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Background Radial artery obstruction is the most common complication of coronary angiography performed via transradial access. Patent hemostasis can significantly reduce the risk of radial artery occlusion. Previous studies utilized sophisticated methods to evaluate radial artery patency. Simplified and easily applicable methods for successful patent hemostasis are currently lacking. Aim To determine which method (pulse oximeter vs the traditional radial artery palpation) is better to achieve patent hemostasis. Methods This prospective, single center study included 299 consecutive patients who underwent coronary angiography or percutaneous coronary intervention between November 2017 and July 2019. Patients less than 18 years old, with a history of radial artery disease, or no palpable artery pulse were excluded from the study. Patients were randomly assigned to two groups. In the first group, radial artery flow was assessed by palpation of the artery during hemostasis (traditional method). In the second group, radial artery patency was estimated with the use of a pulse oximeter. Two different compression devices were used for hemostasis (air chamber and pressure valve). The primary study endpoint was the achievement of successful patent hemostasis. Results The two groups (pulse oximeter vs artery palpation) had no significant differences in age, sex, body mass index, risk factors, or comorbidities except for supraventricular arrhythmias. The percentage of patients with successful patent hemostasis was significantly higher in the pulse oximeter group (82.2% vs 68.1%, P = 0.005). A lower percentage of patients with spasm was recorded in the pulse oximeter group (9.9% vs 19.0%, P = 0.024). The incidence of local complications, edema, bleeding, hematoma, vagotonia, or pain did not differ between the two groups. In the multivariate analysis, the use of a pulse oximeter (OR: 2.35, 95%CI: 1.34-4.13, P = 0.003) and advanced age (OR: 1.04, 95%CI: 1.01-1.07, P = 0.006), were independently associated with an increased probability of successful patent hemostasis. The type of hemostatic device did not affect patent hemostasis (P = 0.450). Conclusion Patent hemostasis with the use of pulse oximeter is a simple, efficient, and safe method that is worthy of further investigation. Larger randomized studies are required to consider its clinical implications.

Hemolytic anemias are a group of uncommon disorders affecting both genders, frequently occurring at the reproductive age. While a link between hemolysis and hypercoagulability has been suggested based on the elucidation of certain involved pathophysiological mechanisms, the extent of thrombotic risk in pregnant women with hemolytic anemia remains debatable. Due to the paucity of pregnancy-related data, risk assessment of gestations in women with hemolytic anemia is complicated. This review will highlight the latest advances in the diagnosis and management of these challenging disorders in pregnancy.

The aim of our study was to establish reference ranges for neonatal coagulation and fibrinolysis parameters and to investigate their relationship with gestational age (GA) and birth weight (BW).A single-centre prospective study was conducted in all healthy neonates born in our hospital during the study period, excluding those with maternal or neonatal disorders and diseases that affect haemostasis. The following parameters were measured: fibrinogen, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT) as well as factors II, V, VII, VIII, IX, X, XI and XII, von Willebrand (vWF), protein C, free protein S, antithrombin (AT), activated protein C resistance (APCr), tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1).Study population consisted of 327 neonates. Fibrinogen, AT III, proteins C and S, PAI-1, vWF and factors II, V, VIII, IX, XI and XII were positively correlated, while PT, aPPT, INR, APCr and tPA were negatively correlated with GA and BW. Proteins C and S, factors II, VIII, IX, XI and vWF, as well AT III and PAI-1 had a significant positive linear correlation with GA, while aPTT had a significant negative one. Fibrinogen, and factors V, VII and XII had a significant positive linear correlation with BW, while factor VIII, tPA, as well PT and INR had a significant negative one.Fibrinogen, AT III, proteins C and S, PAI-1, vWF and factors II, V, VIII, IX, XI and XII increase with GA and BW.

A variety of real-world robotic applications assume reliable grasping mechanisms to facilitate the effective management of objects. Vacuum technology has been frequently used for the development of end of arm tools for industrial robotic applications. Besides its effectiveness, the vacuum technology may occasionally face issues when the surface of the object to grasp is full of cavities or has an arbitrary non-flat shape. The present work studies the development of vacuum gripping mechanism for industrial environments, by assessing the importance of the vacuum generator technology, the use of shock absorber and the plasticity of the suction cup. The vacuum system is integrated in the end-effector of a delta-robot that is used for sorting recyclable wastes, thus providing the opportunity to assess vacuum performance on difficult and demanding situations. The obtained results show that the use of different vacuum generators has rather minimal effect on the performance of the composite system. On the opposite side, the use of the shock absorber and the plasticity of the suction cup may greatly affect system performance, especially for gripping objects with complex surfaces. To overcome the relevant issues, we have implemented a custom made suction cup that significantly facilitates gripping, even for dirty and oily objects. The composite system has been tested on a realistic recyclable waste sorting scenario with high success rates in gripping recyclable objects.

The Third Modeling Workshop focusing on bioprocess modeling was held in Kenilworth, NJ in May 2019. A summary of these Workshop proceedings is captured in this manuscript. Modeling is an active area of research within the biotechnology community, and there is a critical need to assess the current state and opportunities for continued investment to realize the full potential of models, including resource and time savings. Beyond individual presentations and topics of novel interest, a substantial portion of the Workshop was devoted toward group discussions of current states and future directions in modeling fields. All scales of modeling, from biophysical models at the molecular level and up through large scale facility and plant modeling, were considered in these discussions and are summarized in the manuscript. Model life cycle management from model development to implementation and sustainment are also considered for different stages of clinical development and commercial production. The manuscript provides a comprehensive overview of bioprocess modeling while suggesting an ideal future state with standardized approaches aligned across the industry.

Nowadays the business world is characterized by complexity since market environment is changing quickly. Delivery practice and methods for project, program and portfolio management have changed over the decades to align themselves to the changing environment. Unlike traditional methods used in delivery of projects and programs, agile methods are marked by responding to change over following a plan and by extensive collaboration with customer over contract negotiation and offering a variety of benefits that make them attractive to researchers. Although the latter methods [1] claimed to be beneficial presenting advantages such as accelerate time to market, increase in quality and productivity, new trends and hybrid methods and tailored processes are being discussed and developed. In this study the authors provide a report analysis of proposed tested frameworks already presented in the relative literature, tailored methodologies, a review of most used and popular agile practices and approaches and the trends in our subject area conducting a literature review ranging from 2000 to 2017. Our research strategy following a systematic approach [2] revealed 524 studies, of which 71 had been identified to answer our research questions. This is part of further work based on the first authors’ PhD work. The results will be a guide to choose the most appropriate blend of practices for a given project, adapt them to the changing needs and develop an innovative framework methodology.

Integrated process and control design approach for cyclic distillation columns is proposed. The design methodology is based on application of simple graphical design approaches, known from simpler conventional distillation columns. Here, a driving force approach and McCabe-Thiele type analysis is combined. It is demonstrated, through closed-loop and open-loop analysis, that operating the column at the largest available driving force results in an optimal design in terms of controllability and operability. The performance of a cyclic distillation column designed to operate at the maximum driving force is compared to alternative sub-optimal designs. The results suggest that operation at the largest driving force is less sensitive to disturbances in the feed and inherently has the ability to efficiently reject disturbances.

The application of model-based methods for design and analysis of operational improvements of an industrial glucose isomerization (GI) process is highlighted. First, a multi-scale mathematical model representing important phenomena encountered in the reaction system of a glucose isomerization reactor is developed. Next, model analysis, model identification and model validation based on available reactor operational data are performed. The reactor model is found to describe accurately important phenomena, such as, reaction kinetics, enzyme decay and internal diffusion of the substrate in the enzymatic pellet as a function of the temperature, thereby confirming that the model is ready for use in design-analysis studies. Operation of the GI process is then analyzed in a single reactor and based on this, the reactor model is used as a building block to represent the operation of a GI reactor plant consisting of 10–20 reactors in parallel. The design of the GI plant operation is evaluated through the analysis of simulated results of different operational scenarios.

BACKGROUND Phosphorus and nitrogen recovery from municipal and/or industrial wastewater treatment plants in the form of magnesium ammonium phosphate hexahydrate (MgNH4PO4⋅6H2O, MAP, Struvite) is an attractive alternative for the valorization of wastes. Although efforts have been focused in the recovery of nitrogen and phosphorus nutrients from wastewater at alkaline pH, removal of these nutrients in weakly acid pH is still challenging. The advantage of acid pH is that the precipitation of heavy metals in the form of insoluble hydroxides is avoided on the condition that their concentrations are relatively low. RESULTS The metastable zone width of solutions, supersaturated with respect to MAP at pH 6.50 was investigated. The kinetics of MAP formation both in unseeded and in seeded solutions was investigated in batch reactors at constant supersaturation. The rates of crystal growth, of MAP on seed crystals showed a parabolic depenedence on the relative supersaturation. The concentration of the inoculating seed crystals affected the rates of crystal growth. CONCLUSIONS It is possible to crystallize MAP at pH values of 6.50 provided that the supersaturation is sufficient. From the rate dependence on relative supersaturation (parabolic) it was concluded that the crystal growth mechanism was surface diffusion controlled for the integration of the growth units at the active crystal growth sites. Secondary nucleation, depending on the solution supersaturation, was observed within the stable domain of the metastable zone. The morphology of MAP seed crystals remained unchanged, while the mean particle size increased reaching comparable sizes irrespective of the degree of supersaturation.

A method for the selection of appropriate solvents for the solvent swap task in pharmaceutical processes has been developed. This solvent swap method is based on the solvent selection method of Gani et al. (2006) and considers additional selection criteria such as boiling point difference, volatility difference, VLE phase diagram analysis, and azeotropic information that are particularly important for the solvent swap task. The method employs a solvent-swap database together with calculation tools for properties–functions of solvents. The database contains solvents that are commonly used in pharmaceutical processes as well as new solvent swap alternatives. The method takes into account process considerations such as batch distillation and crystallization to achieve the swap task. Rigorous model based simulations of the swap operation are performed to evaluate and compare the performance of the selected solvents. A guide and a software tool that allow the fast and reliable identification of the swap solvent have been developed. The main features and the applicability of the method are highlighted through several practical examples.

To date, clinical experience with prothrombin complex concentrate (PCC) in the neonatal population has been limited.The objective of this study was to describe our experience regarding the effectiveness and safety of PCC administration in newborns with severe bleeding or coagulopathy resistant to conventional therapy.We retrospectively analyzed data from 37 neonates with intractable bleeding or severe coagulation disturbances. All patients received intravenous bolus administration of 20 or 30 u/kg of PCC per dose, as a rescue procedure.Hemostasis was achieved in the majority of neonates and we observed statistically significant improvement in prothrombin time, international normalized ratio, and activated partial thromboplastin time (P0.001, P=0.044, P0.001, respectively). Thirteen neonates survived, whereas 24 did not survive. In those who survived, PCC had been administered earlier (24 h) in the disease process compared with those who died (P=0.043). Neither acute adverse events nor thromboembolic complications were observed in all neonates.In our study, PCC seemed to be a safe and effective intervention for hemostasis and early intervention was more effective as a rescue therapy, without any adverse event. Further prospective controlled trials are required to determine optimal dose and timing of PCC administration in neonates.

Model-based methods and tools are applied to preliminary analysis of a mobile heat integrated horizontal separation system. An economic model, based on Guthrie’s modular approach, is developed for analysis of capital and operational expenditures. The separation system consists of two, co-axially arranged tubes. The inner one is serving as a stripping section and the outer one as rectifying section. First, a steady state model is developed using n non-equilibrium stages based on mass transfer modeling. Sensitivity analysis has been performed to assess the impact on system performance, of variations of transport coefficients and design variables. The model together with an economic model has been applied to identify design and operational limitations on such a unit. The analysis investigates the total annual cost dependence of heat transfer area, alcohol concentration in the feed and rejected amount of water in the stripping section for different locations of interest. It has been found that the overall operating costs are significantly reduced for higher alcohol concentration in the feed and high discharge of water at the end of the stripping section. On the other hand, increased heat transfer area between the stripping and rectifying section leads to higher capital costs and is not necessarily balanced by lower operating costs.

Treatment of HER2+ breast cancer with trastuzumab is effective and combination anti-HER2 therapies have demonstrated benefit over monotherapy in the neoadjuvant and metastatic settings. This study investigated the therapeutic potential of targeting the BAG-1 protein co-chaperone in trastuzumab-responsive or -resistant cells. In the METABRIC dataset, BAG-1 mRNA was significantly elevated in HER2+ breast tumors and predicted overall survival in a multivariate analysis (HR = 0.81; p = 0.022). In a breast cell line panel, BAG-1 protein was increased in HER2+ cells and was required for optimal growth as shown by siRNA knockdown. Overexpression of BAG-1S in HER2+ SKBR3 cells blocked growth inhibition by trastuzumab, whereas overexpression of a mutant BAG-1S protein (BAG-1S H3AB), defective in binding HSC70, potentiated the effect of trastuzumab. Injection of a Tet-On SKBR3 clone, induced to overexpress myc-BAG-1S into the mammary fat pads of immunocompromised mice, resulted in 2-fold larger tumors compared to uninduced controls. Induction of myc-BAG-1S expression in two Tet-On SKBR3 clones attenuated growth inhibition by trastuzumab in vitro. Targeting endogenous BAG-1 by siRNA enhanced growth inhibition of SKBR3 and BT474 cells by trastuzumab, while BAG-1 protein-protein interaction inhibitor (Thio-S or Thio-2) plus trastuzumab combination treatment synergistically attenuated growth. In BT474 cells this reduced protein synthesis, caused G1/S cell cycle arrest and targeted the ERK and AKT signaling pathways. In a SKBR3 subpopulation with acquired resistance to trastuzumab BAG-1 targeting remained effective and either Thio-2 or BAG-1 siRNA reduced growth more compared to trastuzumab-responsive parental cells. In summary, targeting BAG-1 function in combination with anti-HER2 therapy might prove beneficial.

Venous thromboembolism, presenting as deep vein thrombosis (DVT) is a disease affected by aging, with a low rate of about 1 per 10,000 annually before the fourth decade of life, rising rapidly after age 45 years, and approaching 5–6 per 1000 annually by age 80.

This paper considers aquatic swimming of a pedundulatory bio-robotic system, inspired by the outstanding aquatic and terrestrial locomotion capabilities of the polychaete annelid marine worms. The robot employs lateral undulations of its elongated body, augmented by the oscillation of active lateral appendages (parapodia), to propel itself. The efficient propulsion and terrain adaptability of such robots on unstructured terrestrial substrates have been demonstrated in previous work. Here, we explore gait generation for underwater propulsion by direct (tail-to-head) lateral body waves, either alone (undulatory modes) or combined with appropriately coordinated parapodial motion (pedundulatory modes). A three-segment compliant-body robotic prototype is used, whose body was fabricated by molding polyurethane elastomers. This robot was tested in a laboratory water tank, to demonstrate the advantage gained from the exploitation of both tail-to-head body undulations and parapodia for underwater swimming. The forward speed may more than double and the propulsive force may increase ten-fold, compared to the case where only undulations are used.

The purpose of this paper is to examine the contemporary needs for the sustainable management of the historic settlements of the Peloponnese, in Southern Greece, as well as the ways in which the capabilities and functions offered by geographical information systems (GIS) can be implemented for optimum results. This is achieved, firstly, by addressing some theoretical and methodological issues, concerning the management of historic settlements, based on their special characteristics and international conventions and, secondly, by examining the potential of GIS to tackle different management issues, like the preservation of their architectural identity, the management of different protection zones and the protection of the surrounding natural environment. In the last part, there will be a presentation of some preliminary results, regarding the practical application of GIS in the management of the historic settlement of Leontari, focusing on the protection of the monuments, its sustainable expansion and the preservation of its vernacular character.

A model-based approach is demonstrated, to analyze a heat integrated horizontal distillation system for separation of light alcohol mixtures from second-generation biomass. The objective is to develop an engineering tool, based on process systems engineering concepts. This tool is used to analyze and evaluate the proposed separation system to provide guidelines with respect to specific design and process variables. The model is simulated and comparative studies for different mixtures containing alcohols are carried out. It is shown that separation of mixtures with low concertation of light alcohol content requires less energy compared to conventional distillation systems.

This article describes the development of a reaction database with the objective to collect data for multiphase reactions involved in small molecule pharmaceutical processes with a search engine to retrieve necessary data in investigations of reaction-separation schemes, such as the role of organic solvents in reaction performance improvement. The focus of this reaction database is to provide a data rich environment with process information available to assist during the early stage synthesis of pharmaceutical products. The database is structured in terms of reaction classification of reaction types; compounds participating in the reaction; use of organic solvents and their function; information for single step and multistep reactions; target products; reaction conditions and reaction data. Information for reactor scale-up together with information for the separation and other relevant information for each reaction and reference are also available in the database. Additionally, the retrieved information obtained from the database can be evaluated in terms of sustainability using well-known “green” metrics published in the scientific literature. The application of the database is illustrated through the synthesis of ibuprofen, for which data on different reaction pathways have been retrieved from the database and compared using “green” chemistry metrics.

Antiphospholipid syndrome (APS) is an autoimmune systemic disease characterized by vascular thrombosis (arterial or venous) and/or pregnancy complications associated with the occurrence of autoantibodies, specifically lupus anticoagulant, anticardiolipin antibodies, and/or anti-β2 glycoprotein-I antibodies confirmed at least twice over a 12 week period according to the 2006 Sydney criteria. Antiphospholipid antibodies are encountered in the general population with a reported prevalence of 1% to 5% However, APS is far more infrequent with a prevalence of 40-50/100,000 persons and an incidence of about 5 new patients/100,000 persons. APS can be diagnosed in patients with no apparent clinical or laboratory pathology (primary APS) or it may be related to numerous other conditions, autoimmune diseases (usually systemic lupus erythematosus), malignancies, infections and drugs (secondary APS). Women are at risk for APS since the disease is encountered in both the primary and the secondary state in females more often than in men. In addition, women in their reproductive years can develop APS (either classical or obstetric), and special attention is warranted in pregnant women with a diagnosis of APS. The benefits of hormonal therapy in the form of contraception or hormone replacement treatment should be carefully weighed against the increased risk for vascular complications in women with APS.

Objective: To estimate markers of prothrombotic state and endothelial dysfunction in youths with type 1 diabetes mellitus (T1DM) and investigate possible associations with anthropometric/demographic data, glycaemic control and lipid profile. Methods: In a cross-sectional design, we recruited 155 youths with T1DM and determined levels of plasminogen activator inhibitor-1-antigen (PAI-1-Ag), von Willebrand factor-antigen (vWF-Ag), fibrinogen (FB), lipids and glycosylated haemoglobin (HbA1c). Results: Of all the participants, 76 (49%) had increased levels of at least one of prothrombotic factors. Suboptimal glycaemic control was associated with a worse lipid profile and an eightfold increased risk of elevated vWF-Ag levels. Higher vWF-Ag concentrations were also correlated with impaired lipid profile and increased HbA1c values, whereas PAI-1-Ag was positively correlated only with triglyceride levels. After adjustment for potential confounders, only HbA1c contributed independently to the variation in vWF-Ag levels. Conclusion: Impaired prothrombotic state and consequently endothelial dysfunction are present in youths with T1DM, representing a cumulative risk factor for future cardiovascular disease (CVD). Achievement and maintenance of euglycaemia and normolipidaemia are crucial to decelerate progress of this process.

Protein–protein interactions mediated through the C-terminal Bcl-2–associated athanogene (BAG) domain of BAG-1 are critical for cell survival and proliferation. Thioflavin S (NSC71948)—a mixture of compounds resulting from the methylation and sulfonation of primulin base—has been shown to dose-dependently inhibit the interaction between BAG-1 and Hsc70 in vitro. In human breast cancer cell lines, with high BAG-1 expression levels, Thioflavin S reduces the binding of BAG-1 to Hsc70, Hsp70, or CRAF and decreases proliferation and viability. Here, we report the development of a protocol for the purification and isolation of biologically active constituents of Thioflavin S and the characterization of the novel compound Thio-2. Thio-2 blocked the growth of several transformed cell lines, but had much weaker effects on untransformed cells. Thio-2 also inhibited the proliferation of melanoma cell lines that had become resistant to treatment with PLX4032, an inhibitor of mutant BRAF. In transformed cells, Thio-2 interfered with intracellular signaling at the level of RAF, but had no effect on the activation of AKT. Thio-2 decreased binding of BAG-1 to Hsc70 and to a lesser extent BRAF in vitro and in vivo, suggesting a possible mechanism of action. Given that tumors frequently develop resistance to kinase inhibitors during treatment, Thio-2 and related compounds may offer promising alternative strategies to currently available therapies. Mol Cancer Ther; 12(11); 2400–14. ©2013 AACR.

Temporal and spatial variations of environmental and water quality parameters and their relations with macrobenthic flora were investigated in an eastern Mediterranean lagoon. Kaiafas is a mesohaline lagoon, which is influenced by point and diffused sources from the adjacent agricultural land and the nearby city. Water samples were analyzed for physicochemical parameters, microbial load and primary production, on a seasonal and spatial scale, while heavy metal concentrations were measured into two different sediment cores. An overall analysis of seasonal dynamics of water parameters and Chl-a based on trophic index TSI pointed out the lagoon as eutrophic. According to water quality parameters the lagoon was separated into two parts. The southern sector of the lagoon which was more affected by human activities showed higher nutrients, Chl-a, heavy metals and total Coliforms concentrations. Sediment texture and distribution of macrophytes were detected through the acoustic side scan sonar method, which proved to be a promising tool for defining and monitoring vegetation coverage of shallow lagoons. A number of distinct echo types and three different sediment types were revealed on the basis of the backscatter level and the variability of low and high backscatter areas. Furthermore, the extension and the coverage of Potamogeton pectinatus and Chara hispida f. corfuensis were successively depicted by combining the data of SSS and ground truthing samples. Meadows of P. pectinatus were established to the lagoon limits where high turbidity and silty substrate occurred, while C. hispida f. corfuensis was limited in deep and high transparent waters with sandy substrate.

Mammary MCF-10A cells seeded on reconstituted basement membrane form spherical structures with a hollow central lumen, termed acini, which are a physiologically relevant model of mammary morphogenesis. Bcl-2-associated athanogene 1 (Bag-1) is a multifunctional protein overexpressed in breast cancer and ductal carcinoma in situ. When present in the nucleus Bag-1 is predictive of clinical outcome in breast cancer. Bag-1 exists as three main isoforms, which are produced by alternative translation initiation from a single mRNA. The long isoform of Bag-1, Bag-1L, contains a nuclear localisation sequence not present in the other isoforms. When present in the nucleus Bag-1L, but not the other Bag-1 isoforms, can interact with and modulate the activities of estrogen-, androgen- and vitamin D-receptors. Overexpression of Bag-1 mRNA in MCF-10A is known to produce acini with luminal filling reminiscent of ductal carcinoma in situ. As this mRNA predominantly overexpresses the short isoform of Bag-1, Bag-1S, we set out to examine whether the nuclear Bag-1L isoform is sufficient to drive premalignant change by developing a Bag-1L-overexpressing MCF-10A model. Two clones differentially overexpressing Bag-1L were grown in two-dimensional (2D) and three-dimensional (3D) cultures and compared with an established model of HER2-driven transformation. In 2D cultures, Bag-1L overexpression reduced proliferation but did not affect growth factor responsiveness or clonogenicity. Acini formed by Bag-1L-overexpressing cells exhibited reduced luminal clearing when compared with controls. An abnormal branching morphology was also observed which correlated with the level of Bag-1L overexpression, suggesting further malignant change. Treatment with Thio-2, a small-molecule inhibitor of Bag-1, reduced the level of branching. In summary, 3D cultures of MCF-10A mammary epithelial cells overexpressing Bag-1L demonstrate a premalignant phenotype with features of ductal carcinoma in situ. Using this model to test the small-molecule Bag-1 inhibitor, Thio-2, reveals its potential to reverse the atypical branched morphology of acini that characterizes this premalignant change.

This paper describes the development and the application of a general integrated framework based on systematic model-based methods and computer-aided tools with the objective to achieve more sustainable process designs and to improve the process understanding. The developed framework can be applied to a wide range of problems, including the design of new processes as well as retrofit of existing batch-continuous production systems. The overview of the framework together with results from two case studies is presented to highlight the key aspects and the applicability of the framework. These case studies involve multiphase reaction systems for the synthesis of active pharmaceutical ingredients.

RIETE is an ongoing registry of consecutive patients with acute venous thromboembolism (VTE). First we learned that in RIETE the prevalence of positive tests was 32%. One in every 2 patients younger than 50 years tested positive, with no differences between idiopathic or secondary, first event or recurrent VTE. In contrast, one in every 4 patients older than 50 years tested positive. Then, we found that the younger age of women with factor V Leiden or prothrombin G20210A may be attributed to the higher proportion of women who had the VTE during pregnancy or contraceptive use. At variance with this, 60% of men had idiopathic VTE, and only those with factor V Leiden were younger than those who tested negative. We need more patients, more data and a longer follow-up. In a near future we might be able to learn more about the outcome of VTE patients.

Obesity in childhood increases the risk for early adult cardiovascular disease. However, the underlying mechanism is not fully known. The aims of this study were to measure levels of prothrombotic factors and examine their possible association with obesity and insulin resistance in obese children and adolescents. A total of 313 obese children and adolescents were recruited. In a cross-sectional design, we measured anthropometric parameters, plasminogen activator inhibitor-1-antigen (PAI-1-Ag), von Willebrand factor-antigen (vWF-Ag), fibrinogen (FB), lipids, fasting glucose, and insulin (FI) levels. Insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA-IR) index. Boys presented significantly higher PAI-1-Ag levels than girls (82.6 vs. 71.3 ng/ml, p = 0.01). Higher levels of PAI-1-Ag (96.8 vs. 69 ng/ml, p

Myeloproliferative disorders are commonly associated with thrombohemorrhagic manifestations. The current review highlights recent advances in understanding the epidemiology and pathogenetic mechanisms of thrombotic and bleeding complications. Therapeutic modalities and prophylactic interventions corresponding to the specific disease states are also discussed.

Stent components acting as potential antigens and promoting intracoronary mast cell activation can lead to catastrophic intrastent thrombosis. Patients with drug-eluting stent (DES) implantation are prone to hypersensitivity reactions from five potential antigens namely, nickel strut, polymer coating, eluted drug, as well as, concomitant drugs clopidogrel and aspirin. These events may be more common than suspected because it is hard to document them, unless they become systemic, in which case they manifest themselves as the Kounis syndrome characterized by the concurrence of acute coronary events with hypersensitivity reactions. This report concerns of a patient with implanted DES who developed an acute myocardial infarction in the stent area following an allergic reaction to contrast material.

We report a fatal case of a rhino-cerebral zygomycosis, caused by Rhizopus arrhizus (oryzae). The patient was suffering from idiopathic thrombopenic purpura, diagnosed 1 year earlier. He was already treated with methylprednisolone 5 months prior to his admission to the hospital for a loss of vision and pain in the left eye as well as left orbital cellulitis. After an initial empirical treatment with broad spectrum antibiotics and voriconazole (infection of unknown origin), the patient was treated with liposomal amphotericin as soon as a positive fungal culture revealed a zygomycete. Unfortunately, the mould was resistant to amphotericin B (MIC: 16 microg ml(-1)) and probably to posaconazole (MIC: 4 microg ml(-1)), which was co-administrated a few days later.

Background Clinical and experimental researches have linked smoking to disturbances of coagulation and fibrinolysis. Several potential mechanisms are incriminated involving inflammation, fibrinogen synthesis and clotting factors. Based on the fact that the majority of tobacco components cross the placental barrier, the objective of our current study is to investigate the influence of smoking during pregnancy on neonatal haemostasis. Study design The study was based on a comparative evaluation of coagulation and fibronolysis between healthy full term infants of women who smoked during pregnancy and a control group. Subjects consisted of 39 newborns of smoking and 43 newborns of nonsmoking mothers. Blood samples were obtained shortly after birth and before the administration of vitamin K. Investigation included: PT, INR, aPTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, vWillebrand (vWF), protein C and S, APCr, anti-thrombin (AT), t-PA and PAI-1. The independent t- test was used to compare the differences between the values of coagulation and fibrinolytic parameters at the p Results We discovered a statistically significant decrease in factor II and protein S levels and an elevation in t-PA and factor VIII concentrations in newborns of smoking mothers, without clinical manifestations of altered haemostasis. There were no significant differentiations in other coagulation or fibrinolytic parameters. Conclusion The alteration in factor II, protein S, t-PA and factor VIII in neonates exposed in utero to tobacco smoke is not accompanied by loss in the balance between coagulation and fibrinolytic pathways.