Rate, characteristics, and factors associated with high emergency department utilization

Background: Patients with high emergency department (ED) utilization account for a disproportionate number of ED visits. The existing research on high ED utilization has raised doubts about the homogeneity of the frequent ED user. Attention to differences among the subgroups of frequent visitors (FV) and highly frequent visitors (HFV) is necessary in order to plan more effective interventions. In the Netherlands, the incidence of high ED utilization is unknown. The purpose of this study was to investigate if the well-documented international high ED utilization also exists in the Netherlands and if so, to characterize these patients. Therefore, we assessed the proportion of FV and HFV; compared age, sex, and visit outcomes between patients with high ED utilization and patients with single ED visits; and explored the factors associated with high ED utilization. Methods: A 1-year retrospective descriptive correlational study was performed in two Dutch EDs, using thresholds of 7 to 17 visits for frequent ED use, and greater than or equal to 18 visits for highly frequent ED use. Results: FV and HFV (together accounting for 0.5% of total ED patients) attended the ED 2,338 times (3.3% of the total number of ED visits). FV and HFV were equally likely to be male or female, were less likely to be self-referred, and they suffered from urgent complaints more often compared to patients with single visits. FV were significantly older than patients with single visits and more often admitted than patients with single visits. Several chief complaints were indicative for frequent and highly frequent ED use, such as shortness of breath and a psychiatric disorder. Conclusions: Based on this study, high ED utilization in the Netherlands seems to be less a problem than outlined in international literature. No major differences were found between FV and HFV, they presented with the same, often serious, problems. Our study supports the notion that most patients with high ED utilization visit the ED for significant medical problems. © 2014 van der Linden et al.; licensee Springer

Substrate Specifity Profiling of the Aspergillus fumigatus Proteolytic Secretome Reveals Consensus Motifs with Predominance of Ile/Leu and Phe/Tyr

The filamentous fungus Aspergillus fumigatus (AF) can cause devastating infections in immunocompromised individuals. Early diagnosis improves patient outcomes but remains challenging because of the limitations of current methods. To augment the clinician's toolkit for rapid diagnosis of AF infections, we are investigating AF secreted proteases as novel diagnostic targets. The AF genome encodes up to 100 secreted proteases, but fewer than 15 of these enzymes have been characterized thus far. Given the large number of proteases in the genome, studies focused on individual enzymes may overlook potential diagnostic biomarkers.As an alternative, we employed a combinatorial library of internally quenched fluorogenic probes (IQFPs) to profile the global proteolytic secretome of an AF clinical isolate in vitro. Comparative protease activity profiling revealed 212 substrate sequences that were cleaved by AF secreted proteases but not by normal human serum. A central finding was that isoleucine, leucine, phenylalanine, and tyrosine predominated at each of the three variable positions of the library (44.1%, 59.1%, and 57.0%, respectively) among substrate sequences cleaved by AF secreted proteases. In contrast, fewer than 10% of the residues at each position of cleaved sequences were cationic or anionic. Consensus substrate motifs were cleaved by thermostable serine proteases that retained activity up to 50°C. Precise proteolytic cleavage sites were reliably determined by a simple, rapid mass spectrometry-based method, revealing predominantly non-prime side specificity. A comparison of the secreted protease activities of three AF clinical isolates revealed consistent protease substrate specificity fingerprints. However, secreted proteases of A. flavus, A. nidulans, and A. terreus strains exhibited striking differences in their proteolytic signatures.This report provides proof-of-principle for the use of protease substrate specificity profiling to define the proteolytic secretome of Aspergillus fumigatus. Expansion of this technique to protease secretion during infection could lead to development of novel approaches to fungal diagnosis

Engineering BioBrick vectors from BioBrick parts

<p>Abstract</p> <p>Background</p> <p>The underlying goal of synthetic biology is to make the process of engineering biological systems easier. Recent work has focused on defining and developing standard biological parts. The technical standard that has gained the most traction in the synthetic biology community is the BioBrick standard for physical composition of genetic parts. Parts that conform to the BioBrick assembly standard are BioBrick standard biological parts. To date, over 2,000 BioBrick parts have been contributed to, and are available from, the Registry of Standard Biological Parts.</p> <p>Results</p> <p>Here we extended the same advantages of BioBrick standard biological parts to the plasmid-based vectors that are used to provide and propagate BioBrick parts. We developed a process for engineering BioBrick vectors from BioBrick parts. We designed a new set of BioBrick parts that encode many useful vector functions. We combined the new parts to make a BioBrick base vector that facilitates BioBrick vector construction. We demonstrated the utility of the process by constructing seven new BioBrick vectors. We also successfully used the resulting vectors to assemble and propagate other BioBrick standard biological parts.</p> <p>Conclusion</p> <p>We extended the principles of part reuse and standardization to BioBrick vectors. As a result, myriad new BioBrick vectors can be readily produced from all existing and newly designed BioBrick parts. We invite the synthetic biology community to (1) use the process to make and share new BioBrick vectors; (2) expand the current collection of BioBrick vector parts; and (3) characterize and improve the available collection of BioBrick vector parts.</p

DNA repair pathways as targets for cancer therapy.

DNA repair pathways can enable tumour cells to survive DNA damage that is induced by chemotherapeutic treatments; therefore, inhibitors of specific DNA repair pathways might prove efficacious when used in combination with DNA-damaging chemotherapeutic drugs. In addition, alterations in DNA repair pathways that arise during tumour development can make some cancer cells reliant on a reduced set of DNA repair pathways for survival. There is evidence that drugs that inhibit one of these pathways in such tumours could prove useful as single-agent therapies, with the potential advantage that this approach could be selective for tumour cells and have fewer side effects