Natural antisense transcript of Period2, Per2AS, regulates the amplitude of the mouse circadian clock.

In mammals, a set of core clock genes form transcription-translation feedback loops to generate circadian oscillations. We and others recently identified a novel transcript at the Period2 (Per2) locus that is transcribed from the antisense strand of Per2 This transcript, Per2AS, is expressed rhythmically and antiphasic to Per2 mRNA, leading to our hypothesis that Per2AS and Per2 mutually inhibit each other's expression and form a double negative feedback loop. By perturbing the expression of Per2AS, we found that Per2AS transcription, but not transcript, represses Per2 However, Per2 does not repress Per2AS, as Per2 knockdown led to a decrease in the Per2AS level, indicating that Per2AS forms a single negative feedback loop with Per2 and maintains the level of Per2 within the oscillatory range. Per2AS also regulates the amplitude of the circadian clock, and this function cannot be solely explained through its interaction with Per2, as Per2 knockdown does not recapitulate the phenotypes of Per2AS perturbation. Overall, our data indicate that Per2AS is an important regulatory molecule in the mammalian circadian clock machinery. Our work also supports the idea that antisense transcripts of core clock genes constitute a common feature of circadian clocks, as they are found in other organisms.

Bioabsorbable Screw Fixation Provides Good Results With Low Failure Rates at Mid-term Follow-up of Stable Osteochondritis Dissecans Lesions That Do Not Improve With Initial Conservative Treatment.

Purpose: To evaluate the clinical and radiographic outcomes of patients who have undergone bioabsorbable screw fixation for intact, stable grade I and II osteochondritis dissecans (OCD) lesions for which at least 6 months of conservative management has failed. Methods: A retrospective review of prospectively collected data from a single institution was performed to identify patients who underwent internal fixation of stable grade I and II OCD lesions (according to the Guhl classification) between January 2010 and January 2020. Patients were included regardless of the presence of concomitant procedures. The inclusion criteria consisted of (1) primary surgery, (2) failure of at least 6 months of conservative management, (3) the use of a bioabsorbable screw (or screws), and (4) minimum 2-year clinical follow-up. Radiographs were obtained at a minimum of 1 year postoperatively. Patient demographic characteristics, clinical patient-reported outcomes, complications, and failure rates were noted. Results: Twenty-four knees among 23 patients (96% follow-up) were analyzed and followed up for 6.36 ± 3.42 years (range, 2.0-12.7 years). Patients showed statistically significant postoperative improvements in all patient-reported outcomes including the Lysholm score, International Knee Documentation Committee score, and Knee Injury and Osteoarthritis Outcome Score subscales (P < .05). In 3 knees (12%), a reoperation was required due to failure at an average of 3.64 years after the index procedure. No specific complications were attributed to the use of bioabsorbable screws. Patients in whom primary surgical treatment failed did not differ in demographic characteristics, arthroscopic findings, or surgical treatment from those who had successful treatment. Conclusions: Internal fixation of stable grade I and II OCD lesions with bioabsorbable screws produces reliable results with a 12% rate of failure in appropriately indicated patients in whom at least 6 months of conservative management has failed. Clinical outcomes improved significantly during the mid-term follow-up period. Level of Evidence: Level IV, therapeutic case series.

Minimum 10-Year Clinical Outcomes and Survivorship of Meniscal Allograft Transplantation With Fresh-Frozen Allografts Using the Bridge-in-Slot Technique.

BACKGROUND: Meniscal allograft transplantation (MAT) has been shown to provide clinical benefits in patients with symptomatic meniscal deficiency in the short term and midterm. There is, however, a paucity of data regarding long-term outcomes after MAT using fresh-frozen allografts and the bridge-in-slot technique. PURPOSE: To report clinical outcomes and revision rates after primary MAT with fresh-frozen allografts and the bridge-in-slot technique in a large case series of patients at a 10-year minimum follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective review of prospectively collected data was performed on patients undergoing primary MAT between 2001 and 2012. Lysholm, International Knee Documentation Committee subjective form, and Knee injury and Osteoarthritis Outcome Score subscales were collected preoperatively and at 1-, 2-, 5-, and minimum 10-year follow-ups. Cox proportional hazards modeling was used to identify variables associated with reoperation and failure, defined as revision MAT or conversion to arthroplasty. Reoperation was defined as a subsequent surgical intervention on the transplanted meniscus, including partial or total meniscectomy, meniscal repair, or failure as defined in the previous sentence. RESULTS: A total of 174 patients undergoing MAT met the inclusion criteria and were followed for a mean of 12.7 ± 2.7 years (range, 10.0-21.0 years). The mean age at surgery was 28.3 ± 10.1 years. The patients were predominantly female (n = 92; 53%), and medial MAT was the most commonly performed procedure (n = 91; 52%). Concomitant procedures were performed in 115 patients (66%), with the most common procedure being osteochondral allograft transplantation (n = 59; 34%). Patients demonstrated statistically significant postoperative improvements at all time points for all patient-reported outcome measures (P≤ .0001). A total of 65 patients (37%) underwent a meniscal reoperation at a mean time of 6.6 ± 5.5 years (range, 0.3-16.7 years) postoperatively. A total of 40 patients (23%) met the criteria for failure at a mean time of 7.3 ± 5.0 years (range, 1.0-17.4 years) after MAT, with 22 of these patients having undergone a previous meniscal reoperation. At the final follow-up, 13 patients (7%) had undergone revision MAT and 27 (15%) had converted to arthroplasty. The MAT survival rates free of meniscal reoperation and failure were 73% and 85% at 10 years and 60% and 72% at 15 years, respectively. At the time of the final follow-up, 86% of patients reported that they were satisfied with their overall postoperative condition. CONCLUSION: Primary MAT demonstrates efficacy and durability with high rates of patient satisfaction at a minimum 10-year follow-up. Patients should be counseled that although reoperation rates may approach 40% at 15 years, rates of overall revision MAT and conversion to arthroplasty remain low at long-term follow-up.

Evolution and Trends in Male Versus Female Authorship of Articles in Flagship Orthopaedic Journals From 1995 to 2020.

INTRODUCTION: The gender disparity in orthopaedic surgery has been recognized for many years. Because research affects promotions, this study investigates trends in female authorship in three journals over the past 25 years for both first and senior authors. METHODS: All articles from Journal of Bone and Joint Surgery, Journal of the American Academy of Orthopaedic Surgeons, and Clinical Orthopaedics and Related Research from 1995 to 2020 in 5-year intervals were downloaded, and the data for first and senior authors were extracted. The sex of the first and senior authors was determined using the validated Genderize algorithm. The demographics of the first and senior author cohorts were analyzed using chi square tests. The trends in female authorship controlling for year and journal were assessed with logistic regression models. RESULTS: Within the studied journals, 5,636 individuals were identified as first authors and 4,572 as senior authors. Sex was determined for 82.59% of the authors. Female first authorship increased significantly from 1995 to 2020 (6.70% to 15.37%, P < 0.001). Similarly, female senior authorship increased significantly from 1995 to 2020 (8.22% to 13.65%, P < 0.001). Overall, there was no significant difference in gender composition of authors between journals (P = 0.700 first author and P = 0.098 senior author). Women were much more likely to publish as first or senior author in later years, regardless of the journal (P < 0.001 first author and P < 0.001 senior author). DISCUSSION: Female authorship in prominent orthopaedic journals has increased markedly from 1995 to 2020 with interjournal differences in senior author gender disparity. Although female orthopaedic surgeons publish at rates equal to or greater than their representation in the specialty, additional research is needed into the persistence of gender disparities in orthopaedics.