Update on Extended Treatment for Venous Thromboembolism

The importance of assessing the probability of venous thromboembolism recurrence, a condition that includes deep vein thrombosis and pulmonary embolism, lies in the fact that it is the most important factor in deciding the duration of anticoagulant treatment. Risk of recurrence depends mostly on the presence of a risk factor for developing venous thromboembolism, with patients with unprovoked events being at the higher risk of recurrence. The risk of recurrence needs to be balanced with the risk of bleeding and the potential severity of these thrombotic and hemorrhagic events. In patients with an unprovoked venous thromboembolism who complete treatment for the acute (first 10 days) and post-acute phase of the disease (from day 10 to 3-6 months), decision has to be made regarding prolonged antithrombotic therapy to prevent recurrences. The main goal of extended treatment is preventing recurrences with a safe profile in terms of bleeding risk. Many therapeutic options are now available for these patients, including antiplatelet therapy with aspirin or direct oral anticoagulants. Moreover, apixaban and rivaroxaban at prophylactic doses have demonstrated efficacy in preventing recurrences with a low risk of bleeding

Biomarkers in Heart Failure and Associated Diseases

Biomarkers in heart failure and associated disease

Trichoderma and its secondary metabolites improve yield and quality of grapes

Trichoderma is one of the most studied and applied fungal biocontrol agents. The benefits of these microorganisms to the plant include: suppression of pathogens, growth promotion, enhanced nutrient availability and induction of resistance. The biological activity is related to the variety of metabolites that they produce. These metabolites have been found to directly inhibit the pathogens, increase disease resistance and enhance plant growth. In this study, we have examined the effect of two Trichoderma strains and their secondary metabolites on Vitis vinifera in terms of induction of disease resistance, plant growth promotion and increase of polyphenols or antioxidant activity in the grapes. Applications of T. harzianum M10 or T. atroviride P1, as well as their respective major secondary metabolites, harzianic acid (HA) and 6-pentyl-a-pyrone (6PP), have been conducted in greenhouse by foliar spray or drenching. The treatments suppressed the development of powdery mildew caused by Uncinula necator. In a field experiment, a spore suspension of T. harzianum strain T22 or a 6PP solution was applied until fruit harvest. The results indicated that both T. harzianum T22 and 6PP are able to improve crop yield and increase the total amount of polyphenols and antioxidant activity in the grapes. The effects of the isolated natural compounds were comparable with those obtained by using the living fungus

Trichoderma-based products and their widespread use in agriculture

Governing bodies throughout the world, particularly in Europe, are now implementing legislative mandates with the objective of decreasing dependence on pesticides in agriculture to increase consumer and environmental safety. In order to reduce the risks associated with pesticide applications and reduce dependency on their use, Directives will promote low pesticide-input by implementing integrated pest management (IPM), and provide the means to establish the necessary conditions and measures to employ these practices, as well as to ensure security of commercial products. One approach includes the use of biological control agents and their products as alternatives to synthetic agro-chemicals. Trichoderma spp. are widely studied fungi and are among the most commonly used microbial biological control agents (MBCAs) in agriculture. They are presently marketed as bio-pesticides, biofertilizers, growth enhancers and stimulants of natural resistance. The efficacy of this fungus can be attributed to their ability to protect plants, enhance vegetative growth and contain pathogen populations under numerous agricultural conditions, as well as to act as soil amendments/inoculants for improvement of nutrient ability, decomposition and biodegradation. The living fungal spores (active substance) are incorporated in various formulations, both traditional and innovative, for applications as foliar sprays, pre-planting applications to seed or propagation material, post-pruning treatments, incorporation in the soil during seeding or transplant, watering by irrigation or applied as a root drench or dip. Trichoderma-based preparations are marketed worldwide and used for crop protection of various plant pathogens or increase the plant growth and productivity in diverse cultivated environments such as fields, greenhouses, nurseries; in the production of a variety of horticultural, fruits, trees and ornamental crops. A survey was conducted of Trichoderma-containing products found on the international market to obtain an overall perspective of the: 1) geographical distribution, 2) product composition and identity of Trichoderma species selected, 3) contents combined with Trichoderma in the products - other microbial species or substances in the mix, 4) number of products available globally and geographically, 5) number of products registered or having use specifications, 6) product formulations and applications, 7) manufacturer claims - target use, target pests, product type and effects of applications. The largest distribution of Trichoderma bioproducts is found in Asia, succeeded by Europe, South- Central America and North America. The majority of the labels indicated fungicidal properties, but only 38% of the marketed merchandise are registered. Ten Trichoderma species are specifically indicated, but many labels indicate a generic Trichoderma sp. or spp. mix in the list of ingredients. The most common formulation is a wettable powder, followed by granules. Generally, Trichoderma are applied to the seed or propagation material at the time of planting, then the secondary use is during plant development. On the whole, the target use is for the control of soilborne fungal pathogens such as Rhizoctonia, Pythium and Sclerotinia, and a few foliar pathogens such as Botrytis and Alternaria; whereas the minor use indication is for plant growth promotion. The use of Trichoderma-based biological products will have an important role in agricultural production of the future, in light of changing worldwide perspectives by consumers and governing bodies

The impact of gender in cardiovascular medicine: Lessons from the gender/sex-issue in heart failure

Heart Failure (HF) is a major healthcare issue, given its high prevalence and incidence, the rate of comorbidities, the related high health-care costs and its poor outcome. In the last years mounting evidence revealed several differences between men and women affected by this clinical condition. Apart from the well-known difference in phenotype (HF with reduced ejection fraction (HFrEF) occurs more commonly in men, and HF with preserved ejection fraction (HFpEF) is more frequent in women) other relevant sex-related issues dwell upon epidemiology, presentation, risk stratification and management. These differences shed new lights on the possibility to consider HF as a prototype of the impact of gender/sex issue in cardiovascular medicine. A call for action and future strategies might help in the achievement of a cleaver patient-care

Trichoderma secondary metabolites active on plants and fungal pathogens

Beneficial microbes typically produce bioactive molecules that can affect the interactions of plants with their pathogens. Many secondary metabolites may also have antibiotic properties, which enable the producing microbe to inhibit and/or kill other microorganisms i.e. competing for a nutritional niche. Indeed, some of these compounds have been found to play an important role in the biocontrol of plant diseases by various beneficial microbes used world-wide for crop protection and bio-fertilization. In addition to direct toxic activity against plant pathogens, biocontrol-related metabolites may also increase disease resistance by triggering systemic plant defence activity, and/or enhance root and shoot growth. Fungi belonging to the Trichoderma genus are well known producers of secondary metabolites with a direct activity against phytopathogens and compounds that substantially affect the metabolism of the plant. The widescale application of selected metabolites to induce host resistance and/or to promote crop yield may become a reality in the near future and represents a powerful tool for the implementation of IPM strategies

Change of right heart size and function by long-term therapy with riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

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Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with multiple genetic aberrations. Several molecular pathways involved in the regulation of proliferation and cell death are implicated in the hepatocarcinogenesis. The major etiological factors for HCC are both hepatitis B virus (HBV) and hepatitis C virus infection (HCV)

Reconstruction of the Dark Energy equation of state

One of the main challenges of modern cosmology is to investigate the nature of dark energy in our Universe. The properties of such a component are normally summarised as a perfect fluid with a (potentially) time-dependent equation-of-state parameter $w(z)$. We investigate the evolution of this parameter with redshift by performing a Bayesian analysis of current cosmological observations. We model the temporal evolution as piecewise linear in redshift between `nodes', whose $w$-values and redshifts are allowed to vary. The optimal number of nodes is chosen by the Bayesian evidence. In this way, we can both determine the complexity supported by current data and locate any features present in $w(z)$. We compare this node-based reconstruction with some previously well-studied parameterisations: the Chevallier-Polarski-Linder (CPL), the Jassal-Bagla-Padmanabhan (JBP) and the Felice-Nesseris-Tsujikawa (FNT). By comparing the Bayesian evidence for all of these models we find an indication towards possible time-dependence in the dark energy equation-of-state. It is also worth noting that the CPL and JBP models are strongly disfavoured, whilst the FNT is just significantly disfavoured, when compared to a simple cosmological constant $w=-1$. We find that our node-based reconstruction model is slightly disfavoured with respect to the $\Lambda$CDM model.Comment: 17 pages, 5 figures, minor correction