An Interlaboratory Study to Identify Potential Visible Protein-Like Particle Standards.

Visible protein-like particle standards may improve visual inspection and/or appearance testing practices used in the biotechnology industry. They may improve assay performance resulting in better alignment and more standardized training among different companies. The National Institute of Standards and Technology (NIST) has conducted an interlaboratory study to test whether the standards under development mimic typical proteinaceous particles found in biotherapeutics and if they can be implemented during the visual inspection process. Fourteen organizations from industry and government have participated. A total of 20 labs from these 14 organizations participated with analysts from 6 formulation, 7 analytical, 4 quality control, and 3 manufacturing labs. The circulated samples consisted of abraded ethylene tetrafluoroethylene (ETFE) particles or photolithographic particles. The results consist of qualitative ratings, which varied substantially among organizations and within labs. Polydisperse ETFE particle suspensions, containing particles enriched in greater than 150 µm in size, were rated more favorably than the photolithographic particles by formulation and analytical scientists. The largest monodisperse photolithographic particles (approximately 300 µm in size) were favored equally compared to ETFE by all scientists. Solution modifications to decrease the settling rate or to alter optical properties of the ETFE solutions yielded lower ratings by the analysts. Both particle types received mixed ratings for their usability and for their application for visual inspection and for training purposes. Industry feedback will assist NIST in developing reference material(s) for visible protein-like particles.

Vulvar swelling as the first presentation of Crohn's disease in children-A report of three cases.

Vulvar swelling is a rare manifestation of metastatic Crohn's disease in children. It often predates gastrointestinal symptoms and can be the first presentation of pediatric Crohn's disease. We report three cases of pediatric Crohn's disease presenting with vulvar swelling. We discuss this rare presentation and its treatment and highlight the importance of recognizing it so that prompt investigation and appropriate management can be initiated.

Structural features underlying raloxifene's biophysical interaction with bone matrix.

Raloxifene, a selective estrogen receptor modulator (SERM), reduces fracture risk at least in part by improving the mechanical properties of bone in a cell- and estrogen receptor-independent manner. In this study, we determined that raloxifene directly interacts with the bone tissue. Through the use of multiple and complementary biophysical techniques including nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR), we show that raloxifene interacts specifically with the organic component or the organic/mineral composite, and not with hydroxyapatite. Structure-activity studies reveal that the basic side chain of raloxifene is an instrumental determinant in the interaction with bone. Thus, truncation of portions of the side chain reduces bone binding and also diminishes the increase in mechanical properties. Our results support a model wherein the piperidine interacts with bone matrix through electrostatic interactions with the piperidine nitrogen and through hydrophobic interactions (van der Waals) with the aliphatic groups in the side chain and the benzothiophene core. Furthermore, in silico prediction of the potential binding sites on the surface of collagen revealed the presence of a groove with sufficient space to accommodate raloxifene analogs. The hydroxyl groups on the benzothiophene nucleus, which are necessary for binding of SERMs to the estrogen receptor, are not required for binding to the bone surface, but mediate a more robust binding of the compound to the bone powder. In conclusion, we report herein a novel property of raloxifene analogs that allows them to interact with the bone tissue through potential contacts with the organic matrix and in particular collagen.

New class of competitive inhibitor of bacterial histidine kinases.

Bacterial histidine kinases have been proposed as targets for the discovery of new antibiotics, yet few specific inhibitors of bacterial histidine kinases have been reported. We report here a novel thienopyridine (TEP) compound that inhibits bacterial histidine kinases competitively with respect to ATP but does not comparably inhibit mammalian serine/threonine kinases. Although it partitions into membranes and does not inhibit the growth of bacterial or mammalian cells, TEP could serve as a starting compound for a new class of histidine kinase inhibitors with antibacterial activity.

Work and housework conditions and depressive symptoms among married women: the importance of occupational status.

Using the American Changing Lives Survey, a nationally representative sample of adults residing in the United States, this research examines housewives' subjective evaluations of their housework and the subjective evaluations of paid employment among three groups of married women--professionals, sales-clerical, and service-blue collar wives. A major goal was to assess the usefulness of disaggregating employed women by occupational status. Depressive symptoms were regressed on five work conditions--autonomy, physical and time demands, boredom, and feeling appreciated--along with sociodemographic characteristics. The results indicate professional wives report fewer symptoms than homemakers, sales-clerical, and service-blue collar wives. Differences between professionals and homemakers are largely accounted for by professional women's more advantaged economic position. Nonprofessional employed women are more depressed than professionals even when their disadvantaged working conditions are controlled. We discuss the findings in view of research on the stress of combining full-time employment with homemaking and argue that balancing these two roles may be more difficult for some employed women than for others.