Endothelial Hyper-Permeability Induced by T1D Sera Can be Reversed by iNOS Inactivation

Type 1 Diabetes Mellitus (T1D) is associated with accelerated atherosclerosis that is responsible for high morbidity and mortality. Endothelial hyperpermeability, a feature of endothelial dysfunction, is an early step of atherogenesis since it favours intimal lipid uptake. Therefore, we tested endothelial leakage by loading the sera from T1D patients onto cultured human endothelial cells and found it increased by hyperglycaemic sera. These results were phenocopied in endothelial cells cultured in a medium containing high concentrations of glucose, which activates inducible nitric oxide synthase with a consequent increase of nitric oxide. Inhibition of the enzyme prevented high glucose-induced hyperpermeability, thus pointing to nitric oxide as the mediator involved in altering the endothelial barrier function. Since nitric oxide is much higher in sera from hyperglycaemic than normoglycaemic T1D patients, and the inhibition of inducible nitric oxide synthase prevents sera-dependent increased endothelial permeability, this enzyme might represent a promising biochemical marker to be monitored in T1D patients to predict alterations of the vascular wall, eventually promoting intimal lipid accumulation

Automated experience-based learning for plug and produce assembly systems

YesThis paper presents a self-learning technique for adapting modular automated assembly systems. The technique consists of automatically analysing sensor data and acquiring experience on the changes made on an assembly system to cope with new production requirements or to recover from disruptions. Experience is generalised into operational knowledge that is used to aid engineers in future adaptations by guiding them throughout the process. At each step, applicable changes are presented and ranked based on: (1) similarity between the current context and those in the experience base; (2) estimate of the impact on system performance. The experience model and the self-learning technique reflect the modular structure of the assembly machine and are particularly suitable for plug and produce systems, which are designed to offer high levels of self-organisation and adaptability. Adaptations can be performed and evaluated at different levels: from the smallest pluggable unit to the whole assembly system. Knowledge on individual modules can be reused when modules are plugged into other systems. An experimental evaluation has been conducted on an industrial case study and the results show that, with experience-based learning, adaptations of plug and produce systems can be performed in a shorter time.European Union [grant number 314762]

QCD Sum Rule Analysis of the Decays B→Kℓ+ℓ−B \to K \ell^+ \ell^- and B→K∗ℓ+ℓ−B \to K^* \ell^+ \ell^-

We use QCD sum rules to calculate the hadronic matrix elements governing the rare decays $B \to K \ell^+ \ell^-$ and $B \to K^* \ell^+ \ell^-$ induced by the flavour changing neutral current $b \to s$ transition. We also study relations among semileptonic and rare $B \to K^{(*)}$ decay form factors. The analysis of the invariant mass distribution of the lepton pair in $B \to K^{(*)} \ell^+ \ell^-$ and of the angular asymmetry in $B \to K^* \ell^+ \ell^-$ provides us with interesting tests of the Standard Model and its extensions.Comment: 26 pages REVTEX + 7 figures. Some typos corrected, figure 5 and 7 modified. This version will appear on Physical Review

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

A SEMIANALYTICAL METHOD TO EVOLVE PARTON DISTRIBUTIONS

We present a new method to solve in a semianalytical way the Dokshitzer-Gribov-Lipatov-Altarelli-Parisi evolution equations at NLO order in the x-space. The method allows to construct an evolution operator expressed in form of a rapidly convergent series of matrices, depending only on the splitting functions. This operator, acting on a generic initial distribution, provides a very accurate solution in a short computer time (only a few hundredth of second). As an example, we apply the method, useful to solve a wide class of systems of integrodifferential equations, to the polarized parton distributions. The scaling violation of nucleon structure functions is described in terms of Dokshitzer-Gribov-Lipatov-Altarelli-Parisi (DGLAP) evolution equations [1]. The DGLAP integrodifferential equations describe the Q 2 dependence of the structure functions, which are related, via the operator product expansion, to the parton distributions for which the DGLAP equations are usually writte

Ultrastructural features mirror metabolic derangement in human endothelial cells exposed to high glucose

High glucose-induced endothelial dysfunction is the early event that initiates diabetes-induced vascular disease. Here we employed Cryo Soft X-ray Tomography to obtain three-dimensional maps of high D-glucose-treated endothelial cells and their controls at nanometric spatial resolution. We then correlated ultrastructural differences with metabolic rewiring. While the total mitochondrial mass does not change, high D-glucose promotes mitochondrial fragmentation, as confirmed by the modulation of fission-fusion markers, and dysfunction, as demonstrated by the drop of membrane potential, the decreased oxygen consumption and the increased production of reactive oxygen species. The 3D ultrastructural analysis also indicates the accumulation of lipid droplets in cells cultured in high D-glucose. Indeed, because of the decrease of fatty acid beta-oxidation induced by high D-glucose concentration, triglycerides are esterified into fatty acids and then stored into lipid droplets. We propose that the increase of lipid droplets represents an adaptive mechanism to cope with the overload of glucose and associated oxidative stress and metabolic dysregulation