Physiological Fontan Procedure

© 2019 Corno, Owen, Cangiani, Hall and Rona. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Objective: The conventional Fontan circulation deviates the superior vena cava (SVC = 1/3 of the systemic venous return) toward the right lung (3/5 of total lung volume) and the inferior vena cava (IVC = 2/3 of the systemic venous return) toward the left lung (2/5 of total lung volume). A “physiological” Fontan deviating the SVC toward the left lung and the IVC toward the right lung was compared with the conventional setting by computational fluid dynamics, studying whether this setting achieves a more favorable hemodynamics than the conventional Fontan circulation. Materials and Methods: An in-silico 3D parametric model of the Fontan procedure was developed using idealized vascular geometries with invariant sizes of SVC, IVC, right pulmonary artery (RPA), and left pulmonary artery (LPA), steady inflow velocities at IVC and SVC, and constant equal outflow pressures at RPA and LPA. These parameters were set to perform finite-volume incompressible steady flow simulations, assuming a single-phase, Newtonian, isothermal, laminar blood flow. Numerically converged finite-volume mass and momentum flow balances determined the inlet pressures and the outflow rates. Numerical closed-path integration of energy fluxes across domain boundaries determined the flow energy loss rate through the Fontan circulation. The comparison evaluated: (1) mean IVC pressure; (2) energy loss rate; (3) kinetic energy maximum value throughout the domain volume. Results: The comparison of the physiological vs. conventional Fontan provided these results: (1) mean IVC pressure 13.9 vs. 14.1 mmHg (= 0.2 mmHg reduction); (2) energy loss rate 5.55 vs. 6.61 mW (= 16% reduction); (3) maximum kinetic energy 283 vs. 396 J/m3 (= 29% reduction). Conclusions: A more physiological flow distribution is accompanied by a reduction of mean IVC pressure and by substantial reductions of energy loss rate and of peak kinetic energy. The potential clinical impact of these hemodynamic changes in reducing the incidence and severity of the adverse long-term effects of the Fontan circulation, in particular liver failure and protein-losing enteropathy, still remains to be assessed and will be the subject of future work

Mindfulness meditation targets transdiagnostic symptoms implicated in stress-related disorders: Understanding relationships between changes in mindfulness, sleep quality, and physical symptoms

Mindfulness-Based Stress Reduction (MBSR) is an 8-week meditation program known to improve anxiety, depression, and psychological well-being. Other health-related effects, such as sleep quality, are less well established, as are the psychological processes associated with therapeutic change. This prospective, observational study (n=213) aimed to determine whether perseverative cognition, indicated by rumination and intrusive thoughts, and emotion regulation, measured by avoidance, thought suppression, emotion suppression, and cognitive reappraisal, partly accounted for the hypothesized relationship between changes in mindfulness and two health-related outcomes: sleep quality and stress-related physical symptoms. As expected, increased mindfulness following the MBSR program was directly correlated with decreased sleep disturbance (r=-0.21, p=0.004) and decreased stress-related physical symptoms (r=-0.38, p<0.001). Partial correlations revealed that pre-post changes in rumination, unwanted intrusive thoughts, thought suppression, experiential avoidance, emotion suppression, and cognitive reappraisal each uniquely accounted for up to 32% of the correlation between the change in mindfulness and change in sleep disturbance and up to 30% of the correlation between the change in mindfulness and change in stress-related physical symptoms. Results suggest that the stress-reducing effects of MBSR are due, in part, to improvements in perseverative cognition and emotion regulation, two “transdiagnostic” mental processes that cut across stress-related disorders

Algorithm to Diagnose Leaks or Blockages Downstream of the Secondary Air Injection Reaction (SAIR) Pressure Sensor

A control module and method for an exhaust system of an engine can include a secondary air intake (SAI) pressure module that monitors SAI pressure. An accumulation module can accumulate an SAI string length based on the monitored SAI pressure. A calculation module can determine an average SAI string length based on the accumulated SAI string length. A determination module can determine an operating characteristic of the vehicle exhaust based on the average SAI string length

Extracellular Calcium Modulates Actions of Orthosteric and Allosteric Ligands on Metabotropic Glutamate Receptor 1alpha

SUMMARY: Metabotropic glutamate receptor 1α (mGluR1α), a member of the family C G protein-coupled receptors (GPCRs), is emerging as a potential drug target for various disorders including chronic neuronal degenerative diseases. In addition to being activated by glutamate, mGluR1α is also modulated by extracellular Ca2+. However, the underlying mechanism is unknown. Moreover, it has long been challenging to develop receptor-specific agonists due to homologies within the mGluR family, and the Ca2+-binding site(s) on mGluR1α may provide an opportunity for receptor-selective targeting by therapeutics. In the present study, we show that our previously predicted Ca2+-binding site in the hinge region of mGluR1α is adjacent to the site where orthosteric agonists and antagonists bind on the extracellular domain of the receptor. Moreover, we have found that extracellular Ca2+ enhances mGluR1α-mediated intracellular Ca2+ responses evoked by the orthosteric agonist, L-quisqualate. Conversely, extracellular Ca2+ diminishes the inhibitory effect of the mGluR1α orthosteric antagonist, (s)-MCPG. In addition, selective positive (Ro 67-4853) and negative (CPCCOEt) allosteric modulators of mGluR1α potentiate and inhibit responses to extracellular Ca2+, respectively, in a manner similar to their effects on the response of mGluR1α to glutamate. Mutations at residues predicted to be involved in Ca2+-binding, including E325I, have significant effects on the modulation of responses to the orthosteric agonist, L-quisqualate, and the allosteric modulator Ro 67-4853 by extracellular Ca2+. These studies reveal that binding of extracellular Ca2+ to the predicted Ca2+-binding site in the ECD of mGluR1α modulates not only glutamate-evoked signaling but also the actions of both orthosteric ligands and allosteric modulators on mGluR1α

Steady state free radical budgets and ozone photochemistry during TOPSE

A steady state model, constrained by a number of measured quantities, was used to derive peroxy radical levels for the conditions of the Tropospheric Ozone Production about the Spring Equinox (TOPSE) campaign. The analysis is made using data collected aboard the NCAR/NSF C-130 aircraft from February through May 2000 at latitudes from 40° to 85°N, and at altitudes from the surface to 7.6 km. HO2 + RO2 radical concentrations were measured during the experiment, which are compared with model results over the domain of the study showing good agreement on the average. Average measurement/model ratios are 1.04 (σ = 0.73) and 0.96 (σ = 0.52) for the MLB and HLB, respectively. Budgets of total peroxy radical levels as well as of individual free radical members were constructed, which reveal interesting differences compared to studies at lower latitudes. The midlatitude part of the study region is a significant net source of ozone, while the high latitudes constitute a small net sink leading to the hypothesis that transport from the middle latitudes can explain the observed increase in ozone in the high latitudes. Radical reservoir species concentrations are modeled and compared with the observations. For most conditions, the model does a good job of reproducing the formaldehyde observations, but the peroxide observations are significantly less than steady state for this study. Photostationary state (PSS) derived total peroxy radical levels and NO/NO2ratios are compared with the measurements and the model; PSS-derived results are higher than observations or the steady state model at low NO concentrations

The Multiwavelength Survey by Yale-Chile (MUSYC): Deep Near-Infrared Imaging and the Selection of Distant Galaxies

We present deep near-infrared JHK imaging of four 10'x10' fields. The observations were carried out as part of the Multiwavelength Survey by Yale-Chile (MUSYC) with ISPI on the CTIO 4m telescope. The typical point source limiting depths are J~22.5, H~21.5, and K~21 (5sigma; Vega). The effective seeing in the final images is ~1.0". We combine these data with MUSYC UBVRIz imaging to create K-selected catalogs that are unique for their uniform size, depth, filter coverage, and image quality. We investigate the rest-frame optical colors and photometric redshifts of galaxies that are selected using common color selection techniques, including distant red galaxies (DRGs), star-forming and passive BzKs, and the rest-frame UV-selected BM, BX, and Lyman break galaxies (LBGs). These techniques are effective at isolating large samples of high redshift galaxies, but none provide complete or uniform samples across the targeted redshift ranges. The DRG and BM/BX/LBG criteria identify populations of red and blue galaxies, respectively, as they were designed to do. The star-forming BzKs have a very wide redshift distribution, a wide range of colors, and may include galaxies with very low specific star formation rates. In comparison, the passive BzKs are fewer in number, have a different distribution of K magnitudes, and have a somewhat different redshift distribution. By combining these color selection criteria, it appears possible to define a reasonably complete sample of galaxies to our flux limit over specific redshift ranges. However, the redshift dependence of both the completeness and sampled range of rest-frame colors poses an ultimate limit to the usefulness of these techniques.Comment: 17 pages in emulateapj style, 13 figures. Submitted to the Astronomical Journal. Data will be made available upon publicatio

Influence of Nanoparticle Size and Shape on Oligomer Formation of an Amyloidogenic Peptide

Understanding the influence of macromolecular crowding and nanoparticles on the formation of in-register $\beta$-sheets, the primary structural component of amyloid fibrils, is a first step towards describing \emph{in vivo} protein aggregation and interactions between synthetic materials and proteins. Using all atom molecular simulations in implicit solvent we illustrate the effects of nanoparticle size, shape, and volume fraction on oligomer formation of an amyloidogenic peptide from the transthyretin protein. Surprisingly, we find that inert spherical crowding particles destabilize in-register $\beta$-sheets formed by dimers while stabilizing $\beta$-sheets comprised of trimers and tetramers. As the radius of the nanoparticle increases crowding effects decrease, implying smaller crowding particles have the largest influence on the earliest amyloid species. We explain these results using a theory based on the depletion effect. Finally, we show that spherocylindrical crowders destabilize the ordered $\beta$-sheet dimer to a greater extent than spherical crowders, which underscores the influence of nanoparticle shape on protein aggregation

Multimodality approach of perioperative 18F-FDG PET/CT imaging, intraoperative 18F-FDG handheld gamma probe detection, and intraoperative ultrasound for tumor localization and verification of resection of all sites of hypermetabolic activity in a case of occult recurrent metastatic melanoma

<p>Abstract</p> <p>Background</p> <p>The use of diagnostic ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) imaging for the staging, restaging, and treatment monitoring of melanoma patients has become a well-recognized standard of care. It plays a key role in detecting sites of occult disease and is widely utilized in the medical and surgical planning of such patients. In the current report, we describe an innovative multimodality approach of perioperative ¹⁸F-FDG PET/CT imaging, intraoperative ¹⁸F-FDG handheld gamma probe detection, and intraoperative ultrasound for tumor localization and verification of resection of all sites of hypermetabolic tumor foci in a case of occult recurrent metastatic melanoma.</p> <p>Case presentation</p> <p>This report discusses a case of occult recurrent metastatic melanoma, isolated to three separate sites within the subcutaneous tissues of the left thigh region, which was not clinically apparent but was found on diagnostic restaging whole body ¹⁸F-FDG PET/CT scan utilizing an intravenous injection of 14.8 mCi ¹⁸F-FDG. Then, on the day of surgery, the patient received an intravenous injection of 12.8 mCi ¹⁸F-FDG. A multimodality approach of intraoperative handheld gamma probe detection, intraoperative ultrasound tumor localization, specimen PET/CT imaging, and postoperative PET/CT imaging was utilized for accomplishing and verifying the excision of all three sites of occult recurrent metastatic melanoma within the left thigh region.</p> <p>Conclusion</p> <p>This innovative multimodality approach of perioperative ¹⁸F-FDG PET/CT imaging, intraoperative ¹⁸F-FDG handheld gamma probe detection, and intraoperative ultrasound is promising combined technology for aiding in tumor localization and verification of excision and may ultimately impact positively upon long-term outcome of selected patients.</p