Macrophage autophagy in atherosclerosis

Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP) in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility

Self-cooling of a movable mirror to the ground state using radiation pressure

We show that one can cool a micro-mechanical oscillator to its quantum ground state using radiation pressure in an appropriately detuned cavity (self-cooling). From a simple theory based on Heisenberg-Langevin equations we find that optimal self-cooling occurs in the good cavity regime, when the cavity bandwidth is smaller than the mechanical frequency, but still larger than the effective mechanical damping. In this case the intracavity field and the vibrational mechanical mode coherently exchange their fluctuations. We also present dynamical calculations which show how to access the mirror final temperature from the fluctuations of the field reflected by the cavity.Comment: 4 pages, 3 figure

Mapping the interaction of B cell Leukemia 3 (BCL-3) and nuclear factor κB (NF-κB) p50 identifies a BCL-3-mimetic anti-inflammatory peptide

The NF-κB transcriptional response is tightly regulated by a number of processes including the phosphorylation, ubiquitination, and subsequent proteasomal degradation of NF-κB subunits. The IκB family protein BCL-3 stabilizes a NF-κB p50 homodimer·DNA complex through inhibition of p50 ubiquitination. This complex inhibits the binding of the transcriptionally active NF-κB subunits p65 and c-Rel on the promoters of NF-κB target genes and functions to suppress inflammatory gene expression. We have previously shown that the direct interaction between p50 and BCL-3 is required for BCL-3-mediated inhibition of pro-inflammatory gene expression. In this study we have used immobilized peptide array technology to define regions of BCl-3 that mediate interaction with p50 homodimers. Our data show that BCL-3 makes extensive contacts with p50 homodimers and in particular with ankyrin repeats (ANK) 1, 6, and 7, and the N-terminal region of Bcl-3. Using these data we have designed a BCL-3 mimetic peptide based on a region of the ANK1 of BCL-3 that interacts with p50 and shares low sequence similarity with other IκB proteins. When fused to a cargo carrying peptide sequence this BCL-3-derived peptide, but not a mutated peptide, inhibited Toll-like receptor-induced cytokine expression in vitro. The BCL-3 mimetic peptide was also effective in preventing inflammation in vivo in the carrageenan-induced paw edema mouse model. This study demonstrates that therapeutic strategies aimed at mimicking the functional activity of BCL-3 may be effective in the treatment of inflammatory disease

Quantum noise in ideal operational amplifiers

We consider a model of quantum measurement built on an ideal operational amplifier operating in the limit of infinite gain, infinite input impedance and null output impedance and with a feddback loop. We evaluate the intensity and voltage noises which have to be added to the classical amplification equations in order to fulfill the requirements of quantum mechanics. We give a description of this measurement device as a quantum network scattering quantum fluctuations from input to output ports.Comment: 4 pages, 2 figures, RevTe

Inhibition of in-stent stenosis by oral administration of bindarit in porcine coronary arteries

<p><b>Objective:</b> We have previously demonstrated that bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs), is effective in reducing neointimal formation in rodent models of vascular injury by reducing smooth muscle cell proliferation and migration and neointimal macrophage content, effects associated with the inhibition of MCP-1/CCL2 production. The aim of the current study was to evaluate the efficacy of bindarit on in-stent stenosis in the preclinical porcine coronary stent model.</p> <p><b>Methods and Results:</b> One or 2 bare metal stents (Multi-Link Vision, 3.5 mm) were deployed (1:1.2 oversize ratio) in the coronary arteries of 42 pigs (20 bindarit versus 22 controls). Bindarit (50 mg/kg per day) was administered orally from 2 days before stenting until the time of euthanasia at 7 and 28 days. Bindarit caused a significant reduction in neointimal area (39.4%, P<0.001, n=9 group), neointimal thickness (51%, P<0.001), stenosis area (37%, P<0.001), and inflammatory score (40%, P<0.001) compared with control animals, whereas there was no significant difference in the injury score between the 2 groups. Moreover, treatment with bindarit significantly reduced the number of proliferating cells (by 45%, P<0.05; n=6 group) and monocyte/macrophage content (by 55%, P<0.01; n=5–6 group) in stented arteries at day 7 and 28, respectively. These effects were associated with a significant (P<0.05) reduction of MCP-1 plasma levels at day 28. In vitro data showed that bindarit (10–300 micromol/L) reduced tumor necrosis factor-alpha (50 ng/mL)–induced pig coronary artery smooth muscle cell proliferation and inhibited MCP-1 production.</p> <p><b>Conclusion:</b> Our results show the efficacy of bindarit in the prevention of porcine in-stent stenosis and support further investigation for clinical application of this compound.</p&gt

Back-action cancellation in interferometers by quantum locking

We show that back-action noise in interferometric measurements such as gravitational-waves detectors can be completely suppressed by a local control of mirrors motion. An optomechanical sensor with an optimized measurement strategy is used to monitor mirror displacements. A feedback loop then eliminates radiation-pressure effects without adding noise. This very efficient technique leads to an increased sensitivity for the interferometric measurement, which becomes only limited by phase noise. Back-action cancellation is furthermore insensitive to losses in the interferometer.Comment: 4 pages, 3 figures, RevTe

Quantum fluctuations for drag free geodesic motion

The drag free technique is used to force a proof mass to follow a geodesic motion. The mass is protected from perturbations by a cage, and the motion of the latter is actively controlled to follow the motion of the proof mass. We present a theoretical analysis of the effects of quantum fluctuations for this technique. We show that a perfect drag free operation is in principle possible at the quantum level, in spite of the back action exerted on the mass by the position sensor.Comment: 4 pages, 1 figure, RevTeX, minor change

The IkB kinase inhibitor nuclear factor-kB essential modulator–binding domain peptide for inhibition of balloon injury-induced neointimal formation

Objective—The activation of nuclear factor-kB (NF-kB) is a crucial step in the arterial wall’s response to injury. The identification and characterization of the NF-kB essential modulator– binding domain (NBD) peptide, which can block the activation of the IkB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-kB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation.<br></br> Methods and Results—In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 microg/site) significantly reduced the number of proliferating cells at day 7 (by 40%; P<0.01) and reduced injury-induced neointimal formation (by 50%; P<0.001) at day 14. These effects were associated with a significant reduction of NF-kB activation and monocyte chemotactic protein-1 expression in the carotid arteries of rats treated with the peptide. In addition, the NBD peptide (0.01 to 1 micromol/L) reduced rat smooth muscle cell proliferation, migration, and invasion in vitro. Similar results were observed in apolipoprotein E-/-, mice in which the NBD peptide (150 microg/site) reduced wire-induced neointimal formation at day 28 (by 47%; P<0.01).<br></br> Conclusion—The NBD peptide reduces neointimal formation and smooth muscle cell proliferation/migration, both effects associated with the inhibition of NF-kB activation

Frontal brain asymmetries as effective parameters to assess the quality of audiovisual stimuli perception in adult and young cochlear implant users

How is music perceived by cochlear implant (CI) users? This question arises as "the next step" given the impressive performance obtained by these patients in language perception. Furthermore, how can music perception be evaluated beyond self-report rating, in order to obtain measurable data? To address this question, estimation of the frontal electroencephalographic (EEG) alpha activity imbalance, acquired through a 19-channel EEG cap, appears to be a suitable instrument to measure the approach/withdrawal (AW index) reaction to external stimuli. Specifically, a greater value of AW indicates an increased propensity to stimulus approach, and vice versa a lower one a tendency to withdraw from the stimulus. Additionally, due to prelingually and postlingually deafened pathology acquisition, children and adults, respectively, would probably differ in music perception. The aim of the present study was to investigate children and adult CI users, in unilateral (UCI) and bilateral (BCI) implantation conditions, during three experimental situations of music exposure (normal, distorted and mute). Additionally, a study of functional connectivity patterns within cerebral networks was performed to investigate functioning patterns in different experimental populations. As a general result, congruency among patterns between BCI patients and control (CTRL) subjects was seen, characterised by lowest values for the distorted condition (vs. normal and mute conditions) in the AW index and in the connectivity analysis. Additionally, the normal and distorted conditions were significantly different in CI and CTRL adults, and in CTRL children, but not in CI children. These results suggest a higher capacity of discrimination and approach motivation towards normal music in CTRL and BCI subjects, but not for UCI patients. Therefore, for perception of music CTRL and BCI participants appear more similar than UCI subjects, as estimated by measurable and not self-reported parameters

Endoscopic management of gastrointestinal leaks and fistulae: What option do we have?

Gastrointestinal leaks and fistulae are serious, potentially life threatening conditions that may occur with a wide variety of clinical presentations. Leaks are mostly related to post-operative anastomotic defects and are responsible for an important share of surgical morbidity and mortality. Chronic leaks and long standing post-operative collections may evolve in a fistula between two epithelialized structures. Endoscopy has earned a pivotal role in the management of gastrointestinal defects both as first line and as rescue treatment. Endotherapy is a minimally invasive, effective approach with lower morbidity and mortality compared to revisional surgery. Clips and luminal stents are the pioneer of gastrointestinal (GI) defect endotherapy, whereas innovative endoscopic closure devices and techniques, such as endoscopic internal drainage, suturing system and vacuum therapy, has broadened the indications of endoscopy for the management of GI wall defect. Although several endoscopic options are currently used, a standardized evidence-based algorithm for management of GI defect is not available. Successful management of gastrointestinal leaks and fistulae requires a tailored and multidisciplinary approach based on clinical presentation, defect features (size, location and onset time), local expertise and the availability of devices. In this review, we analyze different endoscopic approaches, which we selected on the basis of the available literature and our own experience. Then, we evaluate the overall efficacy and procedural-specific strengths and weaknesses of each approach