The E3 ubiquitin ligase Ube3a is an important regulator of activity-dependent synapse development and plasticity. Ube3a mutations cause Angelman syndrome and have been associated with autism spectrum disorders (ASD). However, the biological significance of alternative Ube3a transcripts generated in mammalian neurons remains unknown. We report here that Ube3a1 RNA, a transcript that encodes a truncated Ube3a protein lacking catalytic activity, prevents exuberant dendrite growth and promotes spine maturation in rat hippocampal neurons. Surprisingly, Ube3a1 RNA function was independent of its coding sequence but instead required a unique 3' untranslated region and an intact microRNA pathway. Ube3a1 RNA knockdown increased activity of the plasticity-regulating miR-134, suggesting that Ube3a1 RNA acts as a dendritic competing endogenous RNA. Accordingly, the dendrite-growth-promoting effect of Ube3a1 RNA knockdown in vivo is abolished in mice lacking miR-134. Taken together, our results define a noncoding function of an alternative Ube3a transcript in dendritic protein synthesis, with potential implications for Angelman syndrome and ASD.

Purpose The aim of this study was to determine patient and anatomic factors that influence anteroposterior and rotational laxity in knees with ACL tears. Based on the findings of biomechanical studies, we hypothesized that static and dynamic anterior tibial translation (ATT) as well as positive pivot shift would increase with female gender, tibial slope, and meniscal tears. Methods The authors prospectively collected preoperative data and intraoperative findings of 417 patients that underwent ACL reconstruction. The exclusion criteria were: revision ACL procedures (n = 53), other surgical antecedents (n = 27), prior osteotomies (n = 7) or concomitant ligament tears on the ipsilateral knee (n = 34), and history of ACL tears in the contralateral knee (n = 45), leaving a study cohort of 251 patients. Their preoperative anteroposterior knee laxity was assessed objectively using 'static' monopodal weight-bearing radiographs and 'dynamic' instrumented differential measurements of ATT. Rotational laxity was assessed subjectively using the pivot shift test. Results Multivariable regression showed that static ATT increases only with tibial slope (β = 0.30; p < 0.001), but dynamic ATT increases with tibial slope (β = 0.19; p = 0.041), medial meniscal tears (β = 1.27; p = 0.007), complete ACL tears (β = 2.06; p < 0.001), and to decrease with age (β = − 0.09; p < 0.001). Multivariable regression also indicated that high-grade pivot shift decreases with age (OR 0.94; p < 0.001) and for women (OR 0.25; p < 0.001), and to be higher for knees with complete ACL tears (OR 3.04; p = 0.002) or medial meniscal tears (OR 2.28; p = 0.010). Conclusion Contrary to expectations based on biomechanical studies, static ATT was only affected by high posterior tibial slope, while dynamic ATT was affected by both high posterior tibial slopes and medial meniscal tears, but not by gender or lateral meniscal tears. Likewise, pivot shift was affected by gender and medial meniscal tears, but not lateral meniscal tears or posterior tibial slope. These findings are relevant to guide surgeons in optimizing their surgical procedures, such as conserving the menisci when possible, and rehabilitation protocols, by delaying full weight-bearing and return to sports in patients with anatomic and lesional risk factors. Level of evidence Cohort study, Level IV.

Purpose Unexplained pain and stiffness after total knee arthroplasty (TKA) often result from mismatch between implant geometry and knee morphology, which depends on patient size, sex, and ethnicity. This study aimed to determine whether size, sex, or ethnicity are independently associated with distal femoral morphology in healthy Caucasian and Asian knees, and to compare anatomic ratios to those of commercially available TKA implants. Methods Two series of computed tomography (CT) angiograms from France (264 knees) and China (259 knees) were used to digitize osteometric landmarks at the level of the femoral epicondyles, to measure anteroposterior (AP) and mediolateral (ML) dimensions at the anterior, posterior, medial, and lateral zones. The aspect (ML/AP), trapezoidicity (MLp/MLa), and asymmetry (APl/APm) ratios, as well as the sulcus angle were calculated and compared to those of 9 TKA models. Multivariable analyses were performed to determine whether anatomic ratios were independently associated with sex, origin, or size. Results Multivariable analyses revealed that, independently from size, female knees were narrower (β = − 0.03; p < 0.001) and more asymmetric (β = 0.02; p < 0.001), while Chinese knees were more trapezoidal (β = 0.04; p = 0.002) and asymmetric (β = 0.02; p < 0.001) with shallower trochleae (β = 6.4°; p < 0.001). Compared to native knees, most implants were too wide, and many of the recent models too ‘trapezoidal’. Most prosthetic trochleae were too shallow compared to French knees, but within the third quartile of Chinese knees. Conclusions The morphology of the distal femur depends on sex and ethnicity independently from size. The wide spectrum of morphotypes observed cannot be covered by ‘off‐the‐shelf’ TKA models, and until customized implants become more accessible, prosthetic overhang, and under‐coverage remain inevitable. Level of evidence III, Retrospective comparative study.

PurposeTo determine demographic, anatomic, and surgical factors associated with static and dynamic Anterior Tibial Translation (ATT) following ACL reconstruction. The hypothesis was that both static and dynamic ATT would be greater in knees with high tibial slope or that required meniscectomy. MethodsThe authors prospectively enrolled 280 consecutive patients that had primary ACL reconstruction using hamstring autografts at one center for which preoperative tear type, meniscal tears, and medial tibial slope were documented. A total of 137 were excluded due to concomitant extra‐articular tenodesis or surgical antecedents on either knee, and 18 were lost to follow‐up, leaving 125 that were evaluated at a minimum of 6 months including: static ATT on monopodal weight‐bearing radiographs, and dynamic ATT on differential stress radiographs using the Telos™ device. ResultsBoth postoperative static and dynamic ATT were strongly associated with preoperative static and dynamic ATT (respectively, β = 0.068 and β = 0.50, p < 0.001). Multivariable regression confirmed that postoperative static ATT increased with tibial slope (β = 0.24; CI 0.01–0.47; p = 0.042) and in knees that had partial medial meniscectomy (β = 2.05; CI 0.25–3.84; p = 0.025), while dynamic ATT decreased with age (β = − 0.11; CI − 0.16 to − 0.05; p < 0.001), and increased with tibial slope (β = 0.27; CI 0.04–0.49; p = 0.019) and in knees that had partial medial meniscectomy (β = 2.20; CI 0.35–4.05; p = 0.019). ConclusionBoth static and dynamic ATT following ACL reconstruction increased with tibial slope and in knees that had partial medial meniscectomy. These findings could help surgeons tailor their techniques and ‘à la carte’ rehabilitation protocols, by preserving the menisci and sometimes delaying full weight‐bearing and return to sport in patients at risk, and hence improve outcomes and prevent graft failures. Study designCohort study. Level of evidenceV.

Background: Disruptions in cerebrospinal fluid (CSF) flow during aging could compromise protein clearance from the brain and contribute to the etiology of Alzheimer’s Disease (AD). Objective: To determine whether CSF flow is associated with cognitive deficit in elderly patients (>70 years). Methods: We studied 92 patients admitted to our geriatric unit for non-acute reasons using phase-contrast magnetic resonance imaging (PC-MRI) to calculate their ventricular and spinal CSF flow, and assessed their global cognitive status, memory, executive functions, and praxis. Multivariable regressions with backward selection (criterion p < 0.15) were performed to determine associations between cognitive tests and ventricular and spinal CSF flow, adjusting for depression, anxiety, and cardiovascular risk factors. Results: The cohort comprised 71 women (77%) and 21 (33%) men, aged 84.1 ± 5.2 years (range, 73–96). Net ventricular CSF flow was 52 ± 40 μL/cc (range, 0–210), and net spinal CSF flow was 500 ± 295 μL/cc (range, 0–1420). Ventricular CSF flow was associated with the number of BEC96 figures recognized (β = 0.18, CI, 0.02–0.33; p = 0.025). Spinal CSF flow was associated with the WAIS Digit Span Backward test (β = 0.06, CI, 0.01–0.12; p = 0.034), and categoric verbal fluency (β = 0.53, CI, 0.07–0.98; p = 0.024) and semantic verbal fluency (β = 0.55, CI, 0.07–1.02; p = 0.024). Conclusion: Patients with lower CSF flow had significantly worse memory, visuo-constructive capacities, and verbal fluency. Alterations in CSF flow could contribute to some of the cognitive deficit observed in patients with AD. Diagnosis and treatment of CSF flow alterations in geriatric patients with neurocognitive disorders could contribute to the prevention of their cognitive decline.