Alexander Scott

The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.

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Rationale: The distal attachment of the triceps surae muscle onto the Achilles tendon is variable, leading to inter-individual diversity in the length of the free Achilles tendon. A longer free tendon may be more prone to injury due to reduced muscular buttressing.Objective: The purpose of this study was to compare the free Achilles tendon dimensions and structure between those with midportion or insertional Achilles tendinopathy (AT) and healthy controls using magnetic resonance imaging (MRI).Methods: MRI scans from 132 patients were compared. The insertional AT group consisted of 25 patients (median age 61, height 163 cm, weight 81.7 kg) and were matched by 25 controls (median age 55, height 168 cm, weight 78 kg). The midportion AT group consisted of 41 patients (median age 55, height 168 cm, weight 83.9 kg) and were matched by 41 controls (median age 52, height 170 cm, weight 77.1 kg). The primary outcome measure was free Achilles tendon length. Secondary outcome measures included cross-sectional area (CSA), anteroposterior thickness, location of pathology and extent of pathology. All measurements were assessed twice and the mean was reported.Results: Midportion AT cases had significantly longer free tendons (Mdn = 51.2 mm, IQR = 26.9 mm) compared to controls (Mdn = 40.8 mm, IQR = 20.0 mm), p = .007. However, there was not a significant difference between the free Achilles tendon lengths in insertional AT cases (Mdn = 47.9 mm, IQR = 15.1 mm) and controls (Mdn = 39.2 mm, SD = 17.9 mm), p = .158. Free Achilles tendon length was also correlated with the extent of pathology among those with AT, rτ = 0.18, p = .03.Conclusion: Having a long free Achilles tendon is associated with the presence of midportion Achilles tendinopathy.

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Rigid taping, intending to minimize the occurrence of awkward wrist postures, hasbeen suggested to reduce the incidence of de Quervain’s tendinopathy in tree planters.However, the ability of rigid taping to reduce wrist postures during planting has not yet beenformally evaluated. Furthermore, published observations of tree wrist postures duringplanting are scarce. Objectives: The primary aim was to test the effect of wrist rigid tapingon wrist postures during tree planting tasks. Secondary aims were to: evaluate the effect ofrigid taping of the wrist on static measures of active and passive range of motion (AROMand PROM) and on maximal voluntary contraction (MVC) grip force exertion; and conductexploratory analyses of the wrist rigid taping injury intervention acceptability and of treewrist postures throughout the planting cycle. Methods: A randomized cross-over, withinparticipant, repeated-measures design in an outdoor environment was used. With onlineposts, eleven tree planters were recruited to plant 50 trees in three conditions: no-tape (NT),tape-on-the-dorsum-of-the-hand (T1) and tape-on-the-thumb (T2). Electrogoniometers (EG)recorded continuous wrist postures (flexion, extension, radial deviation, ulnar deviation) anda camera video-recorded planting trials. Video observations were used to segment EG tracesof each planting cycle (one planted tree) into 4 kinematically distinct Phases. The tree andshovel wrist were analyzed separately. Before and after planting trials, static AROM andPROM, MVC, and intervention acceptability were recorded with EGs, a hand dynamometer,and an acceptability questionnaire, respectively. Results: Two-factor (2x4) repeated-measures analysis-of-variance found that T1 did not significantly reduce peak flexion of thetree wrist (F(1,7)=2.336,p=0.17) or shovel wrist (F(1,5)=1.741,p=0.244). T2 significantlyreduced peak ulnar deviation of the tree wrist (F(1,7)=9.101,p=0.019) but not the shovelwrist (F(1,6)=1.002,p=0.356). One-tailed Wilcoxon signed-rank tests found that thefrequency of shovel-wrist awkward frontal plane postures (>10° ulnar/radial deviation) wassignificantly reduced in the T2 condition (p0.05). One-tailed paired t-tests found tapedconditions significantly reduced AROM (t(4.03)=5,p=0.00502), PROM (z(4)=-2.02,p0.05)and MVC (z(10)=-2.7562,p=0.00289). Rigid taping was found to be an acceptable injuryintervention by tree planters (median score 6/7). The tree wrist experienced high peakpostures at the start and end of the planting cycle.

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Sport is evolving into a more competitive industry, leaving athletes prone to injuries. Monitoring athletes using wearable technology provides a way to potentially manage training and competition loads with the goal of reducing injuries. One such technology is the VERT, a commercially available discrete wearable device that measures vertical displacement from the center of mass. While several studies have examined the accuracy of the VERT’s measures of jump height and jump count, landing impact has not yet been investigated. The objective of this research study was to explore the potential utility of the VERT as a load monitoring tool in elite volleyball players. This was done by (1) examining the accuracy of the VERT landing impact values in university volleyball players and (2) retrospectively analyzing a VERT data set collected over the course of a university volleyball season, documenting whether established relationships were observed between various load characteristics and knee pain. We hypothesized that the VERT landing impact values would fall within 10% of those derived from a research-grade accelerometer, the Shimmer. In the data set, we expected to see agreement with the literature in that acute:chronic workload ratio (ACR), average jump height, jump count and session rating of perceived exertion (sRPE) were positively associated with knee pain. We also expected knee pain to increase over the course of the season and for leftsides/middle blockers to report the highest pain. Methodology for the validation study included recruiting 14 players, having each perform 10 jumps while wearing both devices. For the retrospective analysis, we used linear mixed effect modelling. The results of the validation showed that VERT landing impacts were variable (limits of agreement of -84.13% and 52.37%) and had a propensity to be lower (mean bias of -15.88%) when compared to the Shimmer. In the retrospective analysis, average jump height (p=0.041) and date (p=0.032) were negatively associated with knee pain (however the associations were of small magnitude). In conclusion, the validity of the VERT device’s landing impact values are generally poor, with respect to Shimmer. The relationships in the data set were partially consistent with what previous literature has shown.

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Familial hypercholesterolemia (FH) is a genetic condition characterized by the inability to properly metabolize low-density lipoprotein cholesterol (LDL-C). In addition to serious cardiovascular health complications, FH carriers often develop intratendinous cholesterol deposits, most notably located in the Achilles tendon, known as Achilles tendon xanthoma (ATX). Clinically, physical detection of ATX relies upon visual assessment and palpation. This practice is insensitive and is not capable of distinguishing FH from conditions with similar symptomology, such as Achilles tendinopathy (ATE). Advances in medical imaging, specifically Dixon method for magnetic resonance imaging (MRI) and ultrasound tissue characterization (UTC) for ultrasound (US), may be able to differentiate between ATX and ATE. The Dixon method allows for quantification of relative lipid and water contents within tissue and UTC allows for characterization of tendon structure through echo-type evaluation. We hypothesized that ATX will demonstrate greater relative lipid and water content than ATE or a healthy control population (C), and that ATX and ATE will demonstrate decreased tendon organization compared to C.To test the hypotheses, US and MRI scans of 59 tendons from 30 participants (n=10 ATX, n=10 ATE, n=10 C) were analyzed for relative lipid and water content, UTC echo-type I values, as well as Achilles tendon thickness (ATT). Relative lipid content was not greater in ATX compared to ATE and controls (ATX – ATE, p = 0.23; ATX – Control, p = 0.31; ATE – Control, p = 0.98). Relative water content was greater in ATX compared to controls (p = 0.04) but not compared to ATE (p = 0.16) and did not differ between ATE and control (p = 0.76). ATX tendons were significantly thicker than both ATE and control tendons (p = 0.04 and 0.002, respectively). UTC echo-type I values were significantly lower in ATX than ATE (p = 0.04) and nearly significantly lower in ATX than C (p=0.055), indicating decreased collagen organization in ATX.Results suggest that both US and MRI may serve as viable approaches to aid clinical detection of ATX as well as to differentiate ATX and ATE pathology.

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The Achilles tendon is the largest and strongest tendon in the human body and is vital for locomotion. One of the most important indicators of tendon function is tendon stiffness. Tendinopathic Achilles tendon displays reduced stiffness compared to healthy tissue, meaning that it experiences more strain for a given load, putting the tendon at a higher risk of damage. Recently, in vivo measures of Achilles tendon stiffness have become more common, although they are limited to the research setting due to low reliability values. In order to address these limitations, we have begun validating a newly available technology, the MyotonPRO. This is a handheld, digital palpation device that sends out a small impulse into the tendon through a probe which houses an accelerometer. The measured deformation and acceleration determined by the device, are then used to derive the transverse stiffness of the tendon. The aim of this cross-sectional pilot study is to assess whether the transverse stiffness of tendinopathic Achilles tendon (the mid-portion tendinopathy group) is lower than those who are free from symptoms (the control group). We hypothesized that the injured tendons will be significantly less stiff than the tendons of the control group. To test this hypothesis, we used the MyotonPRO to measure the Achilles tendons of 25 individuals who either had midportion tendinopathy (n=10) or who were healthy controls (n=15), and compared their transverse stiffness values taken at the same average location on the tendon (3.7cm from the insertion). We found that there was a significantly lower transverse stiffness in tendinopathic subjects compared to controls (p=0.006). These findings suggest that the MyotonPRO can provide information about the tendon mechanical properties that may be useful in understanding how tendinopathy affects tendon function.This study opens the door to the continued investigation of a relatively inexpensive, accessible and easy-to-interpret device. We believe that this device could be used to monitor the healing in tendinopathy patients as well as predicting and preventing injuries and monitoring adaptive changes in tendons in response to exercise.

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Familial hypercholesterolemia (FH), a common genetic metabolic disorder characterized by high cholesterol levels, is involved in the development of atherosclerosis and other preventable diseases. FH can also cause tendinous abnormalities, such as thickening and xanthoma (tendon lipid accumulation) in the Achilles and extensor tendons, which may impact and impede tendon biomechanics. There is evidence that high cholesterol may lead to tendon injury or pain, but tendon biomechanics has received little investigation in people with FH. The objective of this study was to investigate how FH can affect Achilles tendon biomechanics, in vivo. 16 FH participants were recruited locally from the British Columbia FH Registry database. 16 control participants were recruited from purposeful convenience sampling. All participants completed preferred pace walking trials, shod, on a fully instrumented treadmill to collect gait impact data. Achilles tendon (AT) biomechanical data was obtained according to previously published methodology; simultaneously, lower limb kinematics, and muscle-tendon junction displacement were measured by motion capture and b-mode ultrasound imaging, respectively. AT strain, stiffness and hysteresis were calculated using a custom built Matlab program. AT biomechanical outcomes were assessed for statistical differences using MANCOVA.16 FH participants (10 males, 6 females, 37±6 years, BMI of 28±4 kg/m²) and 16 control participants (10 males, 6 females, 36±7 years, BMI of 27±3 kg/m2) were recruited. FH participants displayed similar AT peak strain (FH: 5.07±0.9%, Controls: 4.95±0.9%; p=0.790), lower stiffness (FH: 87±20 N/mm, Controls: 111±18 N/mm; p=0.001), and higher hysteresis (FH: 56±17%, Controls: of 35±12%; p=0.007), when compared to controls. To the best of our knowledge, this is the first study that evaluates the impact of FH on AT biomechanics, in vivo. The results of the current study provide evidence that cholesterol accumulation can negatively affect AT biomechanics and potentially increase the chance of injury. The findings of this study will be of interest to clinicians, and people with FH and high cholesterol.

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There has been growing interest in studying the possible effects of statins on tendons due to case studies and retrospective chart reviews that reported a potential relationship between statin use and tendon pathology, as well as laboratory studies demonstrating that statins directly influence tenocyte metabolism. However, a recent epidemiological study found no association between statin use and the risk of tendon rupture. Since statins are widely used cholesterol-lowering medications, it is important to understand the potential relationship between statin use and tendon health. With the use of Ultrasound Tissue Characterization (UTC), the aims of this pilot cross-sectional study were to see if there were signs of reduced collagen organization or increased cross-sectional area (CSA) of the Achilles tendon in individuals who had been taking statins for at least a year (the Statin group), compared to those who had never taken a statin (the Control group). We hypothesized that individuals in the Statin group would demonstrate a greater cross-sectional area and reduced collagen organization (determined by the percent of echo-type I) of their Achilles tendons compared to individuals in the Control group. To test this hypothesis, we analyzed the UTC scans of 66 individuals who were either taking Statins (n=33) or who had never taken statins (n=33, control group) and compared their resulting Achilles tendon CSA and echo-type I values. There were no significant differences in Achilles tendon CSA or proportion of echo-type I patterns between the two groups, implying that statins do not negatively impact the health of the Achilles tendon. In the entire cohort (n=66), there were significant effects of age (r = -0.31, p = 0.012) and BMI (r = -0.31, p = 0.012) on echo-type I values. These findings support previous work which demonstrated a lack of association betweenstatin use and tendon pathology, but demonstrate the negative effects of aging and elevated BMI on tendon health.

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Achilles tendon (AT) is the strongest tendon in the body. One of the major causes of AT pathology, chronic tendinopathy, is frequently due to excessive loading. Despite the risk of overuse injury, exercise training with appropriate mechanical loading parameters has been found to trigger an adaptation response in the AT. However, the influence of some loading parameters, such as the duration of rest periods between exercise repetitions, remains unknown. Therefore, the aim of this study was to examine the effect of 10s rest insertion during isometric resistance training (Long rest training; LRT) on the morphological properties of human AT, compared with same training intensity and volume but with 3s rest insertion (short rest training; SRT). I hypothesized that ATs exposed to LRT would demonstrate increased tendon collagen organization and tendon cross-sectional area (CSA) compared with baseline, but that SRT would not demonstrate any change in either variable.To test my hypothesis, we recruited healthy adults, and randomly allocated one leg to LRT and the other to SRT. The exercise protocol consisted of 5 sets of 10 isometric calf presses at 90% of maximum voluntary contraction, three times a week over a 12-weeks training period. Tendon collagen organization (proportion of type I echoes) and CSA were measured by ultrasound tissue characterization before and after the 12-weeks period. The primary outcome was the proportion of type I echoes.In contrast to our hypothesis, neither LRT nor SRT induced an improvement in collagen organization or tendon CSA. However, tendons exposed to SRT demonstrated a reduction in the proportion of type I echoes following exercise from 0.66 (95% CI= 0.60 to 0.70) to 0.55 (95% CI=0.49 to 0.60), (p 0.05), whereas tendons that were exposed to LRT didn’t demonstrate any reduction in the proportion of type I echoes from baseline (0.60, 95% CI= 0.56 to 0.65) to post-intervention (0.62, 95% CI= 0.57 to 0.67), (p = 0.58). Neither type of exercise had a measurable effect on the AT CSA. Further research is needed to examine the biological changes and mechanical effects that influence tendon morphological change associated with different exercise parameters.

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Background: Resistance exercise is effective in relieving pain and improving grip strength in patients with lateral epicondylalgia (LE). However, patients’ activity-related pain can hinder their active participation in an exercise program. Acupuncture, particularly electro-acupuncture (EA), may be an effective complementary modality for pain control in order to promote patients’ participation in an exercise program and further to enhance therapeutic effects. Objectives: 1) assess the feasibility of a study designed to compare the effect size of analgesia induced by EA vs. standard acupuncture (SA); 2) estimate the time course of the analgesic effect of EA and SA for patients with LE; and 3) investigate if the analgesic effect of either intervention is associated with a change in pain-free grip strength. Methods: A double-blind, parallel-group randomized controlled feasibility trial was conducted at a research centre located in Vancouver, Canada. Twenty-one participants with unilateral LE lasting more than 6 weeks duration were enrolled in the study. The participants were randomly allocated to receive a single treatment of either EA (10-30 Hz) or SA. The primary outcome measure was pain-free grip strength, and the secondary outcome measures included the severity of lateral elbow pain (numeric rating scale), and patients’ global rating of change. Outcomes were measured over a 72-hour period. Results: No significant differences in outcome measures were found between the two treatment groups at any time point. A pattern of gradual improvement of pain-free grip strength (approximately 12N /day) over the 72-hour monitoring period in both treatment groups was observed, and this improvement was statistically significant compared to baseline at the 72-hour time point (38 ± 13N). In contrast, there was a statistically significant reduction in patients’ perceived pain level immediately after either treatment, and this improvement was maintained throughout the 72-hour follow-up period (-0.99~-1.59 ± 0.35). After 24 hours, 5% of patients reported themselves as feeling ‘much better’, 55% ‘slightly better’, 15% ‘unchanged’, 10% ‘slightly worse’, 10% ‘moderately worse’ and 5% ‘much worse’. Conclusion: Acupuncture may complement the therapeutic effect of rehabilitation exercise program as it provides immediate pain relief for patients with chronic LE.Trial registration: ISRCTN14667535Funding: none

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Chronic non-cancer pain is widespread and has no standard treatment. Interdisciplinary pain management has demonstrated favourable outcomes for chronic pain patients, but essential program components are not known, and the evidence is limited by lack of standardization in the literature. The purpose of this study was to evaluate the impact of the 6-week, outpatient Interdisciplinary Pain Management Program at OrionHealth Vancouver on four primary outcomes. Two other aims were to determine whether increased pain knowledge predicts clinical outcomes, and to collect participant feedback on two 90-minute pain neurophysiology education sessions in the program and to identify barriers to the uptake of information from those sessions. To accomplish this, a single group pre-test/post-test anonymous chart review was conducted and five t-tests, three hierarchical multiple regressions, and one content analysis were carried out. One hundred and thirty three clients provided data for the study, and 102 completed the program. Program completers significantly improved their scores on pain knowledge, pain interference, pain severity, depression, and opioid intake between assessment and discharge from the program, although only pain knowledge, depression, and opioid intake saw substantial increases. Pain knowledge did not significantly predict any clinical outcomes (depression, pain intensity, pain severity). The most common barriers to knowledge intake were pain intensity, pain medication, language/content of the education sessions, and the amount of information presented. The majority of participants found the information provided in the education sessions valuable, and qualitatively reported positive feedback for the education sessions. This study provides further support for interdisciplinary pain management using internationally recommended outcome measures, especially on cognitive and behavioural variables. In addition, pain knowledge was concluded not to be a candidate for predicting clinical success. However, pain neurophysiology education may be beneficial for chronic pain sufferers due to deep learning or nonspecific factors.

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Background: Exercise-based rehabilitation for chronic Achilles tendinopathy (CAT) has proven to be effective, but it can be a painful process. The purpose of this research is to see if a topically applied non-steroidal anti-inflammatory drug, diclofenac, will be able to relieve the pain associated with chronic tendinopathy. The effects of diclofenac on subjects’ pain and mechanical hyperalgesia will be evaluated at rest and during simple calf exercises. It is expected that diclofenac will reduce pain among subjects with Achilles tendinopathy. Methods:19 subjects (22 Achilles) with CAT were randomly assigned to a crossover treatment order (active gel containing 10% diclofenac, or placebo). The primary outcome measure was pain level during tendon loading (hopping) and at rest. The secondary outcome measures evaluated tendon loading characteristics, and mechanical hyperalgesia over the lesion, and over the bilateral trapezius muscles.Results:Pain was significantly reduced from baseline with the use of diclofenac during tendon loading (p=0.0003) and rest (p=0.0313). At baseline the average resting pain was 3.05 (+/-1.43), with the use of diclofenac the pain was 2.32 (+/- 1.52), and with the use of placebo the pain was 2.68 (+/- 2.03). At baseline the average hopping pain was 4.82 (+/-2.1), with the use of diclofenac the average hopping pain was 3.05 (+/-1.81), and with the use of placebo the average pain was 3.77 (+/-2.76). During the hopping test, subjects were able to generate significantly more force when experiencing less pain (p0.0001). The pressure pain threshold at the Achilles tendon was significantly increased from baseline with diclofenac treatment (p = 0.0275). There was no statistically significant difference between the diclofenac and placebo treatment in all cases. Conclusion: Diclofenac was able to improve symptoms and reduce pain during tendon loading and rest in subjects with CAT. Future studies can look at using topical diclofenac with loading exercises to build a more effective and tolerable rehabilitation program while determining the potential clinical significance of diclofenac vs placebo treatment. The pressure pain threshold at the Achilles tendon and distant regions should be further investigated to gain a better understanding of the pain mechanisms involved with this disorder.

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The presence or absence of inflammatory cells in chronic Achilles tendinopathy has been a controversial subject in previous studies. Macrophages, T lymphocytes, and neutrophils have previously been detected in injured human Achilles tendons, whereas other authors have reported that there is no evidence for their occurrence. This controversy may stem from the fact that human Achilles tendon overuse injuries usually develop gradually over time, and the time course of inflammation in response to overuse has been difficult to establish in clinical populations. The aim of my study was to examine the presence of inflammatory cells in the Achilles tendon of rabbits that were subjected to repetitive mechanical loading of defined durations. Twenty-Four New Zealand male rabbits were subjected to repetitive mechanical loading of the Achilles tendon and grouped into four groups in this study, according to the exercise time period for each group: 0, 1, 3, and 6 weeks. Achilles tendons were harvested at the end of each time period. Achilles tendons sections were stained with Hematoxylin and Eosin to examine the histological changes. Both Neutrophils and T-lymphocytes were detected by Immunohistochemistry. Macrophages were detected using the Prussian blue staining. A very small number of inflammatory cells were detected in some tissue sections in the control group. Tissue sections from exercised groups 1, 3, and 6 weeks respectively, showed some qualitative changes in tendon morphology. Collagen bundles were disorganized, and hyalinized patches and spaces between collagen fibers were observed. Tenocyte nuclei were rounder and basophilic, and there was an increase in their numbers with loss of parallel alignment. Macrophages, T-lymphocytes, and neutrophils were detected in tendon sections, specifically in the paratenon. Statistically both lymphocytes and macrophages were significantly higher than control at 6 weeks. While the number of macrophages in the control was lower than the 6 weeks group, there was no significant difference between 1 week and 3 weeks. However, no lymphocytes were found at week 3. Neutrophils in all groups showed no significant difference. The evidence of inflammation was not evenly distributed, as some tissue sections from the same groups showed no evidence of inflammatory cells.

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Tendinopathy is a major cause of morbidity in athletic populations and in the work force, traditionally thought to occur as a consequence of an imbalance between damage (resulting from mechanical loading) and repair. However, one third of the cases for midportion Achilles tendinopathy occur in sedentary individuals, and recent data suggests an association between hypercholesterolemia and the occurrence of tendon rupture or tendinopathy. The aim of this study was to examine the link between elevated lipids and tendon pathology. We used an apolipoprotein E-knockout model (ApoE-KO), in which apolipoprotein E deficiency leads to development of atherosclerosis. We hypothesized that tendons from ApoE-KO mice fed a high fat diet, in comparison to those fed a regular chow diet and the wild type (non-atherosclerotic mice), will demonstrate increased lipid deposition, increased cross-sectional area, and increased expression levels of collagen genes (Col1a1 and Col3a1), a growth factor gene (TGF-β), and an indicator of mast cell presence (Cpa3). To test these hypotheses, ApoE-KO and control mice were fed a regular or high fat diet and sacrificed at different time points: 0, 15, and 30 weeks. The morphological properties were examined on H&E stained Achilles tendon sections while the lipid content was analyzed with Oil Red O staining. Tendon thickening was measured by ultrasonography of patellar tendon cross-sectional area. qPCR analysis was carried out on tail tendons at 30 week time point to analyze gene expression of Cpa3, TGF-β, Col1a1, and Col3a1. ApoE-KO mice developed xanthomatous lesions, and showed less weight gain than control mice. ApoE-KO mice showed no appreciable changes in tendon histomorphology. Compared to control mice, ApoE-KO mice had lower tendon lipid content but demonstrated an increase in tendon cross-sectional area. Col1a1 gene expression levels were decreased in ApoE-KO mice. Cpa3, TGF-β, and Col3a1 showed no differences between strains; however, Cpa3 expression was decreased in mice that were fed the high fat diet. ApoE-KO mice demonstrated significant tendon alterations, demonstrating thicker tendons with decreased collagen expression. Future work is required to determine the mechanism involved and the potential impact on tendon function.

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