perivascular space of smaller vessels (not resolved by DCE-MRI). Importantly, this work supports perivascular convection along penetrating blood vessels.

Antimicrobial laser-activated sealants for combating surgical site infections.

Surgical-site infections (SSIs) occur in 2-5% of patients undergoing surgery in the US alone, impacting 300 000-500 000 lives each year, and presenting up to 11 times greater risk of death compared to patients without SSIs. The most common cause of SSI is Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) is the most common pathogen in community hospitals. Current clinical devices used for approximating incisions and traumatic lacerations include sutures, adhesives, tapes, or staples with or without antimicrobial incorporation. However, current closure technologies may not provide adequate protection against infection, are susceptible to wound dehiscence, and can result in delayed biomechanical recoveries. Laser-activated tissue repair is a sutureless technique in which chromophore-loaded sealants convert laser light energy to heat in order to induce rapid tissue sealing. Here, we describe the generation and evaluation of laser-activated sealant (LASE) biomaterials, in which, indocyanine green (ICG), an FDA-approved dye, was embedded in a silk fibroin matrix and cast into films as wound sealants. Silk-ICG films were subjected to different near-infrared (NIR) laser powers to identify temperatures optimal for laser sealing of soft tissues. A mathematical model was developed in order to determine the photothermal conversion efficiency of LASEs following laser irradiation. NIR laser activation of silk-ICG LASEs increased the recovery of skin biomechanical strength compared to sutured skin in full-thickness incisional wounds in immunocompetent mice, and live animal imaging indicated persistence of silk-ICG LASEs over several days. LASEs loaded with the antibiotic vancomycin demonstrated higher efficacies for combating MRSA infections in a mouse model of surgical site infection compared to antibacterial sutures. Our results demonstrate that LASEs can be loaded with antimicrobial drugs and may serve as new multifunctional biomaterials for rapid tissue sealing, repair and surgical site protection following surgery.

In response to "Is solute movement within the extracellular spaces of brain gray matter brought about primarily by diffusion or flow?"

In our work, "Analysis of Convective and Diffusive Transport in the Brain Interstitium", published in this journal (2019, 16:6), we estimate the interstitial superficial velocity by comparison of transport model simulations to published experimental Real-Time Iontophoresis (RTI) data. In the Discussion section, we calculate a value for perfusion rate, or volumetric flow rate per unit mass of tissue, from these fundamental results of superficial velocity. Drs. Hladky and Barrand have proposed an alternative method for choosing the surface area per volume used to calculate perfusion rate from superficial velocity, using our model domain. Their method seems reasonable to us, as does ours. Upon reflection, a range of volumetric flow per unit mass values should have been reported in our paper, 1-40 µL/min-g. The value calculated using Drs. Hladky and Barrand surface area is a likely upper-bound on this range and the value in the paper is a low estimate at the bottom of the range. We are confident in the estimates of interstitial velocity reported in our article, using the assumptions of the model. Peclet (Pe) numbers, which compare convective and diffusive transport rates for different molecules, were calculated using the superficial velocity estimates; and we continue to believe these values are correct along with all other major results and conclusions presented in the paper.

Analysis of convective and diffusive transport in the brain interstitium.

BACKGROUND: Despite advances in in vivo imaging and experimental techniques, the nature of transport mechanisms in the brain remain elusive. Mathematical modelling verified using available experimental data offers a powerful tool for investigating hypotheses regarding extracellular transport of molecules in brain tissue. Here we describe a tool developed to aid in investigation of interstitial transport mechanisms, especially the potential for convection (or bulk flow) and its relevance to interstitial solute transport, for which there is conflicting evidence. METHODS: In this work, we compare a large body of published experimental data for transport in the brain to simulations of purely diffusive transport and simulations of combined convective and diffusive transport in the brain interstitium, incorporating current theories of perivascular influx and efflux. RESULTS: The simulations show (1) convective flow in the interstitium potentially of a similar magnitude to diffusive transport for molecules of interest and (2) exchange between the interstitium and perivascular space, whereby fluid and solutes may enter or exit the interstitium, are consistent with the experimental data. Simulations provide an upper limit for superficial convective velocity magnitude (approximately [Formula: see text] = 50 µm min-1), a useful finding for researchers developing techniques to measure interstitial bulk flow. CONCLUSIONS: For the large molecules of interest in neuropathology, bulk flow may be an important mechanism of interstitial transport. Further work is warranted to investigate the potential for bulk flow.

Competitive resource allocation to metabolic pathways contributes to overflow metabolisms and emergent properties in cross-feeding microbial consortia.

Resource scarcity is a common stress in nature and has a major impact on microbial physiology. This review highlights microbial acclimations to resource scarcity, focusing on resource investment strategies for chemoheterotrophs from the molecular level to the pathway level. Competitive resource allocation strategies often lead to a phenotype known as overflow metabolism; the resulting overflow byproducts can stabilize cooperative interactions in microbial communities and can lead to cross-feeding consortia. These consortia can exhibit emergent properties such as enhanced resource usage and biomass productivity. The literature distilled here draws parallels between in silico and laboratory studies and ties them together with ecological theories to better understand microbial stress responses and mutualistic consortia functioning.

Effects of Spatial Localization on Microbial Consortia Growth.

Microbial consortia are commonly observed in natural and synthetic systems, and these consortia frequently result in higher biomass production relative to monocultures. The focus here is on the impact of initial spatial localization and substrate diffusivity on the growth of a model microbial consortium consisting of a producer strain that consumes glucose and produces acetate and a scavenger strain that consumes the acetate. The mathematical model is based on an individual cell model where growth is described by Monod kinetics, and substrate transport is described by a continuum-based, non-equilibrium reaction-diffusion model where convective transport is negligible (e.g., in a biofilm). The first set of results focus on a single producer cell at the center of the domain and surrounded by an initial population of scavenger cells. The impact of the initial population density and substrate diffusivity is examined. A transition is observed from the highest initial density resulting in the greatest cell growth to cell growth being independent of initial density. A high initial density minimizes diffusive transport time and is typically expected to result in the highest growth, but this expected behavior is not predicted in environments with lower diffusivity or larger length scales. When the producer cells are placed on the bottom of the domain with the scavenger cells above in a layered biofilm arrangement, a similar critical transition is observed. For the highest diffusivity values examined, a thin, dense initial scavenger layer is optimal for cell growth. However, for smaller diffusivity values, a thicker, less dense initial scavenger layer provides maximal growth. The overall conclusion is that high density clustering of members of a food chain is optimal under most common transport conditions, but under some slow transport conditions, high density clustering may not be optimal for microbial growth.

Combining existing numerical models with data assimilation using weighted least-squares finite element methods.

A new approach has been developed for combining and enhancing the results from an existing computational fluid dynamics model with experimental data using the weighted least-squares finite element method (WLSFEM). Development of the approach was motivated by the existence of both limited experimental blood velocity in the left ventricle and inexact numerical models of the same flow. Limitations of the experimental data include measurement noise and having data only along a two-dimensional plane. Most numerical modeling approaches do not provide the flexibility to assimilate noisy experimental data. We previously developed an approach that could assimilate experimental data into the process of numerically solving the Navier-Stokes equations, but the approach was limited because it required the use of specific finite element methods for solving all model equations and did not support alternative numerical approximation methods. The new approach presented here allows virtually any numerical method to be used for approximately solving the Navier-Stokes equations, and then the WLSFEM is used to combine the experimental data with the numerical solution of the model equations in a final step. The approach dynamically adjusts the influence of the experimental data on the numerical solution so that more accurate data are more closely matched by the final solution and less accurate data are not closely matched. The new approach is demonstrated on different test problems and provides significantly reduced computational costs compared with many previous methods for data assimilation. Copyright © 2016 John Wiley & Sons, Ltd.

Simulation of nanoparticle transport in airways using Petrov-Galerkin finite element methods.

The transport and deposition properties of nanoparticles with a range of aerodynamic diameters ( 1 nm ≤ d ≤ 150 nm) were studied for the human airways. A finite element code was developed that solved both the Navier-Stokes and advection-diffusion equations monolithically. When modeling nanoparticle transport in the airways, the finite element method becomes unstable, and, in order resolve this issue, various stabilization methods were considered in terms of accuracy and computational cost. The stabilization methods considered here include the streamline upwind, streamline upwind Petrov-Galerkin, and Galerkin least squares approaches. In order to compare the various stabilization approaches, the approximate solution from each stabilization approach was compared to the analytical Graetz solution, which is a model for monodispersed, dilute particle transport in a straight cylinder. The optimal stabilization method, especially with regard to accuracy, was found to be the Galerkin least squares approach for the Graetz problem when the Péclet number was larger than 10(4). In the human airways geometry, the Galerkin least squares stabilization approach once more provided the most accurate approximate solution for particles with an aerodynamic diameter of 10 nm or larger, but mesh size had a much greater effect on accuracy than the choice of stabilization method. The choice of stabilization method had a greater impact than mesh size for particles with an aerodynamic diameter 10 nm or smaller, but the most accurate stabilization method was streamline upwind Petrov-Galerkin in these cases.

Left ventricular flow analysis: recent advances in numerical methods and applications in cardiac ultrasound.

The left ventricle (LV) pumps oxygenated blood from the lungs to the rest of the body through systemic circulation. The efficiency of such a pumping function is dependent on blood flow within the LV chamber. It is therefore crucial to accurately characterize LV hemodynamics. Improved understanding of LV hemodynamics is expected to provide important clinical diagnostic and prognostic information. We review the recent advances in numerical and experimental methods for characterizing LV flows and focus on analysis of intraventricular flow fields by echocardiographic particle image velocimetry (echo-PIV), due to its potential for broad and practical utility. Future research directions to advance patient-specific LV simulations include development of methods capable of resolving heart valves, higher temporal resolution, automated generation of three-dimensional (3D) geometry, and incorporating actual flow measurements into the numerical solution of the 3D cardiovascular fluid dynamics.

A model of filiform hair distribution on the cricket cercus.

Crickets and other orthopteran insects sense air currents with a pair of abdominal appendages resembling antennae, called cerci. Each cercus in the common house cricket Acheta domesticus is covered with between 500 to 750 filiform mechanosensory hairs. The distribution of the hairs on the cerci, as well as the global patterns of their movement axes, are very stereotypical across different animals in this species, and the development of this system has been studied extensively. Although hypotheses regarding the mechanisms underlying pattern development of the hair array have been proposed in previous studies, no quantitative modeling studies have been published that test these hypotheses. We demonstrate that several aspects of the global pattern of mechanosensory hairs can be predicted with considerable accuracy using a simple model based on two independent morphogen systems. One system constrains inter-hair spacing, and the second system determines the directional movement axes of the hairs.

Effect of model selection on prediction of periodic behavior in gene regulatory networks.

One of the current challenges for cell biology is understanding of the system level cellular behavior from the knowledge of a network of the individual subcellular agents. We address a question of how the model selection affects the predicted dynamic behavior of a gene network. In particular, for a fixed network structure, we compare protein-only models with models in which each transcriptional activation is represented both by mRNA and protein concentrations. We compare linear behavior near equilibria for both cyclic feedback systems and a general system. We show that, in general, explicit inclusion of the mRNA in the model weakens the stability of equilibria. We also study numerically dynamics of a particular gene network and show significant differences in global dynamics between the two types of models.

Weighted least-squares finite element method for cardiac blood flow simulation with echocardiographic data.

As both fluid flow measurement techniques and computer simulation methods continue to improve, there is a growing need for numerical simulation approaches that can assimilate experimental data into the simulation in a flexible and mathematically consistent manner. The problem of interest here is the simulation of blood flow in the left ventricle with the assimilation of experimental data provided by ultrasound imaging of microbubbles in the blood. The weighted least-squares finite element method is used because it allows data to be assimilated in a very flexible manner so that accurate measurements are more closely matched with the numerical solution than less accurate data. This approach is applied to two different test problems: a flexible flap that is displaced by a jet of fluid and blood flow in the porcine left ventricle. By adjusting how closely the simulation matches the experimental data, one can observe potential inaccuracies in the model because the simulation without experimental data differs significantly from the simulation with the data. Additionally, the assimilation of experimental data can help the simulation capture certain small effects that are present in the experiment, but not modeled directly in the simulation.

Quantitative characterization of the filiform mechanosensory hair array on the cricket cercus.

BACKGROUND: Crickets and other orthopteran insects sense air currents with a pair of abdominal appendages resembling antennae, called cerci. Each cercus in the common house cricket Acheta domesticus is approximately 1 cm long, and is covered with 500 to 750 filiform mechanosensory hairs. The distribution of the hairs on the cerci, as well as the global patterns of their movement vectors, have been characterized semi-quantitatively in studies over the last 40 years, and have been shown to be very stereotypical across different animals in this species. Although the cercal sensory system has been the focus of many studies in the areas of neuroethology, development, biomechanics, sensory function and neural coding, there has not yet been a quantitative study of the functional morphology of the receptor array of this important model system. METHODOLOGY/PRINCIPAL FINDINGS: We present a quantitative characterization of the structural characteristics and functional morphology of the cercal filiform hair array. We demonstrate that the excitatory direction along each hair's movement plane can be identified by features of its socket that are visible at the light-microscopic level, and that the length of the hair associated with each socket can also be estimated accurately from a structural parameter of the socket. We characterize the length and directionality of all hairs on the basal half of a sample of three cerci, and present statistical analyses of the distributions. CONCLUSIONS/SIGNIFICANCE: The inter-animal variation of several global organizational features is low, consistent with constraints imposed by functional effectiveness and/or developmental processes. Contrary to previous reports, however, we show that the filiform hairs are not re-identifiable in the strict sense.

Particle transport modeling in pulmonary airways with high-order elements.

Inhaled particles can be either harmful (e.g., smoke, exhaust, viruses) or beneficial (e.g., a therapeutic drug). The accurate and computationally efficient simulation of particle transport and deposition remains a challenge because it requires the simultaneous solution of the Navier-Stokes equations and multiple advection-diffusion mass transport equations when the particles are modeled as multiple mono-dispersed populations. The solution of these equations requires that multiple length scales be resolved since the ratio of advection to diffusion varies among the different equations. Here, the spectral element method is examined because the high-order approximation provides greater flexibility in resolving multiple length scales. The problem geometry is based on the Weibel model A of the human airway for convergence tests and the first three generations of a typical rat airway for experimental validation. Particles in the size range 1 to 100 nm are simulated for deposition results. The particle concentration and flux were determined using meshes of varying coarseness to represent the geometry along with basis polynomials of order 5 to 11. The higher-order elements accurately propagate the short wavelengths contained in the advection-diffusion solution without sacrificing efficiency for the more computationally expensive Navier-Stokes solution. As the diffusion coefficient in the advection-diffusion equation decreases (i.e., particle size increases) the advantages of the spectral elements become apparent for the coupled system.

Flow velocity vector fields by ultrasound particle imaging velocimetry: in vitro comparison with optical flow velocimetry.

OBJECTIVES: We performed an in vitro study to assess the precision and accuracy of particle imaging velocimetry (PIV) data acquired using a clinically available portable ultrasound system via comparison with stereo optical PIV. METHODS: The performance of ultrasound PIV was compared with optical PIV on a benchmark problem involving vortical flow with a substantial out-of-plane velocity component. Optical PIV is capable of stereo image acquisition, thus measuring out-of-plane velocity components. This allowed us to quantify the accuracy of ultrasound PIV, which is limited to in-plane acquisition. The system performance was assessed by considering the instantaneous velocity fields without extracting velocity profiles by spatial averaging. RESULTS: Within the 2-dimensional correlation window, using 7 time-averaged frames, the vector fields were found to have correlations of 0.867 in the direction along the ultrasound beam and 0.738 in the perpendicular direction. Out-of-plane motion of greater than 20% of the in-plane vector magnitude was found to increase the SD by 11% for the vectors parallel to the ultrasound beam direction and 8.6% for the vectors perpendicular to the beam. CONCLUSIONS: The results show a close correlation and agreement of individual velocity vectors generated by ultrasound PIV compared with optical PIV. Most of the measurement distortions were caused by out-of-plane velocity components.

Impact of pericardial adhesions on diastolic function as assessed by vortex formation time, a parameter of transmitral flow efficiency.

BACKGROUND: Pericardial adhesions are a pathophysiological marker of constrictive pericarditis (CP), which impairs cardiac filling by limiting the total cardiac volume compliance and diastolic filling function. We studied diastolic transmitral flow efficiency as a new parameter of filling function in a pericardial adhesion animal model. We hypothesized that vortex formation time (VFT), an index of optimal efficient diastolic transmitral flow, is altered by patchy pericardial-epicardial adhesions. METHODS: In 8 open-chest pigs, the heart was exposed while preserving the pericardium. We experimentally simulated early pericardial constriction and patchy adhesions by instilling instant glue into the pericardial space and using pericardial-epicardial stitches. We studied left ventricular (LV) function and characterized intraventricular blood flow with conventional and Doppler echocardiography at baseline and following the experimental intervention. RESULTS: Significant decreases in end-diastolic volume, ejection fraction, stroke volume, and late diastolic filling velocity reflected the effects of the pericardial adhesions. The mean VFT value decreased from 3.61 ± 0.47 to 2.26 ± 0.45 (P = 0.0002). Hemodynamic variables indicated the inhibiting effect of pericardial adhesion on both contraction (decrease in systolic blood pressure and +dP/dt decreased) and relaxation (decrease in the magnitude of -dP/dt and prolongation of Tau) function. CONCLUSION: Patchy pericardial adhesions not only negatively impact LV mechanical functioning but the decrease of VFT from normal to suboptimal value suggests impairment of transmitral flow efficiency.

Spatiotemporal temperature distribution and cancer cell death in response to extracellular hyperthermia induced by gold nanorods.

Plasmonic nanoparticles have shown promise in hyperthermic cancer therapy, both in vitro and in vivo. Previous reports have described hyperthermic ablation using targeted and nontargeted nanoparticles internalized by cancer cells, but most reports do not describe a theoretical analysis for determining optimal parameters. The focus of the current research was first to evaluate the spatiotemporal temperature distribution and cell death induced by extracellular hyperthermia in which gold nanorods (GNRs) were maintained in the dispersion outside human prostate cancer cells. The nanorod dispersion was irradiated with near-infrared (NIR) laser, and the spatiotemporal distribution of temperature was determined experimentally. This information was employed to develop and validate theoretical models of spatiotemporal temperature profiles for gold nanorod dispersions undergoing laser irradiation and the impact of the resulting heat generation on the viability of human prostate cancer cells. A cell injury/death model was then coupled to the heat transfer model to predict spatial and temporal variations in cell death and injury. The model predictions agreed well with experimental measurements of both temperature and cell death profiles. Finally, the model was extended to examine the impact of selective binding of gold nanorods to cancer cells compared to nonmalignant cells, coupled with a small change in cell injury activation energy. The impact of these relatively minor changes results in a dramatic change in the overall cell death rate. Taken together, extracellular hyperthermia using gold nanorods is a promising strategy, and tailoring the cellular binding efficacy of nanorods can result in varying therapeutic efficacies using this approach.

Revisiting the simplified bernoulli equation.

BACKGROUND: The assessment of the severity of aortic valve stenosis is done by either invasive catheterization or non-invasive Doppler Echocardiography in conjunction with the simplified Bernoulli equation. The catheter measurement is generally considered more accurate, but the procedure is also more likely to have dangerous complications. OBJECTIVE: The focus here is on examining computational fluid dynamics as an alternative method for analyzing the echo data and determining whether it can provide results similar to the catheter measurement. METHODS: An in vitro heart model with a rigid orifice is used as a first step in comparing echocardiographic data, which uses the simplified Bernoulli equation, catheterization, and echocardiographic data, which uses computational fluid dynamics (i.e., the Navier-Stokes equations). RESULTS: For a 0.93cm(2) orifice, the maximum pressure gradient predicted by either the simplified Bernoulli equation or computational fluid dynamics was not significantly different from the experimental catheter measurement (p > 0.01). For a smaller 0.52cm(2) orifice, there was a small but significant difference (p < 0.01) between the simplified Bernoulli equation and the computational fluid dynamics simulation, with the computational fluid dynamics simulation giving better agreement with experimental data for some turbulence models. CONCLUSION: For this simplified, in vitro system, the use of computational fluid dynamics provides an improvement over the simplified Bernoulli equation with the biggest improvement being seen at higher valvular stenosis levels.

Increase in the late diastolic filling force is associated with impaired transmitral flow efficiency in acute moderate elevation of left ventricular afterload.

OBJECTIVE: Analysis of intraventricular flow force and efficiency is a novel concept of quantitatively assessing left ventricular (LV) hemodynamic performance. We have parametrically characterized diastolic filling flow by early inflow force, late inflow force, and total inflow force and by vortex formation time (VFT), a fundamental parameter of fluid transport efficiency. The purpose of this study was to determine what changes in inflow forces characterize a decrease in diastolic blood transport efficiency in acute moderate elevation of LV afterload. METHODS: In 8 open-chested pigs, the flow force and VFT parameters were calculated from conventional and flow Doppler echocardiographic measurements at baseline and during a brief (3-minute) moderate elevation of afterload induced by increasing the systolic blood pressure to 130% of the baseline value. RESULTS: Systolic LV function decreased significantly during elevated afterload. Early inflow force did not significantly change, whereas late inflow force increased from 5,822.09 +/- 1,656.5 (mean +/- SD) to 13,948.25 +/- 9,773.96 dyne (P = .049), and total inflow force increased from 13,783.35 +/- 4,816.58 to 21,836.67 +/- 8,635.33 dyne (P = .031). Vortex formation time decreased from 4.09 +/- 0.29 to 2.79 +/- 1.1 (P = .0068), confirming suboptimal flow transport efficiency. CONCLUSIONS: Even a brief moderate increase of LV afterload causes a significant increase in late diastolic filling force and impairs transmitral flow efficiency.