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Masoomeh Poorghorban,1 Umashankar Das,2 Osama Alaidi,1 Jackson M Chitanda,2 Deborah Michel,1 Jonathan Dimmock,1 Ronald Verrall,3 Pawel Grochulski,1,4 Ildiko Badea1 1Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, 2Department of Chemical and Biological Engineering, 3Department of Chemistry, University of Saskatchewan, Saskatoon, SK, Canada; 4Canadian Light Source, Saskatoon, SK, Canada Background: Curcumin analogs, including the novel compound NC 2067, are potent cytotoxic agents that suffer from poor solubility, and hence, low bioavailability. Cyclodextrin-based carriers can be used to encapsulate such agents. In order to understand the interaction between the two molecules, the physicochemical properties of the host–guest complexes of NC 2067 with β-cyclodextrin (CD) or β-cyclodextrin–gemini surfactant (CDgemini surfactant) were investigated for the first time. Moreover, possible supramolecular structures were examined in order to aid the development of new drug delivery systems. Furthermore, the in vitro anticancer activity of the complex of NC 2067 with CDgemini surfactant nanoparticles was demonstrated in the A375 melanoma cell line.Methods: Physicochemical properties of the complexes formed of NC 2067 with CD or CDgemini surfactant were investigated by synchrotron-based powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Synchrotron-based small- and wide-angle X-ray scattering and size measurements were employed to assess the supramolecular morphology of the complex formed by NC 2067 with CDgemini surfactant. Lastly, the in vitro cell toxicity of the formulations toward A375 melanoma cells at various drug-to-carrier mole ratios were measured by cell viability assay.Results: Physical mixtures of NC 2067 and CD or CDgemini surfactant showed characteristics of the individual components, whereas the complex of NC 2067 and CD or CDgemini surfactant presented new structural features, supporting the formation of the host–guest complexes. Complexes of NC 2067 with CDgemini surfactants formed nanoparticles having sizes of 100–200 nm. NC 2067 retained its anticancer activity in the complex with CDgemini surfactant for different drug-to-carrier mole ratios, with an IC50 (half-maximal inhibitory concentration) value comparable to that for NC 2067 without the carrier.Conclusion: The formation of host–guest complexes of NC 2067 with CD or CDgemini surfactant has been confirmed and hence the CDgemini surfactant shows good potential to be used as a delivery system for anticancer agents. Keywords: inclusion complex, supramolecular arrangement, small-angle X-ray scattering, powder X-ray diffraction, cytotoxic activity

Accurate magnification calibration for transmission electron microscopy is best achieved with the use of appropriate standards and an objective calibration technique. We have developed a reliable method for calibrating the magnification of images from frozen-hydrated specimens. Invariant features in radial density plots of a standard are compared with the corresponding features in a "defocused" X-ray model of the same standard. Defocused X-ray models were generated to mimic the conditions of cryo-electron microscopy. The technique is demonstrated with polyoma virus, which was used as an internal standard to calibrate micrographs of bovine papilloma virus type 1 and bacteriophage phi X174. Calibrations of the micrographs were estimated to be accurate to 0.35%-0.5%. Accurate scaling of a three-dimensional structure allows additional calibrations to be made with radial density plots computed from two- or three-dimensional data.

Accurate magnification calibration for transmission electron microscopy is best achieved with appropriate external or internal standards. The use of the icosahedral polyoma virus as a standard in frozen-hydrated preparations was previously described. This method used the known diameter of polyoma (from x-ray measurements) as a reference to calibrate the diameters of other viruses. Measurements were made from circular averages computed from individual particle images or from an average image of many individual particle images. The measured diameters of several different spherical viruses are in good agreement with measurements of the same viruses made with x-ray crystallographic and solution scattering techniques.We found, however, that it is very difficult to accurately measure particle diameters in images taken from frozen-hydrated specimens. This difficulty is attributable to several factors including i) uncertainty about the solvent density level, ii) superposition of density features that occur in two-dimensional projections of three-dimensional objects, iii) uneven outer surfaces of virus particles, iv) characteristically high noise and low contrast levels in micrographs, and v) contrast transfer function (CTF) effects.

Introduction Screening driving ability is challenging in psychiatry due to the fluctuating nature of psychiatric diagnoses, psychosocial factors, and the impact of medications. An examination of best practice and a literature review yielded few results, highlighting the need for the development of a driving screening framework. The goal was to develop a clinical reasoning guide, agreed upon by psychiatric occupational therapists, to improve systematic driving screening for this population. Method A series of surveys distributed to occupational therapists examined the key components to consider, utilizing a modified Delphi technique. Data from 94 completed questionnaires over three rounds were filtered, analyzed, summarized, and redistributed. Survey distribution and guideline amendment continued until consensus was achieved. Findings The Saskatchewan Psychiatric Occupational Therapy Driving Screen (SPOT-DS) has been developed as the first comprehensive clinical reasoning guide for screening drivers with psychiatric conditions. Conclusion The SPOT-DS can assist in protecting clients’ driving privileges, while ensuring public safety on the roads by providing a systematic approach to screening drivers. Further testing on its validity is warranted. [ABSTRACT FROM AUTHOR]