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Standard models of the visual object recognition pathway hold that a largely feedforward process from the retina through inferotemporal cortex leads to object identification. A subsequent feedback process originating in frontoparietal areas through reciprocal connections to striate cortex provides attentional support to salient or behaviorally-relevant features. Here, we review mounting evidence that feedback signals also originate within extrastriate regions and begin during the initial feedforward process. This feedback process is temporally dissociable from attention and provides important functions such as grouping, associational reinforcement, and filling-in of features. Local feedback signals operating concurrently with feedforward processing are important for object identification in noisy real-world situations, particularly when objects are partially occluded, unclear, or otherwise ambiguous. Altogether, the dissociation of early and late feedback processes presented here expands on current models of object identification, and suggests a dual role for descending feedback projections.

How does the brain learn to recognize objects visually, and perform this difficult feat robustly in the face of many sources of ambiguity and variability? We present a computational model based on the biology of the relevant visual pathways that learns to reliably recognize 100 different object categories in the face of of naturally-occurring variability in location, rotation, size, and lighting. The model exhibits robustness to highly ambiguous, partially occluded inputs. Both the unified, biologically plausible learning mechanism and the robustness to occlusion derive from the role that recurrent connectivity and recurrent processing mechanisms play in the model. Furthermore, this interaction of recurrent connectivity and learning predicts that high-level visual representations should be shaped by error signals from nearby, associated brain areas over the course of visual learning. Consistent with this prediction, we show how semantic knowledge about object categories changes the nature of their learned visual representations, as well as how this representational shift supports the mapping between perceptual and conceptual knowledge. Altogether, these findings support the potential importance of ongoing recurrent processing throughout the brain's visual system and suggest ways in which object recognition can be understood in terms of interactions within and between processes over time.

How does the brain bind together visual features that are processed concurrently by different neurons into a unified percept suitable for processes such as object recognition? Here, we describe how simple, commonly accepted principles of neural processing can interact over time to solve the brain's binding problem. We focus on mechanisms of neural inhibition and top-down feedback. Specifically, we describe how inhibition creates competition among neural populations that code different features, effectively suppressing irrelevant information, and thus minimizing illusory conjunctions. Top-down feedback contributes to binding in a similar manner, but by reinforcing relevant features. Together, inhibition and top-down feedback contribute to a competitive environment that ensures only the most appropriate features are bound together. We demonstrate this overall proposal using a biologically realistic neural model of vision that processes features across a hierarchy of interconnected brain areas. Finally, we argue that temporal synchrony plays only a limited role in binding -- it does not simultaneously bind multiple objects, but does aid in creating additional contrast between relevant and irrelevant features. Thus, our overall theory constitutes a solution to the binding problem that relies only on simple neural principles without any binding-specific processes.

Background: Optimal glenosphere positioning in reverse shoulder arthroplasty (RSA) remains highly debated. We aimed to characterize the association between the prosthesis scapular neck angle (PSNA) and postoperative range of motion (ROM) and clinical outcome scores., Methods: A retrospective review of 284 RSAs using a single design with minimum 2-year follow-up was performed. Glenosphere tilt was measured postoperatively using PSNA. ROM and functional outcome scores were assessed preoperatively and at latest follow-up. The PSNA was dichotomized to inferior or superior groups (>90° vs ≤ 90°, respectively) and stratified into quartiles; ROM and outcome score measures were compared between groups controlling for inferior glenosphere overhang., Results: No range of PSNA was consistently associated with superior ROM, clinical outcome scores, or rates of complications including scapular notching. However, greater preoperative to postoperative improvement in active FE was found for superiorly (PSNA ≤ 90°) versus inferiorly tilted glenospheres (37° ± 33° vs 53° ± 35°, P   =  0.005) and the greater improvement in active FE (57° ± 35°, P   =  0.004) was further isolated to the first quartile (mean 85.1° ± 3.5°)., Discussion: A lack of variation in clinical outcomes based on PSNA suggests negligible short-term (median follow-up 3.1 years) clinical significance when glenosphere tilt falls within the distribution of this cohort (mean 92.6° ± 6.2°)., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TWW is a consultant and receives royalties from Exactech, Inc. JJK is a consultant for Exactech, Inc and LinkBio Corp. BSS is a paid consultant for Exactech. He receives royalties from Exactech, Innomed, and Responsive Arthroscopy. KWF is consultant for Exactech, Inc and Arthrex Inc. The other authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article., (© The Author(s) 2023.)

Background: Deltoid tensioning secondary to humeral lengthening after reverse shoulder arthroplasty (RSA) is commonly theorized to be crucial to improving range of motion (ROM) but may predispose patients to acromial/scapular spine fractures and neurologic injury. Clinical evidence linking patient outcomes to humeral lengthening is limited. This study assesses the relationship between humeral lengthening and clinical outcomes after RSA., Methods: A single institution review of 284 RSAs performed in 265 patients was performed. Humeral lengthening was defined as the difference in the subacromial height preoperatively to postoperatively as measured on Grashey radiographs. The subacromial height was measured as the vertical difference between the most inferolateral aspect of the acromion and the most superior aspect of the greater tuberosity. The relationship between humeral lengthening and clinical outcomes was assessed on a continuous basis. Secondarily, clinical outcomes were assessed using a dichotomous definition of humeral lengthening (≤25 vs. >25mm) based on prior clinical and biomechanical work purporting a correlation with clinical outcomes. Improvement exceeding the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) for ROM and outcome scores after RSA were also compared., Results: Humeral lengthening demonstrated a nonlinear relationship with postoperative ROM, clinical outcome scores, and shoulder strength and their improvement preoperatively to postoperatively. Furthermore, there were minimal differences in ROM measures, outcome scores, and shoulder strength when stratified using the dichotomous definition of humeral lengthening. No difference in the proportion of patients exceeding the MCID or SCB when stratified by humeral lengthening ≤25 vs. >25mm was found. There was no difference in humeral lengthening in patients with versus without complications., Conclusion: No clear relationship between humeral lengthening and clinical outcomes was identified. The previously purported 25mm threshold for humeral lengthening did not predict improved patient outcomes. Outcomes after RSA are multifactorial; the relationship between humeral lengthening and outcomes is likely confounded by other patient and surgical factors., Level of Evidence: IV; Case Series., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Previous studies have demonstrated that decreased impingement-free range of motion (ROM) can adversely influence clinical outcomes following reverse shoulder arthroplasty (RSA). Inferior placement of the glenosphere is thought to minimize impingement and its associated sequelae. This study evaluated the relationship between inferior overhang of the glenosphere and clinical outcomes in patients undergoing primary RSA using a lateralized humeral implant design., Methods: By use of a prospectively collected shoulder arthroplasty database, all primary RSAs performed at our institution between 2007 and 2015 with a single implant design (lateralized humerus and medialized glenoid) and minimum 2-year follow-up were evaluated. Glenosphere overhang in relation to the inferior rim of the glenoid was measured in millimeters on postoperative Grashey radiographs of the shoulder and categorized into tertiles (low, <7.1 mm; medium, 7.1 to 9.9 mm; and high, >9.9 mm). Clinical outcomes of interest comprised the changes between preoperative and postoperative values in the following ROM and outcome score measures: active forward elevation (aFE), active external rotation, American Shoulder and Elbow Surgeons score, Constant-Murley score, Shoulder Pain and Disability Index score, and Simple Shoulder Test score. Random-effects linear models were used to assess univariate and multivariable associations between overhang tertile and change in patient outcomes. Differences in outcomes were further compared using the minimal clinically important difference (MCID)., Results: The study identified 284 shoulders in 265 patients. The median follow-up period was 36 months (range, 24-108 months). The median glenosphere inferior overhang was 8.4 mm, with an interquartile range of 6.3-10.6 mm. Plots demonstrated nonlinear relationships between overhang and outcome scores and between overhang and ROM. Patients with high overhang experienced a significantly greater improvement in aFE compared with patients with low overhang (P = .019), which exceeded the MCID. No other differences in ROM and outcome scores between overhang groups exceeded the MCID. For other outcome scores and ROM measurements, there was no significant relationship with glenosphere overhang. Increased overhang was associated with a significantly lower incidence of scapular notching (P = .005)., Conclusion: Patients undergoing RSA using a lateralized humerus design with greater inferior overhang of the glenosphere demonstrated a significantly greater improvement in aFE and lower rate of notching compared with those with low overhang. No ideal glenosphere overhang range was identified to maximize function in this study., (Copyright © 2022 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Introduction: We aimed to determine whether preoperative shoulder strength predicts postoperative values and improvement in strength, range of motion (ROM), and outcome scores after primary reverse total shoulder arthroplasty (rTSA)., Methods: We retrospectively reviewed 264 shoulders with a minimum of 2-year follow-up after primary rTSA. Preoperative external rotation (ER) strength, supraspinatus strength, and abduction strength were analyzed to establish their correlation with postoperative values and improvement in strength, ROM, and outcome scores (Constant score, American Shoulder and Elbow Surgeons Shoulder score, Shoulder Pain and Disability Index, Simple Shoulder Test, and the University of California, Los Angeles score). Multiple linear regression models were used to identify the preoperative shoulder strength measures that most affected postoperative outcomes and improvement in outcomes., Results: Preoperative measures of shoulder strength were positively correlated with all measures of postoperative shoulder strength, active abduction and elevation, and all outcome scores studied. On multivariate analysis, greater preoperative ER, supraspinatus, and abduction strength were significantly associated with greater corresponding postoperative values (P = 0.009, P = 0.041, and P = 0.008, respectively); however, they were also associated with less respective improvement (P < 0.001 for all) because the weakest patients tended to see the largest improvements. Notably, preoperative values of ER and supraspinatus strength exceeding 17.5 and 20.5 lbs were associated with a decline in their respective values postoperatively, but no limit was identified for ROM or outcome score measures. On multivariate analysis, reduced preoperative abduction strength was markedly associated with greater improvement in 3 of 4 ROM measures and 4 of 5 outcome scores., Conclusion: Preoperative shoulder strength, especially abduction strength, predicts superior postoperative outcomes and greater improvement in shoulder strength, ROM, and outcome scores after primary rTSA. However, a minority of patients with well-preserved strength may lose strength after surgery, and patients who are weaker preoperatively tend to see larger improvements in postoperative outcomes., Level of Evidence: Ⅳ, prognostic study., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

Background: Although numerous preoperative factors that influence postoperative outcomes after anatomic total shoulder arthroplasty (aTSA) have been identified, preoperative shoulder strength has not been studied. The purpose of this study was to determine whether preoperative shoulder strength is predictive of postoperative outcomes and improvement after primary aTSA., Methods: We conducted a retrospective review of prospectively collected data from 160 shoulders with minimum 2-year follow-up after primary aTSA. Preoperative external rotation (ER) strength, supraspinatus strength, and abduction strength score were analyzed to determine their correlation with postoperative outcomes and improvement in shoulder strength, range of motion (ROM), and outcome scores. Multiple linear regression models were subsequently used to adjust for covariates and determine the preoperative measures of shoulder strength that most influenced postoperative outcomes and improvement., Results: Preoperative ER strength, supraspinatus strength, and abduction strength score were each moderately correlated with their respective postoperative values and improvement (P < .001 for all). A decrease in ER strength, supraspinatus strength, and abduction strength score postoperatively was identified for preoperative strength values > 8.2 kg, > 6.6 kg, and > 4.5 kg, respectively. In contrast, no upper limit of preoperative shoulder strength led to a decrease in ROM or outcome scores postoperatively. On multivariate analysis, the baseline abduction strength score was a statistically significant predictor of postoperative values and improvement for all 3 measures of shoulder strength, raw and normalized Constant scores, and improvement in active abduction and active elevation., Conclusion: Preoperative shoulder strength is moderately associated with postoperative outcomes and improvements in shoulder strength, ROM, and outcome scores after primary aTSA. It is important to note that we identified preoperative strength values that led to a decrease in strength postoperatively but not ROM or outcome scores. The results of our study demonstrate that abduction strength may be a useful indicator of patient outcomes after aTSA. Our findings will provide surgeons with useful prognostic insight to aid in guiding patient expectations., (Published by Elsevier Inc.)

Background: The rate at which patients regain shoulder strength after anatomic and reverse total shoulder arthroplasty (TSA) is unknown. In this study, we aimed to quantify differences in the timeline during which patients gained shoulder strength after primary anatomic and reverse TSA., Methods: We retrospectively reviewed prospectively collected data from 374 shoulders after primary anatomic TSA (aTSA) and 601 shoulders after primary reverse TSA (rTSA). Postoperative improvement in external rotation (ER) strength and forward elevation (FE) strength from baseline was assessed at 3 months, 6 months, 1 year, and 2 years. Percent change in mean shoulder strength between each time point was determined for anatomic and reverse groups separately. A handheld dynamometer was used to assess ER strength with the involved shoulder in 0° ER, 0° abduction, and the elbow in 90° flexion and FE strength with the involved shoulder in the scapular plane at 30° of flexion and 30° of abduction., Results: Both aTSA and rTSA groups ceased to have statistically significant gains in FE strength after 1 year postoperatively. In contrast, patients continued to have statistically significant gains in ER strength between 1 year and 2 years postoperatively after rTSA ( P  = .001), but not after aTSA ( P  = .476). Both aTSA and rTSA groups saw improvement in strength in both ER (+32.1% and +51.4%, respectively) and FE (+38.3% and +90.3%, respectively) at 2-year follow-up. The aTSA group's ER and FE strength increased the most between 3 and 6 months (+16.2% and +35.7%, respectively). In contrast, the rTSA group gained the most ER strength between 6 months and 1 year (+14.8%) and the greatest FE strength between baseline and 3 months (+40.3%)., Conclusion: Patients gain ER strength earlier and FE strength later after aTSA compared with rTSA. Most gains in strength occurred in the first year. However, statistically significant gains in shoulder ER strength in the rTSA group continued between 1 year and 2 years postoperatively, suggesting that 2-year follow-up may be inadequate to capture the full benefits of rTSA on shoulder strength. The results of this study provide insight into the timeline of strength recovery after aTSA and rTSA that will help inform patient counseling and future study design.

Electrospinning is commonly used to generate polymeric scaffolds for tissue engineering. Using this approach, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-ε-caprolactone-co-l-lactic acid (PCLA) fibers and longitudinally assessed its performance within both the venous and arterial circulations of immunodeficient (SCID/bg) mice. Based on in vitro analysis demonstrating complete loss of graft strength by 12 weeks, we evaluated neovessel formation in vivo over 6-, 12- and 24-week periods. Mid-term observations indicated physiologic graft function, characterized by 100% patency and luminal matching with adjoining native vessel in both the venous and arterial circulations. An active and robust remodeling process was characterized by a confluent endothelial cell monolayer, macrophage infiltrate, and extracellular matrix deposition and remodeling. Long-term follow-up of venous TEVGs at 24 weeks revealed viable neovessel formation beyond graft degradation when implanted in this high flow, low-pressure environment. Arterial TEVGs experienced catastrophic graft failure due to aneurysmal dilatation and rupture after 14 weeks. Scaffold parameters such as porosity, fiber diameter, and degradation rate informed a previously described computational model of vascular growth and remodeling, and simulations predicted the gross differential performance of the venous and arterial TEVGs over the 24-week time course. Taken together, these results highlight the requirement for in vivo implantation studies to extend past the critical time period of polymer degradation, the importance of differential neotissue deposition relative to the mechanical (pressure) environment, and further support the utility of predictive modeling in the design, use, and evaluation of TEVGs in vivo. STATEMENT OF SIGNIFICANCE: Herein, we apply a biodegradable electrospun vascular graft to the arterial and venous circulations of the mouse and follow recipients beyond the point of polymer degradation. While venous implants formed viable neovessels, arterial grafts experienced catastrophic rupture due to aneurysmal dilation. We then inform a previously developed computational model of tissue engineered vascular graft growth and remodeling with parameters specific to the electrospun scaffolds utilized in this study. Remarkably, model simulations predict the differential performance of the venous and arterial constructs over 24 weeks. We conclude that computational simulations should inform the rational selection of scaffold parameters to fabricate tissue engineered vascular grafts that must be followed in vivo over time courses extending beyond polymer degradation., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare the characteristics of pediatric patients with supracondylar humerus fractures transferred to a level I pediatric trauma center to those who presented directly to our institution., Methods: Retrospective chart review of patients with a supracondylar humerus fracture during a 42-month period (2008-2011) at a major level I pediatric trauma center were reviewed. Of 195 patients, 37 were transferred from outside hospitals., Results: After multivariable analysis, it was determined that transferred patients were significantly more likely to present on the weekends (p = 0.003) and require operative treatment (p < 0.001) as compared to nontransferred patients., Conclusions: Injuries requiring operative treatment and presentation on a weekend were independent predictors of the transfer of pediatric patients with supracondylar humerus fractures.

Our approach for fabricating tissue-engineered vascular grafts (TEVG), applied in the surgical management of congenital heart disease, is accomplished by seeding isolated bone marrow-derived mononuclear cells (BM-MNCs) onto biodegradable scaffolds. The current method used for isolation of BM-MNCs is density centrifugation in Ficoll. This is a time-consuming, labor-intensive, and operator-dependent method. We previously demonstrated that a simpler, faster, and operator-independent method for isolating BM-MNCs using a filter elution technique was feasible. In this study, we compare the use of each technique to determine if the BM-MNCs isolated by the filtration elution method are biologically equivalent to BM-MNCs isolated using density centrifugation. Scaffolds were constructed from a nonwoven poly(glycolic acid) fiber mesh coated with 50:50 poly(l-lactide-co-ɛ-caprolactone) sealant. BM-MNCs were isolated from the bone marrow of syngeneic C57BL/6 mice by either density centrifugation with Ficoll or filtration (Ficoll vs. Filter), then statically seeded onto scaffolds, and incubated overnight. The TEVG were implanted in 10-week-old C57BL/6 mice (n=23 for each group) as inferior vena cava interposition grafts and explanted at 14 days for analysis. At 14 days after implantation, there were no significant differences in graft patency between groups (Ficoll: 87% vs. Filter: 78%, p=0.45). Morphometric analysis by hematoxylin and eosin staining showed no difference of graft luminal diameter or neointimal thickness between groups (luminal diameter, Ficoll: 620.3±82.9 μm vs. Filter: 633.3±131.0 μm, p=0.72; neointimal thickness, Ficoll: 37.9±7.8 μm vs. Filter: 37.9±11.2 μm, p=0.99). Histologic examination demonstrated similar degrees of cellular infiltration and extracellular matrix deposition, and endothelial cell coverage on the luminal surface, in either group. Macrophage infiltration showed no difference in the number of F4/80-positive cells or macrophage phenotypes between the two experimental groups (Ficoll: 2041±1048 cells/mm(2) vs. Filter: 1887±907.7 cells/mm(2), p=0.18). We confirmed the biological equivalence of BM-MNCs, isolated using either density centrifugation or filtration, for making TEVG.

There is great clinical demand for synthetic vascular grafts with improved long-term efficacy. The ideal vascular conduit is easily implanted, nonthrombogenic, biocompatible, resists aneurysmal dilatation, and ultimately degrades or is assimilated as the patient remodels the graft into tissue resembling native vessel. The field of vascular tissue engineering offers an opportunity to design the ideal synthetic graft, and researchers have evaluated a variety of methods and materials for use in graft construction. Electrospinning is one method that has received considerable attention within tissue engineering for constructing so-called tissue scaffolds. Tissue scaffolds are temporary, porous structures which are commonly composed of bioresorbable polymers that promote native tissue ingrowth and have degradation kinetics compatible with a patient's rate of extracellular matrix production in order to successfully transit from synthetic conduits into neovessels. In this review, we summarize the history of tissue-engineered vascular grafts (TEVG), focusing on scaffolds generated by the electrospinning process, and discuss in vivo applications. We review the materials commonly employed in this approach and the preliminary results after implantation in animal models in order to gauge clinical viability of the electrospinning process for TEVG construction. Scientists have studied electrospinning technology for decades, but only recently has it been orthotopically evaluated in animal models such as TEVG. Advantages of electrospun TEVG include ease of construction, favorable cellular interactions, control of scaffold features such as fiber diameter and pore size, and the ability to choose from a variety of polymers possessing a range of mechanical and chemical properties and degradation kinetics. Given its advantages, electrospinning technology merits investigation for use in TEVG, but an emphasis on long-term in vivo evaluation is required before its role in clinical vascular tissue engineering can be realized.

We used a murine model to assess the evolving biomechanical properties of tissue engineered vascular grafts (TEVGs) implanted in the arterial circulation. The initial polymeric tubular scaffold was fabricated from poly(lactic acid)(PLA) and coated with a 50:50 copolymer of poly(caprolactone) and poly(lactic acid)(P[PC/LA]). Following seeding with syngeneic bone marrow derived mononuclear cells, TEVGs (n=50) were implanted as aortic interposition grafts in wild-type mice and monitored serially using ultrasound. A custom biaxial mechanical testing device was used to quantify the in vitro circumferential and axial mechanical properties of grafts explanted at 3 or 7 months. At both times, TEVGs were much stiffer than native tissue in both directions. Repeated mechanical testing of some TEVGs treated with elastase or collagenase suggested that elastin did not contribute significantly to the overall stiffness whereas collagen did contribute. Traditional histology and immunostaining revealed smooth muscle cell layers, significant collagen deposition, and increasing elastin production in addition to considerable scaffold at both 3 and 7 months, which likely dominated the high stiffness seen in mechanical testing. These results suggest that PLA has inadequate in vivo degradation, which impairs cell-mediated development of vascular neotissue having properties closer to native arteries. Assessing contributions of individual components, such as elastin and collagen, to the developing neovessel is needed to guide computational modeling that may help to optimize the design of the TEVG., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Tissue-engineered vascular grafts (TEVGs) hold great promise for the improvement of outcomes in pediatric patients with congenital cardiac anomalies. Currently used synthetic grafts have several limitations, including thrombogenicity, increased risk of infection, and lack of growth potential. The first pilot clinical trial of TEVGs demonstrated the feasibility of this new technology and revealed an excellent safety profile. However, long-term follow-up from this trial revealed the primary graft-related complication to be stenosis, affecting 16 percent of grafts within 7 years post-implantation. In order to determine the mechanism behind TEVG stenosis and ultimately to create improved second generation TEVGs, our group has returned to the bench to study vascular neotissue formation in a variety of large and small animal models. The purpose of this report is to review the recent advances in the understanding of neotissue formation and vascular tissue engineering.

A unique aspect of meiosis is the segregation of homologous chromosomes at the meiosis I division. The pairing of homologous chromosomes is a critical aspect of meiotic prophase I that aids proper disjunction at anaphase I. We have used a site-specific recombination assay in Saccharomyces cerevisiae to examine allelic interaction levels during meiosis in a series of mutants defective in recombination, chromatin structure, or intracellular movement. Red1, a component of the chromosome axis, and Mnd1, a chromosome-binding protein that facilitates interhomolog interaction, are critical for achieving high levels of allelic interaction. Homologous recombination factors (Sae2, Rdh54, Rad54, Rad55, Rad51, Sgs1) aid in varying degrees in promoting allelic interactions, while the Srs2 helicase appears to play no appreciable role. Ris1 (a SWI2/SNF2 related protein) and Dot1 (a histone methyltransferase) appear to play minor roles. Surprisingly, factors involved in microtubule-mediated intracellular movement (Tub3, Dhc1, and Mlp2) appear to play no appreciable role in homolog juxtaposition, unlike their counterparts in fission yeast. Taken together, these results support the notion that meiotic recombination plays a major role in the high levels of homolog interaction observed during budding yeast meiosis.