Pulse wave propagation in a model human arterial network: assessment of 1-D numerical simulations against in vitro measurements

A numerical model based on the nonlinear, one-dimensional (1-D) equations of pressure and flow wave propagation in conduit arteries is tested against a well-defined experimental 1:1 replica of the human arterial tree. The tree consists of 37 silicone branches representing the largest central systemic arteries in the human, including the aorta, carotid arteries and arteries that perfuse the upper and lower limbs and the main abdominal organs. The set-up is mounted horizontally and connected to a pulsatile pump delivering a periodic output similar to the aortic flow. Terminal branches end in simple resistance models, consisting of stiff capillary tubes leading to an overflow reservoir that reflects a constant venous pressure. The parameters required by the numerical algorithm are directly measured in the in vitro set-up and no data fitting is involved. Comparison of experimental and numerical pressure and flow waveforms shows the ability of the 1-D time-domain formulation to capture the main features of pulse wave propagation measured throughout the system test. As a consequence of the simple resistive boundary conditions used to reduce the uncertainty of the parameters involved in the simulation, the experimental set-up generates waveforms at terminal branches with additional non-physiological oscillations. The frequencies of these oscillations are well captured by the 1-D model, even though amplitudes are overestimated. Adding energy losses in bifurcations and including fluid inertia and compliance to the purely resistive terminal models does not reduce the underdamped effect, suggesting that wall visco-elasticity might play an important role in the experimental results. Nevertheless, average relative root-mean-square errors between simulations and experimental waveforms are smaller than 4% for pressure and 19% for the flow at all 70 locations studied.     

Comparison of the hemodynamic and thrombogenic performance of two bileaflet mechanical heart valves using a CFD/FSI model

The hemodynamic and the thrombogenic performance of two commercially available bileaflet mechanical heart valves (MHVs)--the ATS Open Pivot Valve (ATS) and the St. Jude Regent Valve (SJM), was compared using a state of the art computational fluid dynamics-fluid structure interaction (CFD-FSI) methodology. A transient simulation of the ATS and SJM valves was conducted in a three-dimensional model geometry of a straight conduit with sudden expansion distal the valves, including the valve housing and detailed hinge geometry. An aortic flow waveform (60 beats/min, cardiac output 4 l/min) was applied at the inlet. The FSI formulation utilized a fully implicit coupling procedure using a separate solver for the fluid problem (FLUENT) and for the structural problem. Valve leaflet excursion and pressure differences were calculated, as well as shear stress on the leaflets and accumulated shear stress on particles released during both forward and backward flow phases through the open and closed valve, respectively. In contrast to the SJM, the ATS valve opened to less than maximal opening angle. Nevertheless, maximal and mean pressure gradients and velocity patterns through the valve orifices were comparable. Platelet stress accumulation during forward flow indicated that no platelets experienced a stress accumulation higher than 35 dyne x s/cm2, the threshold for platelet activation (Hellums criterion). However, during the regurgitation flow phase, 0.81% of the platelets in the SJM valve experienced a stress accumulation higher than 35 dyne x s/cm2, compared with 0.63% for the ATS valve. The numerical results indicate that the designs of the ATS and SJM valves, which differ mostly in their hinge mechanism, lead to different potential for platelet activation, especially during the regurgitation phase. This numerical methodology can be used to assess the effects of design parameters on the flow induced thrombogenic potential of blood recirculating devices.     

The Duration of Hypotension Determines the Evolution of Bacteremia-Induced Acute Kidney Injury in the Intensive Care Unit

Background

Exploration of the impact of severe hypotension on the evolution of acute kidney injury in septic patients.

Methods and Results

We reviewed the hemodynamic parameters of 137 adults with septic shock and proven blood stream infection in the ICU. Severe hypotension was defined as a mean arterial blood pressure (MAP) ≤65 mmHg. The influence of the duration of severe hypotension on the evolution of acute kidney injury was evaluated according to the RIFLE classification, with day 0 defined as the day of a positive blood stream infection. After bloodstream infection, the probability for a patient to be in Failure was significantly higher than before blood stream infection (OR = 1.94, p = 0.0276). Patients have a significantly higher risk of evolving to Failure if the duration of severe hypotension is longer (OR = 1.02 for each 10 minutes increase in duration of a MAP <65 mmHg, p = 0.0472). A cut-off of at least 51 minutes of severe hypotension (<65 mmHg) or at least 5.5 periods of severe hypotension within 1 day identified patients with increased risk to evolve to Failure.

Conclusions

There is a significant influence of both the duration and the number of periods of severe hypotension on the evolution to Failure. Blood stream infection has a significantly negative effect on the relationship between severe hypotension and Failure.     

Evolutionary history of the closely related group 2 coronaviruses: porcine hemagglutinating encephalomyelitis virus, bovine coronavirus, and human coronavirus OC43

The close genetic and antigenic relatedness among the group 2 coronaviruses human coronavirus OC43 (HCoV-OC43), bovine coronavirus (BCoV), and porcine hemagglutinating encephalomyelitis virus (PHEV) suggests that these three viruses with different host specificities diverged fairly recently. In this study, we determined the complete genomic sequence of PHEV (strain PHEV-VW572), revealing the presence of a truncated group 2-specific ns2 gene in PHEV in comparison to other group 2 coronaviruses. Using a relaxed molecular clock approach, we reconstructed the evolutionary relationships between PHEV, BCoV, and HCoV-OC43 in real-time units, which indicated relatively recent common ancestors for these species-specific coronaviruses.     

Genetic Determinants of Swarming in Rhizobium etli

Swarming motility is considered to be a social phenomenon that enables groups of bacteria to move coordinately atop solid surfaces. The differentiated swarmer cell population is embedded in an extracellular slime layer, and the phenomenon has previously been linked with biofilm formation and virulence. The gram-negative nitrogen-fixing soil bacterium Rhizobium etli CNPAF512 was previously shown to display swarming behavior on soft agar plates. In a search for novel genetic determinants of swarming, a detailed analysis of the swarming behavior of 700 miniTn5 mutants of R. etli was performed. Twenty-four mutants defective in swarming or displaying abnormal swarming patterns were identified and could be divided into three groups based on their swarming pattern. Fourteen mutants were completely swarming deficient, five mutants showed an atypical swarming pattern with no completely smooth edge and local extrusions, and five mutants displayed an intermediate swarming phenotype. Sequence analysis of the targeted genes indicated that the mutants were likely affected in quorum-sensing, polysaccharide composition or export, motility, and amino acid and polyamines metabolism. Several of the identified mutants displayed a reduced symbiotic nitrogen fixation activity.     

Numerical study of the uniformity of balloon-expandable stent deployment

Stents are small tubelike structures, implanted in coronary and peripheral arteries to reopen narrowed vessel sections. This endovascular intervention remains suboptimal, as the success rate is limited by restenosis. This renarrowing of a stented vessel is related to the arterial injury caused by stent-artery and balloon-artery interactions, and a local subsequent inflammatory process. Therefore, efforts to optimize the stent deployment remain very meaningful. Several authors have studied with finite element modeling the mechanical behavior of balloon-expandable stents, but none of the proposed models incorporates the folding pattern of the balloon. We developed a numerical model in which the CYPHER stent is combined with a realistic trifolded balloon. In this paper, the impact of several parameters such as balloon length, folding pattern, and relative position of the stent with respect to the balloon catheter on the free stent expansion has been investigated. Quantitative validation of the modeling strategy shows excellent agreement with data provided by the manufacturer and, therefore, the model serves as a solid basis for further investigations. The parametric analyses showed that both the balloon length and the folding pattern have a considerable influence on the uniformity and symmetry of the transient stent expansion. Consequently, this approach can be used to select the most appropriate balloon length and folding pattern for a particular stent design in order to optimize the stent deployment. Furthermore, it was demonstrated that small positioning inaccuracies may change the expansion behavior of a stent. Therefore, the placement of the stent on the balloon catheter should be accurately carried out, again in order to decrease the endothelial damage.     

Flow cytometric testing of green fluorescent protein-tagged Lactobacillus rhamnosus GG for response to defensins

Lactobacillus rhamnosus GG is of general interest as a probiotic. Although L. rhamnosus GG is often used in clinical trials, there are few genetic tools to further determine its mode of action or to develop it as a vehicle for heterologous gene expression in therapy. Therefore, we developed a reproducible, efficient electroporation procedure for L. rhamnosus GG. The best transformation efficiency obtained was 10(4) transformants per microg of DNA. We validated this protocol by tagging L. rhamnosus GG with green fluorescent protein (GFP) using the nisin-controlled expression (NICE) system. Parameters for overexpression were optimized, which allowed expression of gfp in L. rhamnosus GG upon induction with nisin. The GFP+ strain can be used to monitor the survival and behavior of L. rhamnosus GG in vivo. Moreover, implementation of the NICE system as a gene expression switch in L. rhamnosus GG opens up possibilities for improving and expanding the performance of this strain. The GFP-labeled strain was used to demonstrate that L. rhamnosus GG is sensitive to human beta-defensin-2 but not to human beta-defensin-1.     

Alkyllysophospholipid ET-18-OCH3 acts as an activator of protein kinase C in HL-60 cells

HL-60 cells are very sensitive to the cytotoxic action of ether lipids. Several hypotheses have been proposed to explain this cytotoxicity. We investigated the influence of the alkylphospholipid ET-18-OCH₃ on the activity of protein kinase C. HL-60 cells were incubated with ET-18-OCH₃ at a concentration of 20 μg/ml for 4 h. After the incubation the membrane fraction of the HL-60 cells was isolated and the activity of protein kinase C was determined while it was still associated with the membrane, using the synthetic peptide substrate [Ser²⁵]-protein kinase C (19–31) as a protein kinase C specific substrate. The activity of the membrane-bound protein kinase C was increased in HL-60 cells treated with ET-18-OCH₃ compared to untreated HL-60 cells. The increase in protein kinase C activity was not a consequence of translocation and appeared to be additive to the effect of the phorbol ester 12-myristate 13-acetate. In contrast, solubilized protein kinase C from HL-60 cells could be inhibited or stimulated in vitro by ET-18-OCH₃, dependent on the mode of addition of ET-18-OCH₃ and phospholipids.     

Effective symbiosis between Rhizobium etli and Phaseolus vulgaris requires the alarmone ppGpp

The symbiotic interaction between Rhizobium etli and Phaseolus vulgaris, the common bean plant, ultimately results in the formation of nitrogen-fixing nodules. Many aspects of the intermediate and late stages of this interaction are still poorly understood. The R. etli relA gene was identified through a genome-wide screening for R. etli symbiotic mutants. RelA has a pivotal role in cellular physiology, as it catalyzes the synthesis of (p)ppGpp, which mediates the stringent response in bacteria. The synthesis of ppGpp was abolished in an R. etli relA mutant strain under conditions of amino acid starvation. Plants nodulated by an R. etli relA mutant had a strongly reduced nitrogen fixation activity (75% reduction). Also, at the microscopic level, bacteroid morphology was altered, with the size of relA mutant bacteroids being increased compared to that of wild-type bacteroids. The expression of the sigma(N)-dependent nitrogen fixation genes rpoN2 and iscN was considerably reduced in the relA mutant. In addition, the expression of the relA gene was negatively regulated by RpoN2, the symbiosis-specific sigma(N) copy of R. etli. Therefore, an autoregulatory loop controlling the expression of relA and rpoN2 seems operative in bacteroids. The production of long- and short-chain acyl-homoserine-lactones by the cinIR and raiIR systems was decreased in an R. etli relA mutant. Our results suggest that relA may play an important role in the regulation of gene expression in R. etli bacteroids and in the adaptation of bacteroid physiology.