Multilayer scaffolds in orthopaedic tissue engineering.

PURPOSE: The purpose of this study was to summarize the recent developments in the field of tissue engineering as they relate to multilayer scaffold designs in musculoskeletal regeneration. METHODS: Clinical and basic research studies that highlight the current knowledge and potential future applications of the multilayer scaffolds in orthopaedic tissue engineering were evaluated and the best evidence collected. Studies were divided into three main categories based on tissue types and interfaces for which multilayer scaffolds were used to regenerate: bone, osteochondral junction and tendon-to-bone interfaces. RESULTS: In vitro and in vivo studies indicate that the use of stratified scaffolds composed of multiple layers with distinct compositions for regeneration of distinct tissue types within the same scaffold and anatomic location is feasible. This emerging tissue engineering approach has potential applications in regeneration of bone defects, osteochondral lesions and tendon-to-bone interfaces with successful basic research findings that encourage clinical applications. CONCLUSIONS: Present data supporting the advantages of the use of multilayer scaffolds as an emerging strategy in musculoskeletal tissue engineering are promising, however, still limited. Positive impacts of the use of next generation scaffolds in orthopaedic tissue engineering can be expected in terms of decreasing the invasiveness of current grafting techniques used for reconstruction of bone and osteochondral defects, and tendon-to-bone interfaces in near future.

Design architectures for optically multiplexed imaging.

Optically multiplexed imaging is the process by which multiple images are overlaid on a single image surface. Uniquely encoding the discrete images allows scene reconstruction from multiplexed images via post processing. We describe a class of optical systems that can achieve high density image multiplexing through a novel division of aperture technique. Fundamental design considerations and performance attributes for this sensor architecture are discussed. A number of spatial and temporal encoding methods are presented including point spread function engineering, amplitude modulation, and image shifting. Results from a prototype five-channel sensor are presented using three different encoding methods in sparse-scene star tracking demonstration. A six-channel optically multiplexed prototype sensor is used to reconstruct imagery from information rich dense scenes through dynamic image shifting.

Seidel aberrations of the Gabor superlens.

Equations are presented for the third-order Seidel aberrations of the Gabor superlens (GSL) as a function of microtelescope channel position within the aperture array. To reveal the origin and form of increasing aberration with channel height, Seidel coefficients are derived as a function of the accumulating pitch difference between the lens arrays and the aberrations present in the centered channel. Two- and three-element Gabor lenses are investigated and their aberrations are expressed as a function of first-order design parameters. The derived theory is then compared to a real ray trace simulation to demonstrate the accuracy of third-order aberration theory to predict GSL image quality.

High incidence of hemiarthroplasty for shoulder osteoarthritis among recently graduated orthopaedic surgeons.

BACKGROUND: Primary glenohumeral osteoarthritis is a common indication for shoulder arthroplasty. Historically, both total shoulder arthroplasty (TSA) and hemi-shoulder arthroplasty (HSA) have been used to treat primary glenohumeral osteoarthritis. The choice between procedures is a topic of debate, with HSA proponents arguing that it is less invasive, faster, less expensive, and technically less demanding, with quality of life outcomes equivalent to those of TSA. More recent evidence suggests TSA is superior in terms of pain relief, function, ROM, strength, and patient satisfaction. We therefore investigated the practice of recently graduated orthopaedic surgeons pertaining to the surgical treatment of this disease. QUESTIONS/PURPOSES: We hypothesized that (1) recently graduated, board eligible, orthopaedic surgeons with fellowship training in shoulder surgery are more likely to perform TSA than surgeons without this training; (2) younger patients are more likely to receive HSA than TSA; (3) patient sex affects the choice of surgery; (4) US geographic region affects practice patterns; and (5) complication rates for HSA and TSA are not different. METHODS: We queried the American Board of Orthopaedic Surgery's database to identify practice patterns of orthopaedic surgeons taking their board examination. We identified 771 patients with primary glenohumeral osteoarthritis treated with TSA or HSA from 2006 to 2011. The rates of TSA and HSA were compared based on the treating surgeon's fellowship training, patient age and sex, US geographic region, and reported surgical complications. RESULTS: Surgeons with fellowship training in shoulder surgery were more likely (86% versus 72%; OR 2.32; 95% CI, 1.56-3.45, p<0.001) than surgeons without this training to perform TSA rather than HSA. The mean age for patients receiving HSA was not different from that for patients receiving TSA (66 versus 68, years, p=0.057). Men were more likely to receive HSA than TSA when compared to women (RR 1.54; 95% CI, 1.19-2.00, p=0.0012). The proportions of TSA and HSA were similar regardless of US geographic region (Midwest HSA 21%, TSA 79%; Northeast HSA 25%, TSA 75%; Northwest HSA 16%, TSA 84%; South HSA 27%, TSA 73%; Southeast HSA 24%, TSA 76%; Southwest HSA 23%, TSA 77%; overall p=0.708). The overall complication rates were not different with the numbers available: 8.4% (15/179) for HSA and 8.1% (48/592) for TSA (p=0.7555). CONCLUSIONS: The findings of this study are at odds with the recommendations in the current clinical practice guidelines for the treatment of glenohumeral osteoarthritis published by the American Academy of Orthopaedic Surgeons. These guidelines favor using TSA over HSA in the treatment of shoulder arthritis. Further investigation is needed to clarify if these practice patterns are isolated to recently graduated board eligible orthopaedic surgeons or if the use of HSA continues with orthopaedic surgeons applying for recertification. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

AKAP150-anchored PKA regulation of synaptic transmission and plasticity, neuronal excitability and CRF neuromodulation in the lateral habenula.

Numerous studies of hippocampal synaptic function in learning and memory have established the functional significance of the scaffolding A-kinase anchoring protein 150 (AKAP150) in kinase and phosphatase regulation of synaptic receptor and ion channel trafficking/function and hence synaptic transmission/plasticity, and neuronal excitability. Emerging evidence also suggests that AKAP150 signaling may play a critical role in brain's processing of rewarding/aversive experiences. Here we focused on an unexplored role of AKAP150 in the lateral habenula (LHb), a diencephalic brain region that integrates and relays negative reward signals from forebrain striatal and limbic structures to midbrain monoaminergic centers. LHb aberrant activity (specifically hyperactivity) is also linked to depression. Using whole cell patch clamp recordings in LHb of male wildtype (WT) and ΔPKA knockin mice (with deficiency in AKAP-anchoring of PKA), we found that the genetic disruption of PKA anchoring to AKAP150 significantly reduced AMPA receptor (AMPAR)-mediated glutamatergic transmission and prevented the induction of presynaptic endocannabinoid (eCB)-mediated long-term depression (LTD) in LHb neurons. Moreover, ΔPKA mutation potentiated GABAA receptor (GABAAR)-mediated inhibitory transmission postsynaptically while increasing LHb intrinsic neuronal excitability through suppression of medium afterhyperpolarizations (mAHPs). Given that LHb is a highly stress-responsive brain region, we further tested the effects of corticotropin releasing factor (CRF) stress neuromodulator on synaptic transmission and intrinsic excitability of LHb neurons in WT and ΔPKA mice. As in our earlier study in rat LHb, CRF significantly suppressed GABAergic transmission onto LHb neurons and increased intrinsic excitability by diminishing small-conductance potassium (SK) channel-mediated mAHPs. ΔPKA mutation-induced suppression of mAHPs also blunted the synaptic and neuroexcitatory actions of CRF in mouse LHb. Altogether, our data suggest that AKAP150 complex signaling plays a critical role in regulation of AMPAR and GABAAR synaptic strength, glutamatergic plasticity and CRF neuromodulation possibly through AMPAR and potassium channel trafficking and eCB signaling within the LHb.

Pharmacokinetics of yohimbine following intravenous administration to horses.

Yohimbine is an alpha 2 adrenergic receptor antagonist used most commonly in veterinary medicine to reverse the effects of the alpha 2 receptor agonists, xylazine and detomidine. Most notably, yohimbine has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. The recent identification of a yohimbine positive urine sample collected from a horse racing in California has led to the investigation of the pharmacokinetics of this compound. Eight healthy adult horses received a single intravenous dose of 0.12 mg/kg yohimbine. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 72 h post drug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry (LC-MS) and data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentration was 114.5 + 31.8 ng/mL and occurred at 0.09 + 0.03 h. Mean ± SD systemic clearance (Cls) and steady-state volume of distribution (Vdss) were 13.5 + 2.1 mL/min/kg and 3.3 + 1.3 L/kg following noncompartmental analysis. For compartmental analysis, plasma yohimbine vs. time data were best fitted to a two compartment model. Mean ± SD Cls and Vdss of yohimbine were 13.6 ± 2.0 mL/min/kg and 3.2 ± 1.1 L/kg, respectively. Mean ± SD terminal elimination half-life was 4.4 ± 0.9 h following noncompartmental analysis. Immediately following administration, two horses showed signs of sedation, while the other six appeared behaviorally unaffected. Gastrointestinal sounds were moderately increased compared to baseline while fecal consistency appeared normal.

Should we be teaching information management instead of evidence-based medicine?

BACKGROUND: To encourage high-quality patient care guided by the best evidence, many medical schools and residencies are teaching techniques for critically evaluating the medical literature. While a large step forward in many regards, these skills of evidence-based medicine are necessary but not sufficient for the practice of contemporary medicine and surgery. Incorporating the best evidence into the real world of busy clinical practice requires the applied science of information management. Clinicians must learn the techniques and skills to focus on finding, evaluating, and using information at the point of care. This information must be both relevant to themselves and their patients and be valid. WHERE ARE WE NOW?: Today, orthopaedic surgery is in the post-Flexner era of passive didactic learning combined with the practical experience of surgery as taught by supervising experts. The medical student and house officer fill their memory with mountains of facts and classic references 'just in case' that information is needed. With libraries and now internet repositories of orthopaedic information, all orthopaedic knowledge can be readily accessed without having to store much in one's memory. Evidence is often trumped by the opinion of a teacher or expert in the field. WHERE DO WE NEED TO GO?: To improve the quality of orthopaedic surgery there should be application of the best evidence, changing practice where needed when evidence is available. To apply evidence, the evidence has to find a way into practice without the long pipeline of change that now exists. Evidence should trump opinion and unfounded practices. HOW DO WE GET THERE?: To create a curriculum and learning space for information management requires effort on the part of medical schools, residency programs and health systems. Internet sources need to be created that have the readily available evidence-based answers to patient issues so surgeons do not need to spend all the time necessary to research the questions on their own. Information management is built on a platform created by EBM but saves the surgeon time and improves accuracy by having experts validate the evidence and make it easily available.

Toward a universal law of generalization for psychological science.

A psychological space is established for any set of stimuli by determining metric distances between the stimuli such that the probability that a response learned to any stimulus will generalize to any other is an invariant monotonic function of the distance between them. To a good approximation, this probability of generalization (i) decays exponentially with this distance, and (ii) does so in accordance with one of two metrics, depending on the relation between the dimensions along which the stimuli vary. These empirical regularities are mathematically derivable from universal principles of natural kinds and probabilistic geometry that may, through evolutionary internalization, tend to govern the behaviors of all sentient organisms.

Multidimensional scaling, tree-fitting, and clustering.

American mathematical psychologists have developed computer-based methods for constructing representations of the psychological structure of a set of stimuli on the basis of pairwise measures of similarity or confusability. Applications to perceptual and semantic data illustrate how complementary aspects of the underlying psychological structure are revealed by different types of representations, including multidimensional spatial configurations and nondimensional tree-structures or clusterings.

Mental rotation of three-dimensional objects.

The time required to recognize that two perspective drawings portray objects of the same three-dimensional shape is found to be (i) a linearly increasing function of the angular difference in the portrayed orientations of the two objects and (ii) no shorter for differences corresponding simply to a rigid rotation of one of the two-dimensional drawings in its own picture plane than for differences corresponding to a rotation of the three-dimensional object in depth.

Path-guided apparent motion.

A curved gray path, briefly flashed between two alternately displayed black dots, induced a compelling illusion of a single dot moving back and forth over that path. The minimum interval between dot onsets yielding this apparent motion increased not with the direct distance between the dots but, linearly, with the length of the curved path.

Auditory illusions demonstrating that tones are assimilated to an internalized musical scale.

Judgments of relations between tones in a sequence derived from the major diatonic scale (do, re, mi, . . .) by systematic distortions (either equalization or stretching of intervals) reveal that Western listeners interpret the tones relative to that musical scale even when they try to judge the purely physical relations between the tones.

Perceptual illusion of rotation of three-dimensional objects.

Perspective views of the same three-dimensional object in two orientations, when presented in alternation, produced an illusion of rigid rotation. The minimum cycle duration required for the illusion increased linearly with the angular difference between the orientations and at the same slope for rotations in depth and in the picture plane.

Association of intestinal peptide transport with a protein related to the cadherin superfamily.

The first step in oral absorption of many medically important peptide-based drugs is mediated by an intestinal proton-dependent peptide transporter. This transporter facilitates the oral absorption of beta-lactam antibiotics and angiotensin-converting enzyme inhibitors from the intestine into enterocytes lining the luminal wall. A monoclonal antibody that blocked uptake of cephalexin was used to identify and clone a gene that encodes an approximately 92-kilodalton membrane protein that was associated with the acquisition of peptide transport activity by transport-deficient cells. The amino acid sequence deduced from the complementary DNA sequence of the cloned gene indicated that this transport-associated protein shares several conserved structural elements with the cadherin superfamily of calcium-dependent, cell-cell adhesion proteins.

Npas4 deficiency interacts with adolescent stress to disrupt prefrontal GABAergic maturation and adult cognitive flexibility.

Healthy cognitive and emotional functioning relies on a balance between excitatory and inhibitory neurotransmission in the prefrontal cortex (PFC). This balance is largely established during early postnatal and adolescent developmental periods by maturation of the γ-aminobutyric acid (GABA) system, including increased density of parvalbumin (PV) cells and perineuronal nets (PNNs). Genetic and/or environmental factors during adolescence can disrupt GABAergic maturation and lead to behavioral dysfunction in adulthood. The present study examined the interaction between chronic mild stress during adolescence and genetic deficiency of neuronal Per-Arnt-Sim domain 4 (Npas4), a brain-specific transcription factor that regulates inhibitory neurotransmission and that contributes to adolescent prefrontal GABAergic maturation. Male Npas4 wild-type (WT) and heterozygous (HET) mice were exposed to adolescent chronic stress and tested in adulthood for cognitive function using the attention set shifting task. When Npas4 deficiency was combined with adolescent stress, mice displayed impaired cognitive flexibility as observed by poor performance on the extra-dimensional set shift task. At the cellular level, adolescent stress increased the percentage of PV cells surrounded by PNNs in the PFC of adult WT animals, an effect that was not observed in HET mice. Additionally, Npas4 deficiency and/or adolescent stress dysregulated expression of certain GABAergic system markers. These results suggest that Npas4 mediates susceptibility to adolescent stress and subsequent cognitive functioning and inhibitory tone in adulthood. This shows a novel gene by environment interaction related to resilience vs vulnerability to stress, with implications for adolescent onset disorders like schizophrenia.

Quantitative and topographical evaluation of ankle articular cartilage using high resolution MRI.

The objectives of this study were to quantitatively evaluate the articular cartilage layers of the ankle and describe the cartilage topographical distribution across the joint surfaces using high resolution MRI and image segmentation. An anisotropic diffusion noise reduction algorithm and a directional gradient vector flow (dGVF) snake segmentation algorithm were applied to cartilage sensitive MR images. Eight cadaveric ankles were studied. Six repeated data sets were acquired in five of the ankles. Quantitative parameters were calculated for each cartilage layer; coefficients of variation (CV) were calculated from the six repeated data sets; and 3D thickness distribution maps were generated. The noise reduction algorithm produced marked image enhancement. Mean cartilage thickness ranged from 0.91 +/- 0.08 mm in the fibula to 1.34 +/- 0.14 mm in the talus. Mean cartilage volume was 3.32 +/- 0.55 ml, 1.72 +/- 0.25 ml, and 0.35 +/- 0.06 ml for the talus, tibia, and fibula, respectively. Mean CV ranged 2.82%-5.04% for quantitative parameters in the talus and tibia. The reported noise reduction and segmentation technique allow precise extraction of ankle cartilage and 3D reconstructions show that the thickest cartilage occurs over the talar shoulders, where osteochondritits dissecans (OCD) lesions commonly occur.

Measuring Surgical Skills in Simulation-based Training.

Simulation-based surgical skills training addresses several concerns associated with the traditional apprenticeship model, including patient safety, efficient acquisition of complex skills, and cost. The surgical specialties already recognize the advantages of surgical training using simulation, and simulation-based methods are appearing in surgical education and assessment for board certification. The necessity of simulation-based methods in surgical education along with valid, objective, standardized techniques for measuring learned skills using simulators has become apparent. The most commonly used surgical skill measurement techniques in simulation-based training include questionnaires and post-training surveys, objective structured assessment of technical skills and global rating scale of performance scoring systems, structured assessments using video recording, and motion tracking software. The literature shows that the application of many of these techniques varies based on investigator preference and the convenience of the technique. As simulators become more accepted as a teaching tool, techniques to measure skill proficiencies will need to be standardized nationally and internationally.

Functional Outcomes for Nonoperatively Treated Proximal Fifth Metatarsal Fractures.

Fractures of the proximal fifth metatarsal are relatively common and can be treated with a variety of treatment modalities. The goals of the current study were to answer the following questions: (1) Is there a difference in functional outcomes with different nonoperative treatment modalities for avulsion and Jones fractures? (2) What is the long-term functional impairment? This study included 53 patients who were treated for proximal fifth metatarsal fracture at 1 university health care system between 2004 and 2013. Treatment methods included shoe modification, cast, and boot. Patients completed a telephone questionnaire that included selected questions from the Musculoskeletal Outcomes Data Evaluation and Management System (MODEMS). Treatment groups were stratified as shoe modification or immobilization, and the results of the MODEMS survey were compared. At most recent follow-up, no significant difference was found between the 2 patient groups (P=.062) for self-reported effects of the injury on work and quality of life. No significant difference was found for frequency of use of pain medication (P=.157), patient satisfaction with current symptoms (P=.633), ambulatory status (P=.281), or pain level with strenuous activity (P=.772). Obese patients were more likely to have severe pain with strenuous activity (P=.015). Most (87%) patients were able to ambulate without the need for assistive devices. Of the study patients, 79% could wear dress shoes, excluding high heels, comfortably. The findings showed that patients who were treated with a variety of nonoperative methods for closed proximal fifth metatarsal fracture had acceptable functional outcomes, regardless of treatment method. [Orthopedics. 2017; 40(6):e1030-e1035.].

Obese Patients Have Fewer Wound Complications Following Fixation of Ankle Fractures.

Outcomes following ankle fracture surgery have been well studied; however, factors associated with surgical wound healing specifically are less clear. We aimed to study the relationship between wound healing and body mass index, as well as other variables following surgical treatment of ankle fractures. There were 127 consecutive, isolated, closed, malleolar ankle fractures treated with open reduction and internal fixation at a level-1 trauma center from 2008 to 2012. Patient, injury, and treatment variables were recorded and clinical records were reviewed to identify wound complications. There were 6 major and 18 minor wound complications. The overall rate of wound complication of any type was significantly lower in obese patients at 11.7% (7/60) compared with 25.4% (17/67, P < .05) in nonobese patients. When controlling for other variables obesity was associated with a significantly lower risk of developing a wound complication (OR 0.267, 95% CI 0.087-0.822), as was low energy mechanism (OR 0.246, 95% CI 0.067-0.906). No other covariates tested were associated with an increased risk of a wound infection. Ankle anatomy may present a unique situation whereby obesity may be protective against wound complications. Further studies are needed to confirm this clinical observation, and to demonstrate the mechanism through which this may occur. LEVELS OF EVIDENCE: Therapeutic, Level IV: Retrospective.

The Core Competencies for General Orthopaedic Surgeons.

BACKGROUND: With the changing delivery of orthopaedic surgical care, there is a need to define the knowledge and competencies that are expected of an orthopaedist providing general and/or acute orthopaedic care. This article provides a proposal for the knowledge and competencies needed for an orthopaedist to practice general and/or acute care orthopaedic surgery. METHODS: Using the modified Delphi method, the General Orthopaedic Competency Task Force consisting of stakeholders associated with general orthopaedic practice has proposed the core knowledge and competencies that should be maintained by orthopaedists who practice emergency and general orthopaedic surgery. RESULTS: For relevancy to clinical practice, 2 basic sets of competencies were established. The assessment competencies pertain to the general knowledge needed to evaluate, investigate, and determine an overall management plan. The management competencies are generally procedural in nature and are divided into 2 groups. For the Management 1 group, the orthopaedist should be competent to provide definitive care including assessment, investigation, initial or emergency care, operative or nonoperative care, and follow-up. For the Management 2 group, the orthopaedist should be competent to assess, investigate, and commence timely non-emergency or emergency care and then either transfer the patient to the appropriate subspecialist's care or provide definitive care based on the urgency of care, exceptional practice circumstance, or individual's higher training. This may include some higher-level procedures usually performed by a subspecialist, but are consistent with one's practice based on experience, practice environment, and/or specialty interest. CONCLUSIONS: These competencies are the first step in defining the practice of general orthopaedic surgery including acute orthopaedic care. Further validation and discussion among educators, general orthopaedic surgeons, and subspecialists will ensure that these are relevant to clinical practice. CLINICAL RELEVANCE: These competencies provide many stakeholders, including orthopaedic educators and orthopaedists, with what may be the minimum knowledge and competencies necessary to deliver acute and general orthopaedic care. This document is the first step in defining a practice-based standard for training programs and certification groups.