Methods in molecular biology
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A wide variety of bioimaging techniques (e.g., ultrasound, computed X-ray tomography, magnetic resonance imaging (MRI), and positron emission tomography) are commonly employed for clinical diagnostics and scientific research. While all of these methods use a characteristic "energy-matter" interaction to provide specific details about biological processes, each modality differs from another in terms of spatial and temporal resolution, anatomical and molecular details, imaging depth, as well as the desirable material properties of contrast agents needed for augmented imaging. On many occasions, it is advantageous to apply multiple complimentary imaging modalities for faster and more accurate prognosis. ⋯ Multimodal contrast agents offer improvements in patient care, and at the same time can reduce costs and enhance safety by limiting the number of contrast agent administrations required for imaging purposes. Herein, we describe the synthesis and characterization of nanoparticulate-based multimodal contrast agent for noninvasive bioimaging using MRI, optical, and photoacoustic tomography (PAT)-imaging modalities. The synthesis of these agents is described using microemulsions, which enable facile integration of the desired diversity of contrast agents and material components into a single entity.
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Inflammation is a complex, multiscale biological response to threats - both internal and external - to the body, which is also required for proper healing of injured tissue. In turn, damaged or dysfunctional tissue stimulates further inflammation. ⋯ We have suggested the concept of translational systems biology, defined as a focused application of computational modeling and engineering principles to pathophysiology primarily in order to revise clinical practice. This chapter reviews the existing, translational applications of computational simulations and related approaches as applied to inflammation.
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Clostridium difficile is a spore-forming, toxin-producing, anaerobic bacterium abundant in soils and water. Frequent and early colonization of the human intestinal flora is common and often asymptomatic. Antimicrobials given commonly disrupt the intestinal microflora and through proliferation in colon and production of toxin A and B it precipitates C. difficile infection (CDI). ⋯ Both the current epidemic like this and other local outbreaks from resistant or virulent strains warrant culture to be routinely performed enabling susceptibility testing and typing of the pathogen. Genotyping is most commonly done today by pulse-field gel electrophoresis (PFGE) or PCR ribotyping but multilocus variable-number tandem-repeat analysis (MLVA) seems promising. Epidemiological surveillance using all these tools will help us to better understand the global spread of C. difficile.
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The principles of fluorescence resonance energy transfer have been utilized to develop a high-throughput assay which detects compounds that interfere with interaction between retinol-binding protein (RBP) and transthyretin (TTR). In this assay, the intrinsic fluorescence from the RBP-retinol complex excites a probe molecule which is covalently coupled to TTR. ⋯ Thus, compounds which bind to RBP must compete with retinol in order to affect RBP-TTR interaction. This feature of the assay will be useful to identify test compounds which are more likely to have an effect in vivo.
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In the last decade, radiological neuroimaging techniques have enhanced the study of mechanisms involved in the development and maintenance of neuropathic pain. Recent findings suggest that neuropathic pain in certain pain syndromes (e.g., complex regional pain syndrome/reflex sympathic dystrophy, phantom-limb pain) is associated with a functional reorganization and hyperexitability of the somatosensory and motor cortex. Studies showing that the reversal of cortical reorganization in patients with spontaneous or provoked pain is accompanied by pain relief stimulated the search for novel alternatives how to modulate the cortical excitability as a strategy to relieve pain. ⋯ Both techniques (TMS and tDCS) have been clinically investigated in healthy volunteers as well as in patients with various clinical pathologies and variety of pain syndromes. Although there is less evidence on tDCS as compared with TMS, the findings on tDCS in patients with pain are promising, showing an analgesic effect of tDCS, and observations up to date justify the use of tDCS for the treatment of pain in selected patient populations. tDCS has been shown to be very safe if utilized within the current protocols. In addition, tDCS has been proven to be easy to apply, portable and not expensive, which further enhances great clinical potential of this technique.