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Convergence of posterior semicircular canal and saccular inputs in single vestibular nuclei neurons in cats.

Convergence between posterior canal (PC) and saccular (SAC) inputs in single vestibular nuclei neurons was investigated in decerebrated cats. Postsynaptic potentials were recorded intracellularly after selective stimulation of the SAC and PC nerves. Stimulation of either the SAC or PC nerve orthodromically activated 143 vestibular nuclei neurons. Of these, 61 (43%) were antidromically activated by stimulation of the C1-C2 junction, 14 (10%) were antidromically activated by stimulation of the oculomotor or trochlear nucleus, and 14 (10%) were antidromically activated by stimulation of both the oculomotor or trochlear nucleus and the spinal cord. Fifty-four (38%) neurons were not activated by stimulation of either or both. We named these neurons vestibulospinal (VS), vestibulo-ocular (VO), vestibulooculo-spinal (VOS) and vestibular (V) neurons, respectively. Both PC and SAC inputs converged in 47 vestibular nuclei neurons (26 VS, 2 VO, 6 VOS and 13 V neurons). Of these, 19 received monosynaptic excitatory inputs from both nerves. This input pattern was frequently seen in VS neurons. Approximately half of the convergent VS neurons descended to the spinal cord through the lateral vestibulospinal tract. The remaining half and all the convergent VOS neurons descended to the spinal cord through the medial vestibulospinal tract. Most of the convergent neurons were located in the lateral nucleus or descending nucleus.

Animals↗

Quantification of tricuspid regurgitation by means of the proximal flow convergence method: a clinical study.

Quantitation of valvular regurgitation remains an important goal in clinical cardiology. It has been described previously that with the use of color Doppler flow mapping, simple measurements of apparent jet size do not correlate closely with quantitative regurgitant indices. Recently the proximal flow convergence method has been proposed to quantify valvular regurgitation by analysis of the converging flow field proximal to a regurgitant lesion. Assuming hemispherical convergence, flow rate Q can be calculated as Q = 2 pi r2va, where va is the aliasing velocity at a distance r from the orifice. For maximal accuracy, previously validated correction factors must be used to account for the flattening effect of the isovelocity contours close to the orifice and for the actual sector angle subtended by the valve leaflets (alpha), to yield a flow rate formula Q = 2 pi r2va.(vp/vp - va).(alpha/180), where vp is the orifice velocity obtained by continuous wave Doppler. In 45 patients (35 in sinus rhythm, 10 with atrial fibrillation) with tricuspid regurgitation, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated using the proximal flow convergence method and were compared with values obtained by the Doppler two-dimensional echocardiographic method. Regurgitant stroke volumes (SV) calculated by the proximal flow convergence method correlated very closely with values obtained by the Doppler two-dimensional method with r = 0.95 (y = 0.94x + 0.99) and delta SV = -0.3 +/- 5.2 cm3. Regurgitant flow rates (Q) calculated by both methods showed a similar correlation: r = 0.96 (y = 0.97x + 45) and delta Q = 1.6 +/- 429 cm3/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Color flow Doppler determination of transmitral flow and orifice area in mitral stenosis: experimental evaluation of the proximal flow-convergence method.

To evaluate the in vivo accuracy of color Doppler flow-convergence methods for determining transmitral flow volumes and effective orifice areas in mitral stenosis, we studied two models for flow-convergence surface geometry, a hemispheric (HS) model and an oblate hemispheroid (OH) model in a chronic animal model with quantifiable mitral flows. Color Doppler flow mapping of the proximal flow-convergence region has been reported to be useful for evaluation of intracardiac flows. Flow-convergence methods in patients with mitral stenosis that use HS assumption for the isovelocity surface have resulted in underestimation of actual flows. Chronic mitral stenosis was created surgically in six sheep with annuloplasty rings (group 1) and 11 sheep with bioprosthetic porcine valves (group 2). Hemodynamic and echocardiographic/Doppler studies (n = 18 in group 1; n = 21 in group 2) were performed 20 to 34 weeks later. Left ventricular inflow obstruction was of varied severity, with mean transmitral valve gradients in group 1 ranging from 1.3 to 18 mm Hg and in group 2 ranging from 6.3 to 25.6 mm Hg. Although transmitral flows derived by both geometric flow convergence models showed significant correlations with reference cardiac outputs, the correlations for the OH model were better than those for the HS model (group 1, r = 0.86 for the OH model vs r = 0.72 for the HS model; group 2; r = 0.84 for the OH model vs r = 0.62 for the HS model). The OH model was also superior to the HS model in determining effective orifice areas compared to reference orifice areas determined by postmortem planimetry of anatomic orifices (group 1 only, r = 0.64 for OH vs 0.58 for HS), by the Gorlin and Gorlin formula (group 1, r = 0.63 for OH vs 0.72 for HS; group 2, r = 0.82 for OH vs 0.76 for HS), and by the Doppler pressure half-time method (group 1, r = 0.76 for OH vs 0.69 for HS; group 2, r = 0.84 for OH vs 0.62 for HS).(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

Depression of activities of dorsal horn convergent neurones by propriospinal mechanisms triggered by noxious inputs; comparison with diffuse noxious inhibitory controls (DNIC).

The ability of heterotopic noxious stimuli to inhibit the activity of dorsal horn convergent neurones was investigated in both intact anesthetized, and spinal unanesthetized rats. Forty-four convergent neurones in lumbar dorsal horn were recognized by their ability to respond to both noxious and non-noxious natural stimuli and by their characteristic responses corresponding to A- and C-fibre activity following electrical stimulation of their cutaneous excitatory receptive fields on the ipsilateral hindpaw. The application of a sustained pinch to the excitatory receptive field resulted in an initial phasic activation of the neurone, which adapted to a stable tonic level of activity (mean 31.8 +/- 2.2 spikes/s). The levels of activity produced in this fashion were not appreciably different between the two types of preparation. In the intact anesthetized rat, the tonic activity produced by the sustained pinch could be strongly depressed by noxious conditioning stimuli applied to various parts of the body for all 10 neurones studied: heating the tail or pinching the contralateral hindpaw, the tail or a forepaw during 30 s each resulted in comparable inhibitions which had mean values in the order of 80% and which were always marked by post-effects lasting for upwards of 30 s. These inhibitory effects have been called Diffuse Noxious Inhibitory Controls (DNIC). In the spinal unanesthetized rat, the tonic activity was depressed to some extent by the same conditioning stimuli, for only 16/34 neurones studied. By comparison with the intact animals these inhibitions were weak, adapted to base-line levels within 30 s and were more marked for conditioning stimuli applied to structures proximal (tail, contralateral hindpaw) to the excitatory receptive field than for stimuli applied more distally (forepaws). The differences between the inhibitions found in the intact and spinal preparations were subsequently confirmed in a series of experiments in which single convergent neurones were studied before and after the pharmacological blocking of the cervical spinal cord in anaesthetized rats. The results in the spinal preparations provide evidence for the existence of some propriospinal modulatory processes, triggered by the onset of noxious stimulation and acting on convergent neurones. These processes appear to be different from those mediating DNIC, which have been shown to involve supraspinal structures, to concern all convergent neurones, to be very potent and associated with long-lasting post-effects whether the conditioning noxious stimuli are applied to parts of the body proximal or distal to the excitatory receptive field.

Action Potentials↗

Electrophysiologic properties and nature of ventrolateral thalamic nucleus neurons reactive to converging inputs of paleo- and neocerebellar origin.

Acute experiments were carried out in chloralose-anesthetized, curarized, and artificially ventilated cats to investigate the consistency and functional characteristics of converging cerebellar nuclear (fastigial, interpositus, dentate nuclei) inputs to single neurons of the ventrolateral thalamic nucleus, and the nature (thalamocortical relay or interneuronal) of its convergent neuronal population responsive to stimulation of the cerebellar nuclei. From unitary analysis of both extra- and juxtacellular recordings, we conclude that convergence of paleo- and neocerebellar impulses on thalamic ventrolateral neurons occurs widely, and that both excitatory (mono- and polysynaptic) and inhibitory (di- and polysynaptic) effects are induced on the same neurons by cerebellar nuclei stimulation; these effects concern about 40% of the thalamic ventrolateral neuronal population tested using the extracellular recording technique and about 75% of the ventrolateral nucleus neurons tested using the juxtacellular recording; activation of neocerebellar nuclear outputs generates mainly excitatory and excitatory-inhibitory response patterns, whereas activation of the paleocerebellar nuclear outputs evokes predominantly inhibitory and excitatory-inhibitory response patterns; the convergent paleo- neocerebellar neurons are found commonly in the more anterior ventrolateral nucleus stereotaxic planes; and from the results obtained by stimulation of the somatomotor cortical areas, a large proportion of the ventrolateral nucleus convergent units consists of thalamocortical relay cells. The results have implications for a possible integration between posture and voluntary movements at the level of the thalamic relay nucleus of the cerebellar-cortical pathway, and an interaction between central feedback and peripheral feedback in the programming, execution, and correction of voluntary movements.

Animals↗

Three-dimensional reconstruction of color Doppler flow convergence regions and regurgitant jets: an in vitro quantitative study.

OBJECTIVES: This study sought to investigate the applicability of a current implementation of a three-dimensional echocardiographic reconstruction method for color Doppler flow convergence and regurgitant jet imaging. BACKGROUND: Evaluation of regurgitant flow events, such as flow convergences or regurgitant jets, using two-dimensional imaging ultrasound color flow Doppler systems may not be robust enough to characterize these spatially complex events. METHODS: We studied two in vitro models using steady flow to optimize results. In the first constant-flow model, two different orifices were each mounted to produce flow convergences and free jets--a circular orifice and a rectangular orifice with orifice area of 0.24 cm(2). In another flow model, steady flows through a circular orifice were directed toward a curved surrounding wall to produce wall adherent jets. Video composite data of color Doppler flow images from both free jet and wall jet models were reconstructed and analyzed after computer-controlled 180 degrees rotational acquisition using a TomTec computer. RESULTS: For the free jet model there was an excellent relation between actual flow rates and three-dimensional regurgitant jet volumes for both circular and rectangular orifices (r = 0.99 and r = 0.98, respectively). However, the rectangular orifice produced larger jet volumes than the circular orifice, even at the same flow rates (p < 0.0001). Calculated flow rates by the hemispheric model using one axial measurement of the flow convergence isovelocity surface from two-dimensional color flow images underestimated actual flow rate by 35% for the circular orifice and by 44% for the rectangular orifice, whereas a hemielliptic method implemented using three axial measurements of the flow convergence zone derived using three-dimensional reconstruction correlated well with and underestimated actual flow rate to a lesser degree (22% for the circular orifice, 32% for the rectangular orifice). In the wall jet model, the jets were flattened against and spread along the wall and had reduced regurgitant jet volumes compared with free jets (p < 0.01). CONCLUSIONS: Three-dimensional reconstruction of flow imaged by color Doppler may add quantitative spatial information to aid computation methods that have been used for evaluating valvular regurgitation, especially where they related to complex geometric flow events.

Echocardiography, Doppler, Color↗

Convergent evolution: the need to be explicit.

Convergence as a phenomenon in molecular evolution is an issue that confuses many discussions. Often the problem is that not enough care is taken to state exactly what kind of convergence one has in mind. Functional and mechanistic convergence are both common, and some structural convergence has probably occurred, but a convincing case for genuine sequence convergence has yet to be made.

Amino Acid Sequence↗

Integrin alpha5beta1 and fibronectin regulate polarized cell protrusions required for Xenopus convergence and extension.

BACKGROUND: Integrin recognition of fibronectin is required for normal gastrulation including the mediolateral cell intercalation behaviors that drive convergent extension and the elongation of the frog dorsal axis; however, the cellular and molecular mechanisms involved are unclear. RESULTS: We report that depletion of fibronectin with antisense morpholinos blocks both convergent extension and mediolateral protrusive behaviors in explant preparations. Both chronic depletion of fibronectin and acute disruptions of integrin alpha5beta1 binding to fibronectin increases the frequency and randomizes the orientation of polarized cellular protrusions, suggesting that integrin-fibronectin interactions normally repress frequent random protrusions in favor of fewer mediolaterally oriented ones. In the absence of integrin alpha5beta1 binding to fibronectin, convergence movements still occur but result in convergent thickening instead of convergent extension. CONCLUSIONS: These findings support a role for integrin signaling in regulating the protrusive activity that drives axial extension. We hypothesize that the planar spatial arrangement of the fibrillar fibronectin matrix, which delineates tissue compartments within the embryo, is critical for promoting productive oriented protrusions in intercalating cells.

Animals↗

Electrophoretic motion of a spherical particle in a converging-diverging nanotube.

A charged spherical particle is concentrically positioned in a converging-diverging nanotube filled with an electrolyte solution, resulting in an electric double layer (EDL) forming around the particle's surface. In the presence of an axially applied electric field, the particle electrophoretically migrates along the axis of the nanotube due to the electrostatic and hydrodynamic forces acting on the particle. In contrast to a cylindrical nanotube with a constant cross-sectional area in which the electric field is almost uniform, the presence of a converging-diverging section in a nanotube alters the electric field, perturbs the charge distribution, and induces a pressure gradient and a recirculating flow that affect the electrostatic and hydrodynamic forces acting on both the particle and the fluid. Depending on the magnitude of the surface charge density along the nanotube's wall, the particle's electrophoretic motion may be significantly accelerated as the particle transverses the converging-diverging section. A continuum model consisting of the Nernst-Planck, Poisson, and Navier-Stokes equations for the ionic concentrations, electric potential, and flow field is implemented to compute the particle's velocity as a function of the particle's size, the nanotube's geometry, surface charges, electric field intensity, bulk electrolyte concentration, and the particle's location. When the particle is negatively charged and the wall of the nanotube is uncharged, the particle migrates in the direction opposite to that of the applied electric field and the presence of the converging-diverging section significantly accelerates the particle's motion. This, however, is not always true when the nanotube's wall is charged with the same sign as that of the particle. Once the ratio of the surface charge density of the nanotube's wall to that of the particle exceeds a certain value, the negatively charged particle will not translocate through the tube toward the anode and does not attain the maximum velocity at the throat of the converging-diverging section. One can envision such a device to be a nanofilter that allows molecules with surface charge densities much higher than that of the wall to go through the nanofilter, while preventing molecules with surface charge densities lower than that of the wall from passing through the nanofilter. The induced recirculating flow may be used to enhance mixing and to stretch, fold, and trap molecules in nanofluidic detectors and reactors.

Journal Article↗

Convergence and global molecular epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc3 virulence locus: a population genomic analysis.

BACKGROUND: Klebsiella pneumoniae is an important pathogen of humans and animals. In the past five years, increasing reports of convergent strains that carry both virulence factors and antimicrobial resistance genes (ARGs) have raised serious public health concerns. The aim of this study is to describe the global diversity of plasmids carrying iuc3 (a key virulence factor in K pneumoniae associated with pigs and clinical isolates) from diverse settings, and their role in the emergence of convergent strains through hybridisation with plasmids carrying ARGs. METHODS: This population genomic analysis study was designed to describe both the global and local diversity of iuc3-carrying plasmids from diverse sources, and the co-occurrence of iuc3 with ARGs. We used all 4148 Klebsiella spp isolates from two large One-Health studies (SpARK, Italy, and OH-DART, Thailand), including 191 Klebsiella isolates from pigs, 635 from clinical isolates, 1040 from hospital and community carriage, and 2282 from other sources. Short-read sequencing of Klebsiella isolates was performed as part of the SpARK study. We sequenced Klebsiella isolates from the OH-DART (MicrobesNG, Birmingham, UK; HiSeq and NovaSeq, Illumina San Diego, CA, USA; GridION, Oxford Nanopore Technologies, Oxford, UK) and SpARK (MinION or GridION, Oxford Nanopore Technologies, Oxford, UK) studies. We also retrieved plasmid sequences carrying iuc3 from the National Centre for Biotechnology Information (NCBI). To ascertain the degree of diversity, evolutionary dynamics, and structuring across ecological and geographical axes, we detected ARGs and virulence loci, analysed clustering patterns and generated approximate maximum-likelihood phylogenetic trees. FINDINGS: We identified 48 K pneumoniae isolates with iuc3 in the SpARK data and 79 in the OH-DART data. Three (2&#xb7;4%) of these 127 isolates were from clinical sources, 73 (57&#xb7;5%) were from pig or pork meat. iuc3 isolates corresponded to multiple (n=47) host sequence types (STs), with ST35, ST45, ST881, ST25, and ST967 harbouring iuc3 in both datasets. We generated hybrid assemblies for 44 (SpARK) and 36 (OH-DART) isolates, plus a single iuc3 isolate from Germany. 53 (65&#xb7;4%) of these isolates were from pigs, three (3&#xb7;7%) from clinical sources, and 25 (30&#xb7;9%) from other sources. There were an additional 48 iuc3 positive isolates from our collections for which only short read data was available. A single iuc3-positive Klebsiella oxytoca isolate from a pig farm was detected in the SpARK data, which was also sequenced. We identified 330 iuc3-positive isolates and 58 iuc3-carrying plasmid assemblies from NCBI, of which 83 (21&#xb7;4%) were from clinical sources, 120 from pigs (30&#xb7;9%), and 185 (47&#xb7;7%) from other sources or of unknown provenance. These isolates were from K pneumoniae except two isolates of Klebsiella quasipneumoniae subsp similipneumoniae and one of Enterobacter hormaechei. The combined dataset of 517 iuc3 plasmids ranged in size from 110&#x2009;375 bp to 365&#x2009;580 bp and mostly corresponded to multiple IncFIB(K) and IncFII replicon types. We found seven convergent K pneumoniae plasmids in the Thai data: six from fresh markets and one from a neighbouring hospital. These plasmids emerged through the hybridisation of cocirculating iuc3 plasmids and plasmids encoding extended-spectrum &#x3b2;-lactamases (ESBLs), although none of these seven plasmids carried genes encoding carbapenemases. We also identified putative cocirculating parental plasmids carrying iuc3 and ESBL-encoding genes. Clustering and phylogenetic analysis resolved the iuc3 plasmid sequences into three groups, which were consistent using both complete plasmid sequences (n=139) and short-read data (n=517). In the complete plasmid sequence data, 66 strains contained group 1 plasmids, 38 strains contained group 2 plasmids, and 35 strains contained group 3 plasmids. Group 3 plasmids are mostly carried by isolates circulating in hospitals throughout Asia, with occasional examples in Europe and elsewhere, and carry multiple ARGs and potential virulence factors. By contrast, group 1 plasmids are commonly carried by porcine isolates in Europe, and group 2 are a heterogeneous mixture of geographical and ecological sources. INTERPRETATION: Plasmid hybridisation occurs frequently outside of the health-care environment and can lead to the convergence of resistance and virulence traits. Generating complete plasmid sequences from regional population-scale samples facilitates the identification of convergent plasmids and their putative parental plasmids. Three robust groups of iuc3 plasmids were resolved, which show both epidemiological and geographical differences; one of these groups was associated with clinical isolates in Asia and warrants targeted plasmid surveillance. FUNDING: UKRI, JPIAMR, Evolution Education Trust, and a Schlumberger Foundation Fellowship.

Plasmids↗

Evidence for senescent convergence during human aging.

'Senescent convergence' is the observation that, with advancing age, multiple measurements of organ/body size, chemistry or function, reveal values for the higher percentiles which decrease faster than those of the lower percentiles. That is, values of the extremes appear to be converging with advanced age. In some cases, the equations for describing this can be modified to include a term that accounts for the percentile of the observation. Examples were given of calculating the age at which values of 2 different percentiles, of the property being measured, become identical ('age at convergence'). Exceptions to senescent convergence, such as related to diseases like osteoporotic vertebral fractures, were mentioned. It was noted that the curves of senescent convergence resembled the inverse of those of postnatal growth.

Aging↗

Improved convergence and speed for the distance geometry program APA to determine protein structure.

The alternating projections algorithm (APA) is a program that is based on alternating projections and is designed to determine the three dimensional structure of proteins using distance geometry. The sampling and convergence properties of APA, as tested on bovine pancreatic trypsin inhibitor (BPTI) were previously reported in this journal. The results confirmed the program's earlier success with poly-L-alanine. However, the asymptotic convergence of the alternating projections was slow. We show that after good convergence is first obtained via alternating projections, that a weighted quadratic penalty function then produces the final conformation with better convergence in half the time required by the asymptotic convergence of alternating projections.

Algorithms↗

Food choices among newly married couples: convergence, conflict, individualism, and projects.

Individuals entering marriage merge their personal food systems to create a joint spousal food system. This investigation examined newly married couples' food choices. Qualitative interviews conducted with 20 couples as they entered marriage and again 1 year later revealed that some reported initial food homogamy, while others had varying degrees of compatibility in food preferences and tolerances. All couples reported some dietary convergence. Convergence was initially symmetrical (similar merging for both partners) or asymmetrical (one partner changed more), and sometimes convergence patterns evolved further. Unresolved food choice negotiations led to food conflicts. Prior food broadening experiences, initial dietary congruity, health/weight philosophies, foodwork, and commensal patterns were conditions shaping couples' food choice negotiations and dietary convergence patterns. Some food individualism persisted for most partners, helping to alleviate food choice conflicts. Food projects occurred when one partner was committed to molding the other's food choices. Overall, food choice negotiations involving both convergence and conflict were important components of marital adjustments that may have later health consequences.

Adult↗

Low doses of N-methyl-D-aspartate antagonists in superficial laminae of medulla oblongata facilitate wind-up of convergent neurones.

In this study, a trigeminal model was used in which high threshold C-fibre-evoked activities of convergent neurones located in the subnucleus oralis of the trigeminal complex are modulated through the superficial part, the substantia gelatinosa, of the subnucleus caudalis. The two subnuclei are located 3 mm apart, therefore, it was possible to inject dizocilpine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, into either the superficial or the deep parts of subnucleus caudalis without interfering with ongoing recording of convergent neurones in subnucleus oralis. A differential NMDA-dependent modulation of wind-up was observed according to the dose and the injection target. (1) The injections of small non-diffusible doses (0.12 microg) of dizocilpine into the superficial part of subnucleus caudalis facilitated wind-up. The effect peaked at 25 min with a mean increase above control of 173+/-31%. Injection (0.5 microg) of either the less active enantiomer dizocilpine or saline into superficial subnucleus caudalis had no significant effect on subnucleus oralis convergent neurones. This suggests that NMDA-dependent interneurones, probably located in substantia gelatinosa of subnucleus caudalis, exert, in normal conditions, an inhibitory control on wind-up of convergent subnucleus oralis neurones. (2) The injection of larger doses (0.5 microg) into the superficial part of subnucleus caudalis induced a predominant inhibitory effect on wind-up. The mean peak effect at 15 min was 46+/-7% compared to control (100%). Small and large doses of dizocilpine injected into the deep part of subnucleus caudalis had a predominant inhibitory effect. The inhibition of wind-up of subnucleus oralis neurones after injection of NMDA receptor antagonists in superficial or deep subnucleus caudalis indicates that wind-up may be due, at least in part, to NMDA activation at synapses that do not involve the recorded convergent neurones.

Animals↗

Effects of noxious hindpaw immersion on evoked and spontaneous firing of contralateral convergent dorsal horn neurons in both intact and spinalized rats.

The effects of immersing a hindpaw in 60 degrees C water for 15 s on spontaneous and pinch-evoked activity recorded from 77 convergent neurons in the contralateral lumbar enlargement were examined. Cells were recorded from intact rats anesthetized with either ketamine or pentobarbital, or in rats that were decerebrated-intact or decerebrated-spinalized to determine if the heterotopic modulation was altered under these different conditions. In 47 neurons with background firing, immersion of the contralateral hindpaw inhibited the on-going activity in 6 of 19 cells recorded from ketamine anesthetized rats, 4 of 12 from pentobarbital anesthetized rats, 7 of 12 from decerebrate-spinalized rats, and 0 of 4 from decerebrate-intact rats. However, this inhibition was variable, both between and within neurons, because not every convergent neuron was inhibited, and there were trials in which immersion had no effect on the on-going activity of a neuron that had been previously inhibited by identical stimulation. In all 77 neurons, across all groups, discharges evoked by pinching the ipsilateral hindpaw were unaffected by contralateral immersion, even in cells where on-going activity was inhibited. Immersion of a hindpaw inhibited on-going, but not evoked, activity of contralateral convergent neurons. This inhibition was observed in rats under varied anesthetic conditions and in spinalized and intact rats. However, not all convergent neurons were inhibited by the remote stimulation even in intact rats, an observation inconsistent with the DNIC model of supraspinally mediated heterotopic modulation. This indicates that the effect of remote noxious stimulation in intact animals is not, under every experimental condition, a widespread inhibition of all convergent neurons.

Animals↗

A comparison of flow convergence with other transthoracic echocardiographic indexes of prosthetic mitral regurgitation.

Prosthetic shadowing of the left atrium may prevent detection of mitral regurgitation during transthoracic echocardiography. In 60 patients with mitral valves, Carpentier-Edwards (n = 20), St. Jude (n = 22), and cage-ball (n = 18), we blindly evaluated the accuracy of three transthoracic Doppler signs of significant (> 2+) mitral regurgitation: (1) color Doppler flow convergence, (2) a color Doppler jet of significant regurgitation in the left atrium, and (3) an intense continuous wave Doppler signal. All 60 patients had transesophageal echocardiography, 26 had cardiac catheterization, and 28 had surgery. The sensitivity and specificity of flow convergence for significant regurgitation by transesophageal echocardiography was 73% and 70%, respectively, compared with 33% and 93% for left atrial color Doppler, and 15% and 97% for continuous wave Doppler. The sensitivity of flow convergence in Carpentier-Edwards, St. Jude, and cage-ball valves was 80%, 73%, and 67%, respectively; whereas the sensitivity of left atrial color Doppler was 70%, 27%, and 0%, and the sensitivity of continuous wave Doppler was 33%, 0%, and 13%. Flow convergence was the only sign of significant regurgitation in 12 of 30 patients (40%); 10 of these patients had mechanical valves. We conclude flow convergence is a more sensitive, though less specific, predictor of significant mitral regurgitation than color Doppler, spatial mapping of the left atrium, and continuous wave Doppler, especially when a mechanical valve is present.

Adult↗

Flow convergence flow rates from 3-dimensional reconstruction of color Doppler flow maps for computing transvalvular regurgitant flows without geometric assumptions: An in vitro quantitative flow study.

OBJECTIVE: This study was designed to develop and test a 3-dimensional method for direct measurement of flow convergence (FC) region surface area and for quantitating regurgitant flows with an in vitro flow system. BACKGROUND: Quantitative methods for characterizing regurgitant flow events such as flow convergence with 2-dimensional color flow Doppler imaging systems have yielded variable results and may not be accurate enough to characterize those more complex spatial events. METHOD: Four differently shaped regurgitant orifices were studied: 3 flat orifices (circular, rectangular, triangular) and a nonflat one mimicking mitral valve prolapse (all 4 orifice areas = 0.24 cm(2)) in a pulsatile flow model at 8 to 9 different regurgitant flow rates (10 to 50 mL/beat). An ultrasonic flow probe and meter were connected to the flow model to provide reference flow data. Video composite data from the color Doppler flow images of the FC were reconstructed after computer-controlled 180 degrees rotational acquisition was performed. FC surface area (S cm(2)) was calculated directly without any geometric assumptions by measuring parallel sliced flow convergence arc lengths through the FC volume and multiplying each by the slice thickness (2.5 to 3.2 mm) over 5 to 8 slices and then adding them together. Peak regurgitant flow rate (milliliters per second) was calculated as the product of 3-dimensional determined S (cm(2)) multiplied by the aliasing velocity (centimeters per second) used for color Doppler imaging. RESULTS: For all of the 4 shaped orifices, there was an excellent relationship between actual peak flow rates and 3-dimensional FC-calculated flow rates with the direct measurement of the surface area of FC (r = 0.99, mean difference = -7.2 to -0.81 mL/s, % difference = -5% to 0%), whereas a hemielliptic method implemented with 3 axial measurements of the flow convergence zone from 2-dimensional planes underestimated actual flow rate by mean difference = -39.8 to -18.2 mL/s, % difference = -32% to -17% for any given orifice. CONCLUSIONS: Three-dimensional reconstruction of flow based on 2-dimensional color Doppler may add quantitative spatial information, especially for complex flow events. Direct measurement of 3-dimensional flow convergence surface areas may improve accuracy for estimation of the severity of valvular regurgitation.

Blood Flow Velocity↗

Converging populations of f-actin promote breakage of associated microtubules to spatially regulate microtubule turnover in migrating cells.

BACKGROUND: In migrating cells, the retrograde flow of filamentous actin (f-actin) from the leading edge toward the cell body is accompanied by the synchronous motion of microtubules (MTs, ), whose plus ends undergo net growth. Thus, MTs must depolymerize elsewhere in the cell to maintain polymer mass over time. The source and location of depolymerized MTs is unknown. Here, we test the hypothesis that MT polymer loss occurs in central cell regions and is induced by the convergence of actin retrograde and anterograde flow, which buckles and breaks associated MTs and promotes minus-end depolymerization. RESULTS: We characterized the effects of calyculin A and ML-7 on the movement of f-actin and MTs by multi-spectral fluorescence recovery after photobleaching (FRAP) and fluorescent speckle microscopy (FSM). Our studies show that these drugs affect the rate of f-actin and MT convergence and MT buckling in a central cell region we call the "convergence zone." Increases in f-actin convergence are associated with faster MT turnover and an increase in both MT breakage and minus-end depolymerization, but they have no effect on MT plus end dynamic instability. CONCLUSIONS: We propose that f-actin movement into the convergence zone plays a major role in spatially modulating MT turnover during cell migration by regulating MT breakage, and thus minus-end dynamics, in central cell regions.

Actins↗