Genome-wide analyses of Liberibacter species provides insights into evolution, phylogenetic relationships, and virulence factors.

'Candidatus Liberibacter' species are insect-transmitted, phloem-limited α-Proteobacteria in the order of Rhizobiales. The citrus industry is facing significant challenges due to huanglongbing, associated with infection from 'Candidatus Liberibacter asiaticus' (Las). In order to gain greater insight into 'Ca. Liberibacter' biology and genetic diversity, we have performed genome sequencing and comparative analyses of diverse 'Ca. Liberibacter' species, including those that can infect citrus. Our phylogenetic analysis differentiates 'Ca. Liberibacter' species and Rhizobiales in separate clades and suggests stepwise evolution from a common ancestor splitting first into nonpathogenic Liberibacter crescens followed by diversification of pathogenic 'Ca. Liberibacter' species. Further analysis of Las genomes from different geographical locations revealed diversity among isolates from the United States. Our phylogenetic study also indicates multiple Las introduction events in California and spread of the pathogen from Florida to Texas. Texan Las isolates were closely related, while Florida and Asian isolates exhibited the most genetic variation. We have identified conserved Sec translocon (SEC)-dependent effectors likely involved in bacterial survival and virulence of Las and analysed their expression in their plant host (citrus) and insect vector (Diaphorina citri). Individual SEC-dependent effectors exhibited differential expression patterns between host and vector, indicating that Las uses its effector repertoire to differentially modulate diverse organisms. Collectively, this work provides insights into the evolution of 'Ca. Liberibacter' species, the introduction of Las in the United States and identifies promising Las targets for disease management

Toward optimal hemodynamics: computer modeling of the fontan circuit

The construction of efficient designs with minimal energy losses is especially important for cavopulmonary connections. The science of computational fluid dynamics has been increasingly used to study the hemodynamic performance of surgical operations. Three-dimensional computer models can be accurately constructed of typical cavopulmonary connections used in clinical practice based on anatomic data derived from magnetic resonance scans, angiocardiograms, and echocardiograms. Using these methods, the hydraulic performance of the hemi-Fontan, bidirectional Glenn, and a variety of types of completion Fontan operations can be evaluated and compared. This methodology has resulted in improved understanding and design of these surgical operations

Ten years of modelling to achieve haemodynamic optimisation of the total cavopulmonary connection.

The techniques of computational fluid dynamics are among the most powerful tools available to engineers dealing with the motion of fluids and the exchange of mass, momentum, and energy. They have recently been shown to have an increasing number of applications to the human cardiovascular system, including the fluid dynamics of surgical reconstruction of congenitally malformed parts of the cardiovascular system. In vitro models are the alternative laboratory tools with which to study fluid dynamics. The advantages of computational fluid dynamics over the in vitro models are the easy quantification of haemodynamic variables, such as rates of flow, pressure, and distribution of shear stress, and changes in geometric and fluid dynamics parameters. Furthermore, using computational fluid dynamics allows the development of three-dimensional models to reproduce both the complex anatomy of the investigated region and the details of the surgical reconstruction, especially with the recent developments in magnetic resonance imaging. On the basis of the results, it is possible quantitatively to evaluate the surgical correction. This technology, which benefits greatly from the continuous improvement in hardware and software, enables cardiovascular experts and bioengineers to look at the fluid dynamics of various cardiovascular regions with increasing sophistication..

Global mathematical modelling of the Norwood circulation: a multiscale approach for the study of the pulmonary and coronary arterial perfusions.

The Norwood procedure involves three separate stages of operative corrections. The first stage involves re-fashioning the pulmonary trunk into a neo-aorta so that it is possible to establish an unrestricted systemic circulation. An interpositional, or systemic-to-pulmonary arterial, shunt is then created between the neo-aorta and the pulmonary arteries to allow pulmonary perfusion and gas exchange. Two of the available options for the systemic-to-pulmonary shunt are the central shunt and the right modified Blalock-Taussig shunt. In the setting of a central shunt, pulmonary perfusion is derived from a conduit placed between the pulmonary arterial bed and the neo-aorta whereas, in the modified Blalock-Taussig shunt, the conduit is interposed between one of the pulmonary arteries and the brachiocephalic artery. In subsequent stages, pulmonary perfusion is provided directly by deoxygenated blood. This is achieved by connecting, first, the superior caval vein, and then the inferior caval vein, to the pulmonary arteries. It is usually during the second stage that the systemic-to-pulmonary shunt is removed...

Multiscale Modelling of the cardiovascular system: application to the study of pulmonary and coronary perfusions in univentricular circulation

The objective of this studyis to compare the coronaryand pulmonaryblood flow dynamics resulting from two configurations of systemic-to-pulmonary artery shunts currently utilized during the Norwood procedure: the central (CS) and modified Blalock Taussig (MBTS) shunts. A lumped parameter model of the neonatal cardiovascular circulation and detailed 3-D models of the shunt based on the finite volume method were constructed. Shunt sizes of 3, 3.5 and 4mm were considered. A multiscale approach was adopted to prescribe appropriate and realistic boundaryconditions for the 3-D models of the Norwood circulation. Results showed that the average shunt flow rate is higher for the CS option than for the MBTS and that pulmonaryflow increases with shunt size for both options. Cardiac output is higher for the CS option for all shunt sizes. Flow distribution between the left and the right pulmonaryarteries is not completely balanced, although for the CS option the discrepancyis low (50–51% of the pulmonaryflow to the right lung) while for the MBTS it is more pronounced with larger shunt sizes (51–54% to the left lung). The CS option favors perfusion to the right lung while the MBTS favors the left. In the CS option, a smaller percentage of aortic flow is distributed to the coronarycirculation, while that percentage rises for the MBTS. These findings mayhave important implications for coronaryblood flow and ventricular function

Multiscale modelling in biofluidynamics: application to reconstructive paediatric cardiac surgery.

Multiscale computing is a challenging area even in biomechanics. Application of such a methodology to quantitatively compare postoperative hemodynamics in congenital heart diseases is very promising. In the treatment of hypoplastic left heart syndrome, which is a congenital heart disease where the left ventricle is missing or very small, the necessity to feed the pulmonary and systemic circulations is obtained with an interposition shunt. Two main options are available and differ from the sites of anastomoses: (i) the systemic-to-pulmonary conduit (Blalock–Taussig shunt known as the Norwood Operation (NO)) connecting the innominate artery (NO-BT) or the aorta (NO-CS) to the right pulmonary artery and (ii) the right ventricle to pulmonary artery shunt (known as Sano operation (SO)). The proposition that the SO is superior to the NO remains controversial. 3-D computer models of the NO (NO-BT and NO-CS) and SO were developed and investigated using the finite volume method. Conduits of 3, 3.5 and 4mm were used in the NO models, whereas conduits of 4, 5 and 6mm were used in the SO model. The hydraulic nets (lumped resistances, compliances, inertances and elastances) which represent the systemic, coronary and pulmonary circulations and the heart were identical in the two models. A multiscale approach was adopted to couple the 3-D models with the circulation net. Computer simulation results were compared with post-operative catheterization data. Results showed that (i) there is a good correlation between predicted and observed data: higher aortic diastolic pressure, decreased pulmonary arterial pressure, lower pulmonary-to-systemic flow ratio and higher coronary perfusion pressure in SO; (ii) there is a minimal regurgitant flow in the SO conduit. The close correlation between predicted and observed clinical data supports the use of mathematical modelling, with a mandatory multiscale approach, in the design and assessment of surgical procedures

Management of a stenotic right ventricle-pulmonary artery shunt early after the Norwood procedure

BACKGROUND: Inadequate pulmonary blood flow through a right ventricle-to-pulmonary artery (RV-PA) shunt early after the Norwood operation can be remedied by adding a modified Blalock-Taussig (mBT) shunt. We used multiscale computational modeling to determine whether the stenotic RV-PA shunt should be left in situ or removed. METHODS: Models of the Norwood circulation were constructed with (1) a 5-mm RV-PA shunt, (2) a RV-PA shunt with 3- or 2-mm stenosis at the RV anastomosis, (3) a stenotic RV-PA shunt plus a 3.0- or 3.5-mm mBT shunt, or (4) a 3.5-mm mBT shunt. A hydraulic network that mathematically describes an entire circulatory system with pre-stage 2 hemodynamics was used to predict local dynamics within the Norwood circulation. Global variables including total cardiac output, mixed venous oxygen saturation, stroke work, and systemic oxygen delivery can be computed. RESULTS: Proximal stenosis of the RV-PA shunt results in decreased pulmonary blood flow, total cardiac output, mixed venous saturation, and oxygen delivery. Addition of a 3.0- or 3.5-mm mBT shunt leads to pulmonary overcirculation, lowers systemic oxygen delivery, and decreases coronary perfusion pressure. Diastolic runoff through the stenotic RV-PA shunt dramatically increases retrograde flow into the single ventricle. Removal of the stenotic RV-PA shunt balances systemic and pulmonary blood flow, eliminates regurgitant flow into the single ventricle, and improves systemic oxygen delivery. CONCLUSIONS: Adding a mBT shunt to remedy a stenotic RV-PA shunt early after a Norwood operation can lead to pulmonary overcirculation and may decrease systemic oxygen delivery. The stenotic RV-PA shunt should be taken down. Conversion to an optimal mBT shunt is preferable to augmenting a stenotic RV-PA shunt with a smaller mBT shunt