Mutations in GJB2 (Cx26) cause either deafness, or deafness associated with skin diseases. That different disorders can be caused by distinct mutations within the same gene suggests that unique channel activities are influenced by each class of mutation. We have examined the functional characteristics of two human mutations, Cx26-H73R and Cx26-S183F, causing palmoplantar keratoderma (PPK) and deafness. Both failed to form gap junction channels or hemichannels when expressed alone. Co-expression of the mutants with wild-type Cx43 showed a trans-dominant inhibition of Cx43 gap junction channels, without reductions in Cx43 protein synthesis. In addition, the presence of mutant Cx26 shifted Cx43 channel gating and kinetics towards a more Cx26-like behavior. Co-immunoprecipitation showed Cx43 being pulled down more efficiently with mutant Cx26, than wild-type, confirming the enhanced formation of heteromeric connexons. Finally, the formation of heteromeric connexons resulted in significantly increased Cx43 hemichannel activity in the presence of Cx26 mutants. These findings suggest a common mechanism whereby Cx26 mutations causing PPK and deafness trans-dominantly influence multiple functions of wild-type Cx43. They also implicate a role for aberrant hemichannel activity in the pathogenesis of PPK, and further highlight an emerging role for Cx43 in genetic skin diseases.

Highlights d Hippocampus-engaged exploration induces functional hyperemia in the dentate gyrus d Functional hyperemia is critical to exploration-induced hippocampal neurogenesis d Parvalbumin-expressing neurons increase blood flow via nitric-oxide signaling d Functional hyperemia elevates IGF-1 pathway activity in the dentate gyrus

Background: The most common indications for revision total hip arthroplasty are instability/dislocation and mechanical loosening. Efforts to address this have included the use of dual mobility (DM) articulations. The aim of this study is to report on the use of cemented DM cups in complex acetabular revision total hip arthroplasty cases with a high risk of recurrent instability. Methods: A multicenter, retrospective study was conducted. Patients who received a novel acetabular construct consisting of a monoblock DM cup cemented into a fully porous metal shell were included. Outcome data included 90-day complications and readmissions, revision for any reason, and Harris Hip Scores. Results: Thirty-eight hips in 38 patients were included for this study. At a median follow-up of 215.5 days (range 6-783), the Harris Hip Score improved from a mean of 50 ± 12.2 to 78 ± 11.2 (P < .001). One (2.6%) patient experienced a dislocation on postoperative day 1, and was closed reduced with no further complications. There was 1 (2.6%) reoperation for periprosthetic joint infection treated with a 2-stage exchange. Conclusions: In this complex series of patients, cementation of a monoblock DM cup into a newly implanted fully porous revision shell reliably provided solid fixation with a low risk of dislocation at short-term follow-up. Although longer term follow-up is needed, utilization of this novel construct should be considered in patients at high risk for instability.

Background Specialized tables for direct anterior (DA) approach total hip arthroplasty (THA) have required an unscrubbed assistant for manipulation of the operative limb. A novel surgical table attachment designed for the DA approach is fully surgeon controlled and partially automated. The purpose of this study is to compare the clinical outcomes in patients who underwent THA through a DA approach with an assistant-controlled vs the surgeon-controlled (SC) table. Methods This is a retrospective study of 343 patients who underwent primary THA between January 2017 and October 2017. Two cohorts were established based on the surgical table used. Surgical and clinical data included the surgical time, length of stay, presence of pain (groin, hip, or thigh pain) at latest follow-up, and revision for any reason. Immediate postoperative radiographs were compared with latest follow-up radiographs to assess for leg length discrepancy, stem alignment, and stem subsidence. Results One hundred sixty-seven (48.7%) cases were performed using the assistant-controlled table, and 176 (51.3%) cases were performed using the SC table. The surgical time was significantly greater for surgeries using the SC table (70.2 minutes vs 66.1 minutes, P < .001). Neither group experienced any intraoperative fractures or postoperative dislocations. There were no significant differences in any other clinical or radiographic outcomes. Conclusions Although the surgical time with the self-controlled table was longer by approximately 4 minutes, this discrepancy disappeared with progression through the learning curve. In our experience, the SC table allows for greater autonomy for the operating surgeon and eliminates the need for a full-time employee in the operating room workflow.

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