Metabolic Syndrome and Outcomes after Renal Intervention

Metabolic syndrome significantly increases the risk for cardiovascular disease and chronic kidney disease. The increased risk for cardiovascular diseases can partly be caused by a prothrombotic state that exists because of abdominal obesity. Multiple observational studies have consistently shown that increased body mass index as well as insulin resistance and increased fasting insulin levels is associated with chronic kidney disease, even after adjustment for related disorders. Metabolic syndrome appears to be a risk factor for chronic kidney disease, likely due to the combination of dysglycemia and high blood pressure. Metabolic syndrome is associated with markedly reduced renal clinical benefit and increased progression to hemodialysis following endovascular intervention for atherosclerotic renal artery stenosis. Metabolic syndrome is associated with inferior early outcomes for dialysis access procedures

Theory of valley-orbit coupling in a Si/SiGe quantum dot

Electron states are studied for quantum dots in a strained Si quantum well, taking into account both valley and orbital physics. Realistic geometries are considered, including circular and elliptical dot shapes, parallel and perpendicular magnetic fields, and (most importantly for valley coupling) the small local tilt of the quantum well interface away from the crystallographic axes. In absence of a tilt, valley splitting occurs only between pairs of states with the same orbital quantum numbers. However, tilting is ubiquitous in conventional silicon heterostructures, leading to valley-orbit coupling. In this context, "valley splitting" is no longer a well defined concept, and the quantity of merit for qubit applications becomes the ground state gap. For typical dots used as qubits, a rich energy spectrum emerges, as a function of magnetic field, tilt angle, and orbital quantum number. Numerical and analytical solutions are obtained for the ground state gap and for the mixing fraction between the ground and excited states. This mixing can lead to valley scattering, decoherence, and leakage for Si spin qubits.Comment: 18 pages, including 4 figure

Modeling the effect of vaccination on selection for antibiotic resistance in Streptococcus pneumoniae

Vaccines against bacterial pathogens can protect recipients from becoming infected with potentially antibiotic-resistant pathogens. However, by altering the selective balance between antibiotic-sensitive and antibiotic-resistant bacterial strains, vaccines may also suppress-or spread-antibiotic resistance among unvaccinated individuals. Predicting the outcome of vaccination requires knowing what drives selection for drug-resistant bacterial pathogens and what maintains the circulation of both antibiotic-sensitive and antibiotic-resistant strains of bacteria. To address this question, we used mathematical modeling and data from 2007 on penicillin consumption and penicillin nonsusceptibility in Streptococcus pneumoniae (pneumococcus) invasive isolates from 27 European countries. We show that the frequency of penicillin resistance in S. pneumoniae can be explained by between-host diversity in antibiotic use, heritable diversity in pneumococcal carriage duration, or frequency-dependent selection brought about by within-host competition between antibiotic-resistant and antibiotic-sensitive S. pneumoniae strains. We used our calibrated models to predict the impact of non-serotype-specific pneumococcal vaccination upon the prevalence of S. pneumoniae carriage, incidence of disease, and frequency of S. pneumoniae antibiotic resistance. We found that the relative strength and directionality of competition between drug-resistant and drug-sensitive pneumococcal strains was the most important determinant of whether vaccination would promote, inhibit, or have little effect upon the evolution of antibiotic resistance. Last, we show that country-specific differences in pathogen transmission substantially altered the predicted impact of vaccination, highlighting that policies for managing antibiotic resistance with vaccines must be tailored to a specific pathogen and setting

Within-host dynamics shape antibiotic resistance in commensal bacteria

The spread of antibiotic resistance, a major threat to human health, is poorly understood. Simple population-level models of bacterial transmission predict that above a certain rate of antibiotic consumption in a population, resistant bacteria should completely eliminate non-resistant strains, while below this threshold they should be unable to persist at all. This prediction stands at odds with empirical evidence showing that resistant and non-resistant strains coexist stably over a wide range of antibiotic consumption rates. Not knowing what drives this long-term coexistence is a barrier to developing evidence-based strategies for managing the spread of resistance. Here, we argue that competition between resistant and sensitive pathogens within individual hosts gives resistant pathogens a relative fitness benefit when they are rare, promoting coexistence between strains at the population level. To test this hypothesis, we embed mechanistically explicit within-host dynamics in a structurally neutral pathogen transmission model. Doing so allows us to reproduce patterns of resistance observed in the opportunistic pathogens Escherichia coli and Streptococcus pneumoniae across European countries and to identify factors that may shape resistance evolution in bacteria by modulating the intensity and outcomes of within-host competition

1030-13 Alterations in Endothelial Cell Adenosine Receptors Mediate Endothelium-Dependent Vasoconstriction in Experimental Vein Grafts

Adenosine is a potent endogenous vasodilator which mediates its action through A1 and A2 receptor subtypes located on both vascular endothelial and vascular smooth muscle cells (SMC). Adenosine-mediated relaxation in vein grafts has not been examined. This study assesses the in vitro isometric tension responses to specific adenosine receptor agonists (A1: R-phenyl-isopropyl-adenosine and A2: CSG-21680; 10–9 to 10–4 M) of common carotid external jugular vein bypass grafts (VG) in New Zealand White rabbits. These responses were compared to those obtained in the extemal jugular vein (JV) and in the common carotid artery (CA). All vessels were precontracted with prostaglandin F2a (10–5 M). Endothelialized and de-endothelialized vessels were examined. The A1 mediated relaxation in JV was endothelium-independent, whereas A2 mediated relaxation was endothelium-dependent. In CA, A1 mediated relaxation was partially endothelium-dependent, while A2 mediated relaxation was endotheliumindependent. In VG, Al activation induced endothelium-dependent vasoconstriction. Endothelial denudation restored Al mediated relaxation, but reduced compared to that of JV (max. 19±9%). A2 relaxation in VG was endothelium-independent (max. 39±4%). Primary cultures of arterial and vein graft SMC expressed both A1 and A2 receptors on northern blot analysis. There was, however, a marked reduction in the A1 affinity of the SMC from the VG compared to the arterial SMC (40.9±1.3% arterial binding). This study, therefore, demonstrates that there is a substantial change in the adenosine mediated vasoreactivity in VG compared to JV, due to a change in endothelial A1 receptor mediated response from relaxation to constriction, coupled with a decreased affinity of the A1 receptors on the VG SMC. The adenosine responses of the VG are also different from CA. Therefore, the endothelial celis of VG appear to be unique, in that functionally they neither maintain a venous phenotype nor acquire an arterial phenotype in response to adenosine

Antineutrino Geophysics with Liquid Scintillator Detectors

Detecting the antineutrinos emitted by the decay of radioactive elements in the mantle and crust could provide a direct measurement of the total abundance of uranium and thorium in the Earth. In calculating the antineutrino flux at specific sites, the local geology of the crust and the background from the world's nuclear power reactors are important considerations. Employing a global crustal map, with type and thickness data, and using recent estimates of the uranium and thorium distribution in the Earth, we calculate the antineutrino event rate for two new neutrino detectors. We show that spectral features allow terrestrial antineutrino events to be identified above reactor antineutrino backgrounds and that the uranium and thorium contributions can be separately determined.Comment: Published paper differs from original submitted preprint because reviewers suggested updated continental crust U/Th abundances. Kamioka geographical location error was in preprint, partially corrected in published version. This version is the same as the published paper, with Kamioka fully corrected. Because of recent interest in this topic, this version is being made available, despite this work being 8 years ol

Endovascular management of acute and subacute venous thoracic outlet syndrome

Approximately 3% of all patients presenting with Thoracic Outlet Syndrome have a venous etiology (vTOS), which is considered “effort thrombosis”. These patients will present with symptomatic deep venous thrombosis or focal subclavian vein (SCV) stenosis. Endovascular management of vTOS occurs in several phases: diagnostic, preoperative therapeutic intervention before decompression, postoperative interventions after decompression, and delayed interventions in the follow-up after decompression. In the diagnostic phase, dynamic SCV venography can establish functional vTOS. Approximately 4,000 patients have been treated for vTOS and reported in the literature since 1970. Declotting of the SCV was followed by surgical decompression in 53% of patients, while in the remainder, surgical decompression alone (18%), endovascular intervention alone (15%), or conservative therapy with anticoagulation (15%) was performed. The initial intervention was predominantly catheter-directed thrombolysis, with <10% of cases undergoing concomitant balloon angioplasty. 93% of cases were successful. In the postoperative phase, balloon angioplasty was performed to correct residual intrinsic SCV disease after vTOS decompression in under 15% of cases. Stents were rarely deployed. Symptom relief was reported as 94 ± 12% (mean ± SD) and 90 ± 23%, respectively for declotting with decompression and declotting alone. In the delayed phase, balloon angioplasty was performed in under 15% of cases to re-establish patency

Alterations in wall tension and shear stress modulate tyrosine kinase signaling and wall remodeling in experimental vein grafts

AbstractPurpose: Hemodynamic alterations have been implicated as major stimuli for the development of intimal hyperplasia in vein grafts that are implanted in the arterial circulation. Tyrosine kinase is known to mediate cell signaling. However, its role with in vivo mechanotransduction is not yet well defined. We used a novel bioprosthetic collagen tube to provide an external support to vein grafts and examined the subsequent changes in hemodynamics, tyrosine kinase signaling, wall remodeling, and vasomotor function. Methods: Carotid interposition bypass grafting was performed with the reversed jugular vein in New Zealand white rabbits. In the experimental group (n = 15), after the completion of the proximal anastomosis, the vein was passed through a 4-mm collagen tube and the distal anastomosis was performed. The tube support was fashioned to completely cover the vein grafts. The control animals (n = 14) had no tube support. After surgery, the blood pressure and flow rate were measured and the wall tension and shear stress were calculated in the vein grafts on day 3 or day 28 (n = 5 per group). Tyrosine phosphorylation was assessed with the Western blot test in vein grafts at day 3 (n = 4 per group). The intimal and medial dimensions of the vein grafts were assessed with videomorphometry on day 28 (n = 5 per group). The cumulative dose response curves of the vein grafts to contractile and relaxant agonists were determined in isometric tension studies on day 28 (n = 5 per group). Results: The use of tube support reduced wall tension 1.7-fold (P < .01) and increased shear stress 4.8-fold (P < .001) without altering the flow rate or blood pressure. The tyrosine kinase activity was reduced 15-fold (P < .001) in the tube-supported vein grafts. The intimal thickness was reduced by 45% in the tube-supported vein grafts as compared with the control grafts (46 ± 2 mm vs 84 ± 5 mm, respectively; P < .0001), and the media thickness was reduced by 20% (63 ± 8 mm vs 79 ± 4 mm, respectively; P < .05). Isometric tension studies showed preservation of contractile function and modulation of endothelial-dependent dysfunctional relaxation in tube-supported vein grafts. Conclusion: These results show that reduced wall tension and increased shear stress with an external tube support can effectively modulate the signaling, functional, and hyperplastic responses in vein grafts. We conclude that this simple strategy deserves further study and clinical consideration. (J Vasc Surg 1999;29:334-44.