Endorsing a Biopsychosocial Perspective of Pain in Individuals With Chronic Pain: Development and Validation of a Scale.

OBJECTIVES: Patients' beliefs about pain play an important role in their readiness to engage with chronic pain self-management. The central aim of this study was to validate a self-report instrument to assess a specific set of pain beliefs, patients' endorsement of a biopsychosocial model of chronic pain Patients' Endorsement of a Biopsychosocial Model of Chronic Pain Scale (PEB). METHODS: Interdisciplinary experts in the field of pain were involved in creating an instrument, the PEB Scale, to operationalize patients' endorsement of a biopsychosocial pain model. A sample of 199 patients with chronic pain was recruited to evaluate the factorial structure (principal axis factoring), the internal consistency (Cronbach alpha), the convergent and discriminant validity (correlational analyses), incremental validity (multiple, hierarchical regression analyses), and construct validity (differential population analysis) of the instrument. RESULTS: The factor analysis resulted in a unidimensional, 11-item instrument that explained 51.2% of the total variance. Cronbach alpha (=0.92) indicated high internal consistency of the created set of pain-related beliefs. Regression analyses demonstrated that PEB is a strong predictor of patients' engagement with pain self-management ( P < 0.001) after controlling for demographic variables, anxiety, depression, and other pain-related beliefs. DISCUSSION: Our results show that the PEB Scale is a highly reliable self-report instrument that has the potential to predict patients' readiness to adopt pain self-management. Future research should focus on revalidating the scale to operationalize PEB. Moreover, the PEB Scale should be implemented in longitudinal study designs to investigate its ability to predict the transition from acute to chronic pain and patients' long-term pain management.

Two Specialists, Two Recommendations: Discordance Between Urologists' & Radiation Oncologists' Prostate Cancer Treatment Recommendations.

OBJECTIVE: To examine the treatment recommendation patterns among urologists and radiation oncologists, the level of concordance or discordance between physician recommendations, and the association between physician recommendations and the treatment that patients received. METHOD: The study was a secondary analysis of data from a randomized clinical trial conducted November 2010 to April 2014 (NCT02053389). Eligible participants were patients from the trial who saw both specialists. The primary outcome was physician recommendations that were scored using an adapted version of the validated PhyReCS coding system. Secondary outcomes included concordance between physician recommendations and the treatment patients received. RESULTS: Participants were 108 patients (Mean age 61.9 years; range 43-82; 87% non-Hispanic White). Urologists were more likely to recommend surgery (79% of recommendations) and radiation oncologists were more likely to recommend radiation (68% of recommendations). Recommendations from the urologists and radiation oncologists were concordant for only 33 patients (30.6%). Most patients received a treatment that both physicians recommended (59%); however, 35% received a treatment that only one of their physicians recommended. When discordant, urologists more often recommended surgery and radiation oncologists recommended radiation and surgery as equally appropriate options. CONCLUSION: Urologists and radiation oncologists are more likely to differ than agree in their treatment recommendations for the same patients with clinically localized prostate cancer and more likely to favor treatment aligned with their specialty. Additional studies are needed to better understand how patients make decisions after meeting with two different specialists to inform the development of best practices within oncology clinics.

Changes in Pain Catastrophizing and Fear-Avoidance Beliefs as Mediators of Early Physical Therapy on Disability and Pain in Acute Low-Back Pain: A Secondary Analysis of a Clinical Trial.

OBJECTIVE: The Fear-Avoidance Model (FAM) of chronic pain posits that pain catastrophizing and fear-avoidance beliefs are prognostic for disability and chronicity. In acute low-back pain, early physical therapy (PT) is effective in reducing disability in some patients. How early PT impacts short- and long-term changes in disability for patients with acute pain is unknown. Based on the FAM, we hypothesized that early reductions in pain catastrophizing and fear-avoidance beliefs would mediate early PT's effect on changes in disability (primary outcome) and pain intensity (secondary outcome) over 3 months and 1 year. SUBJECTS: Participants were 204 patients with low-back pain of <16 days duration, who enrolled in a clinical trial (NCT01726803) comparing early PT sessions or usual care provided over 4 weeks. METHODS: Patients completed the Pain Catastrophizing Scale (PCS), Fear-Avoidance Beliefs Questionnaire (FABQ work and physical activity scales), and outcomes (Oswestry Disability Index and Numeric Pain Rating Scale) at baseline, 4 weeks, 3 months, and 1 year. We applied longitudinal mediation analysis with single and multiple mediators. RESULTS: Early PT led to improvements in disability and pain over 3 months but not 1 year. In the single mediator model, 4-week reductions in pain catastrophizing mediated early PT's effects on 3-month disability and pain intensity improvements, explaining 16% and 22% of the association, respectively, but the effects were small. Pain catastrophizing and fear-avoidance beliefs did not jointly mediate these associations. CONCLUSIONS: In acute low-back pain, early PT may improve disability and pain outcomes at least partly through reducing patients' catastrophizing.

Mentoring during Uncertain Times.

Scientific success is mainly supported by mentoring, which often occurs through face-to-face interactions. Changes to the research environment incurred by the Coronavirus 2019 (COVID-19) pandemic have necessitated mentorship adaptations. Here, we describe how mentors can broaden their mentorship to support trainee growth and provide reassurance about trainee development amid uncertain circumstances.

Three-Dimensional Porous Trabecular Scaffold Exhibits Osteoconductive Behaviors In Vitro.

In the USA, approximately 500,000 bone grafting procedures are performed annually to treat injured or diseased bone. Autografts and allografts are the most common treatment options but can lead to adverse outcomes such as donor site morbidity and mechanical failure within 10 years. Due to this, tissue engineered replacements have emerged as a promising alternative to the biological options. In this study, we characterize an electrospun porous composite scaffold as a potential bone substitute. Various mineralization techniques including electrodeposition were explored to determine the optimal method to integrate mineral content throughout the scaffold. In vitro studies were performed to determine the biocompatibility and osteogenic potential of the nanofibrous scaffolds. The presence of hydroxyapatite (HAp) and brushite throughout the scaffold was confirmed using energy dispersive X-ray fluorescence, scanning electron microscopy, and ash weight analysis. The active flow of ions via electrodeposition mineralization led to a threefold increase in mineral content throughout the scaffold in comparison to static and flow mineralization. Additionally, a ten-layer scaffold was successfully mineralized and confirmed with an alizarin red assay. In vitro studies confirmed the mineralized scaffold was biocompatible with human bone marrow derived stromal cells. Additionally, bone marrow derived stromal cells seeded on the mineralized scaffold with embedded HAp expressed 30% more osteocalcin, a primary bone protein, than these cells seeded on non-mineralized scaffolds and only 9% less osteocalcin than mature pre-osteoblasts on tissue culture polystyrene. This work aims to confirm the potential of a biomimetic mineralized scaffold for full-thickness trabecular bone replacement.

Patching the Leaks: Revitalizing and Reimagining the STEM Pipeline.

We identify problematic areas throughout the Science, Technology, Engineering and Mathematics (STEM) pipeline that perpetuate racial disparities in academia. Distinct ways to curtail these disparities include early exposure and access to resources, supportive mentoring networks and comprehensive training programs specifically for racially minoritized students and trainees at each career stage. These actions will revitalize the STEM pipeline.

Mentoring minority trainees: Minorities in academia face specific challenges that mentors should address to instill confidence.

A toolkit for mentoring minority students and trainees in science.

Biocompatibility and bioactivity of an FGF-loaded microsphere-based bilayer delivery system.

Many drug delivery systems rely on degradation or dissolution of the carrier material to regulate release. In cases where mechanical support is required during regeneration, this necessitates composite systems in which the mechanics of the implant are decoupled from the drug release profile. To address this need, we developed a system in which microspheres (MS) were sequestered in a defined location between two nanofibrous layers. This bilayer delivery system (BiLDS) enables simultaneous structural support and decoupled release profiles. To test this new system, PLGA (poly-lactide-co-glycolic acid) microspheres were prepared using a water-in-oil-in-water (w/o/w) emulsion technique and incorporated Alexa Fluor-tagged bovine serum albumin (BSA) and basic fibroblast growth factor (bFGF). These MS were secured in a defined pocket between two polycaprolactone (PCL) nanofibrous scaffolds, where the layered scaffolds provide a template for new tissue formation while enabling independent and local release from the co-delivered MS. Scanning electron microscopy (SEM) images showed that the assembled BiLDS could localize and retain MS in the central pocket that was surrounded by a continuous seal formed along the margin. Cell viability and proliferation assays showed enhanced cell activity when exposed to BiLDS containing Alexa Fluor-BSA/bFGF-loaded MS, both in vitro and in vivo. MS delivered via the BiLDS system persisted in a localized area after subcutaneous implantation for at least 4 weeks, and bFGF release increased colonization of the implant. These data establish the BiLDS technology as a sustained in vivo drug delivery platform that can localize protein and other growth factor release to a surgical site while providing a structural template for new tissue formation. STATEMENT OF SIGNIFICANCE: Localized and controlled delivery systems for the sustained release of drugs are essential. Many strategies have been developed for this purpose, but most rely on degradation (and loss of material properties) for delivery. Here, we developed a bilayer delivery system (BiLDS) that decouples the physical properties of a scaffold from its delivery kinetics. For this, biodegradable PLGA microspheres were sequestered within a central pocket of a slowly degrading nanofibrous bilayer. Using this device, we show enhanced cell activity with FGF delivery from the BiLDS both in vitro and in vivo. These data support that BiLDS can localize sustained protein and biofactor delivery to a surgical site while also serving as a mechanical scaffold for tissue repair and regeneration.

Localized delivery of ibuprofen via a bilayer delivery system (BiLDS) for supraspinatus tendon healing in a rat model.

The high prevalence of tendon retear following rotator cuff repair motivates the development of new therapeutics to promote improved tendon healing. Controlled delivery of non-steroidal anti-inflammatory drugs to the repair site via an implanted scaffold is a promising option for modulating inflammation in the healing environment. Furthermore, biodegradable nanofibrous delivery systems offer an optimized architecture and surface area for cellular attachment, proliferation, and infiltration while releasing soluble factors to promote tendon regeneration. To this end, we developed a bilayer delivery system (BiLDS) for localized and controlled release of ibuprofen (IBP) to temporally mitigate inflammation and enhance tendon remodeling following surgical repair by promoting organized tissue formation. In vitro evaluation confirmed the delayed and sustained release of IBP from Labrafil-modified poly(lactic-co-glycolic) acid microspheres within sintered poly(ε-caprolactone) electrospun scaffolds. Biocompatibility of the BiLDS was demonstrated with primary Achilles tendon cells in vitro. Implantation of the IBP-releasing BiLDS at the repair site in a rat rotator cuff injury and repair model led to decreased expression of proinflammatory cytokine, tumor necrotic factor-α, and increased anti-inflammatory cytokine, transforming growth factor-ß1. The BiLDS remained intact for mechanical reinforcement and recovered the tendon structural properties by 8 weeks. These results suggest the therapeutic potential of a novel biocompatible nanofibrous BiLDS for localized and tailored delivery of IBP to mitigate tendon inflammation and improve repair outcomes. Future studies are required to define the mechanical implications of an optimized BiLDS in a rat model beyond 8 weeks or in a larger animal model.

Temperament, childhood illness burden, and illness behavior in early adulthood.

OBJECTIVE: Illness behaviors-or responses to bodily symptoms-predict individuals' recovery and functioning; however, there has been little research on the early life personality antecedents of illness behavior. This study's primary aims were to evaluate (a) childhood temperament traits (i.e., emotionality and sociability) as predictors of adult illness behaviors, independent of objective health; and (b) adult temperament traits for mediation of childhood temperament's associations. METHOD: Participants included 714 (53% male; 350 adoptive family and 364 control family) children and siblings from the Colorado Adoption Project (CAP; Plomin & DeFries, 1983). Structural regression analyses evaluated paths from childhood temperament to illness behavior (i.e., somatic complaints, sick days, and medication use) at two adulthood assessments (CAP years 21 and 30). Analyses controlled for participant age, sex, family type (adoptive or control), adopted status, parent education/occupation, and middle childhood illnesses, doctor visits, and life events stress. RESULTS: Latent illness behavior factors were established across 2 adulthood assessments. Multilevel path analyses revealed that higher emotionality (fearfulness) in adulthood-but not childhood temperament-predicted higher levels of illness behavior at both assessments. Lastly, lower emotionality-fearfulness partially mediated the effect of higher childhood sociability on adult illness behavior. CONCLUSIONS: Results suggest the importance of childhood illness experiences and adult emotionality (fearfulness) in shaping illness behavior in early adulthood. They also suggest a small, protective role of childhood sociability on reduced trait fearfulness in adulthood. These findings broaden our understanding of the prospective links between temperament and illness behavior development, suggesting distinct associations from early life illness experiences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Mechanical and biological evaluation of a hydroxyapatite-reinforced scaffold for bone regeneration.

With over 500,000 bone grafting procedures performed annually in the United States, the advancement of bone regeneration technology is at the forefront of medical research. Many tissue-engineered approaches have been explored to develop a viable synthetic bone graft substitute, but a major challenge is achieving a load-bearing graft that appropriately mimics the mechanical properties of native bone. In this study, sintered hydroxyapatite (HAp) was used to structurally reinforce a scaffold and yield mechanical properties comparable to native bone. HAp was packed into a cylindrical framework and processed under varying conditions to maximize its mechanical properties. The resulting HAp columns were further tested in a 6-week degradation study to determine their physical and mechanical response. The cellular response of sintered HAp was determined using a murine preosteoblast cell line, MC3T3-E1. Cell viability and morphology were studied over a one-week period and MC3T3-E1 differentiation was determined by measuring the alkaline phosphatase levels. Finite element analysis was used to determine the columns' geometric configuration and arrangement within our previously developed composite bone scaffold. It was determined that incorporating four cylindrical HAp columns, fabricated under 44 MPa of pressure and sintered at 1200°C for 5 hr, led to load-bearing properties that match the yield strength of native whole bone. These preliminary results indicate that the incorporation of a mechanically enhanced HAp structural support system is a promising step toward developing one of the first load-bearing bone scaffolds that can also support cell proliferation and osteogenic differentiation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 732-741, 2019.

Investigating processing techniques for bovine gelatin electrospun scaffolds for bone tissue regeneration.

Tissue engineering has emerged as a promising solution to tissue regeneration in the case of significant bone loss due to disease or injury. The ability to promote cellular attachment, migration, and differentiation into tissue is dependent on the scaffold's surface properties and composition. Bovine gelatin is a natural polymer commonly used as a scaffolding material for tissue engineering applications. Nonetheless, due to the hydrophilic behavior of gelatin, cross-linking and additives are necessary to maintain the scaffold's structure and overall strength in vivo. In this article, we discuss various processing techniques to determine the optimal electrospinning, cross-linking, sintering, and mineralization parameters necessary to yield a porous, mechanically enhanced scaffold. The scaffolds were evaluated quantitatively using compressive mechanical testing, and qualitatively using scanning electron microscopy (SEM). Mechanical data concluded the use of biocompatible microbial transglutaminase (mTG) as a cross-linking agent, led to increased compressive strength. SEM images confirmed the presence of individual gelatin and polymeric nanofibers woven into one scaffold. Sintering before leaching the scaffold yielded structured pores throughout the three-dimensional scaffold when compared to the scaffolds that were leached prior to sintering. The results presented in this article will provide novel information about processing techniques that can be utilized to develop a hybrid synthetic and biological based biomimetic mineralized scaffold for trabecular bone tissue regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1131-1140, 2017.

In vitro evaluation of three-dimensional single-walled carbon nanotube composites for bone tissue engineering.

The purpose of this study was to develop three-dimensional single-walled carbon nanotube composites (SWCNT/PLAGA) using 10-mg single-walled carbon nanotubes (SWCNT) for bone regeneration and to determine the mechanical strength of the composites, and to evaluate the interaction of MC3T3-E1 cells via cell adhesion, growth, survival, proliferation, and gene expression. PLAGA (polylactic-co-glycolic acid) and SWCNT/PLAGA microspheres and composites were fabricated, characterized, and mechanical testing was performed. MC3T3-E1 cells were seeded and cell adhesion/morphology, growth/survival, proliferation, and gene expression analysis were performed to evaluate biocompatibility. Imaging studies demonstrated microspheres with uniform shape and smooth surfaces, and uniform incorporation of SWCNT into PLAGA matrix. The microspheres bonded in a random packing manner while maintaining spacing, thus resembling trabeculae of cancellous bone. Addition of SWCNT led to greater compressive modulus and ultimate compressive strength. Imaging studies revealed that MC3T3-E1 cells adhered, grew/survived, and exhibited normal, nonstressed morphology on the composites. SWCNT/PLAGA composites exhibited higher cell proliferation rate and gene expression compared with PLAGA. These results demonstrate the potential of SWCNT/PLAGA composites for musculoskeletal regeneration, for bone tissue engineering, and are promising for orthopedic applications as they possess the combined effect of increased mechanical strength, cell proliferation, and gene expression.

Fabrication and characterization of three-dimensional electrospun scaffolds for bone tissue engineering.

When traumatic injury, tumor removal, or disease results in significant bone loss, reconstructive surgery is required. Bone grafts are used in orthopedic reconstructive procedures to provide mechanical support and promote bone regeneration. In this study, we applied a heat sintering technique to fabricate 3D electrospun scaffolds that were used to evaluate effects of mineralization and fiber orientation on scaffold strength. We electrospun PLLA/gelatin scaffolds with a layer of PDLA and heat sintered them into three-dimensional cylindrical scaffolds. Scaffolds were mineralized by incubation in 10× simulated body fluid for 6, 24, and 48 h to evaluate the effect of mineralization on scaffolds compressive mechanical properties. The effects of heat sintering hydroxyapatite (HA) microparticles directly to the scaffolds on mineral deposition, distribution and mechanical properties of the scaffolds were also evaluated. We found that orientation of the fibers had little effect on the compressive mechanical properties of the scaffolds. However, increasing the mineralization times resulted in an increase in compressive mechanical properties. Also, the direct addition of HA microparticles had no effect on the scaffold mechanical properties, but had a significant effect on the mineral deposition on PLLA/gelatin scaffolds.

Bracing does not improve dynamic stability in chronic ankle instability subjects.

OBJECTIVES: To investigate the effects of an ankle brace on dynamic postural stability, measured with Time to Stabilization (TTS), in subjects with chronic ankle instability (CAI). DESIGN: Two-within (Condition, Side) repeated measures. SETTING: Research laboratory. PARTICIPANTS: Fifteen subjects with unilateral CAI. MAIN OUTCOME MEASURES: Subjects participated in two testing sessions during which a single-limb jump-landing task was performed with one of two conditions: lace-up ankle brace or no ankle brace. Ground reaction forces were used to calculate Resultant Vector TTS (RVTTS). RESULTS: For RVTTS, there were no statistically significant main effects for Side (F(1,14) = 1.005; p = 0.33) or Condition (F(1,14) = 2.48; p = 0.14), as well as no significant interaction effect (F(1,14) = 1.67; p = 0.22). CONCLUSION: While TTS is a useful outcome tool for identifying deficits in subjects with CAI and improvements related to ankle rehabilitation, this measure of dynamic stability does not appear to be sensitive in detecting the influence of the application of an ankle brace in this pathological group. Researchers need to establish what other testing methods will be the best for determining the outcome of the application of an ankle brace in the laboratory setting to coincide with the epidemiology data that support the use of these devices.