The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Shigella spp.

Introduction: Shigella bacteria cause shigellosis, a gastrointestinal infection most often acquired from contaminated food or water. Methods: In this review, the general characteristics of Shigella bacteria are described, cases of laboratory-acquired infections (LAIs) are discussed, and evidence gaps in current biosafety practices are identified. Results: LAIs are undoubtedly under-reported. Owing to the low infectious dose, rigorous biosafety level 2 practices are required to prevent LAIs resulting from sample manipulation or contact with infected surfaces. Conclusions: It is recommended that, before laboratory work with Shigella, an evidence-based risk assessment be conducted. Particular emphasis should be placed on personal protective equipment, handwashing, and containment practices for procedures that generate aerosols or droplets.

Fragment Screening by NMR.

This chapter describes the use of NMR to screen a fragment library as part of a fragment-based lead discovery (FBLD) campaign. The emphasis is on the practicalities involved in fragment screening by NMR, with particular attention to the use of 1D ligand-observed 1H NMR experiments. An overview of the theoretical considerations underlying the choice of method and experimental configuration is given, along with a discussion of steps that can be taken in order to minimize the risk of experimental artifacts often associated with the identification of low-affinity interactions.

Fragment-Based Drug Discovery: Advancing Fragments in the Absence of Crystal Structures.

Fragment-based drug discovery typically requires an interplay between screening methods, structural methods, and medicinal chemistry. X-ray crystallography is generally the method of choice to obtain three-dimensional structures of the bound ligand/protein complex, but this can sometimes be difficult, particularly for early, low-affinity fragment hits. In this Perspective, we discuss strategies to advance and evolve fragments in the absence of crystal structures of protein-fragment complexes, although the structure of the unliganded protein may be available. The strategies can involve other structural techniques, such as NMR spectroscopy, molecular modeling, or a variety of chemical approaches. Often, these strategies are aimed at guiding evolution of initial fragment hits to a stage where crystal structures can be obtained for further structure-based optimization.

Learning from our mistakes: the 'unknown knowns' in fragment screening.

In the past 15 years, fragment-based lead discovery (FBLD) has been adopted widely throughout academia and industry. The approach entails discovering very small molecular fragments and growing, merging, or linking them to produce drug leads. Because the affinities of the initial fragments are often low, detection methods are pushed to their limits, leading to a variety of artifacts, false positives, and false negatives that too often go unrecognized. This Digest discusses some of these problems and offers suggestions to avoid them. Although the primary focus is on FBLD, many of the lessons also apply to more established approaches such as high-throughput screening.

Segmental vessel sparing during convex growth arrest surgery--a modified technique.

BACKGROUND CONTEXT: Further evidence of the importance of segmental vessel ligation in the development of neurological complications has been recently published. The more levels the ligation encompasses, the higher the risk of spinal cord damage. Therefore, caution should be taken when several segmental arteries are to be ligated in the clinical setting. PURPOSE: To prevent ligation of segmental vessels during convex growth arrest surgery and thus decrease the risk of spinal cord ischemia and neurological injury. STUDY DESIGN: A report of a modified technique of convex growth arrest surgery used in two consecutive patients in our unit. METHODS: In two consecutive patients the segmental vessels were mobilized, elevated, and protected by using surgical slings. The rib graft was then slid beneath the elevated vessels into the prepared vertebral body channel and punched into place. The pleura then closed over the rib graft and spared vessels. RESULTS: Three of the five segmental vessels in the first patient were spared. All five segmental vessels were spared in the second patient. No neurological complications occurred. CONCLUSION: We report a straightforward technique, which obviates the need for segmental vessel ligation, and therefore decreases the risk of neurological injury in an already high-risk group.

Traction radiography performed under general anesthetic: a new technique for assessing idiopathic scoliosis curves.

STUDY DESIGN: A prospective review of 24 patients with late-onset idiopathic scoliosis. OBJECTIVES.: To compare curve flexibility measured using supine bending radiography and traction radiography; to examine the correlation of each technique with postoperative correction; and to determine the influence of each technique on the decision to perform concomitant anterior release surgery with posterior instrumentation. SUMMARY OF BACKGROUND DATA: Assessment of curve flexibility is important in decision making before surgical correction of scoliosis. Supine bending radiographs are presently the gold standard technique by which flexibility is assessed, but their reliability has been questioned. No literature has shown a conclusively superior role for traction radiography in assessing idiopathic scoliosis curves. METHODS: Each patient had erect anteroposterior radiographs and supine bending radiographs. On the day of surgery, traction radiography was performed under general anesthetic. The correction obtained in the Cobb angle between the bending and traction radiographs was compared. The influence of the traction radiography on the decision for anterior release surgery and its correlation with postoperative result was examined. RESULTS: Traction radiography demonstrated significantly greater curve flexibility than supine bending radiographs (P < 0.001). Eleven of 13 patients planned for anterior release surgery and posterior instrumentation avoided anterior release after review of the traction radiography. No significant difference was demonstrated between the traction radiography and postoperative correction (P = 0.13). CONCLUSION: Traction radiography is superior to supine bending radiography in assessing curve mobility before surgery. This method benefits patients by allowing them to avoid anterior release surgery and helps predict postoperative correction.