Venous Thromboembolism and Primary Thromboprophylaxis in Perioperative Pancreatic Cancer Care.

Recent studies have shown that patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemo(radio)therapy followed by surgery have an improved outcome compared to patients treated with upfront surgery. Hence, patients with PDAC are more and more frequently treated with chemotherapy in the neoadjuvant setting. PDAC patients are at a high risk of developing venous thromboembolism (VTE), which is associated with decreased survival rates. As patients with PDAC were historically offered immediate surgical resection, data on VTE incidence and associated preoperative risk factors are scarce. Current guidelines recommend primary prophylactic anticoagulation in selected groups of patients with advanced PDAC. However, recommendations for patients with (borderline) resectable PDAC treated with chemotherapy in the neoadjuvant setting are lacking. Nevertheless, the prevention of complications is crucial to maintain the best possible condition for surgery. This narrative review summarizes current literature on VTE incidence, associated risk factors, risk assessment tools, and primary thromboprophylaxis in PDAC patients treated with neoadjuvant chemo(radio)therapy.

[Perspectives and practices of speech therapists regarding friendships after brain injury]. / Visie en werkzaamheden van logopedisten aangaande vriendschappen na hersen­letsel.

BACKGROUND: Acquired brain injury (ABI) is a common comorbidity in the psychiatric population. Consequences of ABI, including social communication problems, negatively affect friendships. However, current speech pathology practices regarding friendships after ABI remain unknown. AIM: To monitor perspectives, practices and facilitating as well as limiting factors with regard to these practices of Dutch speech therapists regarding friendships after ABI. METHOD: Survey study on whether, why, and how speech therapists do (not) perform work on friendships after ABI. RESULTS: Up to 90% of the 36 participating speech therapists believed that work related to friendships after ABI falls within the scope of their responsibilities. 78% of the speech therapists actually performed such activities. The most frequently mentioned facilitating factor in activities regarding friendship was the presence of supporting material, e.g. educational modules. The most frequently reported barrier was the very limited existence of social networks of persons with ABI. CONCLUSIONS: Work activities by speech therapists regarding friendships after ABI are numerous. Speech therapists are in need of material that can be used to support their work on friendships.

Multi-component meningococcal serogroup B (MenB)-4C vaccine induces effective opsonophagocytic killing in children with a complement deficiency.

Vaccination against meningococcal serogroup B is recommended for patients with a complement deficiency; however, although immunogenicity in this patient group has been shown, efficacy has not yet been established. In this study, we collected serum from children with a complement deficiency in the alternative pathway or in late terminal pathway before and after vaccination with multi-component meningococcal serogroup B (MenB)-4C. MenB-4C is a multi-component, protein-based vaccine against MenB consisting of factor H-binding protein, Neisserial heparin-binding protein, Neisserial adhesion A and outer membrane vesicles containing Porin A. We assessed the vaccine immunogenicity and vaccine-mediated protection by a whole cell enzyme-linked immunosorbent assay with Neisseria meningitidis serogroup B strains H44/76, 5/99 and NZ98/254, which shows that vaccination induced antibody titers against meningococcus. We show that the classical serum bactericidal activity assay with exogenous serum indicates the presence of vaccine-induced antibodies and capacity to activate complement-mediated pathogen lysis. However, in children with a late terminal pathway deficiency, no complement-mediated pathogen lysis was observed when autologous serum was applied in the serum bactericidal activity assay, demonstrating a lack of serum bactericidal activity in children with complement deficiencies. However, MenB-4C vaccination still induced effective complement-dependent opsonophagocytic killing against N. meningitidis serogroup B in reconstituted whole blood with autologous serum from children with an alternative pathway or late terminal pathway deficiency. These findings support the recommendation to vaccinate all complement-deficient children against MenB.

Impact of point defects on the electronic and transport properties of silicene nanoribbons.

We study the impact of various point defects on the structural, electronic and ballistic transport properties of armchair silicene nanoribbons, using the density functional theory and the non equilibrium Green's function method. The effect of a Stone-Wales defect, an interior/edge vacancy and an edge dangling bond is examined. Our results show that structural imperfections can alter the electronic structure (energy band structure and density of states) of the nanoribbons and can either increase or decrease the ballistic current. The dependence of the transport properties on the position of the defects (sublattice A or B) and on their distance from the contact is also investigated.

An electric field tunable energy band gap at silicene/(0001) ZnS interfaces.

The interaction of silicene, the silicon counterpart of graphene, with (0001) ZnS surfaces is investigated theoretically, using first-principles simulations. The charge transfer occurring at the silicene/(0001) ZnS interface leads to the opening of an indirect energy band gap of about 0.7 eV in silicene. Remarkably, the nature (indirect or direct) and magnitude of the energy band gap of silicene can be controlled by an external electric field: the energy gap is predicted to become direct for electric fields larger than about 0.5 V Å(-1), and the direct energy gap decreases approximately linearly with the applied electric field. The predicted electric field tunable energy band gap of the silicene/(0001) ZnS interface is very promising for its potential use in nanoelectronic devices.

Unraveling DNA tori under tension.

Motivated by recent experiments, we develop a model for DNA toroids under external tension. We find that tori are the equilibrium states for our model up to a critical tension, above which they become only metastable. Above this tension, we find a cascade of transitions between discrete toroid states that successively lower the winding number, until the ground state (rod) is reached. In this process, this model predicts a nearly constant force plateau as a function of extension, in agreement with experiment.

How DNA coiling enhances target localization by proteins.

Many genetic processes depend on proteins interacting with specific sequences on DNA. Despite the large excess of nonspecific DNA in the cell, proteins can locate their targets rapidly. After initial nonspecific binding, they are believed to find the target site by 1D diffusion ("sliding") interspersed by 3D dissociation/reassociation, a process usually referred to as facilitated diffusion. The 3D events combine short intrasegmental "hops" along the DNA contour, intersegmental "jumps" between nearby DNA segments, and longer volume "excursions." The impact of DNA conformation on the search pathway is, however, still unknown. Here, we show direct evidence that DNA coiling influences the specific association rate of EcoRV restriction enzymes. Using optical tweezers together with a fast buffer exchange system, we obtained association times of EcoRV on single DNA molecules as a function of DNA extension, separating intersegmental jumping from other search pathways. Depending on salt concentration, targeting rates almost double when the DNA conformation is changed from fully extended to a coiled configuration. Quantitative analysis by an extended facilitated diffusion model reveals that only a fraction of enzymes are ready to bind to DNA. Generalizing our results to the crowded environment of the cell we predict a major impact of intersegmental jumps on target localization speed on DNA.

Nucleotide sequence of human alkyl-dihydroxyacetonephosphate synthase cDNA reveals the presence of a peroxisomal targeting signal 2.

Two overlapping clones were isolated from a human liver cDNA library in lambda gt11 that coded for human alkyl-dihydroxyacetonephosphate synthase using guinea pig and PCR-derived human cDNA probes. The open reading frame encodes a protein of 658 amino acids that shows a homology of 92% with the guinea pig homolog and a similarity of 98%. The peroxisomal targeting signal 2 that was recently identified in the presequence of the guinea pig enzyme appeared to be completely preserved in the human enzyme. Supportive confirmation for parts of the sequence of the mature protein was obtained from the Expressed Sequence Tags database of the National Center for Biotechnology Information. This database contained nine cDNA sequences, derived from seven independent clones, that correspond exactly to parts of the cDNA of human alkyl-dihydroxyacetonephosphate synthase. One of these clones most likely represents a not fully processed RNA with a putative intron containing an Alu sequence. An unexpected homology with D-lactate dehydrogenase (cytochrome C) precursor from Saccharomyces cerevisiae and with glycolate oxidase subunit D from Escherichia coli was also revealed.

Inhibition of inositol 1,4,5-trisphosphate-induced Ca2+ release in permeabilized pancreatic acinar cells by hormonal and phorbol ester pretreatment.

Isolated rabbit pancreatic acinar cells, permeabilized by saponin treatment and incubated in the presence of 0.1 microM free Ca2+, accumulated 0.9-1.5 nmol of Ca2+/mg acinar protein in an energy-dependent pool. Uptake into this pool was not altered by pretreatment of acinar cells with the Ca2+ mobilizing secretagogues carbamylcholine and cholecystokinin-octapeptide or the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, indicating that the Ca2+ pump of the internal Ca2+ store was not affected by prolonged activation of the Ca2+ messenger system. Inositol 1,4,5-trisphosphate (1,4,5-IP3) caused a rapid decrease in Ca2+ content of the internal Ca2+ store. The response was maximal within 30 s following addition of 1,4,5-IP3 and no reuptake of Ca2+ was observed over the next 60 s. Up to 55% of the amount of Ca2+ stored in the energy-dependent pool was 1,4,5-IP3 releasable with an EC50 of 1.0 microM. Pretreatment of acinar cells with carbamylcholine or cholecystokinin-octapeptide significantly reduced the effectivity of 1,4,5-IP3 to release Ca2+ from the internal store. The dose-response curve for 1,4,5-IP3-induced release of actively stored Ca2+ from carbamylcholine-treated acinar cells showed both a rightward shift (EC50 value of 1.7 microM) and a decreased maximal response (maximal release value of 44%), which suggests that the affinity of 1,4,5-IP3 for its receptor as well as the number of 1,4,5-IP3 receptors or 1,4,5-IP3-operated Ca2+ channels was reduced upon prolonged activation of the Ca2+ messenger system. Moreover, analysis of the release values in a Hill plot suggested positive cooperativity for 1,4,5-IP3-induced Ca2+ release from the internal store (n values of 1.3 and 1.7 for saline- and carbamylcholine-treated permeabilized acinar cells, respectively). Pretreatment of acinar cells with 12-O-tetradecanoylphorbol 13-acetate partly mimicked the inhibitory effect of carbamylcholine on 1,4,5-IP3-induced release of actively stored Ca2+ in that the dose-response curve was shifted to the right but the maximal response was not affected, suggesting that the effects of carbamylcholine were at least in part mediated by protein kinase C.(ABSTRACT TRUNCATED AT 400 WORDS)