Objective Meniscus injury increases the risk of osteoarthritis; however, the biologic mechanism remains unknown. We hypothesized that pro-inflammatory stimulation of meniscus would increase production of matrix-degrading enzymes, cytokines and chemokines which cause joint tissue destruction and could contribute to osteoarthritis development. Design Meniscus and cartilage tissue from healthy tissue donors and total knee arthroplasties was cultured. Primary cell cultures were stimulated with pro-inflammatory factors [IL-1β, IL-6, or fibronectin fragments (FnF)] and cellular responses were analyzed by real-time PCR, protein arrays and immunoblots. To determine if NF-κB was required for MMP production, meniscus cultures were treated with inflammatory factors with and without the NF-κB inhibitor, hypoestoxide. Results Normal and osteoarthritic meniscus cells increased their MMP secretion in response to stimulation, but specific patterns emerged that were unique to each stimulus with the greatest number of MMPs expressed in response to FnF. Meniscus collagen and connective tissue growth factor gene expression was reduced. Expression of cytokines (IL-1α, IL-1β, IL-6), chemokines (IL-8, CXCL1, CXCL2, CSF1) and components of the NF-κB and tumor necrosis factor (TNF) family were significantly increased. Cytokine and chemokine protein production was also increased by stimulation. When primary cell cultures were treated with hypoestoxide in conjunction with pro-inflammatory stimulation, p65 activation was reduced as were MMP-1 and MMP-3 production. Conclusions Pro-inflammatory stimulation of meniscus cells increased matrix metalloproteinase production and catabolic gene expression. The meniscus could have an active biologic role in osteoarthritis development following joint injury through increased production of cytokines, chemokines, and matrix-degrading enzymes.

Background: Hip arthroscopy for femoroacetabular impingement syndrome (FAIS) is a rapidly expanding field, and preoperative factors predictive of persistent postoperative pain are currently unknown. Purpose: To identify predictors for persistent postoperative pain at the site of surgery after hip arthroscopy for FAIS. Study Design: Case-control study; Level of evidence, 3. Methods: Patients who underwent hip arthroscopy for FAIS and had a minimum 2-year follow-up with patient-reported outcomes (PROs) were included in this study. Patients with previous open hip surgery and diagnoses other than FAIS were excluded. Patients were grouped by visual analog scale scores for pain as limited (<30) and persistent (≥30). Patient factors and outcomes were analyzed with univariate and correlation analyses to build a logistic regression model to identify predictors of persistent postoperative pain. Results: The limited pain (n = 514) and persistent pain (n = 174) groups totaled 688 patients (449 females). There was a statistically significant difference in age between groups, with the persistent pain group being older than the low pain group (35.9 ± 12.2 vs 32.4 ± 12.6, respectively; P = .002). Patients with persistent postoperative pain demonstrated significantly lower preoperative PRO scores in the Hip Outcome Score–Activities of Daily Living (57.6 ± 21.2 vs 67.7 ± 16.8), Hip Outcome Score–Sport Specific (35.9 ± 23.9 vs 44.1 ± 22.7), modified Harris Hip Score (51.6 ± 16.2 vs 59.6 ± 12.9), and International Hip Outcome Tool (32.0 ± 16.8 vs 40.0 ± 17.82) but no significant differences in preoperative visual analog scale scores for pain (7.3 ± 1.8 vs 7.2 ± 1.7). Mean postoperative PRO differences between pain groups were all statistically significant. Bivariate logistic regression analysis demonstrated that history of anxiety or depression (odds ratio, 1.8; 95% CI, 1.02-3.32; P = .042), revision hip arthroscopy (odds ratio, 8.6; 95% CI, 1.79-40.88; P = .007), and a low preoperative modified Harris Hip Score (odds ratio, 0.97; 95% CI, 0.95-0.99; P = .30) were predictors of persistent postoperative pain. Conclusion: Independent predictors for persistent postoperative pain include revision hip arthroscopy and mental health history positive for anxiety and depression. Our analysis demonstrated significant improvements in pain and functional PROs in the limited pain and persistent pain groups; however, those with persistent pain demonstrated significantly lower PRO scores.

ABSTRACT:The current study determined the dose-response relationship for inhibition of muscle force of two commercially available botulinum neurotoxin type-A (BoNTA) preparations (Botox 1 and Neuronox 1 ) in a murine model and characterized the time course of recovery from the toxin-induced muscle paralysis. The effect of freezing reconstituted toxin on toxin potency was also determined. The gastrocnemius muscles in male CD-1 mice were injected with either saline or BoNTA (0.3-3.0 U/kg), and muscle force generation was examined following stimulation of the tibial nerve (single twitch and 15-200 Hz tetany). Botox and Neuronox produced nearly equivalent decrements in muscle force (30%-90%) at 4 days after toxin injection. At 28 days after injection (1 U/kg), muscle force had recovered from the effects of both toxin preparations. Maintaining reconstituted toxin at À808C for up to 5 months did not result in significant loss of toxin activity. The results of this study suggest that Botox and Neuronox produce equivalent responses in a murine model, and, in contrast to other models, muscle recovery is rapid with doses of toxin that produce less than maximal decrements in muscle force. ß

We systematically compare and analyze a set of key components in unsupervised optical flow to identify which photometric loss, occlusion handling, and smoothness regularization is most effective. Alongside this investigation we construct a number of novel improvements to unsupervised flow models, such as cost volume normalization, stopping the gradient at the occlusion mask, encouraging smoothness before upsampling the flow field, and continual self-supervision with image resizing. By combining the results of our investigation with our improved model components, we are able to present a new unsupervised flow technique that significantly outperforms the previous unsupervised state-of-theart and performs on par with supervised FlowNet2 on the KITTI 2015 dataset, while also being significantly simpler than related approaches.

Object-centric representations are a promising path toward more systematic generalization by providing flexible abstractions upon which compositional world models can be built. Recent work on simple 2D and 3D datasets has shown that models with object-centric inductive biases can learn to segment and represent meaningful objects from the statistical structure of the data alone without the need for any supervision. However, such fully-unsupervised methods still fail to scale to diverse realistic data, despite the use of increasingly complex inductive biases such as priors for the size of objects or the 3D geometry of the scene. In this paper, we instead take a weakly-supervised approach and focus on how 1) using the temporal dynamics of video data in the form of optical flow and 2) conditioning the model on simple object location cues can be used to enable segmenting and tracking objects in significantly more realistic synthetic data. We introduce a sequential extension to Slot Attention which we train to predict optical flow for realistic looking synthetic scenes and show that conditioning the initial state of this model on a small set of hints, such as center of mass of objects in the first frame, is sufficient to significantly improve instance segmentation. These benefits generalize beyond the training distribution to novel objects, novel backgrounds, and to longer video sequences. We also find that such initial-state-conditioning can be used during inference as a flexible interface to query the model for specific objects or parts of objects, which could pave the way for a range of weakly-supervised approaches and allow more effective interaction with trained models. Project page: https://slot-attention-video.github.io/ * Equal contribution.

Outcomes reporting is highly variable in the hip arthroscopy literature. More than 20 different PRO instruments have been used, which makes comparison across studies difficult. A uniform set of outcome measures would allow for clearer interpretation of the hip arthroscopy literature and offer potential conclusions from pooled data. On the basis of our comparative responsiveness results and previously reported psychometric properties of the different PRO instruments, we recommend more widespread adoption of the iHOT PROs instruments to assess hip arthroscopy outcomes.

Robots have to face challenging perceptual settings, including changes in viewpoint, lighting, and background. Current simulated reinforcement learning (RL) benchmarks such as DM Control [1] provide visual input without such complexity, which limits the transfer of well-performing methods to the real world. In this paper, we extend DM Control with three kinds of visual distractions (variations in background, color, and camera pose) to produce a new challenging benchmark for vision-based control, and we analyze state of the art RL algorithms in these settings. Our experiments show that current RL methods for vision-based control perform poorly under distractions, and that their performance decreases with increasing distraction complexity, showing that new methods are needed to cope with the visual complexities of the real world. We also find that combinations of multiple distraction types are more difficult than a mere combination of their individual effects.

Hip arthroscopy is widely utilized to treat femoroacetabular impingement syndrome (FAIS). In order to evaluate the postoperative clinical and functional outcomes at 2-year follow up in patients with and without benign joint hypermobility syndrome following hip arthroscopy with capsular plication for FAIS, consecutive female patients with generalized ligamentous laxity undergoing primary hip arthroscopy with complete T-capsulotomy closure via plication for FAIS were prospectively identified. Patients were matched in a 4:1 ratio based on Beighton-Horan joint mobility index (BHJMI) then classified into no generalized joint laxity (NGJL, Score<4) or generalized joint laxity cohort (GJL, Score=4). Patient and surgical-related factors were analyzed using univariate and paired analysis with statistical significance set at a = 0.05. A total of 125 female patients were included in the study: 25 generalized joint laxity (GJL) patients and 100 matched to age, sex and BMI (NGJL cohort). The results demonstrated that there were no significant differences between demographics, preoperative range of motion, or radiographic analysis on univariate analysis. There was no statistical difference in postoperative range of motion between groups, though both groups demonstrated significant increases in postoperative flexion and postoperative internal rotation following hip arthroscopy. Paired analysis demonstrated no significant difference in HOS-SS, HOS-ADL, mHHS or VAS-pain, while GJL patients reported significantly greater patient satisfaction score at 2-years follow-up (p=0.007). In summary, hip arthroscopy with capsular plication is a highly effective treatment for FAIS in patients with and without generalized joint laxity. In our analysis, patients with and without generalized joint laxity demonstrated statistically similar and significant improvement in outcomes.