58 research outputs found

    Mesenteric panniculitis with pedal edema in a 33-year-old Pakistani man: a case report and literature review

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    <p>Abstract</p> <p>Introduction</p> <p>Mesenteric panniculitis is a rare pathology of unknown etiology characterized by inflammation and fibrosis in the mesentery. Its protean clinical and radiological manifestations make it a diagnostic challenge. There is no established treatment available for its management. The clinical outcome is inconsistent, with the prognosis ranging from complete resolution without any treatment to rapid progression culminating in death.</p> <p>Case presentation</p> <p>A 33-year-old Pakistani man presented with vague abdominal pain, an ill-defined epigastric mass and bilateral pedal edema. A detailed review of his history and laboratory investigations did not point to any diagnosis. The patient underwent an exploratory laparotomy based on the finding of mesenteric soft-tissue density on computed tomography. The laparotomy did not prove to be of any diagnostic or therapeutic value. Upon review of the pre-operative computed tomographic scan at our institution, a diagnosis of mesenteric panniculitis was made. An acceptable resolution of abdominal pain and pedal edema was attained after a 4-week trial of immunosuppressive therapy. This is the first reported case of mesenteric panniculitis with pedal edema as part of its presentation.</p> <p>Conclusion</p> <p>An increased awareness may lead to the development of a less invasive diagnostic approach and optimal treatment for this rarely recognized condition.</p

    The Morningside Initiative: Collaborative Development of a Knowledge Repository to Accelerate Adoption of Clinical Decision Support

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    The Morningside Initiative is a public-private activity that has evolved from an August, 2007, meeting at the Morningside Inn, in Frederick, MD, sponsored by the Telemedicine and Advanced Technology Research Center (TATRC) of the US Army Medical Research Materiel Command. Participants were subject matter experts in clinical decision support (CDS) and included representatives from the Department of Defense, Veterans Health Administration, Kaiser Permanente, Partners Healthcare System, Henry Ford Health System, Arizona State University, and the American Medical Informatics Association (AMIA). The Morningside Initiative was convened in response to the AMIA Roadmap for National Action on Clinical Decision Support and on the basis of other considerations and experiences of the participants. Its formation was the unanimous recommendation of participants at the 2007 meeting which called for creating a shared repository of executable knowledge for diverse health care organizations and practices, as well as health care system vendors. The rationale is based on the recognition that sharing of clinical knowledge needed for CDS across organizations is currently virtually non-existent, and that, given the considerable investment needed for creating, maintaining and updating authoritative knowledge, which only larger organizations have been able to undertake, this is an impediment to widespread adoption and use of CDS. The Morningside Initiative intends to develop and refine (1) an organizational framework, (2) a technical approach, and (3) CDS content acquisition and management processes for sharing CDS knowledge content, tools, and experience that will scale with growing numbers of participants and can be expanded in scope of content and capabilities. Intermountain Healthcare joined the initial set of participants shortly after its formation. The efforts of the Morningside Initiative are intended to serve as the basis for a series of next steps in a national agenda for CDS. It is based on the belief that sharing of knowledge can be highly effective as is the case in other competitive domains such as genomics. Participants in the Morningside Initiative believe that a coordinated effort between the private and public sectors is needed to accomplish this goal and that a small number of highly visible and respected health care organizations in the public and private sector can lead by example. Ultimately, a future collaborative knowledge sharing organization must have a sustainable long-term business model for financial support

    Idiopathic sclerosing mesenteritis in paediatrics: Report of a successfully treated case and a review of literature

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    A 6 year old female with symptoms of small bowel obstruction underwent an exploratory laparotomy which revealed widespread evidence of inflammatory fibrotic adhesions involving the jejunal mesentery. In view of persistent growth failure, chronic anaemia, elevated acute phase reactants and imaging evidence of a diffuse progressive inflammatory process, the child was treated with corticosteroids and methotrexate with complete response. The literature on juvenile idiopathic sclerosing mesenteritis has been reviewed

    Characterization of the Promoter, MxiE Box and 5′ UTR of Genes Controlled by the Activity of the Type III Secretion Apparatus in Shigella flexneri

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    Activation of the type III secretion apparatus (T3SA) of Shigella flexneri, upon contact of the bacteria with host cells, and its deregulation, as in ipaB mutants, specifically increases transcription of a set of effector-encoding genes controlled by MxiE, an activator of the AraC family, and IpgC, the chaperone of the IpaB and IpaC translocators. Thirteen genes carried by the virulence plasmid (ospB, ospC1, ospD2, ospD3, ospE1, ospE2, ospF, ospG, virA, ipaH1.4, ipaH4.5, ipaH7.8 and ipaH9.8) and five genes carried by the chromosome (ipaHa-e) are regulated by the T3SA activity. A conserved 17-bp MxiE box is present 5′ of most of these genes. To characterize the promoter activity of these MxiE box-containing regions, similar ∼67-bp DNA fragments encompassing the MxiE box of 14 MxiE-regulated genes were cloned 5′ of lacZ in a promoter probe plasmid; β-galactosidase activity detected in wild-type and ipaB strains harboring these plasmids indicated that most MxiE box-carrying regions contain a promoter regulated by the T3SA activity and that the relative strengths of these promoters cover an eight-fold range. The various MxiE boxes exhibiting up to three differences as compared to the MxiE box consensus sequence were introduced into the ipaH9.8 promoter without affecting its activity, suggesting that they are equally efficient in promoter activation. In contrast, all nucleotides conserved among MxiE boxes were found to be involved in MxiE-dependent promoter activity. In addition, we present evidence that the 5′ UTRs of four MxiE-regulated genes enhance expression of the downstream gene, presumably by preventing degradation of the mRNA, and the 5′ UTRs of two other genes carry an ancillary promoter

    Expression, maturation and turnover of DrrS, an unusually stable, DosR regulated small RNA in Mycobacterium tuberculosis

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    Mycobacterium tuberculosis depends on the ability to adjust to stresses encountered in a range of host environments, adjustments that require significant changes in gene expression. Small RNAs (sRNAs) play an important role as post-transcriptional regulators of prokaryotic gene expression, where they are associated with stress responses and, in the case of pathogens, adaptation to the host environment. In spite of this, the understanding of M. tuberculosis RNA biology remains limited. Here we have used a DosR-associated sRNA as an example to investigate multiple aspects of mycobacterial RNA biology that are likely to apply to other M. tuberculosis sRNAs and mRNAs. We have found that accumulation of this particular sRNA is slow but robust as cells enter stationary phase. Using reporter gene assays, we find that the sRNA core promoter is activated by DosR, and we have renamed the sRNA DrrS for DosR Regulated sRNA. Moreover, we show that DrrS is transcribed as a longer precursor, DrrS+, which is rapidly processed to the mature and highly stable DrrS. We characterise, for the first time in mycobacteria, an RNA structural determinant involved in this extraordinary stability and we show how the addition of a few nucleotides can lead to acute destabilisation. Finally, we show how this RNA element can enhance expression of a heterologous gene. Thus, the element, as well as its destabilising derivatives may be employed to post-transcriptionally regulate gene expression in mycobacteria in combination with different promoter variants. Moreover, our findings will facilitate further investigations into the severely understudied topic of mycobacterial RNA biology and into the role that regulatory RNA plays in M. tuberculosis pathogenesis

    The katG mRNA of Mycobacterium tuberculosis and Mycobacterium smegmatis is processed at its 5' end and is stabilized by both a polypurine sequence and translation initiation

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    <p>Abstract</p> <p>Background</p> <p>In <it>Mycobacterium tuberculosis </it>and in <it>Mycobacterium smegmatis </it>the <it>furA</it>-<it>katG </it>loci, encoding the FurA regulatory protein and the KatG catalase-peroxidase, are highly conserved. In <it>M. tuberculosis furA-katG </it>constitute a single operon, whereas in <it>M. smegmatis </it>a single mRNA covering both genes could not be found. In both species, specific 5' ends have been identified: the first one, located upstream of the <it>furA </it>gene, corresponds to transcription initiation from the <it>furA </it>promoter; the second one is the <it>katG </it>mRNA 5' end, located in the terminal part of <it>furA</it>.</p> <p>Results</p> <p>In this work we demonstrate by in vitro transcription and by RNA polymerase Chromatin immunoprecipitation that no promoter is present in the <it>M. smegmatis </it>region covering the latter 5' end, suggesting that it is produced by specific processing of longer transcripts. Several DNA fragments of <it>M. tuberculosis </it>and <it>M. smegmatis </it>were inserted in a plasmid between the <it>sigA </it>promoter and the <it>lacZ </it>reporter gene, and expression of the reporter gene was measured. A polypurine sequence, located four bp upstream of the <it>katG </it>translation start codon, increased beta-galactosidase activity and stabilized the <it>lacZ </it>transcript. Mutagenesis of this sequence led to destabilization of the mRNA. Analysis of constructs, in which the polypurine sequence of <it>M. smegmatis </it>was followed by an increasing number of <it>katG </it>codons, demonstrated that mRNA stability requires translation of at least 20 amino acids. In order to define the requirements for the 5' processing of the <it>katG </it>transcript, we created several mutations in this region and analyzed the 5' ends of the transcripts: the distance from the polypurine sequence does not seem to influence the processing, neither the sequence around the cutting point. Only mutations which create a double stranded region around the processing site prevented RNA processing.</p> <p>Conclusion</p> <p>This is the first reported case in mycobacteria, in which both a polypurine sequence and translation initiation are shown to contribute to mRNA stability. The <it>furA-katG </it>mRNA is transcribed from the <it>furA </it>promoter and immediately processed; this processing is prevented by a double stranded RNA at the cutting site, suggesting that the endoribonuclease responsible for the cleavage cuts single stranded RNA.</p

    A Review of the Status of Brain Structure Research in Transsexualism

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