Non-invasive assessment of arterial stiffness using oscillometric blood pressure measurement

<p>Abstract</p> <p>Background</p> <p>Arterial stiffness is a major contributor to cardiovascular diseases. Because current methods of measuring arterial stiffness are technically demanding, the purpose of this study was to develop a simple method of evaluating arterial stiffness using oscillometric blood pressure measurement.</p> <p>Methods</p> <p>Blood pressure was conventionally measured in the left upper arm of 173 individuals using an inflatable cuff. Using the time series of occlusive cuff pressure and the amplitudes of pulse oscillations, we calculated local slopes of the curve between the decreasing cuff pressure and corresponding arterial volume. Whole pressure-volume curve was derived from numerical integration of the local slopes. The curve was fitted using an equation and we identified a numerical coefficient of the equation as an index of arterial stiffness (Arterial Pressure-volume Index, API). We also measured brachial-ankle (baPWV) PWV and carotid-femoral (cfPWV) PWV using a vascular testing device and compared the values with API. Furthermore, we assessed carotid arterial compliance using ultrasound images to compare with API.</p> <p>Results</p> <p>The slope of the calculated pressure-volume curve was steeper for compliant (low baPWV or cfPWV) than stiff (high baPWV or cfPWV) arteries. API was related to baPWV (<it>r </it>= -0.53, <it>P </it>< 0.05), cfPWV (<it>r </it>= -0.49, <it>P </it>< 0.05), and carotid arterial compliance (<it>r </it>= 0.32, <it>P </it>< 0.05). A stepwise multiple regression analysis demonstrated that baPWV and carotid arterial compliance were the independent determinants of API, and that API was the independent determinant of baPWV and carotid arterial compliance.</p> <p>Conclusions</p> <p>These results suggest that our method can simply and simultaneously evaluate arterial stiffness and blood pressure based on oscillometric measurements of blood pressure.</p

Search for Lepton Flavor Violating Decay at FASER

FASER is one of the promising experiments which search for long-lived particles beyond the Standard Model. In this paper, we consider charged lepton flavor violation (CLFV) via a light and weakly interacting boson and discuss the detectability by FASER. We focus on four types of CLFV interactions, i.e., the scalar-, pseudoscalar-, vector-, and dipole-type interaction, and calculate the sensitivity of FASER to each CLFV interaction. We show that, with the setup of FASER2, a wide region of the parameter space can be explored. Particularly, it is found that FASER2 has a sensitivity to very small coupling regions in which the rare muon decays, such as $\mu \rightarrow e\gamma$, cannot place bounds, and that there is a possibility to detect CLFV decays of the new light bosons.Comment: 27 pages; v2: minor changes, final versio

Dark Photon from Light Scalar Boson Decays at FASER

FASER is one of the promising experiments which search for long-lived particles beyond the Standard Model. In this paper, we focus on dark photon associating with an additional U(1) gauge symmetry, and also a scalar boson breaking this U(1) gauge symmetry. We study the sensitivity to the dark photon originated from U(1)-breaking scalar decays. We find that a sizable number of dark photon signatures can be expected in wider parameter space than previous studies.Comment: 12 pages, 3 figures; v2: typos corrected, discussions and references added; v3: added references, figures, and comments on the light scalar case, calculated event number by Monte Carlo simulations, version to be published in JHE

New Constraint on Dark Photon at T2K Off-Axis Near Detector

The T2K experiment is one of the most powerful long-baseline experiments to investigate neutrino oscillations. The off-axis near detector called ND280 is installed 280 m downstream from the neutrino production target to measure the neutrino energy spectrum. In this paper, we study the capability of the ND280 detector to search for the dark photon produced through the meson rare decay and proton bremsstrahlung processes at the proton beam dump. We find that the ten-year operation of T2K with the ND280 detector excludes the unexplored parameter region for the dark photon mass and kinetic mixing. We also show that a broader parameter region can be searched by the ND280 in the future T2K operation for dark photon as well as U(1)$_{B-L}$ gauge boson.Comment: v1: 22 pages, v2: 23 pages, discussion on background added, acccepted versio

Necdin modulates leukemia-initiating cell quiescence and chemotherapy response

Acute myeloid leukemia (AML) is a devastating illness which carries a very poor prognosis, with most patients living less than 18 months. Leukemia relapse may occur because current therapies eliminate proliferating leukemia cells but fail to eradicate quiescent leukemia-initiating cells (LICs) that can reinitiate the disease after a period of latency. While we demonstrated that p53 target gene Necdin maintains hematopoietic stem cell (HSC) quiescence, its roles in LIC quiescence and response to chemotherapy are unclear. In this study, we utilized two well-established murine models of human AML induced by MLL-AF9 or AML1-ETO9a to determine the role of Necdin in leukemogenesis. We found that loss of Necdin decreased the number of functional LICs and enhanced myeloid differentiation in vivo, leading to delayed development of leukemia induced by MLL-AF9. Importantly, Necdin null LICs expressing MLL-AF9 were less quiescent than wild-type LICs. Further, loss of Necdin enhanced the response of MLL-AF9+ leukemia cells to chemotherapy treatment, manifested by decreased viability and enhanced apoptosis. We observed decreased expression of Bcl2 and increased expression of p53 and its target gene Bax in Necdin null leukemia cells following chemotherapy treatment, indicating that p53-dependent apoptotic pathways may be activated in the absence of Necdin. In addition, we found that loss of Necdin decreased the engraftment of AML1-ETO9a+ hematopoietic stem and progenitor cells in transplantation assays. However, Necdin-deficiency did not affect the response of AML1-ETO9a+ hematopoietic cells to chemotherapy treatment. Thus, Necdin regulates leukemia-initiating cell quiescence and chemotherapy response in a context-dependent manner. Our findings suggest that pharmacological inhibition of Necdin may hold potential as a novel therapy for leukemia patients with MLL translocations

Mineralocorticoid receptor stimulation induces urinary storage dysfunction via upregulation of epithelial sodium channel expression in the rat urinary bladder epithelium

AbstractWe aimed to evaluate mineralocorticoid receptor (MR) expression in rat bladder and the physiological role of the MR-epithelial sodium channel (ENaC) pathway in controlling bladder function in 10–12-week-old, male Sprague–Dawley rats. First, we examined the mRNA expression of MR and localization of MR and ENaC-α proteins in the urinary bladder. MR mRNA expression was observed in untreated-rat urinary bladders, and MR and ENaC-α proteins were localized in the epithelium. Next, rats were treated with vehicle (controls) or fludrocortisone (an MR agonist) for 3 days, and ENaC-α protein expression levels and bladder function were evaluated on day 4. ENaC-α protein expression was significantly higher in fludrocortisone-treated rats than in controls. In addition, cystometry was performed during intravesical infusion of saline and amiloride (an ENaC inhibitor). While intercontraction intervals (ICIs) during saline infusion were significantly shorter in the fludrocortisone group than in the controls, infusion of amiloride normalized the ICIs in the fludrocortisone group. However, no intra- or inter-group differences in maximum intravesical pressure were observed. Taken together, MR protein is localized in the rat urinary bladder epithelium, and may regulate ENaC expression and bladder afferent input. The MR-ENaC pathway may be a therapeutic target for ameliorating storage symptoms