Publications by authors named "David R Wilson"

136 Publications

The effects of cholesterol accumulation on Achilles tendon biomechanics: A cross-sectional study.

PLoS One 2021 16;16(9):e0257269. Epub 2021 Sep 16.

Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Familial hypercholesterolemia, a common genetic metabolic disorder characterized by high cholesterol levels, is involved in the development of atherosclerosis and other preventable diseases. Familial hypercholesterolemia can also cause tendinous abnormalities, such as thickening and xanthoma (tendon lipid accumulation) in the Achilles, which may impede tendon biomechanics. The objective of this study was to investigate the effect of cholesterol accumulation on the biomechanical performance of Achilles tendons, in vivo. 16 participants (10 men, 6 women; 37±6 years) with familial hypercholesterolemia, diagnosed with tendon xanthoma, and 16 controls (10 men, 6 women; 36±7 years) underwent Achilles biomechanical assessment. Achilles biomechanical data was obtained during preferred pace, shod, walking by analysis of lower limb kinematics and kinetics utilizing 3D motion capture and an instrumented treadmill. Gastrocnemius medialis muscle-tendon junction displacement was imaged using ultrasonography. Achilles stiffness, hysteresis, strain and force were calculated from displacement-force data acquired during loading cycles, and tested for statistical differences using one-way ANOVA. Statistical parametric mapping was used to examine group differences in temporal data. Participants with familial hypercholesterolemia displayed lower Achilles stiffness compared to the control group (familial hypercholesterolemia group: 87±20 N/mm; controls: 111±18 N/mm; p = 0.001), which appeared to be linked to Achilles loading rate rather than an increased strain (FH: 5.27±1.2%; controls: 4.95±0.9%; p = 0.413). We found different Achilles loading patterns in the familial hypercholesterolemia group, which were traced to differences in the centre of pressure progression that affected ankle moment. This finding may indicate that individuals with familial hypercholesterolemia use different Achilles loading strategies. Participants with familial hypercholesterolemia also demonstrated significantly greater Achilles hysteresis than the control group (familial hypercholesterolemia: 57.5±7.3%; controls: 43.8±10%; p<0.001), suggesting that walking may require a greater metabolic cost. Our results indicate that cholesterol accumulation could contribute to reduced Achilles function, while potentially increasing the chance of injury.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257269PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445482PMC
September 2021

Tibiofemoral contact and alignment in patients with anterior cruciate ligament rupture treated nonoperatively versus reconstruction : an upright, open MRI study.

Bone Joint J 2021 Sep;103-B(9):1505-1513

Centre for Hip Health and Mobility, Vancouver, Canada.

Aims: Anterior cruciate ligament (ACL) rupture commonly leads to post-traumatic osteoarthritis, regardless of surgical reconstruction. This study uses standing MRI to investigate changes in contact area, contact centroid location, and tibiofemoral alignment between ACL-injured knees and healthy controls, to examine the effect of ACL reconstruction on these parameters.

Methods: An upright, open MRI was used to directly measure tibiofemoral contact area, centroid location, and alignment in 18 individuals with unilateral ACL rupture within the last five years. Eight participants had been treated nonoperatively and ten had ACL reconstruction performed within one year of injury. All participants were high-functioning and had returned to sport or recreational activities. Healthy contralateral knees served as controls. Participants were imaged in a standing posture with knees fully extended.

Results: Participants' mean age was 28.4 years (SD 7.3), the mean time since injury was 2.7 years (SD 1.6), and the mean International Knee Documentation Subjective Knee Form score was 84.4 (SD 13.5). ACL injury was associated with a 10% increase (p = 0.001) in contact area, controlling for compartment, sex, posture, age, body mass, and time since injury. ACL injury was associated with a 5.2% more posteriorly translated medial centroid (p = 0.001), equivalent to a 2.6 mm posterior translation on a representative tibia with mean posteroanterior width of 49.4 mm. Relative to the femur, the tibiae of ACL ruptured knees were 2.3 mm more anteriorly translated (p = 0.003) and 2.6° less externally rotated (p = 0.010) than healthy controls. ACL reconstruction was not associated with an improvement in any measure.

Conclusion: ACL rupture was associated with an increased contact area, posteriorly translated medial centroid, anterior tibial translation, and reduced tibial external rotation in full extension. These changes were present 2.7 years post-injury regardless of ACL reconstruction status. Cite this article:  2021;103-B(9):1505-1513.
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http://dx.doi.org/10.1302/0301-620X.103B9.BJJ-2020-1955.R1DOI Listing
September 2021

Clinical findings in patellofemoral osteoarthritis compared to individually-matched controls: a pilot study.

BMJ Open Sport Exerc Med 2020 9;6(1):e000877. Epub 2020 Dec 9.

Department of Family Practice, The University of British Columbia, Vancouver, Canada.

Objective: To explore clinical characteristics in individuals with patellofemoral osteoarthritis (PFOA) compared to individually-matched asymptomatic controls. We also explored associations between functional performance and patient-reported symptoms with patellofemoral alignment.

Methods: We assessed 15 individuals with PFOA and 15 individually-matched asymptomatic controls. In addition to physical examination and patient-reported questionnaires, we evaluated functional performance, lower extremity strength and range of motion, and patellar alignment (using MRI). We analysed group differences with Wilcoxon's matched-pairs signed rank tests, and within-group associations with Spearman's rank correlations.

Results: We included 24 (80%) women with median (IQR) age of 56 (9) years and BMI of 22.8 (5.9) kg/m. Individuals with PFOA reported lower quality of life (8/100 points lower EQ-5D-5L, p=0.02), and performed worse on two functional tests: repeated one-leg rises (median 16 fewer rises, p=0.04) and timed stair climb (1.2 s slower, p=0.03). There were no differences in strength tests performed or range of motion. Patellar proximal translation correlated with worse functional performance and worse patient-reported pain, function and self-efficacy, while lateral translation and lateral tilt correlated with worse knee-related quality of life (Spearman's r ranging from 0.5 to 0.7).

Conclusion: Functional performance was worse in individuals with PFOA, despite those individuals having no significant differences on lower extremity strength testing. Patellofemoral alignment was associated with worse functional performance as well as worse patient-reported outcomes, and it may represent one mechanism underpinning PFOA-related symptoms.
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http://dx.doi.org/10.1136/bmjsem-2020-000877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323464PMC
December 2020

Dynamic morphometric changes in degenerative lumbar spondylolisthesis: A pilot study of upright magnetic resonance imaging.

J Clin Neurosci 2021 Sep 10;91:152-158. Epub 2021 Jul 10.

Combined Neurosurgical and Orthopedic Spine Program, Department of Orthopedic Surgery, University of British Columbia, Blusson Spinal Cord Centre, 6(th) Floor, 818 West 10(th) Avenue, Vancouver, BC V5Z 1M9, Canada. Electronic address:

The objectives of this study were to (a) develop a standing MRI imaging protocol, tolerable to symptomatic patients with degenerative spondylolisthesis (DLS), and (b) to evaluate the morphometric changes observed in DLS patients in both supine and standing postures. Patients with single level, Meyerding grade 1 DLS undergoing surgery at a single institution between November 2015 to May 2017 were consented. Patients were imaged in the supine and standing positions in a 0.5 T vertically open MRI scanner (MROpen, Paramed, Genoa, Italy) with sagittal and axial T2 images. The morphometric parameters measured were: cross-sectional area of the thecal sac (CSA), lateral recess height, disc height, degree of anterolisthesis, disc angle, lumbar lordosis, the presence of facet effusion and restabilization signs. Measures from both postures were compared using paired T-test. Associations of posture with the magnitude of change in the various measurements was determined using Pearson correlation or paired T-test when appropriate. All fourteen patients (mean age 64.4 years) included tolerated standing for the time required for image acquisition. All measurements with the exception of lumbar lordosis and disk height showed a statistically significant difference between the postures (p < 0.05). In the standing position, CSA and lateral recess height were reduced by 28% and 50%, respectively. There was no relationship between the change in CSA of the thecal sac and any measures. Standing images acquired in an upright MRI scanner demonstrated postural changes associated with Meyerding grade 1 DLS and images acquisition was tolerated in all patients.
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http://dx.doi.org/10.1016/j.jocn.2021.06.027DOI Listing
September 2021

Size-Controlled and Shelf-Stable DNA Particles for Production of Lentiviral Vectors.

Nano Lett 2021 07 6;21(13):5697-5705. Epub 2021 Jul 6.

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.

Polyelectrolyte complex particles assembled from plasmid DNA (pDNA) and poly(ethylenimine) (PEI) have been widely used to produce lentiviral vectors (LVVs) for gene therapy. The current batch-mode preparation for pDNA/PEI particles presents limited reproducibility in large-scale LVV manufacturing processes, leading to challenges in tightly controlling particle stability, transfection outcomes, and LVV production yield. Here we identified the size of pDNA/PEI particles as a key determinant for a high transfection efficiency with an optimal size of 400-500 nm, due to a cellular-uptake-related mechanism. We developed a kinetics-based approach to assemble size-controlled and shelf-stable particles using preassembled nanoparticles as building blocks and demonstrated production scalability on a scale of at least 100 mL. The preservation of colloidal stability and transfection efficiency was benchmarked against particles generated using an industry standard protocol. This particle manufacturing method effectively streamlines the viral manufacturing process and improves the production quality and consistency.
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http://dx.doi.org/10.1021/acs.nanolett.1c01421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283758PMC
July 2021

Computer-assisted subcapital correction osteotomy in slipped capital femoral epiphysis using individualized drill templates.

3D Print Med 2021 Jul 6;7(1):18. Epub 2021 Jul 6.

Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada.

Background: Subcapital osteotomy by means of surgical hip dislocation is a treatment approach offered for moderate-to-severe cases of Slipped Capital Femoral Epiphysis (SCFE). This procedure is demanding, highly dependent on the surgeon's experience, and requires considerable radiation exposure for monitoring and securing the spatial alignment of the femoral head. We propose the use of individualized drill guides as an accurate method for placing K-wires during subcapital correction osteotomies in SCFE patients.

Methods: Five CT scans of the hip joint from otherwise healthy patients with moderate-to-severe SCFE were selected (ages 11-14). Three dimensional models of each patient's femur were reconstructed by manual segmentation and physically replicated using additive manufacturing techniques. Five orthopaedic surgeons virtually identified the optimal entry point and direction of the two threaded wires for each case. 3D printed drill guides were designed specific to each surgical plan, with one side shaped to fit the patient's bone and the other side containing holes to guide the surgical drill. Each surgeon performed three guided (using the drill guides) and three conventional (freehand) simulated procedures on each case. Each femur model was laser scanned and digitally matched to the preoperative model for evaluation of entry points and wire angulations. We compared wire entry point, wire angulation, procedure time and number of x-rays between guided and freehand simulated surgeries.

Results: The guided group (1.4 ± 0.9 mm; 2.5° ± 1.4°) was significantly more accurate than the freehand group (5.8 ± 3.2 mm; 5.3° ± 4.4°) for wire entry location and angulation (p < 0.001). Guided surgeries required significantly less drilling time and intraoperative x-rays (90.5 ± 42.2 s, 3 ± 1 scans) compared to the conventional surgeries (246.8 ± 122.1 s, 14 ± 5 scans) (p < 0.001).

Conclusions: We conclude that CT-based preoperative planning and intraoperative navigation using individualized drill guides allow for improved accuracy of wires, reduced operative time and less radiation exposure in simulated hips.

Clinical Relevance: This preliminary study shows promising results, suggesting potential direct benefits to SCFE patients by necessitating less time under anesthesia and less intra-operative radiation exposure to patients, and increasing surgical accuracy.
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http://dx.doi.org/10.1186/s41205-021-00108-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259369PMC
July 2021

T1ρ and T2 MRI show hip cartilage damage in adolescents with healed Legg-Calvé-Perthes disease.

J Pediatr Orthop B 2021 Jun 18. Epub 2021 Jun 18.

Centre for Hip Health and Mobility School of Biomedical Engineering, University of British Columbia Department of Orthopaedic Surgery, BC Children's Hospital Department of Orthopaedics, University of British Columbia Faculty of Medicine, University of British Columbia Department of Mechanical Engineering, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Legg-Calvé-Perthes disease (LCPD) is a juvenile hip disorder associated with residual femoral head deformity, cartilage degeneration and a high risk of early onset hip osteoarthritis. Assessing management of LCPD in the healed phase requires an understanding of when and where hip cartilage damage happens. While it has been shown that cartilage is degenerated in healed LCPD hips in adults, it is not clear when this degeneration begins. Our research question was: Are the MR markers of cartilage degeneration T1ρ and T2 increased in healed LCPD hips in adolescents?

Materials And Methods: Twelve adolescents [10-17 years old (mean 14); 3 female 9 male] with healed LCPD (Stulberg 2-5; 8 unilateral and 4 bilateral) and 15 age- and sex-matched controls were imaged in a 3T MRI using a T1ρ and a T2 sequence. We applied a mixed-effects model adjusted for age and nested by subject to determine the effect of Stulberg grade on overall and regional mean T1ρ and T2 values.

Results: T1ρ was significantly higher overall and in the medial region of Stulberg ≥3 hips, and in the medial region of Stulberg 2 hips than in the control group. T2 was significantly higher in the medial region of Stulberg ≥3 hips than in the control group.

Conclusions: Our results suggest that cartilage damage in LCPD has begun by adolescence and that T1ρ can detect early changes in cartilage associated with LCPD.
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http://dx.doi.org/10.1097/BPB.0000000000000892DOI Listing
June 2021

Delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) Values are Lower in Hips with Bone Marrow Lesions.

Arthritis Care Res (Hoboken) 2021 Jun 16. Epub 2021 Jun 16.

Centre for Hip Health and Mobility, Vancouver, BC, Canada.

Objective: Bone marrow lesions (BML) are associated with painful and progressive osteoarthritis (OA). Quantitative MRI has been used to study early cartilage degeneration in knees with BML, but similar work has not been done in hips. The purpose of this study was to compare mean delayed gadolinium enhanced MRI of cartilage (dGEMRIC) relaxation values (T ) in hips with BML to hips without BML in a population-based study. Reduced T suggests depleted glycosaminoglycan (GAG). Our hypothesis was that mean T is lower in hips with BML compared to hips without BML.

Methods: Study participants (n=128) were recruited from a cross-sectional population-based study of people aged 20-49 years with and without hip pain. dGEMRIC and proton density (PD)-weighted MRI scans of one hip from each participant were used for this analysis. BMLs were identified from PD-weighted fat-suppressed images. We applied a sampling-weighted linear regression model to determine the association of the presence of BMLs with mean cartilage T (significance: p<0.05). The model was adjusted for age, sex, BMI, hip pain, cam/pincer deformity and physical activity.

Results: 32 of the 128 participants (25%) had at least one BML. Subjects with at least one BML, compared to those without, had similar weighted characteristics of age, BMI, physical activity levels, and frequency of hip pain. Mean T was 75.25ms lower (95% CI [-149.69, -0.81]; p=0.048) (9%) in the BML compared to the no-BML group.

Conclusions: Our results suggest that hips with BMLs are associated with hip cartilage degeneration early in the OA disease process.
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http://dx.doi.org/10.1002/acr.24733DOI Listing
June 2021

Estimation and assessment of sagittal spinal curvature and thoracic muscle morphometry in different postures.

Proc Inst Mech Eng H 2021 Aug 12;235(8):883-896. Epub 2021 May 12.

ICORD, University of British Columbia, Vancouver, BC, Canada.

Spine models are typically developed from supine clinical imaging data, and hence clearly do not fully reflect postures that replicate subjects' clinical symptoms. Our objectives were to develop a method to: (i) estimate the subject-specific sagittal curvature of the whole spine in different postures from limited imaging data, (ii) obtain muscle lines-of-action in different postures and analyze the effect of posture on muscle fascicle length, and (iii) correct for cosine between the magnetic resonance imaging (MRI) scan plane and dominant fiber line-of-action for muscle parameters (cross-sectional area (CSA) and position). The thoracic spines of six healthy volunteers were scanned in four postures (supine, standing, flexion, and sitting) in an upright MRI. Geometry of the sagittal spine was approximated with a circular spline. A pipeline was developed to estimate spine geometry in different postures and was validated. The lines-of-action for two muscles, erector spinae (ES) and transversospinalis (TS) were obtained for every posture and hence muscle fascicle lengths were computed. A correction factor based on published literature was then computed and applied to the muscle parameters. The maximum registration error between the estimated spine geometry and MRI data was small (average RMSE∼1.2%). The muscle fascicle length increased (up to 20%) in flexion when compared to erect postures. The correction factor reduced muscle parameters (∼5% for ES and ∼25% for TS) when compared to raw MRI data. The proposed pipeline is a preliminary step in subject-specific modeling. Direction cosines of muscles could be used while improving the inputs of spine models.
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http://dx.doi.org/10.1177/09544119211014668DOI Listing
August 2021

Preliminary investigation of spinal level and postural effects on thoracic muscle morphology with upright open MRI.

JOR Spine 2021 Mar 8;4(1):e1139. Epub 2021 Feb 8.

ICORD University of British Columbia Vancouver Canada.

Objective: Spinal-muscle morphological differences between weight-bearing and supine postures have potential diagnostic, prognostic, and therapeutic applications. While the focus to date has been on cervical and lumbar regions, recent findings have associated spinal deformity with smaller paraspinal musculature in the thoracic region. We aim to quantitatively investigate the morphology of trapezius (TZ), erector spinae (ES) and transversospinalis (TS) muscles in upright postures with open upright MRI and also determine the effect of level and posture on the morphological measures.

Methods: Six healthy volunteers (age 26 ± 6 years) were imaged (0.5 T MROpen, Paramed, Genoa, Italy) in four postures (supine, standing, standing with 30° flexion, and sitting). Two regions of the thorax, middle (T4-T5), and lower (T8-T9), were scanned separately for each posture. 2D muscle parameters such as cross-sectional area (CSA) and position (radius and angle) with respect to the vertebral body centroid were measured for the three muscles. Effect of spinal level and posture on muscle parameters was examined using 2-way repeated measures ANOVA separately for T4-T5 and T8-T9 regions.

Results: The TZ CSA was smaller (40%, = .0027) at T9 than at T8. The ES CSA was larger at T5 than at T4 (12%, = .0048) and at T9 than at T8 (10%, = .0018). TS CSA showed opposite trends at the two spinal regions with it being smaller (16%, = .0047) at T5 than at T4 and larger (11%, = .0009) at T9 than at T8. At T4-T5, the TZ CSA increased (up to 23%), and the ES and TS CSA decreased (up to 10%) in upright postures compared to supine.

Conclusion: Geometrical parameters that describe muscle morphology in the thorax change with level and posture. The increase in TZ CSA in upright postures could result from greater activation while upright. The decrease in ES CSA in flexed positions likely represents passive stretching compared to neutral posture.
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http://dx.doi.org/10.1002/jsp2.1139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984016PMC
March 2021

Effect of posture and femoral neck osteochondroplasty on femur-acetabulum clearance in patients with cam-type femoroacetabular impingement.

J Orthop Res 2021 Mar 18. Epub 2021 Mar 18.

Department of Orthopaedics, The University of British Columbia, Vancouver, British Columbia, Canada.

It is not clear whether femoral neck osteochondroplasty achieves its objective of increasing femoroacetabular clearance. We used an upright open magnetic resonance imaging scanner to image the hip joint in multiple postures to explore the effect of posture and femoral neck osteochondroplasty on femur-acetabulum clearance in patients with cam-type femoroacetabular impingement. We recruited 13 consecutive patients scheduled to undergo arthroscopic femoral neck osteochondroplasty and completed assessments on 10 patients. We scanned each subject before surgery and at 6 months post-op in supine and 3 other physiological postures: supine 90° flexion with adduction and internal rotation (FADIR), sitting deep (maximal flexion with internal rotation and adduction), and sitting crossed leg (maximal adduction with flexion and internal rotation). We measured the alpha angle, which describes the severity of cam deformity, and the beta angle, which defines joint clearance. We also evaluated hip flexion, internal rotation, and adduction before and after surgery. Femoral neck osteochondroplasty significantly decreased alpha angle by 23.9° ± 4.6° (p = 0.001) and increased beta angle across all postures by 28.1° ± 6.3° (p = 0.002). An increase in beta angle represented a decreased chance of impingement. Femoral neck osteochondroplasty significantly increased flexion by an average of 8.6° in the sitting deep posture after surgery (p = 0.007) which might indicate an improvement of joint function. These findings lend support to the hypothesis that arthroscopic osteochondroplasty accomplishes its stated goals of increasing bone-bone clearance in the hip joint and improving joint mechanics for the static postures assessed.
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http://dx.doi.org/10.1002/jor.25037DOI Listing
March 2021

Tibiofemoral Contact Measures During Standing in Toe-In and Toe-Out Postures.

J Appl Biomech 2021 Mar 8;37(3):233-239. Epub 2021 Mar 8.

The University of British Columbia.

Knee osteoarthritis is thought to result, in part, from excessive and unbalanced joint loading. Toe-in and toe-out gait modifications produce alterations in external knee joint moments, and some improvements in pain over the short- and long-term. The aim of this study was to probe mechanisms of altered joint loading through the assessment of tibiofemoral contact in standing with toe-in and toe-out positions using an open magnetic resonance scanner. In this study, 15 young, healthy participants underwent standing magnetic resonance imaging of one of their knees in 3 foot positions. Images were analyzed to determine contact in the tibiofemoral joint, with primary outcomes including centroid of contact and contact area for each compartment and overall. The centroid of contact shifted laterally in the lateral compartment with both toe-in and toe-out postures, compared with the neutral position (P < .01), while contact area in the medial and lateral compartments showed no statistical differences. Findings from this study indicate that changes in the loading anatomy are present in the tibiofemoral joint with toe-in and toe-out and that a small amount of lateralization of contact, especially in the lateral compartment, does occur with these altered lower limb orientations.
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http://dx.doi.org/10.1123/jab.2020-0206DOI Listing
March 2021

Efficiency of Cytosolic Delivery with Poly(β-amino ester) Nanoparticles is Dependent on the Effective p of the Polymer.

ACS Biomater Sci Eng 2020 06 18;6(6):3411-3421. Epub 2020 May 18.

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States.

The mechanism by which cationic polymers containing titratable amines mediate effective endosomal escape and cytosolic delivery of nucleic acids is not well understood despite the decades of research devoted to these materials. Here, we utilize multiple assays investigating the endosomal escape step associated with plasmid delivery by polyethylenimine (PEI) and poly(β-amino esters) (PBAEs) to improve the understanding of how these cationic polymers enable gene delivery. To probe the role of these materials in facilitating endosomal escape, we utilized vesicle membrane leakage and extracellular pH modulation assays to demonstrate the influence of polymer buffering capacity and effective p on the delivery of the plasmid DNA. Our results demonstrate that transfection with PBAEs is highly sensitive to the effective p of the overall polymer, which has broad implications for transfection. In more acidic environments, PBAE-mediated transfection was inhibited, while PEI was relatively unaffected. In neutral to basic environments, PBAEs have high buffering capacities that led to dramatically improved transfection efficacy. The cellular uptake of polymeric nanoparticles overall was unchanged as a function of pH, indicating that microenvironmental acidity was important for downstream intracellular delivery efficiency. Overall, this study motivates the use of polymer chemical characteristics, such as effective p values, to more efficiently evaluate new polymeric materials for enhanced intracellular delivery characteristics.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034557PMC
June 2020

Omega-3 fatty acids accelerate fledging in an avian marine predator: a potential role of cognition.

J Exp Biol 2021 02 24;224(Pt 4). Epub 2021 Feb 24.

Department of Psychology, Memorial University of Newfoundland, St John's, NL, Canada, A1B 3X9.

Consuming omega-3 fatty acids (n-3 LCPUFAs) during development improves cognition in mammals, but the effect remains untested in other taxa. In aquatic ecosystems, n-3 LCPUFAs are produced by phytoplankton and bioaccumulate in the food web. Alarmingly, the warming and acidification of aquatic systems caused by climate change impair n-3 LCPUFA production, with an anticipated decrease of 80% by the year 2100. We tested whether n-3 LCPUFA consumption affects the physiology, morphology, behaviour and cognition of the chicks of a top marine predator, the ring-billed gull. Using a colony with little access to n-3 LCPUFAs, we supplemented siblings from 22 fenced nests with contrasting treatments from hatching until fledging; one sibling received n-3 LCPUFA-rich fish oil and the other, a control sucrose solution without n-3 LCPUFAs. Halfway through the nestling period, half the chicks receiving fish oil were switched to the sucrose solution to test whether n-3 LCPUFA intake remains crucial past the main growth phase (chronic versus transient treatments). Upon fledging, n-3 LCPUFAs were elevated in the blood and brains of chicks receiving the chronic treatment, but were comparable to control levels among those receiving the transient treatment. Across the entire sample, chicks with elevated n-3 LCPUFAs in their tissues fledged earlier despite their morphology and activity levels being unrelated to fledging age. Fledging required chicks to escape fences encircling their nest. We therefore interpret fledging age as a possible indicator of cognition, with chicks with improved cognition fledging earlier. These results provide insight into whether declining dietary n-3 LCPUFAs will compromise top predators' problem-solving skills, and thus their ability to survive in a rapidly changing world.
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http://dx.doi.org/10.1242/jeb.235929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929930PMC
February 2021

Sympatry drives colour and song evolution in wood-warblers (Parulidae).

Proc Biol Sci 2021 01 13;288(1942):20202804. Epub 2021 Jan 13.

Department of Integrative Biology, University of Windsor, Windsor, Ontario N9B 3P4, Canada.

Closely related species often exhibit similarities in appearance and behaviour, yet when related species exist in sympatry, signals may diverge to enhance species recognition. Prior comparative studies provided mixed support for this hypothesis, but the relationship between sympatry and signal divergence is likely nonlinear. Constraints on signal diversity may limit signal divergence, especially when large numbers of species are sympatric. We tested the effect of sympatric overlap on plumage colour and song divergence in wood-warblers (Parulidae), a speciose group with diverse visual and vocal signals. We also tested how number of sympatric species influences signal divergence. Allopatric species pairs had overall greater plumage and song divergence compared to sympatric species pairs. However, among sympatric species pairs, plumage divergence positively related to the degree of sympatric overlap in males and females, while male song bandwidth and syllable rate divergence negatively related to sympatric overlap. In addition, as the number of species in sympatry increased, average signal divergence among sympatric species decreased, which is likely due to constraints on warbler perceptual space and signal diversity. Our findings reveal that sympatry influences signal evolution in warblers, though not always as predicted, and that number of sympatric species can limit sympatry's influence on signal evolution.
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http://dx.doi.org/10.1098/rspb.2020.2804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892414PMC
January 2021

Reliability of tibiofemoral contact area and centroid location in upright, open MRI.

BMC Musculoskelet Disord 2020 Nov 30;21(1):795. Epub 2020 Nov 30.

Centre for Hip Health and Mobility, University of British Columbia, 7/F - 2635 Laurel Street, Robert HN Ho Research Centre, Vancouver, BC, V5Z 1M9, Canada.

Background: Imaging cannot be performed during natural weightbearing in biomechanical studies using conventional closed-bore MRI, which has necessitated simulating weightbearing load on the joint. Upright, open MRI (UO-MRI) allows for joint imaging during natural weightbearing and may have the potential to better characterize the biomechanical effect of tibiofemoral pathology involving soft tissues. However open MRI scanners have lower field strengths than closed-bore scanners, which limits the image quality that can be obtained. Thus, there is a need to establish the reliability of measurements in upright weightbearing postures obtained using UO-MRI.

Methods: Knees of five participants with prior anterior cruciate ligament (ACL) rupture were scanned standing in a 0.5 T upright open MRI scanner using a 3D DESS sequence. Manual segmentation of cartilage regions in contact was performed and centroids of these contact areas were automatically determined for the medial and lateral tibiofemoral compartments. Inter-rater, test-retest, and intra-rater reliability were determined and quantified using intra-class correlation (ICC), standard error of measurement (SEM), and smallest detectable change with 95% confidence (SDC). Accuracy was assessed by using a high-resolution 7 T MRI as a reference.

Results: Contact area and centroid location reliability (inter-rater, test-retest, and intra-rater) for sagittal scans in the medial compartment had ICC values from 0.95-0.99 and 0.98-0.99 respectively. In the lateral compartment, contact area and centroid location reliability ICC values ranged from 0.83-0.91 and 0.95-1.00 respectively. The smallest detectable change in contact area was 1.28% in the medial compartment and 0.95% in the lateral compartment. Contact area and centroid location reliability for coronal scans in the medial compartment had ICC values from 0.90-0.98 and 0.98-1.00 respectively, and in the lateral compartment ICC ranged from 0.76-0.94 and 0.93-1.00 respectively. The smallest detectable change in contact area was 0.65% in the medial compartment and 1.41% in the lateral compartment. Contact area was accurate to within a mean absolute error of 11.0 mm.

Conclusions: Knee contact area and contact centroid location can be assessed in upright weightbearing MRI with good to excellent reliability. The lower field strength used in upright, weightbearing MRI does not compromise the reliability of tibiofemoral contact area and centroid location measures.
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http://dx.doi.org/10.1186/s12891-020-03786-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702694PMC
November 2020

Relationships of song structure to phylogenetic history, habitat, and morphology in the vireos, greenlets, and allies (Passeriformes: Vireonidae).

Evolution 2020 11 10;74(11):2494-2511. Epub 2020 Oct 10.

Department of Psychology, Memorial University of Newfoundland, St. John's, A1B 3X9, Canada.

Acoustic signals show immense variation among passerines, and several hypotheses have been proposed to explain this diversity. In this study, we tested, for the first time, the relationships of song structure to phylogeny, habitat type, and morphology in the vireos and allies (Vireonidae). Every measure of song structure considered in this study had moderate and significant phylogenetic signal. Furthermore, two song-constraining morphological traits, bill shape and body mass, also exhibited significant phylogenetic signal. Song length showed the largest within-clade similarity; longer songs were highly conserved in part of the greenlet (Hylophilus) clade, whereas shorter songs characterized the remaining seven genera. We found no differences in song structure among vireonids living in different habitat types. However, vireonids with shorter, stouter bills and larger bodies sang songs with lower minimum and maximum peak frequency, compared with species with longer, thinner bills and smaller bodies. We conclude that Vireonidae song evolution is driven partially by phylogenetically conserved morphological traits. Our findings support the phylogenetic signal and morphological constraints hypotheses explaining structural diversity in avian acoustic signals.
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http://dx.doi.org/10.1111/evo.14099DOI Listing
November 2020

Alaska Native genomic research: perspectives from Alaska Native leaders, federal staff, and biomedical researchers.

Genet Med 2020 12 25;22(12):1935-1943. Epub 2020 Aug 25.

National Institutes of Health, Bethesda, MD, USA.

Meaningful engagement of Alaska Native (AN) tribes and tribal health organizations is essential in the conduct of socially responsible and ethical research. As genomics becomes increasingly important to advancements in medicine, there is a risk that populations not meaningfully included in genomic research will not benefit from the outcomes of that research. AN people have historically been underrepresented in biomedical research; AN underrepresentation in genomics research is compounded by mistrust based on past abuses, concerns about privacy and data ownership, and cultural considerations specific to this type of research. Working together, the National Human Genome Research Institute and two Alaska Native health organizations, Southcentral Foundation and the Alaska Native Health Board, cosponsored a workshop in July 2018 to engage key stakeholders in discussion, strengthen relationships, and facilitate partnership and consideration of participation of AN people in community-driven biomedical and genomic research. AN priorities related to translation of genomics research to health and health care, return of genomic results, design of research studies, and data sharing were discussed. This report summarizes the perspectives that emerged from the dialogue and offers considerations for effective and socially responsible genomic research partnerships with AN communities.
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http://dx.doi.org/10.1038/s41436-020-0926-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708301PMC
December 2020

Biomechanics during cross-body lunging in individuals with and without painful cam and/or pincer morphology.

Clin Biomech (Bristol, Avon) 2020 06 7;76:105030. Epub 2020 May 7.

Motion Analysis and Biofeedback Laboratory, University of British Columbia, Vancouver, BC, Canada; Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Background: Femoroacetabular impingement is a patho-mechanical hip condition that can lead to restrictions in hip motion, particularly in end-range hip flexion, adduction and/or internal rotation. Radiographic evidence of femoroacetabular impingement - cam and/or pincer morphology - is prevalent in the general and athletic populations. There is, however, a lack of studies that have analyzed the performance of sport-specific movements in people possessing these morphologies. Therefore, the purpose of this study was to compare cross-body lunge biomechanics between individuals with and without painful cam and/or pincer morphology.

Methods: This was an exploratory, cross-sectional study where nine participants with cam and/or pincer morphology and symptoms, thirteen participants with asymptomatic cam and/or pincer morphology, and eleven pain-free controls performed the cross-body lunge during a single session. Trunk, pelvis, hip, knee and ankle kinematics, as well as hip, knee and ankle kinetics and vertical ground reaction forces were examined.

Findings: Overall, the groups performed the movement similarly, with most variables statistically similar between groups. However, pelvis sagittal plane excursion throughout the entire cross-body lunge was significantly larger in those with cam and/or pincer morphology and symptoms compared to those with asymptomatic cam and/or pincer morphology (P = .046, effect size = 0.98).

Interpretation: The results of this study show that cross-body lunge performance is similar across individuals with and without painful cam and/or pincer morphology. However, future research should aim to better understand pelvis biomechanics during sporting activities, as pelvis sagittal plane excursion may have important implications in rehabilitation and sport performance.
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http://dx.doi.org/10.1016/j.clinbiomech.2020.105030DOI Listing
June 2020

Poly(Beta-Amino Ester) Nanoparticles Enable Nonviral Delivery of CRISPR-Cas9 Plasmids for Gene Knockout and Gene Deletion.

Mol Ther Nucleic Acids 2020 Jun 21;20:661-672. Epub 2020 Apr 21.

Department of Biomedical Engineering, Institute for NanoBioTechnology, Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Departments of Ophthalmology, Oncology, Neurosurgery, Materials Science & Engineering, and Chemical & Biomolecular Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address:

The CRISPR-Cas9 system is a powerful gene-editing tool with wide-ranging applications, but the safe and efficient intracellular delivery of CRISPR components remains a challenge. In this study, we utilized biodegradable poly(beta-amino ester) nanoparticles to codeliver plasmid DNA encoding Cas9 and short guide RNA (sgRNA), respectively, to enable gene knockout following a CRISPR-mediated cleavage at one genomic site (1-cut edit), as well as gene deletion following DNA cleavage at two sites flanking a region of interest (2-cut edits). We designed a reporter system that allows for easy evaluation of both types of edits: gene knockout can be assessed by a decrease in near-infrared fluorescent protein (iRFP) fluorescence, whereas deletion of an expression stop cassette turns on a red-enhanced nanolantern fluorescence/luminescence dual reporter. Nanoparticles enabled up to 70% gene knockout due to small indels, as well as 45% gain-of-function expression after a 600-bp deletion edit. The efficiency of 2-cut edits is more sensitive than 1-cut edits to Cas9 and the sgRNA expression level. We demonstrate promising biodegradable nanoparticle formulations for gene editing. Our findings also provide new insights into the screening and transfection requirements for different types of gene edits, which are applicable for designing nonviral delivery systems for the CRISPR-Cas9 platform.
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http://dx.doi.org/10.1016/j.omtn.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210380PMC
June 2020

The effect of posture on lumbar muscle morphometry from upright MRI.

Eur Spine J 2020 09 25;29(9):2306-2318. Epub 2020 Apr 25.

ICORD, Blusson Spinal Cord Centre, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.

Purpose: To assess the effect of upright, seated, and supine postures on lumbar muscle morphometry at multiple spinal levels and for multiple muscles.

Methods: Six asymptomatic volunteers were imaged (0.5 T upright open MRI) in 7 postures (standing, standing holding 8 kg, standing 45° flexion, seated 45° flexion, seated upright, seated 45° extension, and supine), with scans at L3/L4, L4/L5, and L5/S1. Muscle cross-sectional area (CSA) and muscle position with respect to the vertebral body centroid (radius and angle) were measured for the multifidus/erector spinae combined and psoas major muscles.

Results: Posture significantly affected the multifidus/erector spinae CSA with decreasing CSA from straight postures (standing and supine) to seated and flexed postures (up to 19%). Psoas major CSA significantly varied with vertebral level with opposite trends due to posture at L3/L4 (increasing CSA, up to 36%) and L5/S1 (decreasing CSA, up to 40%) with sitting/flexion. For both muscle groups, radius and angle followed similar trends with decreasing radius (up to 5%) and increasing angle (up to 12%) with seated/flexed postures. CSA and lumbar lordosis had some correlation (multifidus/erector spinae L4/L5 and L5/S1, r = 0.37-0.45; PS L3/L4 left, r =  - 0.51). There was generally good repeatability (average ICC(3, 1): posture = 0.81, intra = 0.89, inter = 0.82).

Conclusion: Changes in multifidus/erector spinae muscle CSA likely represent muscles stretching between upright and seated/flexed postures. For the psoas major, the differential level effect suggests that changing three-dimensional muscle morphometry with flexion is not uniform along the muscle length. The muscle and spinal level-dependent effects of posture and spinal curvature correlation, including muscle CSA and position, highlight considering measured muscle morphometry from different postures in spine models.
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http://dx.doi.org/10.1007/s00586-020-06409-4DOI Listing
September 2020

In situ genetic engineering of tumors for long-lasting and systemic immunotherapy.

Proc Natl Acad Sci U S A 2020 02 7;117(8):4043-4052. Epub 2020 Feb 7.

Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21218;

Cancer immunotherapy has been the subject of extensive research, but highly effective and broadly applicable methods remain elusive. Moreover, a general approach to engender endogenous patient-specific cellular therapy, without the need for a priori knowledge of tumor antigen, ex vivo cellular manipulation, or cellular manufacture, could dramatically reduce costs and broaden accessibility. Here, we describe a biotechnology based on synthetic, biodegradable nanoparticles that can genetically reprogram cancer cells and their microenvironment in situ so that the cancer cells can act as tumor-associated antigen-presenting cells (tAPCs) by inducing coexpression of a costimulatory molecule (4-1BBL) and immunostimulatory cytokine (IL-12). In B16-F10 melanoma and MC38 colorectal carcinoma mouse models, reprogramming nanoparticles in combination with checkpoint blockade significantly reduced tumor growth over time and, in some cases, cleared the tumor, leading to long-term survivors that were then resistant to the formation of new tumors upon rechallenge at a distant site. In vitro and in vivo analyses confirmed that locally delivered tAPC-reprogramming nanoparticles led to a significant cell-mediated cytotoxic immune response with systemic effects. The systemic tumor-specific and cell-mediated immunotherapy response was achieved without requiring a priori knowledge of tumor-expressed antigens and reflects the translational potential of this nanomedicine.
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http://dx.doi.org/10.1073/pnas.1916039117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049107PMC
February 2020

Plasticity in the antipredator behavior of the orange-footed sea cucumber under shifting hydrodynamic forces.

Curr Zool 2019 Dec 11;65(6):685-695. Epub 2019 Jan 11.

Department of Ocean Sciences, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.

Marine invertebrates that move too slowly to evade unfavorable environmental change may instead exhibit phenotypic plasticity, allowing them to adjust to varying conditions. The orange-footed sea cucumber is a slow-moving suspension feeder that is preyed on by the purple sunstar . The sea cucumber's antipredator behavior involves changing shape and detaching from the substratum, which might increase its probability of being displaced by water motion into an unsuitable environment. We hypothesized that sea cucumbers' antipredator responses would be diminished under stronger hydrodynamic forces, and that behavioral strategies would be flexible so that individuals could adjust to frequent changes in water flows. In a natural orange-footed sea cucumber habitat, individuals lived along a pronounced hydrodynamic gradient, allowing us to measure antipredator behavior under different water flow strengths. We placed purple sunstars in physical contact with sea cucumbers living at various points along the gradient to elicit antipredator responses. We then repeated this procedure in a laboratory mesocosm that generated weak and strong hydrodynamic forces similar to those observed at the field site. Subjects in the mesocosm experiment were tested in both wave conditions to determine if their antipredator behavior would change in response to sudden environmental change, as would be experienced under deteriorating sea conditions. Antipredator responses did not covary with hydrodynamic forces in the field. However, antipredator responses in the mesocosm experiment increased when individuals were transplanted from strong to weak forces and decreased when transplanted from weak to strong forces. Overall, our results indicate environmentally induced plasticity in the antipredator behavior of the orange-footed sea cucumber.
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http://dx.doi.org/10.1093/cz/zoy100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911852PMC
December 2019

Carboxylated branched poly(β-amino ester) nanoparticles enable robust cytosolic protein delivery and CRISPR-Cas9 gene editing.

Sci Adv 2019 12 6;5(12):eaay3255. Epub 2019 Dec 6.

Department of Biomedical Engineering, Institute for NanoBioTechnology, and Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Efficient cytosolic protein delivery is necessary to fully realize the potential of protein therapeutics. Current methods of protein delivery often suffer from low serum tolerance and limited in vivo efficacy. Here, we report the synthesis and validation of a previously unreported class of carboxylated branched poly(β-amino ester)s that can self-assemble into nanoparticles for efficient intracellular delivery of a variety of different proteins. In vitro, nanoparticles enabled rapid cellular uptake, efficient endosomal escape, and functional cytosolic protein release into cells in media containing 10% serum. Moreover, nanoparticles encapsulating CRISPR-Cas9 ribonucleoproteins (RNPs) induced robust levels of gene knock-in (4%) and gene knockout (>75%) in several cell types. A single intracranial administration of nanoparticles delivering a low RNP dose (3.5 pmol) induced robust gene editing in mice bearing engineered orthotopic murine glioma tumors. This self-assembled polymeric nanocarrier system enables a versatile protein delivery and gene editing platform for biological research and therapeutic applications.
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http://dx.doi.org/10.1126/sciadv.aay3255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897553PMC
December 2019

Prevalence of Femoroacetabular Impingement Syndrome among Young and Middle-aged White Adults.

J Rheumatol 2020 09 1;47(9):1440-1445. Epub 2019 Nov 1.

From the School of Population and Public Health, University of British Columbia, Vancouver; Arthritis Research Canada, Richmond, British Columbia; Centre for Health Evaluation and Outcome Sciences, St. Paul's Hospital; the Department of Medicine, and the Department of Physical Therapy, and the Department of Orthopaedics, and the Department of Radiology, University of British Columbia, Vancouver, British Columbia; Department of Family Medicine, University of Calgary, Calgary, Alberta, Canada; Arthritis Centre and College of Medicine, University of Arizona, Tucson, Arizona, USA.

Objective: The purpose of the study was to determine the prevalence of femoroacetabular impingement syndrome (FAIS) in white adults 20 to 49 years of age.

Methods: Participants were white men and women aged 20-49 years, recruited through random digit dialing from the population of Metro Vancouver, British Columbia, Canada. Participants filled out a self-administered questionnaire and underwent a physical examination and radiographs of both hips. FAIS was defined as a combination of hip symptoms, physical signs of impingement, and radiological findings of cam or pincer morphology as recommended by the Warwick Agreement. All analyses were weighted to reflect the population from which the sample was drawn.

Results: Data were obtained for 500 participants. In the study population, 48.9% were males and the age distribution was 32.2%, 31.4%, and 36.4% in the groups 20-29, 30-39, and 40-49 years, respectively. The physical signs of impingement correlated significantly with symptoms, but there was no significant association between either symptoms or physical examination with radiographic findings. FAIS on either side was found in 3.0% (95% CI 1.5-4.5) of the population.

Conclusion: In this study, FAIS was present in 3% of whites aged 20-49 years. Further research is needed to develop consistent criteria for assessing hip symptoms, physical signs, and hip joint morphology, and to better understand the relationships between them.
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http://dx.doi.org/10.3899/jrheum.190345DOI Listing
September 2020

Nonviral polymeric nanoparticles for gene therapy in pediatric CNS malignancies.

Nanomedicine 2020 01 23;23:102115. Epub 2019 Oct 23.

Department of Neurosurgery, Johns Hopkins University School of Medicine. Electronic address:

Together, medulloblastoma (MB) and atypical teratoid/rhabdoid tumors (AT/RT) represent two of the most prevalent pediatric brain malignancies. Current treatment involves radiation, which has high risks of developmental sequelae for patients under the age of three. New safer and more effective treatment modalities are needed. Cancer gene therapy is a promising alternative, but there are challenges with using viruses in pediatric patients. We developed a library of poly(beta-amino ester) (PBAE) nanoparticles and evaluated their efficacy for plasmid delivery of a suicide gene therapy to pediatric brain cancer models-specifically herpes simplex virus type I thymidine kinase (HSVtk), which results in controlled apoptosis of transfected cells. In vivo, PBAE-HSVtk treated groups had a greater median overall survival in mice implanted with AT/RT (P = 0.0083 vs. control) and MB (P < 0.0001 vs. control). Our data provide proof of principle for using biodegradable PBAE nanoparticles as a safe and effective nanomedicine for treating pediatric CNS malignancies.
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http://dx.doi.org/10.1016/j.nano.2019.102115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027378PMC
January 2020

Protocol development for synchrotron contrast-enhanced CT of human hip cartilage.

Med Eng Phys 2019 11 13;73:1-8. Epub 2019 Sep 13.

Department of Orthopaedics, University of British Columbia, Centre for Hip Health and Mobility, 2635 Laurel St, Vancouver BC V5Z 1M9, Canada. Electronic address:

Understanding hip osteoarthritis requires new investigational tools for quantitative studies of biophysical and biomechanical properties as well as for determination of structure. Three new protocols to study pathological changes in cartilage and to measure cartilage thickness in intact human hips are described using synchrotron contrast enhanced computed tomography (sCECT) with the iodinated contrast agent CA4+. Ten human cadaver hips were prepared and injected with CA4+ using three different methods, all of which included rotation and distraction of the joint. CA4+ diffusion into cartilage was monitored using sCECT. The thickness of acetabular and femoral cartilage was also measured. Diffusion times ranged from 2 h to 75 h, depending on the injection protocol and the cartilage region. Direct single injection of the contrast through the labrum resulted in the fastest diffusion times. The iodine attenuation coefficient, which reflects the contrast agent distribution in the cartilage, ranged from 0.0142/cm to 0.1457/cm. Three injections at the head/neck conjunction area yielded the highest iodine attenuation coefficients in cartilage. The femoral cartilage in the Superior-Medial compartment was significantly thicker than in the other 3 femoral compartments, and femoral cartilage in the Superior-Anterior compartment was significantly thinner than the other 3 femoral compartments. The acetabular cartilage in the Superior compartment was significantly thicker than that in the Superior-Posterior compartment. sCECT with CA4+ allows assessment of hip cartilage thickness with 0.1 mm isotropic voxel size, sufficient for evaluating cartilage pathology and biomechanics.
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http://dx.doi.org/10.1016/j.medengphy.2019.08.003DOI Listing
November 2019

A combinatorial library of biodegradable polyesters enables non-viral gene delivery to post-mitotic human stem cell-derived polarized RPE monolayers.

Regen Eng Transl Med 2019 Sep 24;6(3):273-285. Epub 2019 Jul 24.

Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21231, United States.

Safe and effective delivery of DNA to post-mitotic cells, especially highly differentiated cells, remains a challenge despite significant progress in the development of gene delivery tools. Biodegradable polymeric nanoparticles (NPs) offer an array of advantages for gene delivery over viral vectors due to improved safety, carrying capacity, ease of manufacture, and cell-type specificity. Here we demonstrate the use of a high-throughput screening (HTS) platform to synthesize and screen a library of 148 biodegradable polymeric nanoparticles, successfully identifying structures that enable efficient transfection of human pluripotent stem cell differentiated human retinal pigment epithelial (RPE) cells with minimal toxicity. These NPs can deliver plasmid DNA (pDNA) to RPE monolayers more efficiently than leading commercially available transfection reagents. Novel synthetic polymers are described that enable high efficacy non-viral gene delivery to hard-to-transfect polarized human RPE monolayers, enabling gene loss- and gain-of-function studies of cell signaling, developmental, and disease-related pathways. One new synthetic polymer in particular, 3,3'-iminobis(N,N-dimethylpropylamine)-end terminated poly(1,5-pentanediol diacrylate-co-3 amino-1-propanol) (5-3-J12), was found to form self-assembled nanoparticles when mixed with plasmid DNA that transfect a majority of these human post-mitotic cells with minimal cytotoxicity. The platform described here can be utilized as an enabling technology for gene transfer to human primary and stem cell-derived cells, which are often fragile and resistant to conventional gene transfer approaches.
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http://dx.doi.org/10.1007/s40883-019-00118-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962803PMC
September 2019

Cartilage recovery in runners with and without knee osteoarthritis: A pilot study.

Knee 2019 Oct 18;26(5):1049-1057. Epub 2019 Aug 18.

Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Objective: Running is an easy way of meeting physical activity recommendations for individuals with knee osteoarthritis (KOA); however, it remains unknown how their cartilage reacts to running. The objective of this pilot study was to compare the effects of 30 min of running on T2 and T1ρ relaxation times of tibiofemoral cartilage in female runners with and without KOA.

Methods: Ten female runners with symptomatic KOA (mean age 52.6 ± 7.6 years) and 10 without KOA (mean age 52.5 ± 7.8 years) ran for 30 min on a treadmill. Tibiofemoral cartilage T2 and T1ρ relaxation times were measured using magnetic resonance imaging prior to and immediately after the bout of running. Repeated-measures analyses of covariance (ANCOVA) were conducted to examine between-group differences across scanning times.

Results: No Group × Time interactions were found for T2 (P ≥ 0.076) or T1ρ (P ≥ 0.288) relaxation times. However, runners with KOA showed increased T2 values compared with pre-running in the medial and lateral femur 55 min post-running (5.4 to 5.5%, P < 0.022) and in all four tibiofemoral compartments 90 min post-running (6.9 to 11.1%, P < 0.01). A significant group effect was found for T1ρ in the medial femur, with greater values in those with KOA compared with controls.

Conclusion: While Group × Time interactions in T2 and T1ρ relaxation times remained statistically insignificant, the observed significant increases in T2 in runners with tibiofemoral osteoarthritis TFOA may suggest slower and continuing changes in the cartilage and thus a need for longer recovery after running. Future research should investigate the effects of repeated exposure to running.
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http://dx.doi.org/10.1016/j.knee.2019.07.011DOI Listing
October 2019

Author Correction: Mechanical Metrics of the Proximal Tibia are Precise and Differentiate Osteoarthritic and Normal Knees: A Finite Element Study.

Sci Rep 2019 May 2;9(1):7053. Epub 2019 May 2.

Department of Mechanical Engineering, University of Saskatchewan, Saskatoon, SK, Canada.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-019-43379-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494855PMC
May 2019
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