Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p> Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p> Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p> Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p&gt

Dephasing of Electrons by Two-Level Defects in Quantum Dots

The electron dephasing time $\tau_{\phi}$ in a diffusive quantum dot is calculated by considering the interaction between the electron and dynamical defects, modelled as two-level system. Using the standard tunneling model of glasses, we obtain a linear temperature dependence of $1/\tau_{\phi}$, consistent with the experimental observation. However, we find that, in order to obtain dephasing times on the order of nanoseconds, the number of two-level defects needs to be substantially larger than the typical concentration in glasses. We also find a finite system-size dependence of $\tau_{\phi}$, which can be used to probe the effectiveness of surface-aggregated defects.Comment: two-column 9 page

Localized helium excitations in 4He_N-benzene clusters

We compute ground and excited state properties of small helium clusters 4He_N containing a single benzene impurity molecule. Ground-state structures and energies are obtained for N=1,2,3,14 from importance-sampled, rigid-body diffusion Monte Carlo (DMC). Excited state energies due to helium vibrational motion near the molecule surface are evaluated using the projection operator, imaginary time spectral evolution (POITSE) method. We find excitation energies of up to ~23 K above the ground state. These states all possess vibrational character of helium atoms in a highly anisotropic potential due to the aromatic molecule, and can be categorized in terms of localized and collective vibrational modes. These results appear to provide precursors for a transition from localized to collective helium excitations at molecular nanosubstrates of increasing size. We discuss the implications of these results for analysis of anomalous spectral features in recent spectroscopic studies of large aromatic molecules in helium clusters.Comment: 15 pages, 5 figures, submitted to Phys. Rev.

A quantum spin transducer based on nano electro-mechancial resonator arrays

Implementation of quantum information processing faces the contradicting requirements of combining excellent isolation to avoid decoherence with the ability to control coherent interactions in a many-body quantum system. For example, spin degrees of freedom of electrons and nuclei provide a good quantum memory due to their weak magnetic interactions with the environment. However, for the same reason it is difficult to achieve controlled entanglement of spins over distances larger than tens of nanometers. Here we propose a universal realization of a quantum data bus for electronic spin qubits where spins are coupled to the motion of magnetized mechanical resonators via magnetic field gradients. Provided that the mechanical system is charged, the magnetic moments associated with spin qubits can be effectively amplified to enable a coherent spin-spin coupling over long distances via Coulomb forces. Our approach is applicable to a wide class of electronic spin qubits which can be localized near the magnetized tips and can be used for the implementation of hybrid quantum computing architectures

Urinary Collagen Fragments Are Significantly Altered in Diabetes: A Link to Pathophysiology

Background: The pathogenesis of diabetes mellitus (DM) is variable, comprising different inflammatory and immune responses. Proteome analysis holds the promise of delivering insight into the pathophysiological changes associated with diabetes. Recently, we identified and validated urinary proteomics biomarkers for diabetes. Based on these initial findings, we aimed to further validate urinary proteomics biomarkers specific for diabetes in general, and particularity associated with either type 1 (T1D) or type 2 diabetes (T2D). Methodology/Principal Findings: Therefore, the low-molecular-weight urinary proteome of 902 subjects from 10 different centers, 315 controls and 587 patients with T1D (n = 299) or T2D (n = 288), was analyzed using capillary-electrophoresis mass-spectrometry. The 261 urinary biomarkers (100 were sequenced) previously discovered in 205 subjects were validated in an additional 697 subjects to distinguish DM subjects (n = 382) from control subjects (n = 315) with 94% (95% CI: 92-95) accuracy in this study. To identify biomarkers that differentiate T1D from T2D, a subset of normoalbuminuric patients with T1D (n = 68) and T2D (n = 42) was employed, enabling identification of 131 biomarker candidates (40 were sequenced) differentially regulated between T1D and T2D. These biomarkers distinguished T1D from T2D in an independent validation set of normoalbuminuric patients (n = 108) with 88% (95% CI: 81-94%) accuracy, and in patients with impaired renal function (n = 369) with 85% (95% CI: 81-88%) accuracy. Specific collagen fragments were associated with diabetes and type of diabetes indicating changes in collagen turnover and extracellular matrix as one hallmark of the molecular pathophysiology of diabetes. Additional biomarkers including inflammatory processes and pro-thrombotic alterations were observed. Conclusions/Significance: These findings, based on the largest proteomic study performed to date on subjects with DM, validate the previously described biomarkers for DM, and pinpoint differences in the urinary proteome of T1D and T2D, indicating significant differences in extracellular matrix remodeling

Open and hidden agendas of "asymptomatic" patients who request check-up exams

BACKGROUND: Current guidelines for a check-up recommend routine screening not triggered by specific symptoms for some known risk factors and diseases in the general population. Patients' perceptions and expectations regarding a check-up exam may differ from these principles. However, quantitative and qualitative data about the discrepancy between patient- and provider expectations for this type of clinic consultation is lacking. METHODS: For a year, we prospectively enrolled 66 patients who explicitly requested a "check-up" at our medical outpatient division. All patients actively denied upon prompting having any symptoms or specific health concerns at the time they made their appointment. All consultations were videotaped and analysed for information about spontaneously mentioned symptoms and reasons for the clinic consultation ("open agendas") and for cues to hidden patient agendas using the Roter interaction analysis system (RIAS). RESULTS: All patients initially declared to be asymptomatic but this was ultimately the case in only 7 out of 66 patients. The remaining 59 patients spontaneously mentioned a mean of 4.2 ± 3.3 symptoms during their first consultation. In 23 patients a total of 31 hidden agendas were revealed. The primary categories for hidden agendas were health concerns, psychosocial concerns and the patient's concept of disease. CONCLUSIONS: The majority of patients requesting a general check-up tend to be motivated by specific symptoms and health concerns and are not "asymptomatic" patients who primarily come for preventive issues. Furthermore, physicians must be alert for possible hidden agendas, as one in three patients have one or more hidden reasons for requesting a check-up

Local Oxidative and Nitrosative Stress Increases in the Microcirculation during Leukocytes-Endothelial Cell Interactions

Leukocyte-endothelial cell interactions and leukocyte activation are important factors for vascular diseases including nephropathy, retinopathy and angiopathy. In addition, endothelial cell dysfunction is reported in vascular disease condition. Endothelial dysfunction is characterized by increased superoxide (O2•−) production from endothelium and reduction in NO bioavailability. Experimental studies have suggested a possible role for leukocyte-endothelial cell interaction in the vessel NO and peroxynitrite levels and their role in vascular disorders in the arterial side of microcirculation. However, anti-adhesion therapies for preventing leukocyte-endothelial cell interaction related vascular disorders showed limited success. The endothelial dysfunction related changes in vessel NO and peroxynitrite levels, leukocyte-endothelial cell interaction and leukocyte activation are not completely understood in vascular disorders. The objective of this study was to investigate the role of endothelial dysfunction extent, leukocyte-endothelial interaction, leukocyte activation and superoxide dismutase therapy on the transport and interactions of NO, O2•− and peroxynitrite in the microcirculation. We developed a biotransport model of NO, O2•− and peroxynitrite in the arteriolar microcirculation and incorporated leukocytes-endothelial cell interactions. The concentration profiles of NO, O2•− and peroxynitrite within blood vessel and leukocytes are presented at multiple levels of endothelial oxidative stress with leukocyte activation and increased superoxide dismutase accounted for in certain cases. The results showed that the maximum concentrations of NO decreased ∼0.6 fold, O2•− increased ∼27 fold and peroxynitrite increased ∼30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions. The results show that the onset of endothelial oxidative stress can cause an increase in O2•− and peroxynitrite concentration in the lumen. The increased O2•− and peroxynitrite can cause leukocytes priming through peroxynitrite and leukocytes activation through secondary stimuli of O2•− in bloodstream without endothelial interaction. This finding supports that leukocyte rolling/adhesion and activation are independent events

Mycobacterial PIMs Inhibit Host Inflammatory Responses through CD14-Dependent and CD14-Independent Mechanisms

Mycobacteria develop strategies to evade the host immune system. Among them, mycobacterial LAM or PIMs inhibit the expression of pro-inflammatory cytokines by activated macrophages. Here, using synthetic PIM analogues, we analyzed the mode of action of PIM anti-inflammatory effects. Synthetic PIM1 isomer and PIM2 mimetic potently inhibit TNF and IL-12 p40 expression induced by TLR2 or TLR4 pathways, but not by TLR9, in murine macrophages. We show inhibition of LPS binding to TLR4/MD2/CD14 expressing HEK cells by PIM1 and PIM2 analogues. More specifically, the binding of LPS to CD14 was inhibited by PIM1 and PIM2 analogues. CD14 was dispensable for PIM1 and PIM2 analogues functional inhibition of TLR2 agonists induced TNF, as shown in CD14-deficient macrophages. The use of rough-LPS, that stimulates TLR4 pathway independently of CD14, allowed to discriminate between CD14-dependent and CD14-independent anti-inflammatory effects of PIMs on LPS-induced macrophage responses. PIM1 and PIM2 analogues inhibited LPS-induced TNF release by a CD14-dependent pathway, while IL-12 p40 inhibition was CD14-independent, suggesting that PIMs have multifold inhibitory effects on the TLR4 signalling pathway

Plant perception of β-aminobutyric acid is mediated by an aspartyl-tRNA synthetase

Specific chemicals can prime the plant immune system for augmented defense. β-aminobutyric acid (BABA) is a priming agent that provides broad-spectrum disease protection. However, BABA also suppresses plant growth when applied in high doses, which has hampered its application as a crop defense activator. Here we describe a mutant of Arabidopsis thaliana that is impaired in BABA-induced disease immunity (ibi1) but is hypersensitive to BABA-induced growth repression. IBI1 encodes an aspartyl-tRNA synthetase. Enantiomer-specific binding of the R enantiomer of BABA to IBI1 primed the protein for noncanonical defense signaling in the cytoplasm after pathogen attack. This priming was associated with aspartic acid accumulation and tRNA-induced phosphorylation of translation initiation factor eIF2α. However, mutation of eIF2α-phosphorylating GCN2 kinase did not affect BABA-induced immunity but relieved BABA-induced growth repression. Hence, BABA-activated IBI1 controls plant immunity and growth via separate pathways. Our results open new opportunities to separate broad-spectrum disease resistance from the associated costs on plant growth