Anaesthetic hazards of the 'passion gap' A case report

Dental abnormalities cause problems for both dentist and anaesthetist. The anaesthetic hazards associated with the 'passion gap' - a term used in the western Cape Province for removal of the top four incisor teeth, a practice widespread among members ot the Cape Coloured community - are discussed. Recommendations are made to assist the anaesthetist when dealing with such a patient

Validation of an Immunoassay for Anti-thymidine Phosphorylase Antibodies in Patients with MNGIE Treated with Enzyme Replacement Therapy.

Erythrocyte encapsulated thymidine phosphorylase is recombinant Escherichia coli thymidine phosphorylase encapsulated within human autologous erythrocytes and is under development as an enzyme replacement therapy for the ultra-rare inherited metabolic disorder mitochondrial neurogastrointestinal encephalomyopathy. This study describes the method validation of a two-step bridging electrochemiluminescence immunoassay for the detection of anti-thymidine phosphorylase antibodies in human serum according to current industry practice and regulatory guidelines. The analytical method was assessed for screening cut point, specificity, selectivity, precision, prozone effect, drug tolerance, and stability. Key findings were a correction factor of 129 relative light units for the cut-point determination; a specificity cut point of 93% inhibition; confirmed intra-assay and inter-assay precision; assay sensitivity of 356 ng/mL; no matrix or prozone effects up to 25,900 ng/mL; a drug tolerance of 156 ng/mL; and stability at room temperature for 24 hr and up to five freeze-thaws. Immunogenicity evaluations of serum from three patients who received erythrocyte encapsulated thymidine phosphorylase under a compassionate treatment program showed specific anti-thymidine phosphorylase antibodies in one patient. To conclude, a sensitive, specific, and selective immunoassay has been validated for the measurement of anti-thymidine phosphorylase antibodies; this will be utilized in a phase II pivotal clinical trial of erythrocyte encapsulated thymidine phosphorylase

Tracking research

I began 2016, as so many previous years, with the intention of becoming more productive. As a bibliophile since the age of about 4 years old, my first place to go was therefore the university library – a haven of wonderful ideas in print form. And, quite literally, a gold mine of brilliance in this case. I found Paul Silvia’s How to write a lot , and devoured it in less than 24 hours , then bought a copy for myself . And it prompted the scheduler that Susan Gasson kindly presented at this year’s Doctoral Writing SIG meeting..

β-Glucan is a major growth substrate for human gut bacteria related to Coprococcus eutactus

A clone encoding carboxymethyl cellulase activity was isolated during functional screening of a human gut metagenomic library using Lactococcus lactis MG1363 as heterologous host. The insert carried a glycoside hydrolase family 9 (GH9) catalytic domain with sequence similarity to a gene from Coprococcus eutactus ART55/1. Genome surveys indicated a limited distribution of GH9 domains among dominant human colonic anaerobes. Genomes of C. eutactus-related strains harboured two GH9-encoding and four GH5-encoding genes, but the strains did not appear to degrade cellulose. Instead, they grew well on β-glucans and one of the strains also grew on galactomannan, galactan, glucomannan and starch. Coprococcus comes and Coprococcus catus strains did not harbour GH9 genes and were not able to grow on β-glucans. Gene expression and proteomic analysis of C. eutactus ART55/1 grown on cellobiose, β-glucan and lichenan revealed similar changes in expression in comparison to glucose. On β-glucan and lichenan only, one of the four GH5 genes was strongly upregulated. Growth on glucomannan led to a transcriptional response of many genes, in particular a strong upregulation of glycoside hydrolases involved in mannan degradation. Thus, β-glucans are a major growth substrate for species related to C. eutactus, with glucomannan and galactans alternative substrates for some strains

Antibiotic prescribing practice and adherence to guidelines in primary care in the Cape Town Metro District, South Africa

Background. Knowledge of antibiotic prescribing practice in primary care in South Africa is limited. As 80% of human antibiotic use is in primary care, this knowledge is important in view of the global problem of antibiotic resistance.Objectives. To assess antibiotic prescribing in primary care facilities in the Cape Town Metro District and compare it with current national guidelines, and to assess the reasons why prescriptions were not adherent to guidelines.Methods. A retrospective medical record review was performed in April/May 2016. Records of all patients seen over 2 days in each of eight representative primary care facilities in the Cape Town Metro District were reviewed. The treatment of any patient who raised a new complaint on either of those days was recorded. Prophylactic antibiotic courses, tuberculosis treatment and patients with a non-infection diagnosis were excluded. Treatment was compared with the Standard Treatment Guidelines and Essential Medicines List for South Africa, Primary Healthcare Level, 2014 edition.Results. Of 654 records included, 68.7% indicated that an antibiotic had been prescribed. Overall guideline adherence was 45.1%. Adherence differed significantly between facilities and according to the physiological system being treated, whether the prescription was for an adult or paediatric patient, and the antibiotic prescribed. Healthcare professional type and patient gender had no significant effect on adherence. The main reasons for non-adherence were an undocumented diagnosis (30.5%), antibiotic not required (21.6%), incorrect dose (12.9%), incorrect drug (11.5%), and incorrect duration of therapy (9.5%).Conclusions. This study demonstrates poor adherence to guidelines. Irrational use of antibiotics is associated with increased antibiotic resistance. There is an urgent need to improve antibiotic prescribing practice in primary care in the Cape Town Metro District.

Exogenously added GPI-anchored tissue inhibitor of matrix metal loproteinase-1 (TIMP-1) displays enhanced and novel biological activities

The family of tissue inhibitors of metalloproteinases (TIMPs) exhibits diverse physiological/biological functions including the inhibition of active matrix metalloproteinases, regulation of proMMP activation, cell growth, and the modulation of angiogenesis. TIMP-1 is a secreted protein that can be detected on the cell surface through its interaction with surface proteins. The diverse biological functions of TIMP-1 are thought to lie, in part, in the kinetics of TIMP-1/MMP/surface protein interactions. Proteins anchored by glycoinositol phospholipids (GPIs), when purified and added to cells in vitro, are incorporated into their surface membranes. A GPI anchor was fused to TIMP-1 to generate a reagent that could be added directly to cell membranes and thus focus defined concentrations of TIMP-1 protein on any cell surface independent of protein-protein interaction. Unlike native TIMP-1, exogenously added GPI-anchored TIMP-1 protein effectively blocked release of MMP-2 and MMP-9 from osteosarcoma cells. TIMP-1-GP1 was a more effective modulator of migration and proliferation than TIMP-1. While control hTIMP-1 protein did not significantly affect migration of primary microvascular endothelial cells at the concentrations tested, the GPI-anchored TIMP-1 protein showed a pronounced suppression of endothelial cell migration in response to bFGF. In addition, TIMP-1-GPI was more effective at inducing microvascular endothelial proliferation. In contrast, fibroblast proliferation was suppressed by the agent. Reagents based on this method should assist in the dissection of the protease cascades and activities involved in TIMP biology. Membrane-fixed TIMP-1 may represent a more effective version of the protein for use in therapeutic expression

Chemical Evolution of Galaxies

Chemical evolution of galaxies brings together ideas on stellar evolution and nucleosynthesis with theories of galaxy formation, star formation and galaxy evolution, with all their associated uncertainties. In a new perspective brought about by the Hubble Deep Field and follow-up investigations of global star formation rates, diffuse background etc., it has become necessary to consider the chemical composition of dark baryonic matter as well as that of visible matter in galaxies.Comment: 6 pages, AAS LaTeX macros v5.0, Millennium Essay to appear in PASP, Feb 200

A short-oligonucleotide microarray that allows improved detection of gastrointestinal tract microbial communities

<p>Abstract</p> <p>Background</p> <p>The human gastrointestinal (GI) tract contains a diverse collection of bacteria, most of which are unculturable by conventional microbiological methods. Increasingly molecular profiling techniques are being employed to examine this complex microbial community. The purpose of this study was to develop a microarray technique based on 16S ribosomal gene sequences for rapidly monitoring the microbial population of the GI tract.</p> <p>Results</p> <p>We have developed a culture-independent, semi-quantitative, rapid method for detection of gut bacterial populations based on 16S rDNA probes using a DNA microarray. We compared the performance of microarrays based on long (40- and 50-mer) and short (16–21-mer) oligonucleotides. Short oligonucleotides consistently gave higher specificity. Optimal DNA amplification and labelling, hybridisation and washing conditions were determined using a probe with an increasing number of nucleotide mismatches, identifying the minimum number of nucleotides needed to distinguish between perfect and mismatch probes. An independent PCR-based control was used to normalise different hybridisation results, and to make comparisons between different samples, greatly improving the detection of changes in the gut bacterial population. The sensitivity of the microarray was determined to be 8.8 × 10⁴bacterial cells g^-1faecal sample, which is more sensitive than a number of existing profiling methods. The short oligonucleotide microarray was used to compare the faecal flora from healthy individuals and a patient suffering from Ulcerative Colitis (UC) during the active and remission states. Differences were identified in the bacterial profiles between healthy individuals and a UC patient. These variations were verified by Denaturing Gradient Gel Electrophoresis (DGGE) and DNA sequencing.</p> <p>Conclusion</p> <p>In this study we demonstrate the design, testing and application of a highly sensitive, short oligonucleotide community microarray. Our approach allows the rapid discrimination of bacteria inhabiting the human GI tract, at taxonomic levels ranging from species to the superkingdom bacteria. The optimised protocol is available at: <url>http://www.ifr.ac.uk/safety/microarrays/#protocols</url>. It offers a high throughput method for studying the dynamics of the bacterial population over time and between individuals.</p

Brands in international and multi‐platform expansion strategies: economic and management issues

Powerful media branding has historically facilitated successful international expansion on the part of magazine and other content forms including film and TV formats. Multi-platform expansion is now increasingly central to the strategies of media companies and, as this chapter argues, effective use of branding in order to engage audiences effectively and to secure a prominent presence across digital platforms forms a core part of this. Drawing on original research into the experience of UK media companies, this chapter highlights some of the key economic, management and socio-cultural issues raised by the ever-increasing role of brands and branding in the strategies of international and multi-platform expansion that are increasingly common- place across media