Nasal decolonization of Staphylococcus aureus with mupirocin: strengths, weaknesses and future prospects

Staphylococcus aureus in the nose is a risk factor for endogenous staphylococcal infection. UK guidelines recommend the use of mupirocin for nasal decolonization in certain groups of patients colonized with methicillin-resistant S. aureus (MRSA). Mupirocin is effective at removing S. aureus from the nose over a few weeks, but relapses are common within several months. There are only a few prospective randomized clinical trials that have been completed with sufficient patients, but those that have been reported suggest that clearance of S. aureus from the nose is beneficial in some patient groups for the reduction in the incidence of nosocomial infections. There is no convincing evidence that mupirocin treatment reduces the incidence of surgical site infection. New antibiotics are needed to decolonize the nose because bacterial resistance to mupirocin is rising, and so it will become less effective. Furthermore, a more bactericidal antibiotic than mupirocin is needed, on the grounds that it might reduce the relapse rate, and so clear the patient of MRSA for a longer period of time than mupirocin

Setting the parameters right for two-hop IEEE 802.11e ad hoc networks

Two-hop ad-hoc networks, in which some nodes forward traffic for multiple sources, with which they also compete for channel access suffer from large queues building up in bottleneck nodes. This problem can often be alleviated by using IEEE 802.11e to give preferential treatment to bottleneck nodes. Previous results have shown that differentiation parameters can be used to allocate capacity in a more efficient way in the two-hop scenario. However, the overall throughput of the bottleneck may differ considerably, depending on the differentiation method used. By applying a very fast and accurate analysis method, based on steady-state analysis of an QBD-type infinite Markov chain, we find the maximum throughput that is possible per differentiation parameter. All possible parameter settings are explored with respect to the maximum throughput conditioned on a maximum buffer occupancy. This design space exploration cannot be done with network simulators like NS2 or Opnet, as each simulation run simply takes to long.\ud The results, which have been validated by detailed simulations, show that by differentiating TXOP it is possible to achieve a throughput that is about 50% larger than when differentiating AIFS and CW_min.\u

The Moxee City (Washington) Mammoth: Morphostratigraphic, Taphonomic, and Taxonomic Considerations

A nearly complete, but highly fractured, proboscidean tusk was unearthed during parking lot construction near Moxee City in central Washington in May 2001. Schreger angle analysis revealed that the tusk was from a mammoth. AMS radiocarbon dating of the tusk established that the mammoth died 14,570 14C yr BP. The age, combined with the biogeography of proboscidean finds in the Pacific Northwest, suggests the tusk is from a Columbian mammoth (Mammuthus columbi). The condition of the tusk and its association with basalt and crystalline erratics suggest that a locally derived tusk was swept up in the advancing flood and transported to ∼320 m elevation, where it was deposited in the sediments of the 3rd of 3 Missoula Floods that are preserved in the area. The tusk\u27s weathering indicates subaerial exposure prior to burial in the slackwater sediments. Slackwater deposits at the site are pale, ∼30-100 cm thick, calcareous, fine-textured strata that include occasional coarse basalt and crystalline sand and gravel. They are intruded by numerous clastic dikes. The sediments encapsulating the tusk lack rhythmites because of their deposition in the nearshore zone of an ephemeral slackwater lake. The first 2 floods inundated the site between 15,300 14C yr BP and 14,570 14C yr BP, stripping the A horizon from a well-developed soil formed in alluvial fan sediments sitting above an Ellensburg Formation pediment. The last flood to reach the site occurred later than 14,570 14C yr BP, as indicated by the presence of the dated tusk. Post-flood and post-MSH S tephra loess derived from the Yakima River floodplain mantles these slackwater deposits. The Warden soil is forming in the now-stable loess parent material

Poor Outcome in a Mitochondrial Neurogastrointestinal Encephalomyopathy Patient with a Novel TYMP Mutation: The Need for Early Diagnosis.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped TP therapy) and newer, promising therapies are expected in the near future. However, successful treatment is strictly related to early diagnosis. We report on an incomplete MNGIE phenotype in a young man harboring the novel heterozygote c.199 C>T (Q67X) mutation in exon 2, and the previously reported c.866 A>C (E289A) mutation in exon 7 in TYMP. The correct diagnosis was achieved many years after the onset of symptoms and unfortunately, the patient died soon after diagnosis because of multiorgan failure due to severe malnutrition and cachexia before any therapeutic option could be tried. To date, early diagnosis is essential to ensure that patients have the opportunity to be treated. MNGIE should be suspected in all patients who present with both gastrointestinal and nervous system involvement, even if the classical complete phenotype is lacking

Collagen-Fibrinogen Lyophilised Scaffolds for Soft Tissue Regeneration

A significant body of research has considered collagen as a scaffold material for soft tissue regeneration. The main structural component of extra-cellular matrix (ECM), collagen’s advantages over synthetic polymers are numerous. However, for applications where higher stiffness and stability are required, significant cross-linking may affect bioactivity. A carbodiimide (EDC) cross-linking route consumes carboxylate groups that are key to collagen’s essential cell recognition motifs (GxOGER). Fibrinogen was considered as a promising additive as it plays a key role in the process of wound repair and contains RGD integrin binding sites which bind to a variety of cells, growth factors and cytokines. Fibrinogen’s binding sites however, also contain the same carboxylate groups as collagen. We have successfully produced highly interconnected, porous collagen-fibrinogen scaffolds using a lyophilisation technique and micro-computed tomography demonstrated minimal influence of either fibrinogen content or cross-linking concentration on the scaffold structure. The specific biological effect of fibrinogen additions into cross-linked collagen are considered by using films as a model for the struts of bulk scaffolds. By considering various additions of fibrinogen to the collagen film with increasing degrees of cross-linking, this study demonstrates a significant biological advantage with fibrinogen addition across the cross-linking concentrations typically applied to collagen-based scaffolds.The authors wish to acknowledge the support of the European Research Council for the Advanced Grant 320598 awarded to REC and the EPSRC for the Established Career Fellowship EP/N019938/1 awarded to REC and SMB. They also wish to acknowledge funding for DB from the Peoples Programme of the EU 7th Framework Programme (RAE no: PHF-GA-2013-624904)

Absorption mode two-dimensional NOE spectroscopy of exchangeable protons in oligonucleotides

AbstractA new NMR method is described for the generation of absorption mode two-dimensional NOE spectra of oligonucleotides in H2O solution. The method yields spectra that are free of baseline distortions with excellent suppression of the intense H2O resonance. The method is demonstrated for a sample of the dodecamer d(CGCGAATTCGCG)2. All exchangeable base protons are identified and a number of new types of NOE connectivities are observed

Comparison of four genotyping assays for epidemiological study of methicillin-resistant Staphylococcus aureus

Twenty-six methicillin-resistant Staphylococcus aureus strains were genetically differentiated by interrepeat PCR and the results compared with those of ribotyping, pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA analysis obtained in a previous study for the same strains. The comparison showed that the PCR-mediated assays were as discriminatory as PFGE, whereas ribotyping was the least powerful genotyping method. Due to the ease of performance, PCR fingerprinting may become the method of choice for establishing clonal relationships among Staphylococcus aureus isolates

Conformational flexibility within the small domain of human serine racemase

Serine racemase (SR) is a pyridoxal 5′-phosphate (PLP)-containing enzyme that converts L-serine to D-serine, an endogenous co-agonist for the N-methyl-D-aspartate receptor (NMDAR) subtype of glutamate ion channels. SR regulates D-serine levels by the reversible racemization of L-serine to D-serine, as well as the catabolism of serine by α,β-elimination to produce pyruvate. The modulation of SR activity is therefore an attractive therapeutic approach to disorders associated with abnormal glutamatergic signalling since it allows an indirect modulation of NMDAR function. In the present study, a 1.89 Å resolution crystal structure of the human SR holoenzyme (including the PLP cofactor) with four subunits in the asymmetric unit is described. Comparison of this new structure with the crystal structure of human SR with malonate (PDB entry 3l6b) shows an interdomain cleft that is open in the holo structure but which disappears when the inhibitor malonate binds and is enclosed. This is owing to a shift of the small domain (residues 78–155) in human SR similar to that previously described for the rat enzyme. This domain movement is accompanied by changes within the twist of the central four-stranded β-sheet of the small domain, including changes in the φ–ψ angles of all three residues in the C-terminal β-strand (residues 149–151). In the malonate-bound structure, Ser84 (a catalytic residue) points its side chain at the malonate and is preceded by a six-residue β-strand (residues 78–83), but in the holoenzyme the β-strand is only four residues (78–81) and His82 has φ–ψ values in the α-helical region of the Ramachandran plot. These data therefore represent a crystallographic platform that enables the structure-guided design of small-molecule modulators for this important but to date undrugged target

Characterisation of the differential expression of marker antigens by normal and malignant endometrial epithelium

In order to examine the production of marker proteins, a reproducible method has been established for culturing purified epithelial cells from normal and malignant endometrium. We have examined the differential expression of secretory proteins using immunohistochemistry in frozen tissue sections, immunocytochemistry in cell cultures derived from the same specimens and protein assays on the culture supernatants. Placental protein 14 (PP14) was produced by normal premenopausal epithelium but not by the post-menopausal or malignant endometrial epithelium. In contrast, placental alkaline phosphatase (PLAP) was produced by endometrial cancers and the endometrial adenocarcinoma-derived cell line Ishikawa, but not by the normal endometrial epithelium. Other markers such as CA-125, which was produced by both normal and malignant endometrium but not by the cell line, and human chorionic gonadotrophin (beta-hCG), which was produced by Ishikawa cells but not by any of the fresh tissues, were less cancer specific. Placental alkaline phosphatase is a direct product of endometrial cancers that can be readily assayed in serum using this two-site assay to test its clinical usefulness in monitoring patients at risk for endometrial cancer