Late tibial interference screw extrusion following anterior cruciate ligament reconstruction: A case report.

Introduction: Interference screws are used as back-up fixation in anterior cruciate ligament reconstructions. Historically these were composed of metal, but recently surgeons have switched to using bioabsorbable screws as they cause less symptoms and are biomedically advantageous. Usually these screws are absorbed by the body within one to two years after surgery. Case Presentation: A 32-year-old male presented with aseptic extrusion of his intact tibial bioabsorbable interference screw eight years following successful anterior cruciate ligament reconstruction. Management and Outcomes: Patient underwent laboratory evaluation and magnetic resonance imaging to rule out infection as an underlying cause. He went on to heal the wound without complication. Conclusion: Late aseptic extrusion of tibial interference screw can occur; however, infectious etiologies should be carefully ruled out.

Transient lamellipodia predict sites of dendritic branch formation in hippocampal neurons.

Extensive branching creates the complex dendritic arbor of mammalian CNS neurons but capturing the complete process of branch formation with time-lapse recordings has been challenging. Here, we report that application of BMP7 to cultured hippocampal neurons accelerated dendritic growth sufficiently to document branches forming in less than 20 h via frequent time-lapse imaging (10-min intervals). In these recordings, most branches emerged as collateral sprouts from the shaft of a parent branch. Analysis of the recordings showed that filopodia were abundant and formed transiently throughout the length of dendrites but among these, only a small subset occurred at sites where branches later emerged. Conversely, formation of lamellipodia was rare and coincided with sites where collateral branches emerged. This pattern suggests that lamellipodial structures act as an important intermediate form of cytoskeletal remodeling related to a cellular commitment to branch, whereas filopodia appear to be related to events prior to such commitment.

High Resiliency Linked to Short-Term Patient Reported Outcomes and Return to Duty Following Arthroscopic Knee Surgery.

INTRODUCTION: Resilience is a psychometric construct of a patient's ability to recover from adversity and has been used to predict outcomes but its use in orthopedics has been limited. The purpose of this study was to examine the association between resilience and outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of prospectively collected data of patient who underwent sports knee surgery at a single institution performed by 6 orthopedic surgeons from January 2017 to December 2017. We included active-duty patients with complete preoperative outcomes and a minimum of 6 month follow-up. All patients completed the Brief Resilience Scale (BRS), Veteran's Rand-12 (VR-12), Patient-Reported Outcomes Measurement Information System 43 (PROMIS-43), International Knee Documentation Committee function score (IKDC), and Knee Injury and Osteoarthritis Outcome Score (KOOS). Patients were divided into low resilience (LR) and high resilience (HR) groups based on a score of less than 24 for low and greater than or equal to 24 according to BRS. Outcomes were then compared. RESULTS: We identified 50 active-duty patients who had complete preoperative and postoperative outcomes at a minimum of 6 months. Mean preoperative and postoperative BRS were significantly different (25.8 HR v 18.6 LR, p < 0.001). We found a difference in postop KOOS in pain, sports, and short form (pain 70.9 HR v 55.7 LR, p = 0.03; sports 50.3 HR v 32.2 LR, p = 0.03; short form (72.1 HR v 62.5 LR, p = 0.04). Similarly, there was a significant difference in postoperative IKDC score (58.0 HR v 44.0 LR, p = 0.03). Similarly we found significant differences in postoperative PROMIS-43 (anxiety 44.4 HR v 60.3 LR, p = 0.004; depression 41.6 HR v 58.1 LR, p = 0.004; fatigue 45.1 HR v 58.6 LR, p = 0.001; sleep 52.6 HR v 62.5 LR, p = 0.02; social participation 36.2 HR v 47.6 LR, p < 0.001). Postoperative VR-12 mental was also statistically different between the two groups (53.5 HR v 41.6 LR; p = 0.01). In addition, 2.3% of the HR group changed MOS as a result of their sports knee surgery compared to 22.2% of the LR group. CONCLUSIONS: Active-military patients with high preoperative resilience appear to have significantly better early postoperative outcomes following sports knee surgery in terms of PROMIS-43, KOOS, and IKDC. There was also a lower rate of changing MOS secondary to sports knee surgery in patients with high resilience.

Interactions with Astroglia Influence the Shape of the Developing Dendritic Arbor and Restrict Dendrite Growth Independent of Promoting Synaptic Contacts.

Astroglia play key roles in the development of neurons, ranging from regulating neuron survival to promoting synapse formation, yet basic questions remain about whether astrocytes might be involved in forming the dendritic arbor. Here, we used cultured hippocampal neurons as a simple in vitro model that allowed dendritic growth and geometry to be analyzed quantitatively under conditions where the extent of interactions between neurons and astrocytes varied. When astroglia were proximal to neurons, dendrites and dendritic filopodia oriented toward them, but the general presence of astroglia significantly reduced overall dendrite growth. Further, dendritic arbors in partial physical contact with astroglia developed a pronounced pattern of asymmetrical growth, because the dendrites in direct contact were significantly smaller than the portion of the arbor not in contact. Notably, thrombospondin, the astroglial factor shown previously to promote synapse formation, did not inhibit dendritic growth. Thus, while astroglia promoted the formation of presynaptic contacts onto dendrites, dendritic growth was constrained locally within a developing arbor at sites where dendrites contacted astroglia. Taken together, these observations reveal influences on spatial orientation of growth as well as influences on morphogenesis of the dendritic arbor that have not been previously identified.

Plasmin Prevents Dystrophic Calcification After Muscle Injury.

Extensive or persistent calcium phosphate deposition within soft tissues after severe traumatic injury or major orthopedic surgery can result in pain and loss of joint function. The pathophysiology of soft tissue calcification, including dystrophic calcification and heterotopic ossification (HO), is poorly understood; consequently, current treatments are suboptimal. Here, we show that plasmin protease activity prevents dystrophic calcification within injured skeletal muscle independent of its canonical fibrinolytic function. After muscle injury, dystrophic calcifications either can be resorbed during the process of tissue healing, persist, or become organized into mature bone (HO). Without sufficient plasmin activity, dystrophic calcifications persist after muscle injury and are sufficient to induce HO. Downregulating the primary inhibitor of plasmin (α2-antiplasmin) or treating with pyrophosphate analogues prevents dystrophic calcification and subsequent HO in vivo. Because plasmin also supports bone homeostasis and fracture repair, increasing plasmin activity represents the first pharmacologic strategy to prevent soft tissue calcification without adversely affecting systemic bone physiology or concurrent muscle and bone regeneration. © 2016 American Society for Bone and Mineral Research.

Evidence that angiogenesis lags behind neuron and astrocyte growth in experience-dependent plasticity.

Bill Greenough's work on the cell biology of information storage suggests that we cannot understand the mechanism of long-term memory without understanding the series of cellular transactions that drive coordinated structural changes in neurons, glia, and blood vessels. Here, we show that after 4 days of differential housing, neuropil of EC cortex has expanded significantly, but the vasculature has not, resulting in a dilution of the blood supply. Significant growth of neurons and astrocytes has been reported within this time period, suggesting expression of synaptic plasticity might involve temporally coordinated genomic responses by both neurons and glia. Given that astrocytes appear to couple neuronal and vascular growth during development, we hypothesize that they may also mediate the onset of angiogenesis in response to neural demand in the EC brain. Further, these results may imply that a neuron's capacity for plasticity could be constrained by the rate of vascular expansion.

Synapses on demand require dendrites at the ready: how defining stages of dendritic development in vitro could inform studies of behaviorally driven information storage in the brain.

Bill Greenough's work provides a framework for thinking about synaptogenesis not only as a key step in the initial wiring of neural systems according to a species typical plan (i.e., experience-expectant development), but also as a mechanism for storing information based an individual's unique experience over its lifetime (i.e., experience-dependent plasticity). Analysis of synaptic development in vitro brings a new opportunity to test the limits of expectant-expectant development at the level of the individual neuron. We analyzed dendritic growth, synapse formation, and the development of specialized cytoplasmic microdomains during development in cultured hippocampal neurons, to determine if the timing of each of these events is correlated. Taken together, the findings reported here support the hypotheses that (1) dendritic development is rate limiting in synapse formation and (2) synaptic circuits are assembled in a step-wise fashion consistent with a stage-specific shift from genomically pre-programmed to activity-dependent mechanisms.

Experience-dependent plasticity in the mushroom bodies of the solitary bee Osmia lignaria (Megachilidae).

All members of the solitary bee species Osmia lignaria (the orchard bee) forage upon emergence from their natal nest cell. Conversely, in the honey bee, days-to-weeks of socially regulated behavioral development precede the onset of foraging. The social honey bee's behavioral transition to foraging is accompanied by neuroanatomical changes in the mushroom bodies, a region of the insect brain implicated in learning. If these changes were general adaptations to foraging, they should also occur in the solitary orchard bee. Using unbiased stereological methods, we estimated the volume of the major compartments of the mushroom bodies, the neuropil and Kenyon cell body region, in adult orchard bees. We compared the mushroom bodies of recently emerged bees with mature bees that had extensive foraging experience. To separate effects of general maturation from field foraging, some orchard bees were confined to a cage indoors. The mushroom body neuropil of experienced field foragers was significantly greater than that of both recently emerged and mature caged orchard bees, suggesting that, like the honey bee, this increase is driven by outdoor foraging experience. Unlike the honey bee, where increases in the ratio of neuropil to Kenyon cell region occur in the worker after emerging from the hive cell, the orchard bee emerged from the natal nest cell with a ratio that did not change with maturation and was comparable to honey-bee foragers. These results suggest that a common developmental endpoint may be reached via different development paths in social and solitary species of foraging bees.

Diminished experience-dependent neuroanatomical plasticity: evidence for an improved biomarker of subtle neurotoxic damage to the developing rat brain.

Millions of children are exposed to low levels of environmental neurotoxicants as their brains are developing. Conventional laboratory methods of neurotoxicology can detect maldevelopment of brain structure but are not designed to detect maldevelopment of the brain's capacity for plasticity that could impair learning throughout life. The environmental complexity (EC) paradigm has become classic for demonstrating the modifications in brain structure that occur in response to experience and thus provides a set of indices for plasticity in the healthy brain. In this study, we have tested the hypothesis that if degradation of experience-dependent cortical plasticity is used as a biomarker, then developmental neurotoxic effects will be detected at doses below those that alter cortical morphogenesis overtly. Pregnant Long-Evans hooded rats received a single injection of either saline vehicle or 1, 5, 10, or 25 mg/kg of the well-characterized developmental neurotoxicant methylazoxymethanol acetate (MAM) on the 16th or 17th day of gestation. On postnatal days 35-39, male offspring were assigned to either a complex environment (EC) or an individual cage (IC) for 28 days to stimulate neuroanatomical plasticity. This response was measured as the difference between the thickness of visual cortex of IC and EC littermates at a given dose. The threshold dose for significant reduction of cortical thickness was 25 mg/kg, but the threshold dose for failure of plasticity was much lower and could be detected at 1 mg/kg, the lowest dose used. No other method of assessment has detected lasting effects of prenatal exposure to MAM at such a low dose. These data suggest that this simple test of plasticity could be an efficient way to detect subtle neurotoxic damage to the developing brain.

Circadian dynamics of cytosolic and nuclear Ca2+ in single suprachiasmatic nucleus neurons.

Intracellular free Ca(2+) regulates diverse cellular processes, including membrane potential, neurotransmitter release, and gene expression. To examine the cellular mechanisms underlying the generation of circadian rhythms, nucleus-targeted and untargeted cDNAs encoding a Ca(2+)-sensitive fluorescent protein (cameleon) were transfected into organotypic cultures of mouse suprachiasmatic nucleus (SCN), the primary circadian pacemaker. Circadian rhythms in cytosolic but not nuclear Ca(2+) concentration were observed in SCN neurons. The cytosolic Ca(2+) rhythm period matched the circadian multiple-unit-activity (MUA)-rhythm period monitored using a multiple-electrode array, with a mean advance in phase of 4 hr. Tetrodotoxin blocked MUA, but not Ca(2+) rhythms, while ryanodine damped both Ca(2+) and MUA rhythms. These results demonstrate cytosolic Ca(2+) rhythms regulated by the release of Ca(2+) from ryanodine-sensitive stores in SCN neurons.