Discourse Performance in Adults With Mild Traumatic Brain Injury, Orthopedic Injuries, and Moderate to Severe Traumatic Brain Injury, and Healthy Controls.

INTRODUCTION: Adults with mild traumatic brain injury (mTBI) are at risk for communication disorders, yet studies exploring cognitive-communication performance are currently lacking. AIMS: This aim of this study was to characterize discourse-level performance by adults with mTBI on a standardized elicitation task and compare it to (a) healthy adults, (b) adults with orthopedic injuries (OIs), and (c) adults with moderate to severe TBI. METHOD: This study used a cross-sectional design. The participants included mTBI and OI groups recruited prospectively from an emergency medicine department. Moderate to severe TBI and healthy data were acquired from TalkBank. One-way analyses of variance were used to compare mean linguistic scores. RESULTS: Seventy participants across all groups were recruited. Groups did not differ on demographic variables. The study found significant differences in both content and productivity measures among the groups. Variables did not appear sensitive to differentiate between mTBI and OI groups. DISCUSSION: Cognitive and language performance of adults with mTBI is a pressing clinical issue. Studies exploring language with carefully selected control groups can influence the development of sensitive measures to identify individuals with cognitive-communication deficits.

A new Kunitz-type snake toxin family associated with an original mode of interaction with the vasopressin 2 receptor.

BACKGROUND AND PURPOSE: Venomous animals express numerous Kunitz-type peptides. The mambaquaretin-1 (MQ1) peptide identified from the Dendroaspis angusticeps venom is the most selective antagonist of the arginine-vasopressin V2 receptor (V2R) and the only unique Kunitz-type peptide active on a GPCR. We aimed to exploit other mamba venoms to enlarge the V2R-Kunitz peptide family and gain insight into the MQ1 molecular mode of action. EXPERIMENTAL APPROACH: We used a bio-guided screening assay to identify novel MQs and placed them phylogenetically. MQs were produced by solid-phase peptide synthesis and characterized in vitro by binding and functional tests and in vivo by diuresis measurement in rats. KEY RESULTS: Eight additional MQs were identified with nanomolar affinities for the V2R, all antagonists. MQs form a new subgroup in the Kunitz family, close to the V2R non-active dendrotoxins and to two V2R-active cobra toxins. Sequence comparison between active and non-active V2R Kunitz peptides highlighted five positions, among which four are involved in V2R interaction and belong to the two large MQ1 loops. We finally determined that eight positions, part of these two loops, interact with the V2R. The variant MQ1-K39A showed a higher affinity for the hV2R, but not for the rat V2R. CONCLUSIONS AND IMPLICATIONS: A new function and mode of action is associated with the Kunitz peptides. The number of MQ1 residues involved in V2R binding is large and may explain its absolute selectivity. MQ1-K39A represents the first step in the improvement of the MQ1 design from a medicinal perspective.