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• The adoption of speed camera is essential for appropriate strain measurements within a Split Hopkinson Tensile Bar equipment. • The necking onset causes, at the same time, the strain rate to greatly increase and the strain rate sensitivity to remain locked at the current value. • After necking onset, the stress from SHTB tests does not incorporate anymore the effects of the steeply increasing post-necking strain rate. • The locking mechanism provides an alternative explanation for what is usually implemented as a saturation of the strain rate effect. • SHTB experiments reflect the material dynamics only up to lower strain rates than those actually generated inside the specimen. The flow stress of many metals exhibits a dependence on the strain rate, in the form of a dynamic amplification of the static flow stress which, according to most literature models, saturates at the strain rates typical of Split Hopkinson Tension bar (SHTB), roughly in the range 500–5000 s−1. Recently it was found that the dynamic amplification in a mild steel quits evolving at the necking onset, becoming insensitive to further strain rate variations, and remains locked at that current value, independently of the very steep and uncontrollable rise of the strain rate occurring beyond such stage. The present paper investigates in detail this locking effect, analysing how the strain rate increases the flow stress and the necking influences such increase, and then outlining a modelling strategy for such interactions, whose details are analysed on the basis of both experimental measurements and finite elements (f.e.) simulations. By mean of this approach, the locking phenomenon is compared to the saturating feature modelled by the previous literature models, highlighting the differences between them and evaluating their compatibility with the postnecking strain histories from experiments. High-speed camera measurements of the shrinking diameter enable to assess the suitability of the true variables (stress, strain and strain rate) for identifying the material response and for validating material models. The locking effect is also checked against experimental results from the literature, so referring to materials exhibiting necking initiation at both early and intermediate plastic strains. Finally, the locking effect is found to limit the strain rates up to which the SHTB experiments can really reflect the dynamic response of materials. This limitation is especially pronounced for early-necking materials. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The present work aims at the development of an advanced control system implemented through Adams/View-Matlab/Simulink co-simulation for a high-performance motorcycle dynamics study. In particular, the purpose of this study is to create a model able to consider several aspects of the rider–motorbike dynamic simulation and its control system, generally treated separately in the literature, making also use of an original and accurate modelling of the rider. From a previous multi-body model of motorcycle/virtual rider, developed by the authors, a flexible tool is created to simulate system dynamics to follow any trajectory at a prescribed velocity profile. Considering high-performance motorcycle dynamics are greatly influenced by the rider’s weight, his movements have been accurately replicated to obtain the most realistic results. To simulate the passive impedance of rider’s arms, a torque was applied to the steering as per the literature. The aerodynamic force was modelled as a function of kinematics variables and rider’s posture. The control system is very flexible and adaptable to different manoeuvres realistically reproducing engine and braking performance, steering torque and rider movements. Numerical results show that the control system can accurately direct the motorcycle/rider system along an entire lap of the Monza circuit, following a desired path at a given velocity profile. The model developed allows a complete view of the motorbike-rider dynamic behaviour thus being useful during both design phase and set-up, with a considerable saving in terms of both cost and time; it can also evaluate the influence on the system dynamics of riders with different anatomical characteristics and driving styles. [ABSTRACT FROM AUTHOR]

Blue-fish is particularly abundant in the Ionian Sea and generally consumed as fresh, canned or salted product. According to the amount of anchovies and sardines available, there is a possibility of developing new products. One possible commercial alternative is the production of marinated ready-to-use blue-fish. Nevertheless, polyphenol oxidase (PPO, EC 1.14.18.1) is an enzyme producing pigments responsible for the undesirable dark colors which spoil these products. This research aimed at assessing the efficacy as anti-browning agents of citric acid and marination in readyto- use anchovy and sardine fillets compared to the untreated controls throughout a 5-days chilling storage. The results showed that no significant differences (p* 0.05) were noticed in gas concentration (O2 and CO2) inside the bags during storage. Each anti-browning treatment (citric acid or acidification and marination) produced a significant (p* 0.05) PPO inhibition. The greatest enzymatic reduction as compared to the untreated control samples was observed in marinated anchovies stored up to 4 days. The effectiveness of the preservation treatment with citric acid was confirmed in terms of color parameters, whereas the addition of sunflower oil in marinated blue-fish 'masked' their chromatic changes during storage. Data suggested industrial applications, e.g. the addition of one or more PPO inhibitors into blue-fish packages. [ABSTRACT FROM AUTHOR]

Pink shrimp is an abundant crustacean widespread in Mediterranean Sea, which is strongly affected by oxidation due to polyphenol oxidase (PPO, EC 1.14.18.1), an enzyme producing pigments responsible for the undesirable dark color (melanosis). Sulphites and resorcinol derivatives are the most common and effective additives used to prevent melanosis in crustaceans. However, after having discovered that these antioxidants were related to allergic reactions in some consumers, several researches were carried out with alternative compounds. Several methods such as the addition of antioxidants and the exclusion of oxygen, as well as thermal processing were employed to inhibit the enzymatic reactions in pink shrimp. This work aimed to assessing the efficacy in vitro of some natural anti-browning agents (alginic, ascorbic, benzoic, caffeic, citric, ferulic and glutamic acid) in minimally processed pink shrimp provided from Port of Catania (Sicily, Italy). The crustaceans were washed, allowed to dry in order to remove the water in excess present in surface, and packed in ordinary atmosphere bags (polyethylene terephthalate, PET), covered by a double barrier film and chilled. The enzymatic activity was inhibited by addition of each anti-browning agents and the greater reduction of PPO was observed in the enzymatic assay containing alginic acid, the most effective for melanosis prevention. The effectiveness of the anti-browning treatments decreased with the following order: alginic, ferulic, glutamic, citric, ascorbic, benzoic, and caffeic acid. Data suggested some industrial applications, e.g. the addition of one or more of these inhibitors into fish packages, as alternatives to sulphites and resorcinol derivatives. [ABSTRACT FROM AUTHOR]

The main enzymes associated with browning and softening of "minimally processed vegetables" are reviewed. The enzyme activities considered are those endogenously present in plant tissues and that act during postharvest, processing and/or storage. The results shown are from research conducted by the Food Biotechnology Group of the University of Catania (Italy). The research results are compared with results obtained by other research groups in order to have a better understanding of problems related to extending the shelf-life of fruit and vegetable commodities. [ABSTRACT FROM AUTHOR]

Tartaric and citric acid solutions were used to extract anthocyanins from fresh grape skins, in a non continuous process. The type of solvent and concentration were significant factors in the extraction operation, and tartaric acid was more efficient than citric acid in the extraction yield. Comparative trials were conducted using sulphur dioxide and acidified ethanol as solvents. The extraction yields using the optimal tartaric acid solution differed slightly from those obtained with acidified ethanol but were higher than those obtained with sulphur dioxide. Total amounts of polyphenols, proanthocyanidins and flavans were determined in the extracts obtained from the tartaric acid solutions. Solvent concentration was not a significant factor for flavan extraction yield but was highly significant for the extraction of the other compounds. The stability of the anthocyanins was evaluated at four different storage temperatures and atmospheric conditions. The combined effects of low pH of the extract (2.4), low temperature (2.0°C) and modified atmosphere (N2) provided a long shelf-life. Based on the results, a 0.75% tartaric acid solution is recommended for anthocyanin extraction from fresh grape skin, and could substitute the widely used sulphur dioxide. [ABSTRACT FROM AUTHOR]

This paper is firstly aimed at the quantitative evaluation of the error levels achievable in the dynamic characterization of ductile metals via Hopkinson bar tensile tests, ran according to the classical strain-gauge-based experimental procedure and to the enhanced high-speed-camera-assisted procedure. Also the effect of the specimen slenderness is investigated for checking the sensitivity of both the above techniques to different specimen geometries. Secondly, a material model is proposed here for the dynamic hardening, based on the experimental true stress and on a dynamic postnecking correction derived from the MLR function, originally developed for the quasistatic necking. Finally, the necking onset is demonstrated to freeze the sensitivity of the stress-strain curve to the strain rate; this feature, supported here by both experiments and finite elements analyses, is a novelty according to the authors knowledge, and might have a considerable impact on the whole dynamic characterization of ductile metals undergoing large postnecking strains before failure. [ABSTRACT FROM AUTHOR]

Delamination is a critical failure mode in power electronics packages that can significantly impact their reliability and performance, due to the large amounts of electrical power managed by the most recent devices which induce remarkable thermomechanical loads. The finite element (FE) simulation of this phenomenon is very challenging for the identification of the appropriate modeling tools and their subsequent calibration. In this study, we present an advanced FE modeling approach for delamination, together with fundamental guidelines to calibrate it. Considering a reference power electronics package subjected to thermomechanical loads, FE simulations with a global-local approach are proposed, also including the implementation of a bi-linear cohesive zone model (CZM) to simulate the complex interfacial behavior between the different layers of the package. A parametric study and sensitivity analysis is presented, exploring the effects of individual CZM variables on the delamination behavior, identifying the most crucial ones and accurately describing their underlying functioning. Then, this work gives valuable insights and guidelines related to advanced and aware FE simulations of delamination in power electronics packages, useful for the design and optimization of these devices to mitigate their vulnerability to thermomechanical loads.

The management of heart failure with a reduced ejection fraction is a true success story of modern medicine. Evidence from randomised clinical trials provides the basis for an extensive catalogue of disease-modifying drug treatments that improve both symptoms and survival. These treatments have undergone rigorous scrutiny by licensing and guideline development bodies to make them eligible for clinical use. With an increasing number of drug therapies however, it has become a complex management challenge to ensure patients receive these treatments in a timely fashion and at recommended doses. The tragedy is that, for a condition with many life-prolonging drug therapies, there remains a potentially avoidable mortality risk associated with delayed treatment. Heart failure therapeutic agents have conventionally been administered to patients in the chronological order they were tested in clinical trials, in line with the aggregate benefit observed when added to existing background treatment. We review the evidence for simultaneous expedited initiation of these disease-modifying drug therapies and how these strategies may focus the heart failure clinician on a time-defined smart goal of drug titration, while catering for patient individuality. We highlight the need for adequate staffing levels, especially heart failure nurse specialists and pharmacists, in a structure to provide the capacity to deliver this care. Finally, we propose a heart failure clinic titration schedule and novel practical treatment score which, if applied at each heart failure patient contact, could tackle treatment inertia by a constant assessment of attainment of optimal medical therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Placental function and dysfunction differ by sex but the mechanisms are unknown. Here we show that sex differences in polyamine metabolism are associated with escape from X chromosome inactivation of the gene encoding spermine synthase (SMS). Female placental trophoblasts demonstrate biallelic SMS expression, associated with increased SMS mRNA and enzyme activity. Polyamine depletion in primary trophoblasts reduced glycolysis and oxidative phosphorylation resulting in decreased acetyl-coA availability and global histone hypoacetylation in a sex-dependent manner. Chromatin-immunoprecipitation sequencing and RNA-sequencing identifies progesterone biosynthesis as a target of polyamine regulated gene expression, and polyamine depletion reduced progesterone release in male trophoblasts. The effects of polyamine depletion can be attributed to spermine as SMS-silencing recapitulated the effects on energy metabolism, histone acetylation, and progesterone release. In summary, spermine metabolism alters trophoblast gene expression through acetyl-coA biosynthesis and histone acetylation, and SMS escape from X inactivation explains some features of human placental sex differences., (© 2022. The Author(s).)

The Ti6Al4V alloy is widely adopted in many high-end applications in different fields, including the aerospace, biomechanics, and automotive sectors. Additive manufacturing extends its range of possible applications but also introduces variations in its mechanical performance, depending on the whole manufacturing process and the related control parameters. This work focuses on the detailed tensile stress-strain characterization at low and high strain rates of a Grade 23 Ti alloy manufactured by electron beam melting (EBM). In particular, the main aim is to study the effect of the variation of the EBM process parameters on the performance of the material and their consequent optimization in order to obtain the best printed material in terms of ductility and strength. The adopted optical experimental setups allow the semi-local scale analysis of the neck section which makes possible the accurate estimation of stress, strain, and strain rate, all over the post-necking range and up to the very incipient specimen failure. Among the EBM printing process parameters, the speed function was previously identified as the one mainly affecting the material performance at static rates. Therefore, two different parameter sets, corresponding to the standard value and to an optimized value of the speed function parameter, respectively, are tested here at dynamic rates of 1, 15, and 700 s -1 , for assessing the effect of the speed function on the dynamic material response. The results show that the optimized parameter set has a better performance compared to the standard one in terms of strength and ductility. In particular, in both static and dynamic conditions, it presents an increase of the true stress-strain curve (about 5% on average) and an increase of the failure strain (about 11% on average). Moreover, in respect to the standard parameter set, the optimized one is also characterized by a huge increase of the amplification due to the strain rate (about 49% on average for the considered strain rates).

Aims: The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort., Methods and Results: Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence., Conclusion: Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

Multislice computed tomography (MSCT) is widely used to complement conventional angiography in the diagnosis and characterisation of coronary artery anomalies. MSCT adds relevant 3-dimensional information that relates the course of anomalous vessels to specific anatomical structures of the heart. The utility of MSCT in patients with coronary anomalies is exemplified in a patient with superimposed coronary artery disease.

Aims: Limited data are available on the long-term outcome following PCI with paclitaxel-eluting stent (PES) implantation in patients with unprotected left main coronary artery (LMCA). The objective of this study was to evaluate "real world" long-term outcome following paclitaxel-eluting stent (PES) implantation for unprotected LMCA disease in patients enrolled in the TRUE registry., Methods and Results: From March 2003 to October 2004, 93 consecutive patients (81.7% male) underwent PCI for unprotected LMCA disease. Surveillance angiography was performed at 6.8+/-3.3 months follow-up. The target lesion involved the distal LMCA in 68 (73.1%) patients. Double stenting techniques were performed in 46 (67.6%) distal LMCA, of these 50% were stented using the Crush technique. Clinical follow-up was complete in all patients with 85.8% angiographic follow-up rate. In-segment restenosis occurred in 16 (20.3%) patients and was focal in 72.4% of cases and significantly higher in patients with distal LMCA (36.8% vs. 13.6%, p<0.04). At a median follow-up of 1,450 days (IQR 1281-1595), the overall incidence of MACE was 35.5% and the TLR rate was 25.8% and significantly higher in patients with bifurcation stenting (32.3% vs. 8%, p<0.02). The estimated cardiac survival rate at one and four years was 96.7% and 93.3%, respectively. Total mortality rate was 14.1% and cardiac was 6.5%. There was one (1.1%) definite stent thrombosis (ST) and one (1.1%) probable ST., Conclusions: Treatment of unprotected LMCA disease with PES, after four years follow-up, appears to be safe and effective with a low rate of cardiac mortality and overall risk of ST. The need for target lesion revascularisation in 25.8% of patients highlights the need for more effective PCI especially in patients with distal LMCA disease.

In the recently halted HIV type 1 (HIV-1) vaccine STEP trial, individuals that were seropositive for adenovirus serotype 5 (Ad5) showed increased rates of HIV-1 infection on vaccination with an Ad5 vaccine. We propose that this was due to activation and expansion of Ad5-specific mucosal-homing memory CD4 T cells. To test this hypothesis, Ad5 and Ad11 antibody titers were measured in 20 healthy volunteers. Dendritic cells (DCs) from these individuals were pulsed with replication defective Ad5 or Ad11 and co-cultured with autologous lymphocytes. Cytokine profiles, proliferative capacity, mucosal migration potential, and susceptibility to HIV infection of the adenovirus-stimulated memory CD4 T cells were measured. Stimulation of T cells from healthy Ad5-seropositive but Ad11-seronegative individuals with Ad5, or serologically distinct Ad11 vectors induced preferential expansion of adenovirus memory CD4 T cells expressing alpha(4)beta(7) integrins and CCR9, indicating a mucosal-homing phenotype. CD4 T-cell proliferation and IFN-gamma production in response to Ad stimulation correlated with Ad5 antibody titers. However, Ad5 serostatus did not correlate with total cytokine production upon challenge with Ad5 or Ad11. Expanded Ad5 and Ad11 memory CD4 T cells showed an increase in CCR5 expression and higher susceptibility to infection by R5 tropic HIV-1. This suggests that adenoviral-based vaccination against HIV-1 in individuals with preexisting immunity against Ad5 results in preferential expansion of HIV-susceptible activated CD4 T cells that home to mucosal tissues, increases the number of virus targets, and leads to a higher susceptibility to HIV acquisition.

Background: With the aim of reducing restenosis after percutaneous coronary intervention with bare-metal stents (BMSs) for the treatment of ischemic heart disease, drug-eluting stents (DESs) were introduced in the field of percutaneous coronary intervention in 2002. However, the higher cost of DES in comparison with BMS made it necessary to determine whether their use brings a real economic advantage., Methods: In order to verify the clinical and economic benefit of DES in comparison with BMS and surgical treatment with coronary artery bypass graft (CABG), the Sicily Regional Government arranged for the creation of a directory where patients receiving at least one DES (with sirolimus or with paclitaxel) were enrolled from June 2004 to February 2005. The cost-effectiveness analysis for DES was carried out by means of two decisional models: one referring to patients treated with DES who, without such a device, would have undergone CABG, and the second one referring to patients treated with DES who, without such device, would have received BMS. Cost analysis was carried out from the point of view of the SSR (Servizio Sanitario Regionale, Regional Health Service)., Results: The use of DES on patients destined to CABG generated average unitary differential savings of euro9003, after 9 months of follow-up, and average total differential savings of euro4 438 479. The use of DES on patients destined to BMS gave average unitary differential savings of euro1075, after 9 months of follow-up, and average total differential savings of euro1 052 425. The use of DES instead of BMS and CABG allowed SSR to make average differential savings of euro3760 per successful case. The refund threshold value of DES, setting to zero the SSR average differential savings for patients treated with DES who would otherwise have been treated with BMS, was euro2489., Conclusion: The medium-term results of the proposed models, tested with sensitivity analysis, demonstrate the use of DES to be justified; moreover, these results could positively influence the attitude of the SSR toward these new therapeutic strategies, which are an improvement on standard therapies, both from a clinical and a financial standpoint.

Background: Sirolimus-eluting stents (SES) prevent restenosis and repeat percutaneous coronary intervention (PCI), but safety data in unselected patients are limited, especially for intermediate-term follow-up., Methods: All patients undergoing SES implantation at 4 Italian centers were enrolled into a dedicated database. Baseline, procedural, and outcome data at discharge and at follow-up were abstracted. Outcomes of interest were the occurrence of major adverse cerebrocardiovascular events (MACCE) at 6 months, as well as long-term event-free survival and multivariable event predictors., Results: One thousand four hundred twenty-four patients were enrolled (2,915 lesions, treated with 3,305 stents). Specifically, 1,074 (75.4%) subjects had multivessel disease, 399 (28.1%) had diabetes, 89 (6.3%) had ST-elevation myocardial infarction, and 44 (3.1%) underwent unprotected left main intervention. At 6 months, MACCE had occurred in 121 (9.0%) patients. After a median of 48.7 months (first-third quartile 41.8-55.3), MACCE-free survival was 69.2%+/-2.6%, with definite stent thrombosis occurring acutely in 6 (0.4%), subacutely in 11 (0.8%), after 30 days in 12 (0.8%), and cumulatively in 28 (2.0%). Major multivariable outcome predictors were diabetes (target lesion revascularization [TLR], MACCE), ejection fraction (TLR, MACCE), and maximal balloon length (TLR)., Conclusions: This large cohort of unselected patients supports the overall safety of unrestricted percutaneous SES implantation, as shown by the low rates of stent thrombosis. Event attrition remains, however, high at long-term follow-up, driven mainly by target vessel revascularization, with diabetes and ejection fraction as the most important prognostic factors.

Several randomized trials have shown that sirolimus-eluting stents and paclitaxel-eluting stents (PES) are effective in reducing restenosis in respect to bare-metal stents, including the subset of small vessels. The objective of this study was to evaluate "real world" angiographic and clinical outcomes of a large series of patients enrolled in the TRUE registry and treated with PES for both small vessel and very small vessel lesions. A consecutive series of 675 patients (926 lesions) with reference vessel diameter <2.75 mm measured by quantitative coronary angiography analysis were analyzed. The primary end point was the rate of angiographic in-stent restenosis and 1-year major adverse cardiac events. In this study 390 lesions were identified as small vessel (reference vessel diameter >or=2.25 and <2.75 mm) and 536 lesions as very small vessel (reference vessel diameter <2.25 mm). Overall in-stent restenosis was 15.5% (n = 96). Compared with small vessel, the very small vessel lesions had more in-stent restenosis (21.7% vs 11.4%, p <0.001) and in-segment restenosis (29.3% vs 22.5%, p = 0.055). The majority of the restenotic lesions (n = 125) were focal (57%, n = 71). At 1 year, cardiac death was 1.6% (n = 11), acute myocardial infarction 0.5% (n = 4.), and the target lesion revascularization 12.8% (n = 86). Cumulative major adverse cardiac events rate was 17.3% (n = 119). The rate of definite and probable stent thrombosis was 0.9% (n = 8). In conclusion, in comparison with historical bare-metal stent controls, this large series of small vessel lesions treated with PES confirms previous results reporting the efficacy of PES in small vessels. The rate of subacute and late stent thrombosis was low in this subgroup of patients.

Objectives: To investigate the long-term prognostic implications of complete versus incomplete revascularization in multivessel coronary artery disease (MVD) patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES)., Background: Coronary artery bypass grafting (CABG) in patients with MVD provides better outcomes when complete revascularization is achieved. There is a paucity of data on the outcomes of complete versus incomplete revascularization of MVD patients undergoing PCI, and currently there is no data available with DES., Methods: Patients with MVD undergoing PCI with DES (sirolimus- or paclitaxel-eluting stent) were included. Comparisons of long-term outcomes between completely versus incompletely revascularized patients were made. The primary outcome measure was the composite of cardiac death, nonfatal myocardial infarction (MI), or any revascularization. Secondary endpoints were the components of the composite endpoint., Results: A total of 508 patients were considered for this analysis: 212 (41.7%) and 296 (58.3%) had complete and incomplete revascularization, respectively. The median follow-up was 27.0 (interquartile range: 23.0-37.1) months. After adjusting for baseline characteristics, the hazard ratio (HR, 95% confidence interval) for complete revascularization was 0.43 (0.29-0.63, P < 0.0001) for the primary composite endpoint. Complete revascularization was associated with better outcomes for components of the composite endpoint: 0.37 (0.15-0.92, P = 0.03) for cardiac death, 0.34 (0.16-0.75 P = 0.008) for the composite of cardiac death or MI and 0.45 (0.29-0.69, P = 0.0003) for any repeat revascularization. This association was confirmed in a propensity-matched population., Conclusions: Complete revascularization with DES of MVD patients is associated with lower rates of long-term adverse events., (2008 Wiley-Liss, Inc.)

Background: Acute myocardial infarction (AMI) management aims to ensure the best care for patients while reducing hospital stay. The aim of this study was to evaluate feasibility and safety of early discharge (defined as discharge between 48 and 72 h from AMI) in low-risk patients after uncomplicated infarction., Methods: We prospectively evaluated 321 patients (age: 59 +/- 11.7), who were admitted for AMI between February 2004 and August 2005 and assigned to 'low'-risk and 'high'-risk groups according to clinical and angiographic criteria. Low-risk patients were discharged between 48 and 72 h from admission. After discharge, all patients were re-evaluated after 1 week, 6 weeks and 6 months for AMI. We also retrospectively considered a control group of 68 low-risk patients with AMI admitted to our Coronary Intensive Care Unit (CICU) in the previous 4 months before the beginning of the study with standard discharge after at least 7 days of hospital stay., Results: No events were detected in the first week after discharge. In low-risk patients, the cumulative major adverse event rate was 0.6% after 6 weeks, whereas in high-risk patients, the rate was 9% (P < or = 0.01). After 6 months, in the low-risk group, the cumulative major adverse event rate was 2%, whereas in the high-risk group, it was 10% (P < or = 0.01). The control group showed a cumulative major adverse event rate of 1.5% after 6 months, with no statistically significant difference between controls and low-risk patients. The type of AMI did not influence risk assessment and clinical outcome., Conclusion: Our data support the short-term safety and cost-effectiveness of early discharge in patients with uncomplicated AMI, treated with successful percutaneous coronary intervention.

Objective: This is a multicentre, open label, prospective non-randomized registry, with 9-month angiographic follow-up, conducted to evaluate the safety and effectiveness of drug-eluting stents (DES) when used in high restenosis risk patients from the real world., Methods: From June 2004 to February 2005, a total of 1622 consecutive patients were enrolled to the Sicilian DES Registry, according to specific inclusion criteria. Both paclitaxel-eluting and sirolimus-eluting stents were used. The analysis was performed on 1472 patients because 150 patients were excluded from the study. The primary endpoint was to evaluate the rate of major adverse cardiac events (MACE) within 9 months after DES implantation. Major adverse cardiac events were defined as cardiac death, non-Q-wave or Q-wave myocardial infarction (MI) and target vessel revascularization (TVR). The secondary endpoints were procedural success, angiographic binary restenosis and stent thrombosis within 9 months post-procedure., Results: Patients were more frequently male; 472 (32.1%) were diabetics, of whom 130 (27.5%) were treated with insulin. Mean ejection fraction of the left ventricle was 51.5 +/- 8.7%. Multivessel disease was found and treated in 627 patients (42.6%). A total of 2439 lesions were treated with DES. Final angiographic success was achieved in 2422 (99.3%) lesions. Procedural success was achieved in 1422 (96.6%) patients. The 9-month cumulative incidence of MACE was 7.3% with 0.8% of cardiac deaths, 0.8% non-fatal MI, 7.9% TVR. Binary restenosis was observed in 101 patients (8.3%). Stent thrombosis was documented in 11 patients (0.8%)., Conclusions: Drug-eluting stents appear to be safe and associated with a low incidence of MACE at 9-month follow-up, even in patients selected for their complexity.

Objectives: The aim of the study was the assessment of the clinical, angiographic and procedural characteristics correlated with freedom from adverse events at 1 year in a real life setting of consecutive bifurcation lesions., Background: Even if stent implantation has shown to be superior to conventional balloon angioplasty in most coronary lesions, bifurcation treatment with stent implantation both in main and in side branch (SB) still raises controversy., Methods: We reviewed the results obtained in a prospective multicenter registry of 150 patients with 158 bifurcation lesions involving a SB of sufficient diameter to be treated, if necessary, with a polymer based paclitaxel eluting stent (PES, TAXUS). Two stents were used in 118 lesions (74.7%). Final kissing balloon inflation was performed in 87/118 lesions (73.7%) and in 30/40 lesions (75.0%) of the 2 and 1 stent group respectively., Results: At 1-year clinical follow-up we observed 4 stent thromboses, all involving the SBs of the 2 stents group (2.7%). Unlike previous reports, revascularization involved the main vessel in the majority of patients (21/150, 14.0%). After an exploratory multivariable analysis the only parameter predictive of target lesion revascularization (TLR) (HR 0.52; CI 95% 0.11-0.86; p = 0.02) and target vessel revascularization (TVR) (HR 0.47; CI 95% 0.14-0.90; p = 0.03) was postprocedural main branch minimal lumen diameter (MB-MLD)., Conclusions: In a real life setting of consecutive bifurcation lesions, thrombosis rate, concentrated in the SB and the 2-stents group, and need for target lesion revascularization remain higher than in less complex lesion subgroups treated with PES. No differences in immediate success and TLR were observed between 2 stents and 1 stent groups. The frequently observed suboptimal stent expansion and final MB-MLD predict 1 year revascularization., ((c) 2006 Wiley-Liss, Inc.)

Aims: Coronary dissections left untreated after percutaneous coronary intervention are associated with unfavourable outcomes. However, their role after drug-eluting stent (DES) implantation is still undescribed. We assessed incidence, predictors, and outcomes of residual dissections in DES-treated lesions., Methods and Results: Consecutive patients undergoing DES implantation were enrolled in four Italian centres, with baseline, procedural, and outcome data entered into a dedicated database. Residual dissections were classified according to the National Heart Lung and Blood Institute criteria. End-points of interest were in-hospital, 1-month, and 6-month major adverse cardiovascular events (MACE, i.e. death, myocardial infarction, or target vessel revascularization), and stent thrombosis (ST). Among the 2418 included patients (4630 lesions), a total of 77 (1.7%) final dissections occurred in 67 (2.8%) subjects. Dissections were more frequent in longer and complex lesions and in the left anterior descending, and were associated with increased rates of in-hospital (11.9 vs. 5.2%, P=0.017) and 1-month MACE (13.4 vs. 6.0%, P=0.013), with similar 6-month trends. Cumulative ST was also greater in patients with dissections (6.3 vs. 1.3%, P=0.011). Even non-obstructive dissections with thrombolysis in myocardial infarction 3 flow conferred a significantly worse prognosis., Conclusion: This study, reporting for the first time on incidence, predictors, and outcomes of residual dissections in DES-treated coronary lesions, demonstrates their adverse clinical impact and supports the pursuit of a strategy of sealing dissection flaps with other DES.

Recent studies have indicated that the force-extension properties of single molecules of double stranded (ds) DNA are sensitive to the presence of small molecule DNA binding agents, and also to their mode of binding. These observations raise the possibility of using this approach as a highly sensitive tool for the screening of such agents. However, particularly for studies employing the atomic force microscope (AFM), several non-trivial barriers hinder the progress of this approach to the non-specialist arena and hence also the full realization of this possibility. In this paper, we therefore address a series of key reproducibility and metrological issues associated with this type of measurement. Specifically, we present an improved immobilization method that covalently anchors one end (5' end) of a dual labelled (5'-thiol, 3'-biotin) p53 DNA molecule onto a gold substrate via gold-thiol chemistry, whilst the biotinylated 3' end is available for 'pick-up' using a streptavidin modified AFM tip. We also show that co-surface immobilization of DNA with 6-mercapto-1-hexanol (MCH) can also lead to a further increase the measured contour length. We demonstrate the impact of these improved protocols through the observation of the cooperative transition plateau in a DNA fragment of approximately 118 bp, a significantly smaller fragment than previously investigated. The results of a comparative study of the effects of a model minor groove binder (Hoechst 33258) and an intercalating drug (proflavine), alone, as a mixture and under different buffer conditions, are also presented.

Although predictors of acute intraprocedural stent thrombosis (IPST) in the drug-eluting stent era have been proposed, external validation is lacking. We thus analyzed the occurrence of IPST in the RECIPE study and found that, among 1,320 patients who underwent drug-eluting stent implantation, IPST occurred in 6 (0.5%), with in-hospital major adverse events in 4 (67%). IPST was predicted by number and total length of implanted stents, baseline minimal lumen diameter, and, in a pooled analysis that incorporated values from the present study and a previous study, use of elective glycoprotein IIb/IIIa inhibitors. Such results may provide useful information to guide prevention of this complication.

Stroke is the third cause of death in western countries and its complications lead to significant socio-economic problems related to the prolonged hospitalization and rehabilitation of patients with neurological lesions. Severe atherosclerotic lesions of the carotid artery are the main cause of stroke and transient ischemic attacks. Their incidence may reach 5-7% per year in patients with carotid artery stenosis > 70% with or without symptoms. Time-honored carotid endarterectomy is still regarded as the gold standard therapy for primary and secondary prevention of stroke. However, surgery is not free of complications and the rate of perioperative stroke ranges from 5.1 to 14.3%. A group of patients at a particularly high risk of stroke during surgical endarterectomy is represented by patients with significant carotid stenosis in the presence of an occluded contralateral artery. Indeed, carotid cross-clamping during operative surgery in the absence of an adequate collateral flow may result in a critical flow reduction during the operation and therefore increases the risk of periprocedural strokes. In the North American Symptomatic Carotid Endarterectomy (NASCET) trial, the overall risk of stroke was 5.1%, whereas it increased up to 14.3% in patients with an occluded contralateral carotid artery. Recently, carotid stenting has been increasingly used as an endovascular technique for carotid revascularization, especially after the introduction of neuroprotection devices which improved the safety of the procedure. Therefore, it may be an attractive alternative to carotid endarterectomy, especially when the surgical risk is too high. We describe the immediate and late outcomes of 3 patients treated with carotid artery stenting in the presence of contralateral carotid occlusion.