RESUMEN
Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS). Here, we demonstrate that BBS mice have significant impairments in context fear conditioning, a form of associative learning. Moreover, we show that postnatal deletion of BBS gene function, as well as congenital deletion, specifically in the forebrain, impairs context fear conditioning. Analyses indicated that these behavioral impairments are not the result of impaired hippocampal long-term potentiation. However, our results indicate that these behavioral impairments are the result of impaired hippocampal neurogenesis. Two-week treatment with lithium chloride partially restores the proliferation of hippocampal neurons which leads to a rescue of context fear conditioning. Overall, our results identify a novel role of cilia genes in hippocampal neurogenesis and long-term context fear conditioning.
Asunto(s)
Síndrome de Bardet-Biedl/genética , Miedo/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Neuronas/metabolismo , Animales , Síndrome de Bardet-Biedl/tratamiento farmacológico , Síndrome de Bardet-Biedl/patología , Proliferación Celular/efectos de los fármacos , Cilios/genética , Cilios/metabolismo , Cilios/patología , Modelos Animales de Enfermedad , Miedo/fisiología , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Litio/farmacología , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/genética , Trastornos de la Memoria/patología , Ratones , Proteínas Asociadas a Microtúbulos/genética , Neurogénesis/genética , Neuronas/patologíaRESUMEN
BACKGROUND: Arthroscopic subtalar arthrodesis was first described over 2 decades ago and originally performed in the lateral decubitus or supine position using anterolateral and posterolateral portals situated about the fibula. More recently, several authors have advocated for prone positioning utilizing posteromedial and posterolateral portals with an optional accessory lateral portal. To date, a comparison of these techniques has been limited. PURPOSE: To determine the effect of patient positioning and portal placement on complication rates after arthroscopic subtalar arthrodesis. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Patients were placed into 1 of 3 groups: the lateral group if they were positioned lateral or supine with lateral-based portals; the 2-portal prone group if they were positioned prone with posteromedial and posterolateral portals; or the 3-portal prone group if posteromedial, posterolateral, and accessory lateral portals were utilized in the prone position. Inverse variance-weighted fixed-effects models were used to evaluate pooled estimates. RESULTS: A total of 20 studies examining 484 feet in 468 patients with a mean follow-up of 36.1 months were included for analysis. Overall, 8 studies examined patients in the prone position with 2 posterior portals (n = 111; 22.9%), 7 articles evaluated lateral portals (n = 182; 37.6%), and 5 studies examined patients in the prone position with 3 portals (n = 191; 39.5%). The total complication rate was similar (P = .620) between the 2-portal prone (18.9%), 3-portal prone (17.8%), and lateral (17.6%) groups. There was no difference observed in the rate of complications secondary to portal placement (P ≥ .334), rate of painful hardware (P ≥ .497), and rate of repeat surgery (P ≥ .304). The 2-portal prone group had a significantly higher rate of nonunion than the lateral group (8.1% vs 1.1%, respectively; P = .020) but not the 3-portal prone group (5.8%; P = .198). CONCLUSION: The current study demonstrated a higher rate of nonunion following arthroscopic subtalar arthrodesis with prone patient positioning using posteromedial and posterolateral portals without an accessory lateral portal.
RESUMEN
BACKGROUND: Simple neurectomy is a standard treatment of interdigital nerve neuroma after failure of conservative treatment. Recently, neurectomy with intramuscular implantation of the proximal nerve stump has been proposed as a safe and effective alternative method providing significant pain improvement. However, there remains little evidence supporting one technique over the other. The purpose of this study was to compare functional outcomes and complications of simple neurectomy versus neurectomy with intramuscular implantation. METHODS: Retrospective chart review along with prospectively collected data of 99 consecutive patients (105 feet with 118 neuromas) who were diagnosed with interdigital neuroma of the foot and underwent simple neurectomy (66 patients / 72 feet / 78 neuromas) and neurectomy with intramuscular implantation of proximal nerve stump into intrinsic muscle of foot (33 patients / 33 feet / 40 neuromas) between 2000 and 2013. The minimum follow-up to be included in the study was 6 months for both techniques (mean = 44.6 months, range = 6 to 150 months for simple neurectomy; and mean = 19.3 months, range = 6 to 66 months for neurectomy with intramuscular implantation of proximal nerve stump into the intrinsic muscle). The primary outcomes were Foot Function Index (FFI); pain, disability, activity limitation, and total score, Short Form-36 (SF-36: physical and mental component scores); and visual analog scale (VAS). Secondary outcomes included operative time and complications. Pre- and postoperative SF-36, and FFI, and pain (VAS) scores were obtained and compared using a paired t test. An independent t test was used to assess the functional outcomes and operative time between the 2 groups, and a chi-square test was used to compare the complications between the 2 techniques. RESULTS: Both groups demonstrated signiï¬cant improvement of postoperative functional outcomes (FFI, SF-36, and VAS; P < .001, all) compared to the preoperative period. Neurectomy with intramuscular implantation demonstrated significant improvement of pain compared to simple neurectomy as measured with VAS (P = .002); however, the operative time was significantly longer than the simple neurectomy technique (P = .001). The rest of the functional outcomes measured were comparable between the 2 techniques. Complications in both simple neurectomy and implantation techniques were persistent pain (11.5% vs. 2.5%, P = .07), revision rate (5.1% vs. 0.0%, P = .08), and painful scar (5.1% vs. 5.0%, P = .83), respectively, but it did not reach statistical significance (P > .05, all). CONCLUSION: Both simple neurectomy and neurectomy with intramuscular implantation demonstrated significant improvement in terms of functional outcomes as measured with the FFI, SF-36, and VAS in patients with interdigital neuroma. Although requiring a longer operative time, neurectomy with intramuscular implantation technique might offer superior pain relief with comparable complications to the simple neurectomy technique.