Mechanisms that fine tune the activity of potassium channels are crucial to a cell's ability to integrate and respond to a plethora of internal and external signals. Peptide toxins from venomous creatures have served as vital tools to define the molecular mechanisms underlying K ϩ channel function (1, 2). It has been suggested that toxins evolved from endogenous genes that function in normal cellular pathways (3, 4). Indeed, venomous creatures possess toxins with homology to several proteins, including acetylcholinesterases (5), phospholipases (6, 7), nerve growth factor (8), endothelins (9), Lynx-1 (10, 11), Kunitz-type serine protease inhibitors (12), and the ion channel regulatory (ICR) 5 domains of cysteinerich secretory proteins (CRISPs) (3,13,14). Mammalian proteins containing toxin-like domains (TxDs) that block K ϩ channels have not been characterized previously.BgK, a 37-residue peptide toxin from the sea anemone Bunodosoma granulifera (15,16), and ShK, a 35-residue peptide toxin from the sea anemone Stichodactyla helianthus (17,18) are potent inhibitors of K ϩ channels. The Simple Modular Architecture Research Tool (SMART) (available on the World Wide Web) predicts the existence of a large superfamily of proteins that contain domains (referred to as ShKT domains in the SMART data base) resembling these two toxins (Fig. 1A). Many of these proteins (ϳ70 proteins) are metallopeptidases, whereas others are prolyl-4-hydroxylases, tyrosinases, peroxidases, oxidoreductases, or proteins containing epidermal growth factor-like domains, thrombospondin-type repeats, or trypsin-like serine protease domains (Fig. 1B). The only human protein containing a ShKT domain in the SMART data base is MMP23 (matrix metalloprotease 23). Matrix metalloproteases belong to the metzincin superfamily and play important roles in tissue remodeling, development, and the immune response (19).MMP23 is expressed in many tissues and exists either as a type II transmembrane protein in ER/nuclear membranes or as a secreted form following cleavage of the RRRRY motif just N-terminal to the Zn 2ϩ -dependent metalloprotease domain (20 -23). The ShKT domain of MMP23 (MMP23 TxD ) lies between the metalloprotease domain and an immunoglobulinlike cell adhesion molecule (IgCAM) domain ( Fig. 2A). MMP23 has been implicated in prostate, brain, and breast cancer (24 -26). In humans, two related sequences, MMP23A (a pseudogene) and MMP23B, are co-located on chromosome 1p36 (20). We have investigated MMP23 to gain insight into the structure and physiological functions of ShKT toxin domains and describe the solution structure of the MMP23 TxD domain, its * This work was supported, in whole or in part, by National Institutes of Health

Objective. To assess demographics, charges, and outcome measures by temporal and volume analysis in the treatment of vestibular schwannoma.Design. Cross-sectional analysis.Setting, Subjects, and Methods. The California Hospital Inpatient Discharge Databases from 1996 to 2010.Results. A total of 6545 cases from 1996 to 2010 were identified. Of these, 86.2% occurred at high-volume centers (HVCs), and the number of annual cases decreased by 28.5% over the study period. Patients presenting for surgery were increasingly younger, non-Caucasian, and likely to have comorbidities. Total charges significantly increased over time (P \ .001), with the median total charge in 2006-2010 being $91,338 compared with $38,607.92 in 1996-2000 after adjusting for inflation. Routine discharges (home or residence) were more likely at HVCs (odds ratio [OR] 5.48, P \ .001) and less likely if patients had Medicaid (Medi-Cal; OR 0.51, P = .002) or Medicare (OR 0.55, P = .022), were 65 years or older (OR 0.56, P = .025), or had comorbidities (OR 0.54, P \ .001). Shorter hospital stays were more likely at HVCs (OR 3.77, P \ .001) and less likely if patients had Medicaid (OR 0.36, P \ .001) or comorbidities (OR 0.61, P \ .001). Lesser total charges were more likely at HVCs (OR 2.12, P = .002) and less likely if patients had comorbidities (OR 0.70, P \ .001). Mortality was less likely at HVCs (OR 0.10, P = .011).Conclusion. The profile of patients undergoing vestibular neuroma excision is changing. Surgical volume is decreasing, suggesting a trend toward more conservative management or stereotactic radiation. Patients are best served at HVCs, where routine discharges, shorter length of stay, decreased mortality, and lower total charges are more likely.

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Upper extremity amputations represent a prime opportunity to restore function through replantation. There are a variety of options that treating surgeons use to protect neurovascular repairs and restore function including Kirschner wire fixation, external fixation, wrist arthrodesis, and proximal row carpectomy. Additionally, the dorsal spanning plate may be a valuable tool for protecting neurovascular repairs. Compared to temporary immobilization with Kirschner wire fixation, which has previously been described in conjunction with upper extremity replantation, dorsal spanning plates can be left in place for longer durations with a lower risk of loosening and loss of fixation and for preventing postoperative sabotage or repeat amputation of the replant by the patient.In this article, we describe a unique case of a patient with acute psychiatric illness that presented with a self-inflicted amputation through the radiocarpal joint and was initially treated with emergent replantation and application of a dorsal spanning plate to protect the neurovascular repair from patient sabotage and allow for early rehabilitation. We found the dorsal spanning plate to be an effective option in this complex clinical scenario. This case illustrates the utility of the dorsal spanning plate in protecting complex neurovascular repairs in the setting of severe skeletal and psychiatric instability.