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1.
PLoS Genet ; 17(4): e1009484, 2021 04.
Article in English | MEDLINE | ID: mdl-33886537

ABSTRACT

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.


Subject(s)
Bardet-Biedl Syndrome/genetics , Fear/drug effects , Neurogenesis/drug effects , Neurons/metabolism , Animals , Bardet-Biedl Syndrome/drug therapy , Bardet-Biedl Syndrome/pathology , Cell Proliferation/drug effects , Cilia/genetics , Cilia/metabolism , Cilia/pathology , Disease Models, Animal , Fear/physiology , Hippocampus/metabolism , Hippocampus/pathology , Humans , Lithium/pharmacology , Memory Disorders/drug therapy , Memory Disorders/genetics , Memory Disorders/pathology , Mice , Microtubule-Associated Proteins/genetics , Neurogenesis/genetics , Neurons/pathology
2.
Foot Ankle Int ; 42(6): 768-775, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33508965

ABSTRACT

BACKGROUND: Lateral overload in progressive collapsing foot deformity (PCFD) takes place as hindfoot valgus, peritalar subluxation, and valgus instability of the ankle increase. Fibular strain due to chronic lateral impingement may lead to distraction forces over the distal tibiofibular syndesmosis (DTFS). This study aimed to assess and correlate the severity of the foot and ankle offset (FAO) as a marker of progressive PCFD with the amount of DTFS widening and to compare it to controls. METHODS: In this case-control study, 62 symptomatic patients with PCFD and 29 controls who underwent standing weightbearing computed tomography (WBCT) examination were included. Two fellowship-trained blinded orthopedic foot and ankle surgeons performed FAO (%) and DTFS area measurements (mm2). DTFS was assessed semiautomatically on axial-plane WBCT images, 1 cm proximal to the apex of the tibial plafond. Values were compared between patients with PCFD and controls, and Spearman correlation between FAO and DTFS area measurements was assessed. P values of less than .05 were considered significant. RESULTS: Patients with PCFD demonstrated significantly increased FAO and DTFS measurements in comparison to controls. A mean difference of 6.9% (P < .001) in FAO and 10.4 mm2 (P = .026) in DTFS was observed. A significant but weak correlation was identified between the variables, with a Þ of 0.22 (P = .03). A partition predictive model demonstrated that DTFS area measurements were highest when FAO values were between 7% and 9.3%, with mean (SD) values of 92.7 (22.4) mm2. CONCLUSION: To our knowledge, this was the first study to assess syndesmotic widening in patients with PCFD. We found patients with PCFD to demonstrate increased DTFS area measurements compared to controls, with a mean difference of approximately 10 mm2. A significantly weak positive correlation was found between FAO and DTFS area measurements, with the highest syndesmotic widening occurring when FAO values were between 7% and 9.3%. Our study findings suggest that chronic lateral impingement in patients with PCFD can result in a negative biomechanical impact on syndesmotic alignment, with increased DTFS stress and subsequent widening. LEVEL OF EVIDENCE: Level III, retrospective comparative study.


Subject(s)
Ankle Joint , Foot Deformities , Ankle Joint/diagnostic imaging , Ankle Joint/surgery , Case-Control Studies , Humans , Retrospective Studies , Weight-Bearing
3.
Orthop J Sports Med ; 8(7): 2325967120926451, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32685565

ABSTRACT

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.

4.
Foot Ankle Int ; 41(1): 17-24, 2020 01.
Article in English | MEDLINE | ID: mdl-31650857

ABSTRACT

BACKGROUND: Workers' compensation (WC) has been associated with poor outcomes following a variety of injuries and surgeries, but rates of subsequent pain or injury (SPI) following surgery have not been studied. The purpose of this study was to investigate the rates, locations, and risk factors of SPI in WC patients and non-WC patients who underwent the same surgeries. METHODS: With institutional review board approval, records from foot or ankle surgery performed by author P.P. from 2009 to 2015 were obtained. A retrospective chart review was performed on all WC and non-WC patients with at least 1 Current Procedural Terminology code of interest. SPI was defined as a new injury at a different anatomical location occurring 2 months to 2 years after the index surgery. Chi-square and 2-tailed t tests were used to compare risk factors and rates of SPI in both groups. RESULTS: The WC population had higher rates of SPI than the non-WC population. Specifically, 13 of 56 WC patients (23.2%) vs 12 of 165 non-WC patients (7.3%) reported SPI (P = .001). The hip, knee, and contralateral foot and ankle were common areas of SPI in both groups. Legal representation and increased age were risk factors for SPI in the WC population. Specifically, 10 of 13 WC patients with SPI had legal representation vs 16 of 43 WC patients without SPI (P = .02). Female sex was a risk factor for SPI in the non-WC population. CONCLUSIONS: WC patients had higher rates of subsequent pain or injury than non-WC patients. Legal representation was a risk factor for SPI in the WC population. LEVEL OF EVIDENCE: Level III, comparative series.


Subject(s)
Accidents, Occupational , Ankle Injuries/surgery , Foot Injuries/surgery , Postoperative Complications/etiology , Workers' Compensation/statistics & numerical data , Adult , Female , Humans , Male , Middle Aged , Pain Measurement , Retrospective Studies , Risk Factors
5.
J Hip Preserv Surg ; 6(4): 385-389, 2019 Dec.
Article in English | MEDLINE | ID: mdl-32015891

ABSTRACT

Hip arthroscopy (HA) is technically demanding and associated with a prolonged learning curve. Recently, arthroscopic simulators have been developed to anatomically model various joints including the knee, shoulder and hip. The purpose of this study is to validate a novel HA simulator. Twenty trainees and one sports medicine fellowship-trained orthopaedic surgeon at a single academic institution were recruited to perform a diagnostic HA procedure using the VirtaMed ArthroS hip simulator. Trainee characteristics, including level of training, general arthroscopy experience and hip specific arthroscopy experience, were gathered via questionnaire. For the purpose of this study, participants were categorized as novice (<25), intermediate (25-74) or experienced (≥75) based on the number of prior arthroscopies performed. Various performance metrics, including composite score, time and camera path length were recorded for each attempt. Metrics were analyzed categorically using ANOVA tests with significance set to P < 0.05. Composite performance score in the novice cohort was 114.5 compared with 146.4 and 151.5 in the intermediate and experienced cohorts (P = 0.0019), respectively. Novice arthroscopists performed the simulated diagnostic arthroscopy procedure in an average time of 321 s compared with 202 s and 181 s in the intermediate and experienced cohorts (P < 0.002), respectively. Cartilage damage and simulator safety score did not differ significantly between groups (P = 0.775). Simulator composite score and procedure time showed strong correlation with year of training (r = 0.65 and -0.70, respectively) and number of arthroscopies performed (r = 0.65 and -0.72). The ArthroS hip simulator shows good construct validity and performance correlates highly with total number of arthroscopic cases reported during training.

7.
Foot Ankle Int ; 36(12): 1412-24, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26297693

ABSTRACT

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 significant 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.


Subject(s)
Forefoot, Human/surgery , Neuroma/surgery , Neurosurgical Procedures/methods , Peripheral Nerves/surgery , Peripheral Nervous System Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Disability Evaluation , Female , Follow-Up Studies , Forefoot, Human/innervation , Humans , Male , Middle Aged , Neuralgia/surgery , Operative Time , Retrospective Studies , Visual Analog Scale , Young Adult
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