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

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

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

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

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

Temporal changes in impedance of implanted adults for various cochlear segments

La prima valutazione oggettiva effettuata durante la procedura chirurgica e nel follow-up dei pazienti sottoposti ad impianto cocleare è la misura dellimpedenza degli elettrodi. Tale misura fornisce informazioni sia sullintegrità degli elettrodi sia sul mezzo circostante gli stessi ed è uno dei principali fattori responsabili dei consumi energetici dellimpianto cocleare. In questo studio abbiamo valutato in pazienti adulti con impianto cocleare e array perimodiolare, le variazioni nel tempo dellimpedenza degli elettrodi, valutando le differenze nelle varie partizioni cocleari (basale, medio e apicale) e correlandone i valori ai principali parametri psicoacustici del mappaggio: livelli di T e C. Abbiamo testato 28 pazienti adulti impiantati presso il nostro Dipartimento tra il 2009 e il 2014, tutti impiantati per via cocleostomica con un array perimodiolare completamente inserito, utilizzando la tecnica chirurgia soft surgery. Le impedenze medie sono state misurate in modalità common-ground e MP1+2 per i seguenti segmenti di array: basale (dallelettrodo n.1 al n.7); mediale (dal n.8 al n.14); apicale (dal n.15 al n.22). Lanalisi della varianza (ANOVA) è stata effettuata per valutare le tendenze nelle misure ripetute. Il livello di significatività accettato in tale studio è p<0.05 corretto con metodo Bonferroni. I risultati hanno mostrato una significativa riduzione globale delle impedenze dallattivazione fino a 1 mese e un valore più alto nel tempo dell impedenza nel segmento basale dellarray rispetto al segmento apicale e medio. Lanalisi statistica temporale della correlazione tra i valori dellimpedenza globale e i livelli di T e C ha mostrato una correlazione significativa fino a sei mesi sia per le impedenze registrate in common-ground che in modalità MP1+2. Lanalisi statistica dei vari segmenti cocleari ha mostrato inoltre una significativa correlazione dellimpedenza nel segmento basale e i parametri del fitting fino ad un anno di follow-up. In conclusione gli alti valori dell impedenza nel segmento basale nel tempo possono essere spiegati con la formazione di fibrosi endococleare dopo linserimento dellarray, fenomeno maggiore nel segmento basale della coclea, limitato invece nelle regioni apicali e medie. La correlazione lineare dei valori dellimpedenza con i livelli di T e C diventa infatti statisticamente non significativa dopo tre/sei mesi nei segmenti apicali e medi e resta significativa fino ad un anno per il tratto basale. Questo comportamento sottolinea limportanza nel tempo dellinfluenza dei fattori intra-cocleari sui parametri del fitting nella porzione cocleare basale

DNA uptake into nuclei: Numerical and analytical results

The dynamics of polymer translocation through a pore has been the subject of recent theoretical and experimental works. We have considered theoretical estimates and performed computer simulations to understand the mechanism of DNA uptake into the cell nucleus, a phenomenon experimentally investigated by attaching a small bead to the free end of the double helix and pulling this bead with the help of an optical trap. The experiments show that the uptake is monotonous and slows down when the remaining DNA segment becomes very short. Numerical and analytical studies of the entropic repulsion between the DNA filament and the membrane wall suggest a new interpretation of the experimental observations. Our results indicate that the repulsion monotonically decreases as the uptake progresses. Thus, the DNA is pulled in (i) either by a small force of unknown origin, and then the slowing down can be interpreted only statistically; (ii) or by a strong but slow ratchet mechanism, which would naturally explain the observed monotonicity, but then the slowing down requires additional explanations. Only further experiments can unambiguously distinguish between these two mechanisms.Comment: 12 pages, 6 figures, submitted to J. Phys. Cond. Ma

Analysis of a model for foam improved oil recovery

During improved oil recovery (IOR), gas may be introduced into a porous reservoir filled with surfactant solution in order to form foam. A model for the evolution of the resulting foam front known as ‘pressure-driven growth’ is analysed. An asymptotic solution of this model for long times is derived that shows that foam can propagate indefinitely into the reservoir without gravity override. Moreover, ‘pressure-driven growth’ is shown to correspond to a special case of the more general ‘viscous froth’ model. In particular, it is a singular limit of the viscous froth, corresponding to the elimination of a surface tension term, permitting sharp corners and kinks in the predicted shape of the front. Sharp corners tend to develop from concave regions of the front. The principal solution of interest has a convex front, however, so that although this solution itself has no sharp corners (except for some kinks that develop spuriously owing to errors in a numerical scheme), it is found nevertheless to exhibit milder singularities in front curvature, as the long-time asymptotic analytical solution makes clear. Numerical schemes for the evolving front shape which perform robustly (avoiding the development of spurious kinks) are also developed. Generalisations of this solution to geologically heterogeneous reservoirs should exhibit concavities and/or sharp corner singularities as an inherent part of their evolution: propagation of fronts containing such ‘inherent’ singularities can be readily incorporated into these numerical schemes