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  • 1
    Language: English
    In: Organic letters, 17 February 2017, Vol.19(4), pp.806-809
    Description: Nematophin, a known antibiotic natural product against Staphylococcus aureus for almost 20 years, is produced by all strains of Xenorhabdus nematophila. Despite its simple structure, its biosynthesis was unknown. Its biosynthetic pathway is reported using heterologous production in Escherichia coli. Additionally, the identification, structure elucidation, and biosynthesis of six extended nematophin derivatives from Xenorhabdus PB62.4 carrying an additional valine are reported. Preliminary bioactivity studies suggest a biological role of these compounds in the bacteria-nematode-insect symbiosis.
    Keywords: Anti-Bacterial Agents -- Biosynthesis
    ISSN: 15237060
    E-ISSN: 1523-7052
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  • 2
    In: The Journal of Trauma: Injury, Infection, and Critical Care, 2011, Vol.71(3), pp.523-527
    Description: BACKGROUND:: The optimal method for spinal evaluation after penetrating trauma is currently unknown. The goal of this study was to determine the sensitivity and specificity of a standardized clinical examination for the detection of spinal injuries after penetrating trauma. METHODS:: After Institutional Review Board approval, all evaluable penetrating trauma patients aged 15 years or more admitted to the Los Angeles County + University of Southern California Medical Center were prospectively evaluated for spinal pain, tenderness to palpation, deformity, and neurologic deficit. RESULTS:: During the 6-month study period, 282 patients were admitted after sustaining a penetrating injury; 143 (50.7%) as a result of gunshot wound (GSW) and 139 (49.3%) as a result of stab wound (SW). None of the patients sustaining a SW had a spinal injury. Of the 112 evaluable GSW patients, 9 sustained an injury: 6 with a true-positive and 3 with a false-negative clinical examination. The overall sensitivity, specificity, positive predictive value, and negative predictive value were 66.7%, 89.6%, 46.2% and 95.2%, respectively. For clinically significant injuries requiring surgical intervention, cervical or thoracolumbar spine orthosis, or cord transections, however, the sensitivity of clinical examination was 100.0%, specificity 87.5%, positive predictive value 30.8%, and negative predictive value 87.5%. CONCLUSION:: Clinically significant spinal injury, although rare after SWs, is not uncommon after GSWs. A structured clinical examination of the spine in evaluable patients who have sustained a GSW is highly reliable for identifying those with clinically significant injuries.
    Keywords: Spinal Injuries -- Diagnosis ; Wounds, Gunshot -- Complications ; Wounds, Stab -- Complications;
    ISSN: 0022-5282
    E-ISSN: 15298809
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  • 3
    In: Journal of Evaluation in Clinical Practice, October 2013, Vol.19(5), pp.763-768
    Description: Defining ‘best practice’ is one of the first and crucial steps in any Knowledge Translation (KT) research project. Without a sound understanding of what exactly should happen in practice, it is impossible to measure the extent of existing gaps between ‘desired’ and ‘actual’ care, set implementation goals, and monitor performance. The aim of this paper is to present a practical, stepped and interactive process to develop best practice recommendations that are actionable, locally applicable and in line with the best available research‐based evidence, with a view to adapt these into process measures (quality indicators) for KT research purposes. Our process encompasses the following steps: (1) identify current, high‐quality clinical practice guidelines (CPGs) and extract recommendations; (2) select strong recommendations in key clinical management areas; (3) update evidence and create evidence overviews; (4) discuss evidence and produce agreed ‘evidence statements’; (5) discuss the relevance of the evidence with local stakeholders; and (6) develop locally applicable actionable best practice recommendations, suitable for use as the basis of quality indicators. Actionable definitions of local best practice are a prerequisite for doing KT research. As substantial resources go into rigorously synthesizing evidence and developing CPGs, it is important to make best use of such available resources. We developed a process for efficiently developing locally applicable actionable best practice recommendations from existing high‐quality CPGs that are in line with current research evidence.
    Keywords: Best Practice ; Kt Research ; Methodology
    ISSN: 1356-1294
    E-ISSN: 1365-2753
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  • 4
    Language: English
    In: Chemistry – A European Journal, 20 February 2012, Vol.18(8), pp.2342-2348
    Description: Structure elucidation of natural products including the absolute configuration is a complex task that involves different analytical methods like mass spectrometry, NMR spectroscopy, and chemical derivation, which are usually performed after the isolation of the compound of interest. Here, a combination of stable isotope labeling of and strains and their transaminase mutants followed by detailed MS analysis enabled the structure elucidation of novel cyclopeptides named GameXPeptides including their absolute configuration in crude extracts without their actual isolation. : A combination of labeling experiments with mass spectrometry results in the reliable determination of the sum formula, the nature of the building blocks, and (for peptide natural products) also the determination of the absolute configuration as exemplified for the novel natural products GameXPeptide A–D (see scheme).
    Keywords: Configuration Determination ; Isotopic Labeling ; Mass Spectrometry ; Peptides ; Structure Elucidation
    ISSN: 0947-6539
    E-ISSN: 1521-3765
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  • 5
    Language: English
    In: Angewandte Chemie International Edition, 19 October 2015, Vol.54(43), pp.12702-12705
    Description: Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity. Herein, the identification of bacterial PAs from entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis was elucidated to involve a non‐ribosomal peptide synthetase. The occurrence of these biosynthesis gene clusters in Gram‐negative and Gram‐positive bacteria indicates an important biological function in bacteria. of bacterial pyrrolizidine alkaloids from , the pyrrolizixenamides, have been elucidated by two‐dimensional NMR spectroscopy and mass spectrometry. Their biosynthesis is shown to involve the bimodular non‐ribosomal peptide synthetase PxaA and the unique monooxygenase PxaB.
    Keywords: Baeyer–Villiger Oxidation ; Biosynthesis ; Natural Products ; Non‐Ribosomal Peptide Synthetases ; Pyrrolizidine Alkaloids
    ISSN: 1433-7851
    E-ISSN: 1521-3773
    Source: John Wiley & Sons, Inc.
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  • 6
    Language: English
    In: Angewandte Chemie (International ed. in English), 19 October 2015, Vol.54(43), pp.12702-5
    Description: Pyrrolizidine alkaloids (PAs) are widespread plant natural products with potent toxicity and bioactivity. Herein, the identification of bacterial PAs from entomopathogenic bacteria using differential analysis by 2D NMR spectroscopy (DANS) and mass spectrometry is described. Their biosynthesis was elucidated to involve a non-ribosomal peptide synthetase. The occurrence of these biosynthesis gene clusters in Gram-negative and Gram-positive bacteria indicates an important biological function in bacteria.
    Keywords: Baeyer-Villiger Oxidation ; Biosynthesis ; Natural Products ; Non-Ribosomal Peptide Synthetases ; Pyrrolizidine Alkaloids ; Bacteria -- Metabolism ; Pyrrolizidine Alkaloids -- Chemistry
    ISSN: 14337851
    E-ISSN: 1521-3773
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  • 7
    Article
    Article
    Language: English
    In: JAMA: The Journal of the American Medical Association, 06/09/1989, Vol.261(22), p.3298
    Description: A dramatic, fictional representation of a call that a resident receives early one Sunday morning from the ER doctor is presented. A young man with a gunshot to the temple needs attention.
    Keywords: Short Stories ; Physicians ; Personal Development;
    ISSN: 0098-7484
    E-ISSN: 15383598
    Source: American Medical Association (via CrossRef)
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  • 8
    Language: English
    In: Organic letters, 16 March 2018, Vol.20(6), pp.1563-1567
    Description: Georatusin (1), featuring a highly reduced, methylated polyketide moiety fused to a tryptophan by an amide and ester bond forming a 13-membered ring, was produced by the soil fungus Geomyces auratus. An HMQC-COSY spectrum was measured to build up the connectivities despite the overlapping proton signals. DQF-COSY, HETLOC, J-HMBC, and ROESY were implemented to determine the relative configuration of the flexible moiety. Georatusin (1) shows specific antiparasitic activities against Leishmania donovani and Plasmodium falciparum without obvious cytotoxicity. The biosynthesis of 1 was also proposed.
    Keywords: Ascomycota
    ISSN: 15237060
    E-ISSN: 1523-7052
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  • 9
    Language: English
    In: Journal of the Medical Library Association : JMLA, April 2011, Vol.99(2), pp.157-60
    Description: An evidence map is an overview of a broad research field that describes the volume, nature, and characteristics of research in that field [1]. Evidence maps can indicate research links, gaps, and strengths in a broad clinical context, while systematic reviews focus on a single clinical question [2, 3]. Maps complement systematic reviews by engaging stakeholders to identify and prioritize questions that may be informed by research evidence, highlighting the applicability of research evidence to different populations and contexts, and identifying important gaps that can inform further primary research or systematic reviews [3].
    Keywords: Biomedical Research ; Evidence-Based Medicine
    ISSN: 15365050
    E-ISSN: 1558-9439
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  • 10
    In: Nature Chemical Biology, 2011, Vol.7(12), p.888
    Description: We have identified a new mechanism for the cleavage and activation of nonribosomally made peptides and peptide-polyketide hybrids that are apparently operational in several different bacteria. This process includes the cleavage of a precursor molecule by a membrane-bound and D-asparagine-specific peptidase, as shown here in the biosynthesis of the antibiotic xenocoumacin from Xenorhabdus nematophila.
    Keywords: Peptide Biosynthesis ; Anti-Bacterial Agents -- Biosynthesis ; Prodrugs -- Metabolism ; Xenorhabdus -- Chemistry;
    ISSN: 1552-4450
    E-ISSN: 15524469
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