Effects of Delayed NSAID Administration After Experimental Eccentric Contraction Injury – A Cellular and Proteomics Study

Background Acute muscle injuries are exceedingly common and non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed to reduce the associated inflammation, swelling and pain that peak 1–2 days post-injury. While prophylactic use or early administration of NSAIDs has been shown to delay muscle regeneration and contribute to loss of muscle strength after healing, little is known about the effects of delayed NSAID use. Further, NSAID use following non-penetrating injury has been associated with increased risk and severity of infection, including that due to group A streptococcus, though the mechanisms remain to be elucidated. The present study investigated the effects of delayed NSAID administration on muscle repair and sought mechanisms supporting an injury/NSAID/infection axis. Methods A murine model of eccentric contraction (EC)-induced injury of the tibialis anterior muscle was used to profile the cellular and molecular changes induced by ketorolac tromethamine administered 47 hr post injury. Results NSAID administration inhibited several important muscle regeneration processes and down-regulated multiple cytoprotective proteins known to inhibit the intrinsic pathway of programmed cell death. These activities were associated with increased caspase activity in injured muscles but were independent of any NSAID effect on macrophage influx or phenotype switching. Conclusions These findings provide new molecular evidence supporting the notion that NSAIDs have a direct negative influence on muscle repair after acute strain injury in mice and thus add to renewed concern about the safety and benefits of NSAIDS in both children and adults, in those with progressive loss of muscle mass such as the elderly or patients with cancer or AIDS, and those at risk of secondary infection after trauma or surgery

Cosmic bubble and domain wall instabilities III: The role of oscillons in three-dimensional bubble collisions

We study collisions between pairs of bubbles nucleated in an ambient false vacuum. For the first time, we include the effects of small initial (quantum) fluctuations around the instanton profiles describing the most likely initial bubble profile. Past studies of this problem neglect these fluctuations and work under the assumption that the collisions posess an exact SO(2,1) symmetry. We use three-dimensional lattice simulations to demonstrate that for double-well potentials, small initial perturbations to this symmetry can be amplified as the system evolves. Initially the amplification is well-described by linear perturbation theory around the SO(2,1) background, but the onset of strong nonlinearities amongst the fluctuations quickly leads to a drastic breaking of the original SO(2,1) symmetry and the production of oscillons in the collision region. We explore several single-field models, and we find it is hard to both realize inflation inside of a bubble and produce oscillons in a collision. Finally, we extend our results to a simple two-field model. The additional freedom allowed by the second field allows us to construct viable inflationary models that allow oscillon production in collisions. The breaking of the SO(2,1) symmetry allows for a new class of observational signatures from bubble collisions that do not posess azimuthal symmetry, including the production of gravitational waves which cannot be supported by an SO(2,1) spacetime.Comment: 35 pages + references, 26 figures. Submitted to JCAP. v2: Acknowledgments updates, no other change

Cosmic bubble and domain wall instabilities I: parametric amplification of linear fluctuations

This is the first paper in a series where we study collisions of nucleated bubbles taking into account the effects of small initial (quantum) fluctuations in a fully 3+1-dimensional setting. In this paper, we consider the evolution of linear fluctuations around highly symmetric though inhomogeneous backgrounds. We demonstrate that a large degree of asymmetry develops over time from tiny fluctuations superposed upon planar and SO(2,1) symmetric backgrounds. These fluctuations arise from zero-point vacuum oscillations, so excluding them by enforcing a spatial symmetry is inconsistent in a quantum treatment. We consider the limit of two colliding planar walls, with fluctuation mode functions characterized by the wavenumber transverse to the collision direction and a longitudinal shape along the collision direction $x$, which we solve for. Initially, the fluctuations obey a linear wave equation with a time- and space-dependent mass $m_{eff}(x,t)$. When the walls collide multiple times, $m_{eff}$ oscillates in time. We use Floquet theory to study the fluctuations and generalize techniques familiar from preheating to the case with many coupled degrees of freedom. This inhomogeneous case has bands of unstable transverse wavenumbers $k_\perp$ with exponentially growing mode functions. From the detailed spatial structure of the mode functions in $x$, we identify both broad and narrow parametric resonance generalizations of the homogeneous $m_{eff}(t)$ case of preheating. The unstable $k_\perp$ modes are longitudinally localized, yet can be described as quasiparticles in the Bogoliubov sense. We define an effective occupation number to show they are created in bursts for the case of well-defined collisions in the background. The transverse-longitudinal coupling accompanying nonlinearity radically breaks this localized particle description, with nonseparable 3D modes arising.Comment: 37 pages + references, 20 figures, submitted to JCA

Cosmic bubble and domain wall instabilities II: Fracturing of colliding walls

We study collisions between nearly planar domain walls including the effects of small initial nonplanar fluctuations. These perturbations represent the small fluctuations that must exist in a quantum treatment of the problem. In a previous paper, we demonstrated that at the linear level a subset of these fluctuations experience parametric amplification as a result of their coupling to the planar symmetric background. Here we study the full three-dimensional nonlinear dynamics using lattice simulations, including both the early time regime when the fluctuations are well described by linear perturbation theory as well as the subsequent stage of fully nonlinear evolution. We find that the nonplanar fluctuations have a dramatic effect on the overall evolution of the system. Specifically, once these fluctuations begin to interact nonlinearly the split into a planar symmetric part of the field and the nonplanar fluctuations loses its utility. At this point the colliding domain walls dissolve, with the endpoint of this being the creation of a population of oscillons in the collision region. The original (nearly) planar symmetry has been completely destroyed at this point and an accurate study of the system requires the full three-dimensional simulation.Comment: 23 pages + references, 13 figures. Submitted to JCAP. v2: Acknowledgements updated, no other change

Social Media Does Not Elicit a Physiological Stress Response as Measured by Heart Rate and Salivary Cortisol Over 20-Minute Sessions of Cell Phone Use

The pervasive use of social media has raised concerns about its potential detrimental effects on physical and mental health. Others have demonstrated a relationship between social media use and anxiety, depression, and psychosocial stress. In light of these studies, we examined physiological indicators of stress (heart rate to measure autonomic nervous system activation and cortisol to assess activity of the hypothalamic-pituitary-adrenal axis) associated with social media use and investigated possible moderating influences of sex, age, and psychological parameters. We collected physiological data from 59 subjects ranging in age from 13 to 55 across two cell phone treatments: social media use and a pre-selected YouTube playlist. Heart rate was measured using arm-band heart rate monitors before and during cell phone treatments, and saliva was collected for later cortisol analysis (by enzyme immunoassay) before and after each of the two cell phone treatments. To disentangle the effects of cell phone treatment from order of treatment, we used a crossover design in which participants were randomized to treatment order. Our study uncovered a significant period effect suggesting that both heart rate and cortisol decreased over the duration of our experiment, irrespective of the type of cell phone activity or the order of treatments. There was no indication that age, sex, habits of social media use, or psychometric parameters moderated the physiological response to cell phone activities. Our data suggest that 20-minute bouts of social media use or YouTube viewing do not elicit a physiological stress response