European standarts of youth work security

In this article we consider the peculiar properties of regulation of minor’s workers security within the Law of the European Union. To reveal such peculiar properties of legal regulation of a work security of youth within the Instruction of EU 89/391/EEC, as well as Instructions of 94/33/ЕС. Proper analysis of regulation of rules and rules of guarantees of the workers` rights under the age of 18 years which work on the basis of the labour contract or rules which are determined by the current legislation of the state-member and/or conformed to the current legislation of the state-member was fulfi lled. Thus, we may confirm, that except for some details, within EU territory the complex of the minimal labour standards for stable working environment which now are applied in all states-participants is created

Dietary curcumin : correlation between bioavailability and health potential

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake

Nebivolol: haemodynamic effects and clinical significance of combined beta-blockade and nitric oxide release.

Nebivolol is a third-generation beta-adrenergic receptor antagonist (beta-blocker) with high selectivity for beta(1)-adrenergic receptors. In addition, it causes vasodilatation via interaction with the endothelial L-arginine/nitric oxide (NO) pathway. This dual mechanism of action underlies many of the haemodynamic properties of nebivolol, which include reductions in heart rate and blood pressure (BP), and improvements in systolic and diastolic function. With respect to BP lowering, the NO-mediated effects cause a reduction in peripheral vascular resistance and an increase in stroke volume with preservation of cardiac output. Flow-mediated dilatation and coronary flow reserve are also increased during nebivolol administration. Other haemodynamic effects include beneficial effects on pulmonary artery pressure, pulmonary wedge pressure, exercise capacity and left ventricular ejection fraction. In addition, nebivolol does not appear to have adverse effects on lipid metabolism and insulin sensitivity like traditional beta-blockers. The documented beneficial haemodynamic effects of nebivolol are translated into improved clinical outcomes in patients with hypertension or heart failure. In patients with hypertension, the incidence of bradycardia with nebivolol is often lower than that with other currently available beta-blockers. This, along with peripheral vasodilatation and NO-induced benefits such as antioxidant activity and reversal of endothelial dysfunction, should facilitate better protection from cardiovascular events. In addition, nebivolol has shown an improved tolerability profile, particularly with respect to events commonly associated with beta-blockers, such as fatigue and sexual dysfunction. Data from SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) showed that significantly fewer nebivolol versus placebo recipients experienced the primary endpoint of all-cause mortality or cardiovascular hospitalization. The benefits of nebivolol therapy were shown to be cost effective. Thus, nebivolol is an effective and well tolerated agent with benefits over and above those of traditional beta-blockade because of its effects on NO release, which give it unique haemodynamic effects, cardioprotective activity and a good tolerability profile

Postdischarge assessment after a heart failure hospitalization: the next step forward.

Heart failure (HF) is the most frequent cause of hospitalization for patients >65 years of age. Mortality during the initial hospitalization ranges from 6% to 7% in Europe to 3% to 4% in the United States, depending on the length of hospital stay. Poor outcomes have universally been shown after discharge, with 60- to 90-day mortality rates of 5% to 15% and hospital readmission rates of 30%. Whereas the prognosis of patients with chronic HF has improved in recent years, there has been no change in the high risk of death or rehospitalization after an HF hospitalization. In addition to the lack of new therapies, incomplete relief from fluid overload, insufficient patient education, lack of implementation of evidence-based therapies, and poor postdischarge follow-up planning are among the main causes of these poor outcomes. A better assessment of the patient at the time of discharge and in the following weeks seems therefore as mandatory. This article outlines the main components of such a program. These include the personnel who should be involved, i.e. HF specialists and cardiologists versus non-specialists, the variables which should be assessed, i.e. those related with congestion and fluid overload, the times when they should be assessed, as the phase at highest risk is immediately after discharge from hospital, and, finally, the aims of such programs. We retain that an improvement of post-discharge follow-up will be able to significantly improve patients’ outcomes with a rate of success comparable, if not greater, to that which can be achieved by new therapies

Performance analysis and design optimization of parallel-type slew-rate enhancers for switched-capacitor applications

The design of single-stage OTAs for accurate switched-capacitor circuits involves challenging trade-offs between speed and power consumption. The addition of a Slew-Rate Enhancer (SRE) circuit placed in parallel to the main OTA (parallel-type SRE) constitutes a viable solution to reduce the settling time, at the cost of low-power overhead and no modifications of the main OTA. In this work, a practical analytical model has been developed to predict the settling time reduction achievable with OTA/SRE systems and to show the effect of the various design parameters. The model has been applied to a real case, consisting of the combination of a standard folded-cascode OTA with an existing parallel-type SRE solution. Simulations performed on a circuit designed with a commercial 180-nm CMOS technology revealed that the actual settling-time reduction was significantly smaller than predicted by the model. This discrepancy was explained by taking into account the internal delays of the SRE, which is exacerbated when a high output current gain is combined with high power efficiency. To overcome this problem, we propose a simple modification of the original SRE circuit, consisting in the addition of a single capacitor which temporarily boosts the OTA/SRE currents reducing the internal turn-on delay. With the proposed approach a settling-time reduction of 57% has been demonstrated with an SRE that introduces only a 10% power-overhead with respect of the single OTA solution. The robustness of the results have been validated by means of Monte-Carlo simulations

Old and new intravenous inotropic agents in the treatment of advanced heart failure

Inotropic agents are administered to improve cardiac output and peripheral perfusion in patients with systolic dysfunction and low cardiac output. However, there is evidence of increased mortality and adverse effects associated with current inotropic agents. These adverse outcomes may be ascribed to patient selection, increased myocardial energy expenditure and oxygen consumption, or to specific mechanisms of action. Both sympathomimetic amines and type III phosphodiesterase inhibitors act through an increase in intracellular cyclic adenosine monophoshate and free calcium concentrations, mechanisms that increase oxygen consumption and favor arrhythmias. Concomitant peripheral vasodilation with some agents (phosphodiesterase inhibitors and levosimendan) may also lower coronary perfusion pressure and favor myocardial damage. New agents with different mechanisms of action might have a better benefit to risk ratio and allow an improvement in tissue and end-organ perfusion with less untoward effects. We have summarized the characteristics of the main inotropic agents for heart failure treatment, the data from randomized controlled trials, and future perspectives for this class of drugs

A Low-Power Interface for Capacitive Sensors With PWM Output and Intrinsic Low Pass Characteristic

A compact, low power interface for capacitive sensors, is described. The output signal is a pulse width modulated (PWM) signal, where the pulse duration is linearly proportional to the sensor differential capacitance. The original conversion approach consists in stimulating the sensor capacitor with a triangular-like voltage waveform in order to obtain a square-like current waveform, which is subsequently demodulated and integrated over a clock period. The charge obtained in this way is then converted into the output pulse duration by an approach that includes an intrinsic tunable low pass function. The main non idealities are thoroughly investigated in order to provide useful design indications and evaluate the actual potentialities of the proposed circuit. The theoretical predictions are compared with experimental results obtained with a prototype, designed and fabricated using 0.32 mu M CMOS devices from the BCD6s process of STMicroelectroncs. The prototype occupies a total area of 1025 x 515 mm(2) and is marked by a power consuption of 84 mu W. The input capacitance range is 0-256 fF, with a resolution of 0.8 fF and a temperature sensitivity of 300 ppm/degrees C

Functional Lipids in Autoimmune Inflammatory Diseases

Lipids are apolar small molecules known not only as components of cell membranes but also, in recent literature, as modulators of different biological functions. Herein, we focused on the bioactive lipids that can influence the immune responses and inflammatory processes regulating vascular hyperreactivity, pain, leukocyte trafficking, and clearance. In the case of excessive pro-inflammatory lipid activity, these lipids also contribute to the transition from acute to chronic inflammation. Based on their biochemical function, these lipids can be divided into different families, including eicosanoids, specialized pro-resolving mediators, lysoglycerophospholipids, sphingolipids, and endocannabinoids. These bioactive lipids are involved in all phases of the inflammatory process and the pathophysiology of different chronic autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, type-1 diabetes, and systemic lupus erythematosus

ANTIMICROBIAL PEPTIDES ARE TARGETS FOR BACTERIAL ADP-RIBOSYLTRANSFERASE ENZYMES

Background: Human α-defensins (HNPs 1-3) are small cationic, amphipatic peptides with microbicidal activities. HNP-1 is the physiological target of ART1, an arginine (Arg) specific eucaryotic ribosyltransferase enzyme1. Mono ADP-ribosylation of Arg14 of HNP-1 modulates its biological activities2. Bacterial exotoxins like Cholera Toxin (CT) by Vibrio cholerae, Heat Labile Enterotoxin (LT1) by Escherichia coli and Exoenzyme S (ExoS) by Pseudomonas aeruginosa are arginine ADP-ribosyltransferase enzymes that alter cell functions by modifying protein targets. Objectives: 1. Evaluate the ADP ribosylation of HNP-1 by CT, LT1 and ExoS. 2. Purify modified peptides and identify the ADP-ribosylated Arg. Methods: ADP-ribosylation of HNP-1 will be evaluated with biotinilated NAD by western blot. Purification of modified peptides will be performed by reverse phase HPLC. Identification of modification will be performed by Maldi-Toff analysis. Results: 1. CT and LT1 are effective in ADP-ribosylating HNP-1 as equal as the well known activity of ART1. On the other hand ExoS does not recognize HNP-1 as substrate. 2. Ongoing experiments are purifications and characterization of modified peptides by reverse-phase HPLC and Maldi-Toff analysis. Conclusions: 1. The different ADP-ribosylating activities displayed by CT, LT1 and ExoS on HNP-1 might be explained with differences in microbial pathogenesis, as the toxins released by V. cholerae and E. coli are involved in the early stages of infections, during the interactions with surface epithelial cells, while ExoS by P. aeruginosa is active during blood dissemination, when the pathogen has already overcome epithelial barrier. References: 1 Balducci et al., 1999, Am J Respir Cell Mol Biol, 21, 337-46 2 Paone et al., 2006, J Biol Chem, 281, 17054-6

Discovery of unexpected sphingolipids in almonds and pistachios with an innovative use of triple quadrupole tandem mass spectrometry

The densely packed storage of valuable nutrients (carbohydrates, lipids, proteins, micronutrients) in the endosperm of nuts and seeds makes the study of their complex composition a topic of great importance. Ceramides in the total lipid extract of some ground almonds and pistachios were searched with a systematic innovative discovery precursor ion scan in a triple quadrupole tandem mass spectrometry, where iso-energetic collision activated dissociation was performed. Five descriptors were used to search components with different C18 long chain bases containing different structural motifs (d18:0, d18:1, d18:2, t18:0, t18:1). The presence of hexoside unit was screened with a specific neutral loss experiment under iso-energetic collision activated dissociation conditions. The discovery scans highlighted the presence of two specific hexosyl-ceramides with a modified sphingosine component (d18:2) and C16:0 or C16:0 hydroxy-fatty acids. The hexosyl-ceramide with the non-hydroxylated fatty acid seemed specific of pistachios and was undetected in almonds. The fast and comprehensive mass spectrometric method used here can be useful to screen lipid extracts of several more seeds of nutraceutical interest, searching for unusual and/or specific sphingosides with chemically decorated long chain bases