Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress

Introduction: The etiology of radiation-induced erectile dysfunction (ED) is complex and multifactorial, and it appears to be mainly atherogenic. Aim: To focus on vascular aspects of radiation-induced ED and to elucidate whether the protective effects of sildenafil are mediated by attenuation of oxidative stress and apoptosis in the endothelial cells. Methods: Bovine aortic endothelial cells (BAECs), with or without pretreatment of sildenafil (5 μM at 5 minutes before radiation), were used to test endothelial dysfunction in response to external beam radiation at 10–15 Gy. Generation of reactive oxygen species (ROS) was studied. Extracellular hydrogen peroxide (H2O2) was measured using the Amplex Red assay and intracellular H2O2 using a fluorescent sensor. In addition, ROS superoxide (O2•-) was measured using a O2•- chemiluminescence enhancer. Both H2O2 and O2•- are known to reduce the bioavailability of nitric oxide, which is the most significant chemical mediator of penile erection. Generation of cellular peroxynitrite (ONOO−) was measured using a chemiluminescence assay with the PNCL probe. Subsequently, we measured the activation of acid sphingomyelinase (ASMase) enzyme by radioenzymatic assay using [14C-methylcholine] sphingomyelin as substrate, and the generation of the proapoptotic C16-ceramide was assessed using the diacylglycerol kinase assay. Endothelial cells apoptosis was measured as a readout of these cells’ dysfunction. Main Outcome Measures: Single high-dose radiation therapy induced NADPH oxidases (NOXs) activation and ROS generation via the proapoptotic ASMase/ceramide pathway. The radio-protective effect of sildenafil on BAECs was due to inhibition of this pathway. Results: Here, we demonstrate for the first time that radiation activated NOXs and induced generation of ROS in BAECs. In addition, we showed that sildenafil significantly reduced radiation-induced O2•- and as a result there was reduction in the generation of peroxynitrite in these cells. Subsequently, sildenafil protected the endothelial cells from radiation therapy-induced apoptosis. Strengths and Limitations: This is the first study demonstrating that single high-dose radiation therapy induced NOXs activation, resulting in the generation of O2•- and peroxynitrite in endothelial cells. Sildenafil reduced ROS generation by inhibiting the ASMase/ceramide pathway. These studies should be followed in an animal model of ED. Conclusions: This study demonstrated that sildenafil protects BAECs from radiation-induced oxidative stress by reducing NOX-induced ROS generation, thus resulting in decreased endothelial dysfunction. Therefore, it provides a potential mechanism to better understand the atherogenic etiology of postradiation ED. Wortel RC, Mizrachi A, Li H, et al. Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress. J Sex Med 2019;16:1721–1733. © 201

Hadronic Contributions to the Muon Anomaly in the Constituent Chiral Quark Model

The hadronic contributions to the anomalous magnetic moment of the muon which are relevant for the confrontation between theory and experiment at the present level of accuracy, are evaluated within the same framework: the constituent chiral quark model. This includes the contributions from the dominant hadronic vacuum polarization as well as from the next--to--leading order hadronic vacuum polarization, the contributions from the hadronic light-by-light scattering, and the contributions from the electroweak hadronic $Z\gamma\gamma$ vertex. They are all evaluated as a function of only one free parameter: the constituent quark mass. We also comment on the comparison between our results and other phenomenological evaluations.Comment: Several misprints corrected and a clarifying sentence added. Three figures superposed and two references added. Version to appear in JHE

Gauge links for transverse momentum dependent correlators at tree-level

In this paper we discuss the incorporation of gauge links in hadronic matrix elements that describe the soft hadronic physics in high energy scattering processes. In this description the matrix elements appear in soft correlators and they contain non-local combinations of quark and gluon fields. In our description we go beyond the collinear approach in which case also the dependence on transverse momenta of partons is taken into consideration. The non-locality in the transverse direction leads to a complex gauge link structure for the full process, in which color is entangled, even at tree-level. We show that at tree-level in a 1-parton unintegrated (1PU) situation, in which only the transverse momentum of one of the initial state hadrons is relevant, one can get a factorized expression involving transverse momentum dependent (TMD) distribution functions. We point out problems at the level of two initial state hadrons, even for relatively simple processes such as Drell-Yan scattering.Comment: 25 pages, corrected typos and updated reference

Deriving the number of jobs in proximity services from the number of inhabitants in French rural municipalities

We use a minimum requirement approach to derive the number of jobs in proximity services per inhabitant in French rural municipalities. We first classify the municipalities according to their time distance to the municipality where the inhabitants go the most frequently to get services (called MFM). For each set corresponding to a range of time distance to MFM, we perform a quantile regression estimating the minimum number of service jobs per inhabitant, that we interpret as an estimation of the number of proximity jobs per inhabitant. We observe that the minimum number of service jobs per inhabitant is smaller in small municipalities. Moreover, for municipalities of similar sizes, when the distance to the MFM increases, we find that the number of jobs of proximity services per inhabitant increases.Comment: 6 pages, 5 figure

Light-Front Quantum Chromodynamics: A framework for the analysis of hadron physics

White Paper of International Light Cone Advisory CommitteeAn outstanding goal of physics is to find solutions that describe hadrons in the theory of strong interactions, Quantum Chromodynamics (QCD). For this goal, the light-front Hamiltonian formulation of QCD (LFQCD) is a complementary approach to the well-established lattice gauge method. LFQCD offers access to the hadrons' nonperturbative quark and gluon amplitudes, which are directly testable in experiments at existing and future facilities. We present an overview of the promises and challenges of LFQCD in the context of unsolved issues in QCD that require broadened and accelerated investigation. We identify specific goals of this approach and address its quantifiable uncertainties

Current quark mass dependence of nucleon magnetic moments and radii

A calculation of the current-quark-mass-dependence of nucleon static electromagnetic properties is necessary in order to use observational data as a means to place constraints on the variation of Nature's fundamental parameters. A Poincare' covariant Faddeev equation, which describes baryons as composites of confined-quarks and -nonpointlike-diquarks, is used to calculate this dependence The results indicate that, like observables dependent on the nucleons' magnetic moments, quantities sensitive to their magnetic and charge radii, such as the energy levels and transition frequencies in Hydrogen and Deuterium, might also provide a tool with which to place limits on the allowed variation in Nature's constants.Comment: 23 pages, 2 figures, 4 tables, 4 appendice

Inclusive double-quarkonium production at the Large Hadron Collider

Based on the nonrelativistic QCD (NRQCD) factorization formalism, we investigate inclusive productions of two spin-triplet S-wave quarkonia pp->2J/psi+X, 2Upsilon+X, and J/psi+Upsilon+X at the CERN Large Hadron Collider. The total production rates integrated over the rapidity (y) and transverse-momentum (p_T) ranges |y|<2.4 and p_T<50 GGeV are predicted to be sigma[pp->2J/psi+X] = 22 (35) nb, sigma[pp->2Upsilon+X] = 24 (49) pb, and sigma[pp->J/psi+Upsilon+X] = 7 (13) pb at the center-of-momentum energy sqrt{s} = 7 (14) TeV. In order to provide predictions that can be useful in both small- and large-p_T regions, we do not employ the fragmentation approximation and we include the spin-triplet S-wave color-singlet and color-octet channels for each quarkonium final state at leading order in the strong coupling. The p_T distributions of pp->2J/psi+X and 2Upsilon+X in the low-p_T region are dominated by the color-singlet contributions. At leading order in the strong coupling, the color-singlet channel is absent for pp->J/psi+Upsilon+X. Therefore, the process pp->J/psi+Upsilon+X may provide a useful probe to the color-octet mechanism of NRQCD.Comment: 26 pages, 7 figures, 3 tables, version published in JHE

Charged-Lepton Flavour Physics

This writeup of a talk at the 2011 Lepton-Photon symposium in Mumbai, India, summarises recent results in the charged-lepton flavour sector. I review searches for charged-lepton flavour violation, lepton electric dipole moments and flavour-conserving CP violation. I also discuss recent progress in tau-lepton physics and in the Standard Model prediction of the muon anomalous magnetic moment.Comment: Presented at Lepton-Photon 2011, Mumbai, India; 23 pages, 14 figure

An intervention program to reduce the number of hospitalizations of elderly patients in a primary care clinic

<p>Abstract</p> <p>Background</p> <p>The elderly population consumes a large share of medical resources in the western world. A significant portion of the expense is related to hospitalizations.</p> <p>Objectives</p> <p>To evaluate an intervention program designed to reduce the number of hospitalization of elderly patients by a more optimal allocation of resources in primary care.</p> <p>Methods</p> <p>A multidimensional intervention program was conducted that included the re-engineering of existing work processes with a focus on the management of patient problems, improving communication with outside agencies, and the establishment of a system to monitor quality of healthcare parameters. Data on the number of hospitalizations and their cost were compared before and after implementation of the intervention program.</p> <p>Results</p> <p>As a result of the intervention the mean expenditure per elderly patient was reduced by 22.5%. The adjusted number of hospitalizations/1,000 declined from 15.1 to 10.7 (29.3%). The number of adjusted hospitalization days dropped from 132 to 82 (37.9%) and the mean hospitalization stay declined from 8.2 to 6.7 days (17.9%). The adjusted hospitalization cost ($/1,000 patients) dropped from$32,574 to $18,624 (42.8%). The overall clinic expense, for all age groups, dropped by 9.9%.</p> <p>Conclusion</p> <p>Implementation of the intervention program in a single primary care clinic led to a reduction in hospitalizations for the elderly patient population and to a more optimal allocation of healthcare resources.</p