Sports concussion management: part I.

Concussion is a popular clinical topic that has been the subject of unprecedented recent media coverage. As concerns about the potential short- and long-term implications of repetitive head injury in sports such as football continue to mount, the proper clinical management of concussion seems to increase in importance. The days of ignoring the "ding" on the sideline are definitely over. A series of updated clinical evaluation and management recommendations from international experts are highlighted in this review. The clinical presentation of an acute concussion, both the typical and more subtle variations, may be evaluated with new validated sideline evaluation tools (eg, Sports Concussion Assessment Tool 2). In addition, the role of computerized neuropsychological and balance testing in the acute and ongoing evaluation are discussed, along with how they contribute to the return-to-play decision. Same-day return to play is outdated, and the relative insensitivity of current neuroimaging modalities to demonstrate structural damage is highlighted. New therapeutic interventions such as amantadine and cognitive rest may improve recovery time. The appropriate management of concussion typically results in a normal functional and neurocognitive outcome. The recommendations in this article may guide clinicians, with varying degrees of prior experience managing concussion, to increase the likelihood of an excellent outcome.

Determinants within an 18-amino-acid U1A autoregulatory domain that uncouple cooperative RNA binding, inhibition of polyadenylation, and homodimerization.

The human U1 snRNP-specific U1A protein autoregulates its own production by binding to and inhibiting the polyadenylation of its own pre-mRNA. Previous work demonstrated that a short sequence of U1A protein is essential for autoregulation and contains three distinct activities, which are (i) cooperative binding of two U1A proteins to a 50-nucleotide region of U1A pre-mRNA called polyadenylation-inhibitory element RNA, (ii) formation of a novel homodimerization surface, and (iii) inhibition of polyadenylation by inhibition of poly(A) polymerase (PAP). In this study, we purified and analyzed 11 substitution mutant proteins, each having one or two residues in this region mutated. In 5 of the 11 mutant proteins, we found that particular amino acids associate with one activity but not another, indicating that they can be uncoupled. Surprisingly, in three mutant proteins, these activities were improved upon, suggesting that U1A autoregulation is selected for suboptimal inhibitory efficiency. The effects of these mutations on autoregulatory activity in vivo were also determined. Only U1A and U170K are known to regulate nuclear polyadenylation by PAP inhibition; thus, these results will aid in determining how widespread this type of regulation is. Our molecular dissection of the consequences of conformational changes within an RNP complex presents a powerful example to those studying more complicated pre-mRNA-regulatory systems.