1,336 research outputs found

    Endocarditis due to Neisseria mucosa after tongue piercing

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    A lifeline to treatment: the role of Indian generic manufacturers in supplying antiretroviral medicines to developing countries

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    <p>Abstract</p> <p>Background</p> <p>Indian manufacturers of generic antiretroviral (ARV) medicines facilitated the rapid scale up of HIV/AIDS treatment in developing countries though provision of low-priced, quality-assured medicines. The legal framework in India that facilitated such production, however, is changing with implementation of the World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights, and intellectual property measures being discussed in regional and bilateral free trade agreement negotiations. Reliable quantitative estimates of the Indian role in generic global ARV supply are needed to understand potential impacts of such measures on HIV/AIDS treatment in developing countries.</p> <p>Methods</p> <p>We utilized transactional data containing 17,646 donor-funded purchases of ARV tablets made by 115 low- and middle-income countries from 2003 to 2008 to measure market share, purchase trends and prices of Indian-produced generic ARVs compared with those of non-Indian generic and brand ARVs.</p> <p>Results</p> <p>Indian generic manufacturers dominate the ARV market, accounting for more than 80% of annual purchase volumes. Among paediatric ARV and adult nucleoside and non-nucleoside reverse transcriptase inhibitor markets, Indian-produced generics accounted for 91% and 89% of 2008 global purchase volumes, respectively. From 2003 to 2008, the number of Indian generic manufactures supplying ARVs increased from four to 10 while the number of Indian-manufactured generic products increased from 14 to 53. Ninety-six of 100 countries purchased Indian generic ARVs in 2008, including high HIV-burden sub-Saharan African countries. Indian-produced generic ARVs used in first-line regimens were consistently and considerably less expensive than non-Indian generic and innovator ARVs. Key ARVs newly recommended by the World Health Organization are three to four times more expensive than older regimens.</p> <p>Conclusions</p> <p>Indian generic producers supply the majority of ARVs in developing countries. Future scale up using newly recommended ARVs will likely be hampered until Indian generic producers can provide the dramatic price reductions and improved formulations observed in the past. Rather than agreeing to inappropriate intellectual property obligations through free trade agreements, India and its trade partners - plus international organizations, donors, civil society and pharmaceutical manufacturers - should ensure that there is sufficient policy space for Indian pharmaceutical manufacturers to continue their central role in supplying developing countries with low-priced, quality-assured generic medicines.</p

    Identifying a gene expression signature of cluster headache in blood.

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    Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Gene expression data were analysed by gene and by module of co-expressed genes with particular attention to previously implicated disease pathways including hypocretin dysregulation. Only moderate gene expression differences were identified and no associations were found with previously reported pathogenic mechanisms. At the level of functional gene sets, associations were observed for genes involved in several brain-related mechanisms such as GABA receptor function and voltage-gated channels. In addition, genes and modules of co-expressed genes showed a role for intracellular signalling cascades, mitochondria and inflammation. Although larger study samples may be required to identify the full range of involved pathways, these results indicate a role for mitochondria, intracellular signalling and inflammation in cluster headach

    CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes

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    <p>Abstract</p> <p>Background</p> <p>The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments.</p> <p>Results</p> <p>We have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFAC<sup><it>R </it></sup>database that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool.</p> <p>Conclusion</p> <p>The program CORE_TF is accessible in a user friendly web interface at <url>http://www.LGTC.nl/CORE_TF</url>. It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites.</p

    Successful treatment of Candida parapsilosis and Pseudomonas aeruginosa infection using medical and surgical management in an injecting drug user with mitral and aortic valve endocarditis: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Polymicrobial endocarditis is a well-recognized problem in intravenous drug users and it accounts for 1 to 3% of endocarditis cases overall and up to 9% in other series. The most common combinations of organisms include <it>Staphylococcus aureus</it> and <it>Streptococcus pneumoniae</it> followed by <it>Staphylococcus aureus</it> and <it>Pseudomonas aeruginosa</it>. <it>Candida parapsilosis</it> endocarditis carries a mortality rate of 45%, and each infection with <it>Candida</it> or <it>Pseudomonas</it> endocarditis per se carries a very high mortality rate approaching 85% and 80%, respectively. The combination of <it>P. aeruginosa</it> and <it>C. parapsilosis</it> has never been encountered and there have been no earlier reports of the combination of <it>C. parapsilosis</it> and <it>P. aeruginosa</it> in adult intravenous drug users as a cause of endocarditis.</p> <p>Case presentation</p> <p>We present a 49-year-old man with bivalvular endocarditis with <it>P. aeruginosa</it> and <it>C. parapsilosis</it>. He had a prior bivalvular replacement in 2005 that became infected with the above microorganisms and he was treated with intravenous antibiotics. Because of ongoing intravenous drug use, a second valve replacement was denied. A few days later, the patient presented with septic shock secondary to <it>P. aeruginosa</it> and <it>C. parapsilosis</it> recurrent endocarditis. The infection was cured with a second bivalvular replacement and extended therapy with antibiotics and antifungals.</p> <p>Conclusion</p> <p>This is the first time a patient has presented with <it>P. aeruginosa</it> and <it>C. parapsilosis endocarditis</it>. Relapsing polymicrobial endocarditis can be cured with medical and surgical therapy.</p

    Literature-aided meta-analysis of microarray data: a compendium study on muscle development and disease

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    Background: Comparative analysis of expression microarray studies is difficult due to the large influence of technical factors on experimental outcome. Still, the identified differentially expressed genes may hint at the same biological processes. However, manually curated assignment of genes to biological processes, such as pursued by the Gene Ontology (GO) consortium, is incomplete and limited. We hypothesised that automatic association of genes with biological processes through thesaurus-controlled mining of Medline abstracts would be more effective. Therefore, we developed a novel algorithm (LAMA: Literature-Aided Meta-Analysis) to quantify the similarity between transcriptomics studies. We evaluated our algorithm on a large compendium of 102 microarray studies published in the field of muscle development and disease, and compared it to similarity measures based on gene overlap and over-representation of biological processes assigned by GO. Results: While the overlap in both genes and overrepresented GO-terms was poor, LAMA retrieved many more biologically meaningful links between studies, with substantially lower influence of technical factors. LAMA correctly grouped muscular dystrophy, regeneration and myositis studies, and linked patient and corresponding mouse model studies. LAMA also retrieves the connecting biological concepts. Among other new discoveries, we associated cullin proteins, a class of ubiquitinylation proteins, with genes down-regulated during muscle regeneration, whereas ubiquitinylation was previously reported to be activated during the inverse process: muscle atrophy. Conclusion: Our literature-based association analysis is capable of finding hidden common biological denominators in microarray studies, and circumvents the need for raw data analysis or curated gene annotation databases
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