322 results on '"Best TM"'
Search Results
2. The inflammatory response: friend or enemy for muscle injury? Limiting certain aspects of inflammation may be a useful new treatment for sport related muscle injury
- Author
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Toumi, H and Best, TM
- Subjects
Health ,Sports and fitness - Abstract
Muscle injury can occur through diverse mechanisms such as mechanical injury, muscular dystrophies, infectious diseases, and biochemical toxicities. Several types of skeletal muscle injury fall into the broad category of [...]
- Published
- 2003
3. Stem cells, angiogenesis and muscle healing: A potential role in massage therapies?
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Best, TM, Gharaibeh, B, Huard, J, Best, TM, Gharaibeh, B, and Huard, J
- Abstract
Skeletal muscle injuries are among the most common and frequently disabling injuries sustained by athletes. Repair of injured skeletal muscle is an area that continues to present a challenge for sports medicine clinicians and researchers due, in part, to complete muscle recovery being compromised by development of fibrosis leading to loss of function and susceptibility to re-injury. Injured skeletal muscle goes through a series of coordinated and interrelated phases of healing including degeneration, inflammation, regeneration and fibrosis. Muscle regeneration initiated shortly after injury can be limited by fibrosis which affects the degree of recovery and predisposes the muscle to reinjury. It has been demonstrated in animal studies that antifibrotic agents that inactivate transforming growth factor (TGF)-β1 have been effective at decreasing scar tissue formation. Several studies have also shown that vascular endothelial growth factor (VEGF) can increase the efficiency of skeletal muscle repair by increasing angiogenesis and, at the same time, reducing the accumulation of fibrosis. We have isolated and thoroughly characterised a population of skeletal muscle-derived stem cells (MDSCs) that enhance repair of damaged skeletal muscle fibres by directly differentiating into myofibres and secreting paracrine factors that promote tissue repair. Indeed, we have found that MDSCs transplanted into skeletal and cardiac muscles have been successful at repair probably because of their ability to secrete VEGF that works in a paracrine fashion. The application of these techniques to the study of sport-related muscle injuries awaits investigation. Other useful strategies to enhance skeletal muscle repair through increased vascularisation may include gene therapy, exercise, neuromuscular electrical stimulation and, potentially, massage therapy. Based on recent studies showing an accelerated recovery of muscle function from intense eccentric exercise through massage-based therapie
- Published
- 2013
4. Hyperbaric oxygen therapy for delayed onset muscle soreness and closed soft tissue injury
- Author
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Bennett, M, primary, Babul, S, additional, Best, TM, additional, Lepawsky, M, additional, Orchard, J, additional, and Taunton, J, additional
- Published
- 2004
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5. The Structure of the Iliotibial Band in Relation to Iliotibial Band Friction Syndrome
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Koji Hayashi, Kathleen Lyons, Thomas M. Best, Nicola Phillips, J.A. Fairclough, Michael Benjamin, Hechmi H. Toumi, Best Tm, and Graeme M. Bydder
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Materials science ,Condensed matter physics ,Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine - Published
- 2006
6. Common finger fractures and dislocations.
- Author
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Borchers JR, Best TM, Borchers, James R, and Best, Thomas M
- Abstract
Finger fractures and dislocations are common injuries that are often managed by family physicians. A systematic physical examination is imperative to avoid complications and poor outcomes following these injuries. Radiography (commonly anteroposterior, true lateral, and oblique views) is required in the evaluation of finger fractures and dislocations. Dorsal dislocation of the proximal interphalangeal joint is the most common type of finger dislocation. Finger dislocations should be reduced as quickly as possible and concurrent soft tissue injuries treated appropriately. Referral to a hand specialist is needed if a dislocation cannot be reduced; is unstable following reduction; or involves significant ligament, tendon, or soft tissue injury. Some common finger fractures can be treated conservatively with appropriate reduction and immobilization. Referral to a hand specialist is required if a fracture is unstable, involves a large portion (greater than 30 percent) of the intra-articular surface, or has significant rotation. [ABSTRACT FROM AUTHOR]
- Published
- 2012
7. Efficacy of Surgery for Femoroacetabular Impingement: A Systematic Review.
- Author
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Ng VY, Arora N, Best TM, Xueliang Pan, and Ellis TJ
- Published
- 2010
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8. Effectiveness of sports massage for recovery of skeletal muscle from strenuous exercise.
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Best TM, Hunter R, Wilcox A, and Haq F
- Abstract
OBJECTIVE: Sport massage, a manual therapy for muscle and soft tissue pain and weakness, is a popular and widely used modality for recovery after intense exercise. Our objective is to determine the effectiveness of sport massage for improving recovery after strenuous exercise. DATA SOURCES: We searched MEDLINE, EMBASE, and CINAHL using all current and historical names for sport massage. Reference sections of included articles were scanned to identify additional relevant articles. STUDY SELECTION: Study inclusion criteria required that subjects (1) were humans, (2) performed strenuous exercise, (3) received massage, and (4) were assessed for muscle recovery and performance. Ultimately, 27 studies met inclusion criteria. DATA EXTRACTION: Eligible studies were reviewed, and data were extracted by the senior author (TMB). The main outcomes extracted were type and timing of massage and outcome measures studied. DATA SYNTHESIS: Data from 17 case series revealed inconsistent results. Most studies evaluating post-exercise function suggest that massage is not effective, whereas studies that also evaluated the symptoms of DOMS did show some benefit. Data from 10 randomized controlled trials (RCTs) do, however, provide moderate evidence for the efficacy of massage therapy. The search identified no trend between type and timing of massage and any specific outcome measures investigated. CONCLUSIONS: Case series provide little support for the use of massage to aid muscle recovery or performance after intense exercise. In contrast, RCTs provide moderate data supporting its use to facilitate recovery from repetitive muscular contractions. Further investigation using standardized protocols measuring similar outcome variables is necessary to more conclusively determine the efficacy of sport massage and the optimal strategy for its implementation to enhance recovery following intense exercise. [ABSTRACT FROM AUTHOR]
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- 2008
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9. Cyclic compressive loading facilitates recovery after eccentric exercise.
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Butterfield TA, Zhao Y, Agarwal S, Haq F, and Best TM
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- 2008
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10. Electrocardiograms in athletes: interpretation and diagnostic accuracy.
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Lawless CE and Best TM
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PURPOSE:: Electrocardiography (ECG) has been proposed as a method to enhance the ability of the preparticipation examination (PPE) to detect underlying cardiac conditions that can lead to sudden cardiac death (SCD) in young athletes. METHODS AND RESULTS:: We conducted a Medline review of the published medical literature, using the key terms of cardiovascular screening of athletes, ECG in athletes, SCD in athletes, and ECG in specific cardiac disease states: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, myocarditis, long QT syndrome, Brugada syndrome, coronary artery anomalies, myocardial bridging, aortic stenosis, mitral valve prolapse, and Marfan syndrome. ECG seems to increase the sensitivity of the PPE from 2.5-6% to 50-95%. Overall sensitivity appears to be about 50%; false-positive rates can be as high as 40%, and there is at least a 4-5% false-negative rate. In Europe, ECG-based screening programs have been associated with a decline in the SCD rate in young athletes, but similar programs are currently not recommended in the United States for many reasons: lack of randomized trial data; cost of screening; lack of a clear standard for ECG interpretation in the athlete; the likelihood that asymptomatic athletes with underlying lethal conditions might differ significantly from symptomatic individuals with the same conditions; and concern that ECG screening might actually increase the death rate, via treatment-related procedural complications. CONCLUSIONS:: Although some authorities advocate the use of ECG screening of young athletes, further studies are required to define what constitutes a normal ECG in athletes, and to determine whether ECG-based screening protocols truly are superior, not only in finding disease, but also saving lives. For those who either choose ECG-based screening or interpret ECG in athletes, we propose a simple interpretation scheme and decision tree. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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11. The dual roles of neutrophils and macrophages in inflammation: a critical balance between tissue damage and repair.
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Butterfield TA, Best TM, and Merrick MA
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Objective: To discuss the acute phase of inflammatory response with a focus on the neutrophilic response and its role in inflammation. We discuss the relative balance between the need for inflammation to stimulate repair and the need to limit inflammation because of the additional damage it causes. Data Sources: We conducted a MEDLINE search from 1966 to 2005 for literature related to acute inflammation, muscle injury, and repair using combinations of the key words inflammation, neutrophil, macrophage, and cytokines. Additional literature was acquired through cross-referencing of bibliographies of articles obtained through the MEDLINE searches. Data Synthesis: We reviewed more than 200 relevant articles. Although neutrophils are an important cell population in acute inflammation, few athletic trainers are familiar with the neutrophil's actions or its dichotomous role as both perpetrator of tissue damage and initiator of repair. Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage by macrophages. These actions are orchestrated by numerous cytokines and the expression of their receptors, which represent a potential means for inhibiting selective aspects of inflammation. Conclusions: Neutrophils infiltrate injured tissues but can also be present after noninjurious exercise. These cells have both specific and nonspecific defensive immune system functions that can cause tissue damage in isolation or as sequelae to other tissue injury. It might seem that limiting the action of neutrophils would be clinically beneficial, but these cells are also responsible for initiating the reparative process that is later managed by macrophages. Although achieving a therapeutic balance between limiting inflammation and stimulating repair is important, the duplicitous roles of neutrophils and macrophages in both the inflammation and healing processes create a physiologic paradox for clinicians whose goals are to limit inflammation and to stimulate healing after acute soft tissue injury. [ABSTRACT FROM AUTHOR]
- Published
- 2006
12. Fatigue and muscle-tendon stiffness after stretch-shortening cycle and isometric exercise.
- Author
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Toumi H, Poumarat G, Best TM, Martin A, Fairclough J, and Benjamin M
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- 2006
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13. Upper limb dynamic responses to impulsive forces for selected assembly workers.
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Sesto ME, Radwin RG, Block WF, and Best TM
- Abstract
This study evaluated the upper limb, dynamic, mechanical response parameters for 14 male assembly workers recruited from selected jobs based on power tool use. It was hypothesized that the type of power tool operation would affect stiffness, effective mass, and damping of the upper extremity; and workers with symptoms and positive physical examination findings would have different mechanical responses than asymptomatic workers without physical examination findings. Participants included operators who regularly used torque reaction power hand tools, such as nutrunners and screwdrivers, and nontorque reaction power hand tools, such as riveters. The mechanical parameters of the upper limb were characterized from the loading response of an apparatus having known dynamic properties while worker grasps an oscillating handle in free vibration. In addition, all workers underwent a physical examination, magnetic resonance imaging, and completed a symptom survey. Workers were categorized as controls or cases based on reported forearm symptoms and physical exam findings. A total of seven workers were categorized as cases and had less average mechanical stiffness (46%, p > 0.01), damping (74%, p > 0.01), and effective mass (59%, p > 0.05) than the seven workers categorized as controls. Magnetic resonance imaging (MRI) findings suggestive of muscle edema were observed for two workers classified as cases and who regularly used torque reaction power tools. No MRI enhancement was observed in the seven subjects who did not regularly use torque reaction power tools. The ergonomic consequences of less stiffness, effective mass, and damping in symptomatic workers may include reduced capacity to react against rapidly building torque reaction forces encountered when operating power hand tools. [ABSTRACT FROM AUTHOR]
- Published
- 2006
14. Return to play following muscle strains.
- Author
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Orchard J, Best TM, and Verrall GM
- Abstract
OBJECTIVE: To assess return to play strategies following muscle strains with the desired outcomes of decreased competition play lost and minimized risk for recurrent injury. METHODS: Literature review of previous studies that examine return to play criteria for the commonly seen muscle strain injuries in sport. RESULTS: There have been no studies directly comparing different return to play approaches. Studies have instead concentrated on recurrence risk factors and prognosis assessment, particularly for hamstring injuries. There is some literature support for risk factors for recurrence such as persisting strength deficits, larger injuries seen on diagnostic imaging, players in high-risk positions or sports, inability to complete functional tasks without pain, and strains of specific high-risk muscles (biceps femoris, central tendon of rectus femoris, medial head of gastrocnemius, adductor longus or magnus). CONCLUSIONS: There are no consensus guidelines or agreed-upon criteria for safe return to sport following muscle strains that completely eliminate the risk for recurrence and maximize performance. At this time, it may be a sensible strategy to allow earlier return to play in team sports and accept a low to moderate injury recurrence rate. Improved prognostic assessment of muscle strains with injury identification (MRI) and injury assessment (isokinetic testing) may be assist practitioners to lower, but not eliminate, recurrent injuries. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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15. A systematic review of prolotherapy for chronic musculoskeletal pain.
- Author
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Rabago D, Best TM, Beamsley M, and Patterson J
- Abstract
OBJECTIVE: Prolotherapy, an injection-based treatment of chronic musculoskeletal pain, has grown in popularity and has received significant recent attention. The objective of this review is to determine the effectiveness of prolotherapy for treatment of chronic musculoskeletal pain. DATA SOURCES: We searched Medline, PreMedline, Embase, CINAHL, and Allied and Complementary Medicine with search strategies using all current and historical names for prolotherapy and injectants. Reference sections of included articles were scanned, and content area specialists were consulted. STUDY SELECTION: All published studies involving human subjects and assessing prolotherapy were included. MAIN RESULTS: Data from 34 case reports and case series and 2 nonrandomized controlled trials suggest prolotherapy is efficacious for many musculoskeletal conditions. However, results from 6 randomized controlled trials (RCTs) are conflicting. Two RCTs on osteoarthritis reported decreased pain, increased range of motion, and increased patellofemoral cartilage thickness after prolotherapy. Two RCTs on low back pain reported significant improvements in pain and disability compared with control subjects, whereas 2 did not. All studies had significant methodological limitations. CONCLUSIONS: There are limited high-quality data supporting the use of prolotherapy in the treatment of musculoskeletal pain or sport-related soft tissue injuries. Positive results compared with controls have been reported in nonrandomized and randomized controlled trials. Further investigation with high-quality randomized controlled trials with noninjection control arms in studies specific to sport-related and musculoskeletal conditions is necessary to determine the efficacy of prolotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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16. Common overuse tendon problems: a review and recommendations for treatment.
- Author
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Wilson JJ and Best TM
- Abstract
There is a common misconception that symptomatic tendon injuries are inflammatory; because of this, these injuries often are mislabeled as 'tendonitis.' Acute inflammatory tendinopathies exist, but most patients seen in primary care will have chronic symptoms suggesting a degenerative condition that should be labeled as 'tendinosus' or 'tendinopathy.' Accurate diagnosis requires physicians to recognize the historical features, anatomy, and useful physical examination maneuvers for these common tendon problems. The natural history is gradually increasing load-related localized pain coinciding with increased activity. The most common overuse tendinopathies involve the rotator cuff, medial and lateral elbow epicondyles, patellar tendon, and Achilles tendon. Examination should include thorough inspection to assess for swelling, asymmetry, and erythema of involved tendons; range-of-motion testing; palpation for tenderness; and examination maneuvers that simulate tendon loading and reproduce pain. Plain radiography, ultrasonography, and magnetic resonance imaging can be helpful if the diagnosis remains unclear. Most patients with overuse tendinopathies (about 80 percent) fully recover within three to six months, and outpatient treatment should consist of relative rest of the affected area, icing, and eccentric strengthening exercises. Although topical and systemic nonsteroidal anti-inflammatory drugs are effective for acute pain relief, these cannot be recommended in favor of other analgesics. Injected corticosteroids also can relieve pain, but these drugs should be used with caution. Ultrasonography, shock wave therapy, orthotics, massage, and technique modification are treatment options, but few data exist to support their use at this time. Surgery is an effective treatment that should be reserved for patients who have failed conservative therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2005
17. Hamstring muscle kinematics during treadmill sprinting.
- Author
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Thelen DG, Chumanov ES, Hoerth DM, Best TM, Swanson SC, Li L, Young M, and Heiderscheit BC
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- 2005
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18. Muscle plasticity after weight and combined (weight + jump) training.
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Toumi H, Best TM, Martin A, and Poumarat G
- Abstract
PURPOSE: The purpose of this study was to compare the effects of jump training as a complement to weight training on jump performance and muscle strategy during the squat and countermovement jump. METHOD: Twenty-two male handball players, between the ages of 17 and 24, and in good health, were randomly divided into three groups. Two were trained groups, weight training (WTG) and jump training combined with weight training (CTG), and one was a control group (CG). Maximal isometric force and maximal concentric power were assessed by a supine leg press, squat jump (SJ), counter movement jump (CMJ), and surface EMG was used to determine changes in muscle adaptation before and after the training period. RESULTS: After 6-wk training programs, the two training groups increased maximal isometric force, maximal concentric power, and squat jump performance. However, only combined training presented a significant increase in height jump performance during the countermovement jump (P < 0.05). EMG analysis (as interpreted through the root mean square values) showed that the SJ was performed similarly before and after the training period for the two training groups. However, during the CMJ, only the CTG group adopted a new technique manifested by a short transition phase together with an increase in knee joint stiffness and knee extensor muscle activation and rectus femoris ratio. CONCLUSION: It was suggested that the central activities in knee joint during the transition phase, in conjunction with intrinsic muscle contractile properties, play a major role in the regulation of performance during a CMJ. Furthermore, our study suggests that a change in maximal strength and/or explosive strength does not necessarily cause changes in combined movement such as the stretch shortening cycle. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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19. The painful shoulder: part II. Acute and chronic disorders.
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Woodward TW, Best TM, and Scheckler WE
- Abstract
Fractures of the humerus, scapula and clavicle usually result from a direct blow or a fall onto an outstretched hand. Most can be treated by immobilization. Dislocation of the humerus, strain or sprain of the acromioclavicular and sternoclavicular joints, and rotator cuff injury often can be managed conservatively. Recurrence is a problem with humerus dislocation, and surgical management may be indicated if conservative treatment fails. Rotator cuff tears are often hard to diagnose because of muscle atrophy that impairs the patient's ability to perform diagnostic maneuvers. Chronic shoulder problems usually fall into one of several categories, which include impingement syndrome, frozen shoulder and biceps tendonitis. Other causes of chronic shoulder pain are labral injury, osteoarthritis of the glenohumeral or acromioclavicular joint and, rarely, osteolysis of the distal clavicle. [ABSTRACT FROM AUTHOR]
- Published
- 2000
20. The painful shoulder: part I. Clinical evaluation.
- Author
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Woodward TW, Best TM, Schekler WE, Woodward, T W, and Best, T M
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Family physicians need to understand diagnostic and treatment strategies for common causes of shoulder pain. We review key elements of the history and physical examination and describe maneuvers that can be used to reach an appropriate diagnosis. Examination of the shoulder should include inspection, palpation, evaluation of range of motion and provocative testing. In addition, a thorough sensorimotor examination of the upper extremity should be performed, and the neck and elbow should be evaluated. [ABSTRACT FROM AUTHOR]
- Published
- 2000
21. Hyperbaric oxygen in the treatment of acute muscle stretch injuries: results in an animal model.
- Author
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Best TM, Loitz-Ramage B, Corr DT, and Vanderby R Jr.
- Abstract
Hyperbaric oxygen therapy is an established therapy in several areas of clinical medicine. However, studies have produced conflicting results regarding its efficacy for sports-related soft tissue injuries. This study examines the use of hyperbaric oxygen therapy after an acute muscle stretch injury in an animal model. Two groups of rabbits (nine in each group) were subjected to a partial stretch injury to the tibialis anterior muscle-tendon unit. For all 18 animals, the injuries were induced in the left limb, and the uninjured right limb served as a sham-operated control. In group 1, the animals were exposed to hyperbaric oxygen (> 95% O2 at 2.5 atm) for 60 minutes daily for 5 days. Treatment began 24 hours after injury. Group 2 animals were not exposed to hyperbaric oxygen. Evaluation 7 days after injury demonstrated a functional deficit (percent ankle isometric torque; injured side versus uninjured side) of 14.9% +/- 5.5% (mean +/- SD) for the treated group and 47.5% +/- 5.4% for the untreated group, representing a statistical difference using the Behrens-Fisher version of the t test (P = 0.001). Morphologic studies revealed more complete healing in the treated group. This study suggests that hyperbaric oxygen therapy may play a role in accelerating recovery after acute muscle stretch injury. Further studies are needed before definitive conclusions and treatment recommendations can be made. [ABSTRACT FROM AUTHOR]
- Published
- 1998
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22. An explanation for various rectus femoris strain injuries using previously undescribed muscle architecture.
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Hasselman CT, Best TM, Hughes C IV, Martinez S, and Garrett WE Jr.
- Abstract
We performed cadaveric dissection of the rectus femoris muscle to correlate the various lesions of strain injury seen with imaging studies to the muscular anatomy. The proximal tendon is composed of a superficial, anterior portion from the direct head, and a deep intramuscular portion from the indirect head. The muscle fibers arising from the anterior superficial tendon of the direct head travel in a posterior and distal direction to insert on the posterior tendon of insertion, giving the proximal muscle a unipennate architecture. Muscle fibers from the intramuscular tendon of the indirect head originate on both the medial and lateral sides of the tendon and insert on the distal posterior tendon to create its bipennate structure. Three chronic strain injuries involving the midmuscle belly substance were explored grossly and microscopically. It appears that one type of acute strain injury occurs in the midmuscle belly with disruption of the muscle-tendon junction of the intramuscular tendon resulting in local hemorrhage and edema. More chronically, this hematoma organizes into a fatty, loose connective tissue encasement of the deep intramuscular proximal tendon. Serous fluid from the hematoma may remain within the connective tissue sheath, creating a pseudocyst with the deep intramuscular tendon of the indirect head at its center. The muscle's anatomy helps to explain a different rectus femoris strain injury. [ABSTRACT FROM AUTHOR]
- Published
- 1995
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23. A threshold and continuum of injury during active stretch of rabbit skeletal muscle... including commentary by Jokl P... presented at the interim meeting of the AOSSM, New Orleans, Louisiana, February 27, 1994.
- Author
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Hasselman CT, Best TM, Seaber AV, and Garrett WE Jr.
- Abstract
Previous studies of acute muscle injury with active stretch used cyclic stretching or stretching the muscle to complete muscle-tendon dissociation. This study tried to determine minimal force required for skeletal muscle injury with one active stretch to establish an injury 'threshold.' Tibialis anterior and extensor digitorum longus rabbit muscles were actively stretched at 10 cm/ sec to 60%, 70%, 80%, or 90% of the force required to passively fail tibialis anterior and extensor digitorum longus muscles of the control (contralateral) limb. Maximal isometric contractile force, tensile properties, histology, and electromyography were measures of injury. Both muscles of the 60% group showed no abnormalities in maximal isometric contractile force, tensile properties, histology, or electromyographic activity; 70%, 80%, and 90% groups showed diminished maximal isometric contractile force, muscle fiber disruption, edema, hemorrhage, and decreased electromyographic maximal voltage amplitude. The 90% group also showed alterations in tensile properties at failure along with connective tissue damage. Injury site included fiber disruption both at the distal myotendinous junction and muscle belly, with injury noted initially at the distal myotendinous junction in the 70% group. Electromyographic studies showed maximal isometric contractile force and maximal voltage correlated well as indices of damage. This study shows that a threshold and continuum for active stretch-induced injury exist, with muscle fiber disruption occurring initially and connective tissue disruption occurring only with larger muscle displacements. [ABSTRACT FROM AUTHOR]
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- 1995
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24. Hamstring strains: expediting return to play [corrected] [published erratum appears in PHYSICIAN SPORTSMED 1996 Nov; 24(11): 95].
- Author
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Best TM and Garrett WE Jr.
- Abstract
Strains to the hamstring muscle group are prevalent and, unfortunately, often recurrent, with prolonged rehabilitation and persistent disability. Most hamstring injuries are of a single muscle near the muscle-tendon junction. Rarely, the hamstring muscle group may avulse from the ischial tuberosity. The diagnosis can usually be made by history and physical exam, but MRI can be used to help pinpoint the extent and location of the injury. Initial treatment typically consists of rest, ice, compression, elevation, and pain relief. There is no consensus on optimal rehabilitation, but functional exercises with stretching and strengthening have been emphasized. [ABSTRACT FROM AUTHOR]
- Published
- 1996
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25. The adolescent knee and risk for osteoarthritis - an opportunity or responsibility for sport medicine physicians?
- Author
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Bout-Tabaku S and Best TM
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- 2010
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26. Guest editorial. The management of muscle strain injuries: an early return versus the risk of recurrence.
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Orchard J and Best TM
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- 2002
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27. A growing concern: the older athlete.
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Best TM and Hart L
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- 2008
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28. From study design and analysis to conclusion: new horizons for epidemiological rigor in sport medicine.
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Best TM and Shrier I
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- 2007
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29. The pediatric athlete -- are we doing the right thing?
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Best TM, van Mechelen W, and Verhagen E
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- 2006
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30. Corticosteroid injection compared with extracorporeal shock wave therapy for plantar fasciopathy.
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Borchers JR and Best TM
- Published
- 2006
31. Return to play: the sideline dilemma.
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Best TM and Brolinson PG
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- 2005
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32. Accelerated rehabilitation after anterior cruciate ligament reconstruction.
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Kaeding C and Best TM
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- 2005
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33. Anthropometric and performance measures for high school basketball players.
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Greene JJ, McGuine TA, Leverson G, and Best TM
- Abstract
Objective: To determine possible anthropometric and performance sex differences in a population of high school basketball players. Design and Setting: Measurements were collected during the first week of basketball practice before the 1995-1996 season. Varsity basketball players from 4 high schools were tested on a battery of measures chosen to detect possible anthropometric and performance sex differences. Subjects: Fifty-four female and sixty-one male subjects, from varsity basketball teams at high schools enrolled in the athletic training outreach program at the University of Wisconsin Hospital Sports Medicine Center in Madison, WI, volunteered to take part in this study. Measurements: We took anthropometric measurements on each of the 115 subjects. These included height, weight, body composition, ankle range of motion, and medial longitudinal arch type in weightbearing. Performance measures included the vertical jump, 22.86-m (25-yd) shuttle run, 18.29-m (20-yd) sprint, and single-limb balance time. Results: We compared anthropometric and performance characteristics using a 2-sample t test. The only exception to this was for medial longitudinal arch type, where the 2 groups were compared using a 2-tailed Fisher's exact test. The male subjects were significantly taller and heavier, while the females had a significantly higher percentage of body fat. There were no significant differences found for ankle plantar flexion and dorsiflexion, but the females had significantly more inversion and eversion range of motion. Analysis of medial longitudinal arch type found females to have a higher percentage of pronated arches and males to have a higher percentage of supinated arches. Performance testing revealed that the males were able to jump significantly higher and run the 22.86-m (25-yard) shuttle run and 18.29-m (20-yard) sprint significantly faster than the female subjects. There was no significant difference between the groups for single-limb balance time. Conclusions: We found significant anthropometric and performance sex differences in a cohort of high school basketball players. Further study of these measures is necessary to determine if these differences can predict the risk for ankle injuries in this particular population. [ABSTRACT FROM AUTHOR]
- Published
- 1998
34. Cell-based therapy in the treatment of musculoskeletal diseases.
- Author
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Trapana J, Weinerman J, Lee D, Sedani A, Constantinescu D, Best TM, Hornicek FJ Jr, and Hare JM
- Abstract
A limited number of tissues can spontaneously regenerate following injury, and even fewer can regenerate to a state comparable to mature, healthy adult tissue. Mesenchymal stem cells (MSCs) were first described in the 1960s-1970s by Friedenstein et al as a small population of bone marrow cells with osteogenic potential and abilities to differentiate into chondrocytes. In 1991, Arnold Caplan coined the term "mesenchymal cells" after identifying these cells as a theoretical precursor to bone, cartilage, tendon, ligament, marrow stroma, adipocyte, dermis, muscle, and connective tissues. MSCs are derived from periosteum, fat, and muscle. Another attractive property of MSCs is their immunoregulatory and regenerative properties, which result from crosstalk with their microenvironment and components of the innate immune system. Collectively, these properties make MSCs potentially attractive for various therapeutic purposes. MSCs offer potential in sports medicine, aiding in muscle recovery, meniscal tears, and tendon and ligament injuries. In joint disease, MSCs have the potential for chondrogenesis and reversing the effects of osteoarthritis. MSCs have also demonstrated potential application to the treatment of degenerative disc disease of the cervical, thoracic, and lumbar spine., (© The Author(s) 2024. Published by Oxford University Press.)
- Published
- 2024
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35. A hop testing alternative for functional performance following anterior cruciate ligament reconstruction.
- Author
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Ripic Z, Letter M, Schoenwether B, Kaplan LD, Baraga MG, Costello Ii JP, Eskenazi J, Dennison M, Best TM, Signorile JF, and Eltoukhy M
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- Humans, Male, Female, Adult, Young Adult, Exercise Test methods, Anterior Cruciate Ligament Injuries surgery, Anterior Cruciate Ligament Injuries physiopathology, Quadriceps Muscle physiology, Quadriceps Muscle physiopathology, Physical Functional Performance, Adolescent, Anterior Cruciate Ligament surgery, Anterior Cruciate Ligament physiopathology, Hamstring Muscles physiopathology, Hamstring Muscles physiology, Anterior Cruciate Ligament Reconstruction methods, Muscle Strength physiology, Torque
- Abstract
The purpose of this work was to provide a simple method to determine reactive strength during the 6-meter timed hop test (6mTH) and evaluate its association with isokinetic peak torque in patients following anterior cruciate ligament reconstruction (ACLR). Twenty-nine ACLR patients who were at least four months from surgery were included in this analysis. Participants were brought into the laboratory on one occasion to complete functional testing. Quadriceps and hamstring isokinetic testing was completed bilaterally at 60, 180, and 300 deg∙s-1, using extension peak torque from each speed as the outcome measure. The 6mTH was completed bilaterally using a marker-based motion capture system, and reactive strength ratio (RSR) was calculated from the vertical velocity of the pelvis during the test. An adjustment in RSR was made using the velocity of the 6mTH test to account for different strategies employed across participants. Repeated measures correlations were used to determine associations among isokinetic and hop testing variables. A two-way mixed analysis of variance was used to determine differences in isokinetic and hop testing variables between operated and non-operated legs and across male and female participants. Moderate positive associations were found between RSR (and adjusted RSR) and isokinetic peak torque at all speeds (r = .527 to .577). Mean comparisons showed significant main effects for leg and sex. Patients showed significant deficits in their operated versus non-operated legs in all isokinetic and hop testing variables, yet only isokinetic peak torque and timed hop time showed significant differences across male and female groups. Preliminary results are promising but further development is needed to validate other accessible technologies available to calculate reactive strength during functional testing after ACLR. Pending these developments, the effects of movement strategies, demographics, and levels of participation on RSR can then be explored to translate this simple method to clinical environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ripic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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36. Investigating the association between knee osteoarthritis symptoms with pain catastrophizing domains between Hispanics and non-Hispanic Whites.
- Author
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Nemati D, Quintero D, Best TM, and Kaushal N
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Arthralgia psychology, Arthralgia ethnology, Arthralgia physiopathology, Health Status Disparities, Pain Measurement, Severity of Illness Index, Catastrophization psychology, Catastrophization ethnology, Hispanic or Latino psychology, Osteoarthritis, Knee psychology, Osteoarthritis, Knee ethnology, Osteoarthritis, Knee physiopathology, White psychology
- Abstract
Knee osteoarthritis (KOA) is a chronic disease accompanied by debilitating symptoms including pain, stiffness, and limited physical functionality, which have been shown to be associated with pain catastrophizing. Previous studies have revealed racial discrepancies in pain catastrophizing, notably between Hispanics and non-Hispanics while pointing to potential health disparities. Using a conceptual model, this study aimed to investigate racial differences in associations between KOA symptoms with specific pain catastrophizing domains (rumination, magnification, and helplessness). Patients with KOA (n = 253; 147 Hispanics, 106 non-Hispanic Whites) completed a survey that included measures of knee symptoms, pain catastrophizing, and demographic variables. Structural equation modeling revealed that among Hispanics, each pain catastrophizing domain (rumination, magnification, and helplessness) was associated with at least two symptomatic experiences, including pain severity and difficulty in physical function. Specifically, pain severity was associated with (a) rumination: β = 0.48, p < 0.001, (b) magnification: β = 0.31, p = 0.003; and (c) helplessness: β = 0.39, p < 0.001). Additionally, a lower score in physical function was associated with higher magnification (β = 0.26, p = 0.01), and helplessness (β = 0.25, p = 0.01). Among non-Hispanic White patients, pain severity was further associated with two domains of pain catastrophizing, including rumination (β = 0.39, p < 0.001) and helplessness (β = 0.35, p = 0.01). In addition, association pathways for demographic variables revealed that older Hispanics experienced greater challenges with higher pain severity (β = 0.26, p = 0.01) and greater difficulty with physical function (β = 0.31, p < 0.001) while Hispanics females experienced higher pain (β = 0.19, p = 0.03). These findings highlight the importance of designing tailored interventions that consider key demographic factors such as age, and gender, to improve physical function that might alleviate pain catastrophizing among Hispanics with KOA., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
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37. Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review.
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Gardashli M, Baron M, Huang C, Kaplan LD, Meng Z, Kouroupis D, and Best TM
- Abstract
The importance of mechanical loading and its relationship to orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA) is beginning to receive attention. This review explores the current efficacy of orthobiologic interventions, notably platelet-rich plasma (PRP), bone marrow aspirate (BMA), and mesenchymal stem/stromal cells (MSCs), in combating PTOA drawing from a comprehensive review of both preclinical animal models and human clinical studies. This review suggests why mechanical joint loading, such as running, might improve outcomes in PTOA management in conjunction with orthiobiologic administration. Accumulating evidence underscores the influence of mechanical loading on chondrocyte behavior and its pivotal role in PTOA pathogenesis. Dynamic loading has been identified as a key factor for optimal articular cartilage (AC) health and function, offering the potential to slow down or even reverse PTOA progression. We hypothesize that integrating the activation of mechanotransduction pathways with orthobiologic treatment strategies may hold a key to mitigating or even preventing PTOA development. Specific loading patterns incorporating exercise and physical activity for optimal joint health remain to be defined, particularly in the clinical setting following joint trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gardashli, Baron, Huang, Kaplan, Meng, Kouroupis and Best.)
- Published
- 2024
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38. Hippo-PKCζ-NFκB signaling axis: A druggable modulator of chondrocyte responses to mechanical stress.
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Cai X, Warburton C, Perez OF, Wang Y, Ho L, Finelli C, Ehlen QT, Wu C, Rodriguez CD, Kaplan L, Best TM, Huang CY, and Meng Z
- Abstract
Recent studies have implicated a crucial role of Hippo signaling in cell fate determination by biomechanical signals. Here we show that mechanical loading triggers the activation of a Hippo-PKCζ-NFκB pathway in chondrocytes, resulting in the expression of NFκB target genes associated with inflammation and matrix degradation. Mechanistically, mechanical loading activates an atypical PKC, PKCζ, which phosphorylates NFκB p65 at Serine 536, stimulating its transcriptional activation. This mechanosensitive activation of PKCζ and NFκB p65 is impeded in cells with gene deletion or chemical inhibition of Hippo core kinases LATS1/2, signifying an essential role of Hippo signaling in this mechanotransduction. A PKC inhibitor AEB-071 or PKCζ knockdown prevents p65 Serine 536 phosphorylation. Our study uncovers that the interplay of the Hippo signaling, PKCζ, and NFκB in response to mechanical loading serves as a therapeutic target for knee osteoarthritis and other conditions resulting from mechanical overloading or Hippo signaling deficiencies., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)
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- 2024
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39. Cellular and Structural Changes in Achilles and Patellar Tendinopathies: A Pilot In Vivo Study.
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Kouroupis D, Perucca Orfei C, Correa D, Talò G, Libonati F, De Luca P, Raffo V, Best TM, and de Girolamo L
- Abstract
Tendinopathies continue to be a challenge for both patients and the medical teams providing care as no universal clinical practice guidelines have been established. In general, tendinopathies are typically characterized by prolonged, localized, activity-related pain with abnormalities in tissue composition, cellularity, and microstructure that may be observed on imaging or histology. In the lower limb, tendinopathies affecting the Achilles and the patellar tendons are the most common, showing a high incidence in athletic populations. Consistent diagnosis and management have been challenged by a lack of universal consensus on the pathophysiology and clinical presentation. Current management is primarily based on symptom relief and often consists of medications such as non-steroidal anti-inflammatories, injectable therapies, and exercise regimens that typically emphasize progressive eccentric loading of the affected structures. Implementing the knowledge of tendon stem/progenitor cells (TSPCs) and assessing their potential in enhancing tendon repair could fill an important gap in this regard. In the present pilot in vivo study, we have characterized the structural and cellular alterations that occur soon after tendon insult in models of both Achilles and patellar tendinopathy. Upon injury, CD146
+ TSPCs are recruited from the interfascicular tendon matrix to the vicinity of the paratenon, whereas the observed reduction in M1 macrophage polarization is related to a greater abundance of reparative CD146+ TSPCs in situ. The robust TSPCs' immunomodulatory effects on macrophages were also demonstrated in in vitro settings where TSPCs can effectively polarize M1 macrophages towards an anti-inflammatory therapeutic M2 phenotype. Although preliminary, our findings suggest CD146+ TSPCs as a key phenotype that could be explored in the development of targeted regenerative therapies for tendinopathies.- Published
- 2024
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40. Assessing the role of surface layer and molecular probe size in diffusion within meniscus tissue.
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Schwartz G, Best TM, Chen CB, Travascio F, and Jackson AR
- Subjects
- Animals, Swine, Menisci, Tibial physiology, Fibrocartilage metabolism, Fluoresceins metabolism, Dextrans metabolism, Meniscus metabolism
- Abstract
Diffusion within extracellular matrix is essential to deliver nutrients and larger metabolites to the avascular region of the meniscus. It is well known that both structure and composition of the meniscus vary across its regions; therefore, it is crucial to fully understand how the heterogenous meniscal architecture affects its diffusive properties. The objective of this study was to investigate the effect of meniscal region (core tissue, femoral, and tibial surface layers) and molecular weight on the diffusivity of several molecules in porcine meniscus. Tissue samples were harvested from the central area of porcine lateral menisci. Diffusivity of fluorescein (MW 332 Da) and three fluorescence-labeled dextrans (MW 3k, 40k, and 150k Da) was measured via fluorescence recovery after photobleaching. Diffusivity was affected by molecular size, decreasing as the Stokes' radius of the solute increased. There was no significant effect of meniscal region on diffusivity for fluorescein, 3k and 40k dextrans (p>0.05). However, region did significantly affect the diffusivity of 150k Dextran, with that in the tibial surface layer being larger than in the core region (p = 0.001). Our findings contribute novel knowledge concerning the transport properties of the meniscus fibrocartilage. This data can be used to advance the understanding of tissue pathophysiology and explore effective approaches for tissue restoration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schwartz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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41. Modification of Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles by Calcitonin Gene Related Peptide (CGRP) Antagonist: Potential Implications for Inflammation and Pain Reversal.
- Author
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Liebmann K, Castillo MA, Jergova S, Best TM, Sagen J, and Kouroupis D
- Subjects
- Humans, Calcitonin Gene-Related Peptide metabolism, Substance P, Inflammation, Pain, Anti-Inflammatory Agents, Stromal Cells metabolism, Extracellular Vesicles metabolism, MicroRNAs
- Abstract
During the progression of knee osteoarthritis (OA), the synovium and infrapatellar fat pad (IFP) can serve as source for Substance P (SP) and calcitonin gene-related peptide (CGRP), two important pain-transmitting, immune, and inflammation modulating neuropeptides. Our previous studies showed that infrapatellar fat pad-derived mesenchymal stem/stromal cells (MSC) acquire a potent immunomodulatory phenotype and actively degrade Substance P via CD10 both in vitro and in vivo. On this basis, our hypothesis is that CD10-bound IFP-MSC sEVs can be engineered to target CGRP while retaining their anti-inflammatory phenotype. Herein, human IFP-MSC cultures were transduced with an adeno-associated virus (AAV) vector carrying a GFP-labelled gene for a CGRP antagonist peptide (aCGRP). The GFP positive aCGRP IFP-MSC were isolated and their sEVs' miRNA and protein cargos were assessed using multiplex methods. Our results showed that purified aCGRP IFP-MSC cultures yielded sEVs with cargo of 147 distinct MSC-related miRNAs. Reactome analysis of miRNAs detected in these sEVs revealed strong involvement in the regulation of target genes involved in pathways that control pain, inflammation and cartilage homeostasis. Protein array of the sEVs cargo demonstrated high presence of key immunomodulatory and reparative proteins. Stimulated macrophages exposed to aCGRP IFP-MSC sEVs demonstrated a switch towards an alternate M2 status. Also, stimulated cortical neurons exposed to aCGRP IFP-MSC sEVs modulate their molecular pain signaling profile. Collectively, our data suggest that yielded sEVs can putatively target CGRP in vivo, while containing potent anti-inflammatory and analgesic cargo, suggesting the promise for novel sEVs-based therapeutic approaches to diseases such as OA.
- Published
- 2024
- Full Text
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42. Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients.
- Author
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Baron M, Drohat P, Crawford B, Hornicek FJ, Best TM, and Kouroupis D
- Abstract
Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone regeneration arise. To determine the appropriate amount of bone to be removed, preoperative imaging techniques such as bone and CT scans are employed. To prevent local recurrence, the current standard of care suggests maintaining bony and soft tissue margins from 3 to 7 cm beyond the tumor. The amount of bone removed in an OS patient leaves too large of a deficit for bone to form on its own and requires reconstruction with metal implants or allografts. Both methods require the bone to heal, either to the implant or across the allograft junction, often in the setting of marrow-killing chemotherapy. Therefore, the issue of bone regeneration within the surgically resected margins remains an important challenge for the patient, family, and treating providers. Mesenchymal stem/stromal cells (MSCs) are potential agents for enhancing bone regeneration post tumor resection. MSCs, used with scaffolds and growth factors, show promise in fostering bone regeneration in OS cases. We spotlight two MSC types-bone marrow-derived (BM-MSCs) and adipose tissue-derived (ASCs)-highlighting their bone regrowth facilitation and immunomodulatory effects on immune cells like macrophages and T cells, enhancing therapeutic outcomes. The objective of this review is two-fold: review work demonstrating any ability of MSCs to target the deranged immune system in the OS microenvironment, and synthesize the available literature on the use of MSCs as a therapeutic option for stimulating bone regrowth in OS patients post bone resection. When it comes to repairing bone defects, both MB-MSCs and ASCs hold great potential for stimulating bone regeneration. Research has showcased their effectiveness in reconstructing bone defects while maintaining a non-tumorigenic role following wide resection of bone tumors, underscoring their capability to enhance bone healing and regeneration following tumor excisions.
- Published
- 2023
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43. Impact of Quadriceps Tendon Graft Thickness on Electromechanical Delay and Neuromuscular Performance After ACL Reconstruction.
- Author
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Parrino RL, Adams W, Letter MI, Ripic Z, Baraga MG, Kaplan LD, Harrah T, Tremblay J, Luxenburg D, Conti J, Best TM, and Signorile JF
- Abstract
Background: Both partial- and full-thickness quadriceps tendon (QT) graft harvests are used for anterior cruciate ligament reconstruction (ACLR)., Purpose: To evaluate the impact of QT graft harvest depth (full or partial thickness) on electromechanical delay (EMD), peak torque (PT), and rate of torque development (RTD) after ACLR., Study Design: Controlled laboratory study., Methods: A total of 26 patients who underwent either partial-thickness (n = 14) or full-thickness (n = 12) autograft QT ACLR were recruited between June and November 2021 (>1 year before participation). Patients performed isokinetic knee extension testing with surface electromyography of the quadriceps muscles. Mixed repeated-measures analysis of variance with least significant difference post hoc testing was used to determine significant differences (mean difference [MD] ± SE) or interactions for all variables., Results: A significant speed×depth interaction was seen for the vastus medialis ( P = .005). Pairwise analyses showed significantly longer EMD for the partial-thickness graft than the full-thickness graft (MD ± SE, 19.92 ± 6.33 ms; P = .006). In the partial-thickness graft, the EMD was significantly longer at 90 deg/s versus 180 deg/s (MD ± SE, 19.11 ± 3.95 ms; P < .001) and 300 deg/s (MD ± SE, 16.43 ± 5.30 ms; P = .006). For PT, the full-thickness graft had a significantly lower PT on the operated versus nonoperated side at all speeds (MD ± SE: 90 deg/s, -57.0 ± 10.5 N·m, P < .001; 180 deg/s, -26.0 ± 10.2 N·m, P = .020; 300 deg/s, -20.3 ± 8.9 N·m, P = .034). For RTD, the full-thickness graft showed significantly Slower RTD for the operated versus nonoperated side at all time points (MD ± SD: RTD
0-25 (0-25% of the range of motion), -131.3 ± 50.9 N·m/s, P = .018; RTD25-50 , -197.0 ± 72.5 N·m/s, P = .014; RTD50-75 , -113.3 ± 39.8 N·m/s, P = .013; RTD75-100 , -149.4 ± 35.9 N·m/s, P < .001)., Conclusion: Compared with partial-thickness QT, full-thickness QT showed a shorter vastus medialis EMD at higher loading, and therefore greater stiffness, as well as slower RTD and lower PT across all testing speeds., Clinical Relevance: The impact of full-thickness QT autograft on EMD and neuromuscular performance should be considered for ACLR., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.G.B. has received education payments from Southern Edge Orthopaedics, consulting fees from Arthrex and LifeNet Health, nonconsulting fees from Arthrex, and hospitality payments from Smith & Nephew. L.D.K. has received education payments from Southern Edge Orthopaedics, nonconsulting fees from Arthrex, and royalties from Arthrex and Smith & Nephew. T.M.B. has received consulting fees from Bioventus and hospitality payments from GE Healthcare. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)- Published
- 2023
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44. A comparison of three-dimensional kinematics between markerless and marker-based motion capture in overground gait.
- Author
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Ripic Z, Nienhuis M, Signorile JF, Best TM, Jacobs KA, and Eltoukhy M
- Subjects
- Young Adult, Humans, Aged, Adolescent, Adult, Middle Aged, Aged, 80 and over, Biomechanical Phenomena, Gait, Motion, Motion Capture, Parkinson Disease
- Abstract
Vision-based methods using RGB inputs for human pose estimation have grown in recent years but have undergone limited testing in clinical and biomechanics research areas like gait analysis. The purpose of the present study was to compare lower extremity kinematics during overground gait between a traditional marker-based approach and a commercial multi-view markerless system in a sample of subjects including young adults, older adults, and adults diagnosed with Parkinson's disease. A convenience sample of 35 adults between the age of 18-85 years were included in this study, yielding a total of 114 trials and 228 gait cycles that were compared between systems. A total of 30 time normalized waveforms, including three-dimensional joint centers, segment angles, and joint angles were compared between systems using root mean-squared error (RMSE), range of motion difference (ΔROM), Pearson correlation coefficients (r), and interclass correlation coefficients (ICC). RMSEs for joint center positions were less than 28 mm in all joints with correlations indicating good to excellent agreement. RMSEs for segment and joint angles were in range of previous results, with highest agreement between systems in the sagittal plane. ΔROM differences were within reference values that characterize clinical groups like Parkinson's disease, stroke, or knee osteoarthritis. Further improvements in pelvis tracking, markerless keypoint model definitions, and standardization of comparison study protocols are needed. Nevertheless, markerless solutions seem promising toward unrestricted motion analysis in biomechanics research and clinical settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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45. Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles (MSC-sEVs): A Promising Treatment Modality for Diabetic Foot Ulcer.
- Author
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Kouroupis D, Kaplan LD, Ricordi C, and Best TM
- Abstract
Diabetic foot ulcer (DFU) is associated with neuropathy and/or peripheral artery disease of the lower limb in diabetic patients, affecting quality of life and leading to repeated hospitalizations and infections [...].
- Published
- 2023
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46. Prediction of gait kinetics using Markerless-driven musculoskeletal modeling.
- Author
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Ripic Z, Theodorakos I, Andersen MS, Signorile JF, Best TM, Jacobs KA, and Eltoukhy M
- Subjects
- Kinetics, Biomechanical Phenomena, Motion, Gait, Mechanical Phenomena
- Abstract
Video-based motion analysis systems are emerging in the biomechanics research community, yet there is limited exploration of kinetics prediction using RGB-markerless kinematics and musculoskeletal modeling. This project aimed to provide ground reaction force (GRF) and ground reaction moment (GRM) predictions during over-ground gait by introducing RGB-markerless kinematics into a musculoskeletal modeling framework. Full-body markerless kinematic inputs and musculoskeletal modeling were used to obtain GRF and GRM predictions which were compared to measured force plate values. The markerless-driven predictions yielded average root mean-squared error (RMSE) in the stance phase of 0.035 ± 0.009 N∙BW
-1 , 0.070 ± 0.014 N∙BW-1 , and 0.155 ± 0.041 N∙BW-1 in the mediolateral (ML), anteroposterior (AP), and vertical (V) GRFs. This was accompanied by moderate to high correlations and interclass correlation coefficients (ICC) indicating moderate to good agreement between measured and predicted values (95% Confidence Inervals: ML = [0.479, 0.717], AP = [0.714, 0.856], V = [0.803, 0.905]). For ground reaction moments (GRM), average RMSE was 0.029 ± 0.013 Nm∙BWH-1 , 0.014 ± 0.005 Nm∙BWH-1 , and 0.005 ± 0.002 Nm∙BWH-1 in the sagittal, frontal, and transverse planes. Pearson correlations and ICCs indicated poor agreement between systems for GRMs (95% Confidence Intervals: Sagittal = [0.314, 0.608], Frontal = [0.006, 0.373], Transverse = [0.269, 0.570]). Currently, RMSE is larger than target thresholds set from studies using Kinect, inertial, or marker-based kinematic drivers; but methodological considerations highlighted in this work may help guide follow-up iterations. At this point, further use in research or clinical practice is cautioned until methodological considerations are addressed, although results are promising at this point., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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47. CD10-Bound Human Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles Possess Immunomodulatory Cargo and Maintain Cartilage Homeostasis under Inflammatory Conditions.
- Author
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Kouroupis D, Kaplan LD, Huard J, and Best TM
- Subjects
- Animals, Humans, Knee Joint metabolism, Neprilysin metabolism, Fibrosis, Homeostasis, Stromal Cells metabolism, Synovitis metabolism, Osteoarthritis metabolism, Extracellular Vesicles metabolism, MicroRNAs metabolism, Cartilage, Articular metabolism
- Abstract
The onset and progression of human inflammatory joint diseases are strongly associated with the activation of resident synovium/infrapatellar fat pad (IFP) pro-inflammatory and pain-transmitting signaling. We recently reported that intra-articularly injected IFP-derived mesenchymal stem/stromal cells (IFP-MSC) acquire a potent immunomodulatory phenotype and actively degrade substance P (SP) via neutral endopeptidase CD10 (neprilysin). Our hypothesis is that IFP-MSC robust immunomodulatory therapeutic effects are largely exerted via their CD10-bound small extracellular vesicles (IFP-MSC sEVs) by attenuating synoviocyte pro-inflammatory activation and articular cartilage degradation. Herein, IFP-MSC sEVs were isolated from CD10High- and CD10Low-expressing IFP-MSC cultures and their sEV miRNA cargo was assessed using multiplex methods. Functionally, we interrogated the effect of CD10High and CD10Low sEVs on stimulated by inflammatory/fibrotic cues synoviocyte monocultures and cocultures with IFP-MSC-derived chondropellets. Finally, CD10High sEVs were tested in vivo for their therapeutic capacity in an animal model of acute synovitis/fat pad fibrosis. Our results showed that CD10High and CD10Low sEVs possess distinct miRNA profiles. Reactome analysis of miRNAs highly present in sEVs showed their involvement in the regulation of six gene groups, particularly those involving the immune system. Stimulated synoviocytes exposed to IFP-MSC sEVs demonstrated significantly reduced proliferation and altered inflammation-related molecular profiles compared to control stimulated synoviocytes. Importantly, CD10High sEV treatment of stimulated chondropellets/synoviocyte cocultures indicated significant chondroprotective effects. Therapeutically, CD10High sEV treatment resulted in robust chondroprotective effects by retaining articular cartilage structure/composition and PRG4 (lubricin)-expressing cartilage cells in the animal model of acute synovitis/IFP fibrosis. Our study suggests that CD10High sEVs possess immunomodulatory miRNA attributes with strong chondroprotective/anabolic effects for articular cartilage in vivo. The results could serve as a foundation for sEV-based therapeutics for the resolution of detrimental aspects of immune-mediated inflammatory joint changes associated with conditions such as osteoarthritis (OA).
- Published
- 2023
- Full Text
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48. Nonsteroidal Anti-inflammatory and Corticosteroid Injections for Shoulder Impingement Syndrome: A Systematic Review and Meta-analysis.
- Author
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Ziradkar R, Best TM, Quintero D, and Paultre K
- Subjects
- Aged, United States, Humans, Injections, Intra-Articular, Medicare, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Adrenal Cortex Hormones therapeutic use, Pain, Shoulder Impingement Syndrome drug therapy
- Abstract
Context: To determine optimal treatment strategies for shoulder impingement syndrome (SIS)., Objective: To compare subacromial nonsteroidal anti-inflammatory injections (SNIs) and subacromial corticosteroid injections (SCIs) on pain relief and functional improvement in individuals with SIS. Second, to perform a cost analysis of the 2 injections., Data Sources: MEDLINE, SPORTDiscus, CINAHL, Embase, Web of Science, and SCOPUS databases were searched for randomized controlled trials using several keywords., Study Selection: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized, and 10 studies comparing changes in pain or function in humans with SIS receiving SNIs or SCIs were included. Quality and risk of bias were assessed using the Consolidated Standards of Reporting Trials (CONSORT) 2010 scale and the Cochrane Collaboration tool., Study Design: Systematic review and meta-analysis., Level of Evidence: Level 1., Data Extraction: Baseline and follow-up scores of the visual analog, Constant-Murley, and University of California Los Angeles shoulder scales were extracted to calculate effect sizes (ESs), represented as Cohen d . Metaregression and publication bias analyses were performed. Procedural and medication costs were extracted from Medicare guidelines., Results: A total of 7 high and 3 good quality studies were included, with a mean score of 21.1. Only 1 study had a high risk of bias. The meta-analyses produced pooled ESs of 0.05 ( P = 0.83), 0.12 ( P = 0.71), and 0.07 ( P = 0.79) for each scale, respectively, with CIs crossing 0. Procedural costs were equal between groups, whereas ketorolac was the least costly medication ($0.47). There was no significant difference in side effects between the 2 injections., Conclusion: SNIs are as effective as SCIs for short-term pain relief and improving function in patients with subacromial impingement syndrome. In addition, they are less expensive and cause no major difference in complications, providing a viable, cost-effective alternative for injection therapy in patients with SIS.
- Published
- 2023
- Full Text
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49. Heterogeneity of dynamic shear properties of the meniscus: A comparison between tissue core and surface layers.
- Author
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Schwartz G, Morejon A, Gracia J, Best TM, Jackson AR, and Travascio F
- Subjects
- Animals, Glycosaminoglycans, Meniscus, Swine, Tibia, Water, Menisci, Tibial physiology
- Abstract
Damage to the meniscus has been associated with excessive shear loads. Aimed at elucidating meniscus pathophysiology, previous studies have investigated the shear properties of the meniscus fibrocartilaginous core. However, the meniscus is structurally inhomogeneous, with an external cartilaginous envelope (tibial and femoral surface layers) wrapping the tissue core. To date, little is known about the shear behavior of the surface layers. The objective of this study was to measure the dynamic shear properties of the surface layers and derive empirical relations with their composition. Specimens were harvested from tibial and femoral surface layers and core of porcine menisci (medial and lateral, n = 10 each). Frequency sweep tests yielded complex shear modulus (G*) and phase shifts (δ). Mechanical behavior of regions was described by a generalized Maxwell model. Correlations between shear moduli with water and glycosaminoglycans content of the tissue regions were investigated. The femoral surface had the lowest shear modulus, when compared to core and tibial regions. A 3-relaxation times Maxwell model satisfactorily interpreted the shear behavior of all tissue regions. Inhomogeneous tissue composition was also observed, with water content in the surface layers being higher when compared with tissue core. Water content negatively correlated with shear properties in all regions. The lower measured shear properties in the femoral layer may explain the higher prevalence of meniscal tears on the superior surface of the tissue. The heterogenous behavior of the tissue in shear provides insight into meniscus pathology and has important implications for efforts to tissue engineer replacement tissues., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)
- Published
- 2023
- Full Text
- View/download PDF
50. Hippo Signaling Modulates the Inflammatory Response of Chondrocytes to Mechanical Compressive Loading.
- Author
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Cai X, Warburton C, Perez OF, Wang Y, Ho L, Finelli C, Ehlen QT, Wu C, Rodriguez CD, Kaplan L, Best TM, Huang CY, and Meng Z
- Abstract
Knee osteoarthritis (KOA) is a degenerative disease resulting from mechanical overload, where direct physical impacts on chondrocytes play a crucial role in disease development by inducing inflammation and extracellular matrix degradation. However, the signaling cascades that sense these physical impacts and induce the pathogenic transcriptional programs of KOA remain to be defined, which hinders the identification of novel therapeutic approaches. Recent studies have implicated a crucial role of Hippo signaling in osteoarthritis. Since Hippo signaling senses mechanical cues, we aimed to determine its role in chondrocyte responses to mechanical overload. Here we show that mechanical loading induces the expression of inflammatory and matrix-degrading genes by activating the nuclear factor-kappaB (NFκB) pathway in a Hippo-dependent manner. Applying mechanical compressional force to 3-dimensional cultured chondrocytes activated NFκB and induced the expression of NFκB target genes for inflammation and matrix degradation (i.e., IL1 β and ADAMTS4). Interestingly, deleting the Hippo pathway effector YAP or activating YAP by deleting core Hippo kinases LATS1/2 blocked the NFκB pathway activation induced by mechanical loading. Consistently, treatment with a LATS1/2 kinase inhibitor abolished the upregulation of IL1 β and ADAMTS4 caused by mechanical loading. Mechanistically, mechanical loading activates Protein Kinase C (PKC), which activates NFκB p65 by phosphorylating its Serine 536. Furthermore, the mechano-activation of both PKC and NFκB p65 is blocked in LATS1/2 or YAP knockout cells, indicating that the Hippo pathway is required by this mechanoregulation. Additionally, the mechanical loading-induced phosphorylation of NFκB p65 at Ser536 is blocked by the LATS1/2 inhibitor Lats-In-1 or the PKC inhibitor AEB-071. Our study suggests that the interplay of the Hippo signaling and PKC controls NFκB-mediated inflammation and matrix degradation in response to mechanical loading. Chemical inhibitors targeting Hippo signaling or PKC can prevent the mechanoresponses of chondrocytes associated with inflammation and matrix degradation, providing a novel therapeutic strategy for KOA., Competing Interests: Competing interests: There is no competing interest from all authors.
- Published
- 2023
- Full Text
- View/download PDF
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