Conservative initial postoperative anticoagulation strategy after HeartMate 3 left ventricular assist device implantation

Introduction

Although anticoagulation therapy is mandated after implantation of a left ventricular assist device (LVAD), postoperative bleedings and reoperations occur relatively frequently and are associated with worse outcomes. We evaluated the use of a conservative postoperative anticoagulation protocol in patients implanted with a HeartMate 3 (HM3) LVAD.

Methods

In a single-centre retrospective analysis of postoperative outcomes after HM3 LVAD implantation, a standard (old) anticoagulation protocol (i.e. early, full-dose anticoagulation with low-molecular weight heparin and overlapping vitamin K antagonist) was compared with a new conservative anticoagulation protocol (i.e. slow initiation of vitamin K antagonists without overlapping heparin). Main outcomes were changes in international normalised ratio (INR), lactate dehydrogenase (LDH), bleeding and/or tamponade events requiring reoperation, length of stay and adverse events.

Results

In total, 73 patients (48 in old vs 25 in new protocol group) were evaluated. Mean age was 56 years (standard deviation 13) and most patients (78%) were males. Changes in INR and LDH in the first 14 days were similar in both groups (p?=?0.50 and p?=?0.997 for interaction, respectively). Number of bleeding/tamponade events requiring reoperation was lower in the new than in the old protocol group (4% vs 33%, p?=?0.005). Postoperative 30-day mortality was similar, and we observed no thromboembolic events. Median (25th–75th percentiles) total length of postoperative hospital stay (27 (25–41) vs 21 (19–27) days, p?<?0.001) and length of intensive care unit stay (5 (2–9) vs 2 (2–5) days, p?=?0.022) were significantly shorter in the new protocol group.

Conclusion

These retrospective data suggest that conservative slow initiation of anticoagulation therapy after HM3 LVAD implantation is associated with less bleeding/tamponade events requiring reoperation, a similar safety profile and a shorter duration of stay than the currently advised standard anticoagulation protocol.

     

Phylogenetic community structure during succession: Evidence from three Neotropical forest sites

The phylogenetic structure of communities can reveal forces shaping community assembly, but the vast majority of work on phylogenetic community structure has been conducted in mature ecosystems. Here, we present an analysis of the phylogenetic structure of three Neotropical rain forest communities undergoing succession. In each site, the net relatedness of the community is initially high and consistently declines during succession. This pattern is evident both when comparing plots of different age classes and when comparing stem size classes within each plot: the oldest plots and the youngest stem cohorts, representing the most advanced stages of succession, have the lowest relatedness. Our results suggest that succession leaves a distinct signature in the phylogenetic structure of communities, which may reflect an increasing role of biotic interactions in community assembly during succession. We discuss theoretical explanations for the decline in community phylogenetic relatedness during succession, and suggest directions for future study.     

Vicissitudes of benefit sharing of crop genetic resources: downstream and upstream

In this article, we will first give a historic overview of the concept of benefit sharing and its appearance in official agreements, particularly with respect to crop genetic resources. It will become clear that, at present, benefit sharing is primarily considered as an instrument of compensation or exchange, and thus refers to commutative justice. However, we believe that such a narrow interpretation of benefit sharing disregards, and even undermines, much of its (historical) content and potency, especially where crop genetic resources are concerned. We argue that benefit sharing should not be based merely on commutative justice but rather on a broader model that is also grounded in the concept of distributive justice. This has repercussions for the application of benefit sharing, which we try to clarify by distinguishing between downstream and upstream benefit sharing. Upstream benefit sharing is not so much inspired by compensation for actions done, or the distribution downstream of benefits developed, but by the idea of shared decision-making on the research and development of resources fundamental to human welfare. Going upstream in the research process of crop genetic resources, and determining research agendas and improving crops according to the needs of the poor, benefit sharing may well be a tool to contribute to world food security and global justice. We concretize our ideas on upstream benefit sharing by introducing a set of criteria that determine the success of consultations on agricultural research agenda setting.     

A comparative study of byssogenesis on zebra and quagga mussels: the effects of water temperature, salinity and light-dark cycle

The quagga mussel (Dreissena rostriformis bugensis) and zebra mussel (Dreissena polymorpha) are invasive freshwater bivalves in Europe and North America. The distribution range of both Dreissena species is still expanding and both species cause major biofouling and ecological effects, in particular when they invade new areas. In order to assess the effect of temperature, salinity and light on the initial byssogenesis of both species, 24 h re-attachment experiments in standing water were conducted. At a water temperature of 25°C and a salinity of 0.2 psu, the rate of byssogenesis of D. polymorpha was significantly higher than that of D. rostriformis bugensis. In addition, byssal thread production by the latter levelled out between 15°C and 25°C. The rate of byssogenesis at temperatures<25°C was similar for both species. Neither species produced any byssal threads at salinities of 4 psu or higher. At a salinity of 1 psu and a water temperature of 15°C, D. polymorpha produced significantly more byssal threads than D. rostriformis bugensis. There was no significant effect of the length of illumination on the byssogenesis of either species. Overall, D. polymorpha produced slightly more byssal threads than D. rostriformis bugensis at almost all experimental conditions in 24 h re-attachment experiments, but both species had essentially similar initial re-attachment abilities. The data imply that D. rostriformis bugensis causes biofouling problems identical to those of D. polymorpha.     

The Role of Specific Tomato Volatiles in Tomato-Whitefly Interaction

Bemisia tabaci (whitefly) infestations and the subsequent transfer of viruses are the cause of severe losses in crop production and horticultural practice. To improve biological control of B. tabaci, we investigated repellent properties of plant-produced semiochemicals. The mix of headspace volatiles, collected from naturally repellent wild tomato accessions, influenced B. tabaci initial choice behavior, indicating a role for plant semiochemicals in locating host plants. A collection of wild tomato accessions and introgression lines (Solanum pennellii LA716 × Solanum lycopersicum ‘Moneyberg’) were extensively screened for attractiveness to B. tabaci, and their headspace profiles were determined by means of gas chromatography-mass spectrometry. Correlation analysis revealed that several terpenoids were putatively involved in tomato-whitefly interactions. Several of these candidate compounds conferred repellence to otherwise attractive tomato plants when applied to the plant''s branches on paper cards. The sesquiterpenes zingiberene and curcumene and the monoterpenes p-cymene, α-terpinene, and α-phellandrene had the strongest effects in free-choice bioassays. These terpenes also elicited a response of receptors on the insect''s antennae as determined by electroantennography. Conversely, the monoterpene β-myrcene showed no activity in both assays. B. tabaci apparently uses, besides visual cues, specific plant volatile cues for the initial selection of a host. Altering whitefly choice behavior by manipulation of the terpenoid composition of the host headspace may therefore be feasible.During the last decades, a worldwide spread of the pest insects Bemisia tabaci (Gennadius) and greenhouse whitefly (Trialeurodes vaporariorum) has led to local devastation of vegetable and ornamental crops, resulting in large economic losses. The damage whiteflies cause by their feeding behavior, such as affected biochemistry and development (for review, see Inbar and Gerling, 2008), is far exceeded by the secondary, indirect crop losses due to virus transmission. Specifically B. tabaci outbreaks are associated with the emergence of viruses for which they serve as vectors (Polston and Anderson, 1997). B. tabaci is capable of transmitting >100 different virus species of which the majority belong to the genus Begomovirus, such as Tomato yellow leaf curl virus, Tomato mottle virus (Jones, 2003), and African cassava mosaic virus (Maruthi et al., 2001). Damage caused by virus infection ranges from mild symptoms, such as leaf discolorations, to overall yield reduction, severe fruit necrosis, flower and fruit abortions, and plant death. Viral diseases are particularly severe since no chemical control is available and good sources of virus resistance for interspecific crossing are not always available (Maruthi et al., 2003). To date, only a limited number of virus resistance genes have been identified, and due to high mutation rates, viruses rapidly evolve (Drake and Holland, 1999; García-Andrés et al., 2006) and break monogenic resistances. Herbivores, such as whiteflies and thrips, can apparently benefit from transmitting viruses (Medeiros et al., 2004; Jiu et al., 2007; Belliure et al., 2008).B. tabaci was originally restricted to subtropical regions and greenhouses. However, the new and extremely invasive B and Q biotypes have the ability to rapidly adapt to more temperate zones and new host species (Jones, 2003; Wan et al., 2008). To date, the main control strategy for many crops is the application of insecticides, though effective spraying is complicated because of the insect''s preference for the abaxial side of the leaf (Simmons, 1994). Moreover, B. tabaci is difficult to control chemically due to emerging resistance to active ingredients (Horowitz et al., 2005). A new biological control agent, the phytoseiid predator Typhlodromips swirskii, has only been successful on plants without trichomes in closed greenhouses (Nomikou et al., 2002). The root-knot nematode resistance gene Mi1.2, which confers partial resistance to B. tabaci (Nombela et al., 2003), is widely used in modern tomato (Solanum spp.) varieties but is not sufficient to provide adequate protection against whitefly infestations.During insect host selection, orientation, and landing, both visual and olfactory cues play a predominant role (Visser, 1988). Color is an important factor in host-plant selection, and it was shown that B. tabaci reacts to blue-UV and yellow wavelengths (Van Lenteren and Noldus, 1990). The olfactory stimuli associated with the host plant initiate host targeting, whereas visual cues improve the accuracy of landing. In the initial phase of host targeting, olfaction may cause a positive chemotactic response, i.e. a flight up an odor gradient. Plant odor specificity might be achieved by a particular ratio of constituent volatiles (Bruce et al., 2005a). In the case of whiteflies, the role of olfaction in attraction or repellence has not received much prior attention. After host contact, B. tabaci evaluates host plant quality by labial dabbing and probing using piercing mouthparts. By probing, persistent viruses are transmitted via the insects'' salivary glands and mouthparts (Ghanim et al., 1998; Rosell et al., 1999). Therefore, to avoid virus transmission by B. tabaci, probing should be prevented.Volatile organic compounds released by plants can act as semiochemicals. They play an important role in enabling insects to recognize host plants from a distance (Schütz et al., 1997; Bruce et al., 2005a) or in attracting predators and parasitoids upon herbivory (De Moraes et al., 1998; Van Poecke and Dicke, 2002; Kappers et al., 2005). Moreover, they can play a role in the direct defense against herbivores and pathogens (Kessler and Baldwin, 2001; Shiojiri et al., 2006). A large number of different plant volatiles, with numerous ecological roles, have been identified so far (Sacchettini and Poulter, 1997; Pichersky et al., 2006). The largest class of plant volatiles is derived from the isoprenoid or terpenoid pathway. Solanaceous plants, like tomato, often make use of these terpenes for the defense against herbivores (Snyder et al., 1993; Kennedy, 2003). Some terpenes have been shown to exhibit repellent properties to insects (Peterson et al., 2002; Birkett et al., 2004; Terry et al., 2007). These plant-produced semiochemicals can potentially be used as insect repellents of natural origin, thus providing an alternative to the use of pesticides (Peterson and Coats, 2001). Engineering terpene emission to make crop plants more attractive to herbivore enemies has already been shown to be feasible (Degenhardt et al., 2003; Kappers et al., 2005; Schnee et al., 2006).The aim of this study is to identify the role of plant volatiles in the B. tabaci-tomato host interaction and to identify the terpenes that cause repellence of a selection of wild tomato accessions. The potential of several terpenes as repellent olfactory cues in B. tabaci host-preference behavior has been assessed in behavioral studies and through electroantennography (EAG).     

Human Golgi Antiapoptotic Protein Modulates Intracellular Calcium Fluxes

Golgi antiapoptotic protein (GAAP) is a novel regulator of cell death that is highly conserved in eukaryotes and present in some poxviruses, but its molecular mechanism is unknown. Given that alterations in intracellular Ca²⁺ homeostasis play an important role in determining cell sensitivity to apoptosis, we investigated if GAAP affected Ca²⁺ signaling. Overexpression of human (h)-GAAP suppressed staurosporine-induced, capacitative Ca²⁺ influx from the extracellular space. In addition, it reduced histamine-induced Ca²⁺ release from intracellular stores through inositol trisphosphate receptors. h-GAAP not only decreased the magnitude of the histamine-induced Ca²⁺ fluxes from stores to cytosol and mitochondrial matrices, but it also reduced the induction and frequency of oscillatory changes in cytosolic Ca²⁺. Overexpression of h-GAAP lowered the Ca²⁺ content of the intracellular stores and decreased the efficacy of IP₃, providing possible explanations for the observed results. Opposite effects were obtained when h-GAAP was knocked down by siRNA. Thus, our data demonstrate that h-GAAP modulates intracellular Ca²⁺ fluxes induced by both physiological and apoptotic stimuli.     

Identification of a novel Fasciola hepatica cathepsin L protease containing protective epitopes within the propeptide

Cathepsin L (CL)-like proteases are important candidate vaccine antigens for protection against helminth infections. We previously identified an immunogenic 32 kDa protein specifically present in newly excysted juveniles (NEJs) of Fasciola hepatica. Here we show by N-terminal protein sequencing that this protein represents a CL-like protease still containing the propeptide. Two cDNAs encoding this CL were subsequently isolated from NEJs by RT-PCR. The predicted amino acid sequences of these cDNAs showed approximately 70% sequence homology to both CL1 and CL2 sequences isolated from adult stage F. hepatica and are, therefore, referred to as CL3. The CL3 clones encoded asparagine at position P1 of the propeptide cleavage site, suggesting a dependence on asparaginyl endopeptidases for maturation. Recombinant expression of a CL3 cDNA in Saccharomyces cerevisiae resulted in secretion of the proenzyme form. The propeptide of CL-like proteins was predicted to contain important B-cell epitopes. To determine the contribution of the propeptide to protective immunity, rats were vaccinated with Keyhole Limpet Haemocyanin-conjugated synthetic peptides encoding these putative B-cell epitopes derived from the CL1 or CL3 sequence. A subsequent challenge infection resulted in a significant (P < 0.05) reduction of fluke load compared to adjuvant controls. We conclude that the propeptide of CL3 plays an important role in inducing immunity against F. hepatica infection.