Department of Physical Therapy Articles
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Item Instrument-assisted cross fiber massage increases tissue perfusion and alters microvascular morphology in the vicinity of healing knee ligaments(Springer Nature, 2013-09-28) Loghmani, M. Terry; Warden, Stuart J.; Physical Therapy, School of Health and Human SciencesBackground: Ligament injuries are common clinical problems for which there are few established interventions. Instrument-assisted cross fiber massage (IACFM) was recently shown to accelerate the restoration of biomechanical properties in injured rodent knee medial collateral ligaments (MCL). The current study aimed to investigate the influence of IACFM on regional perfusion and vascularity in the vicinity of healing rodent knee MCL injuries. Methods: Bilateral knee MCL injuries were induced in female Sprague-Dawley rats. Commencing 1 week post-injury, 1 minute of IACFM was introduced unilaterally 3 times/week for 3 weeks. The contralateral injured MCL served as an internal control. Regional tissue perfusion was assessed in vivo throughout healing using laser Doppler imaging, whereas regional microvascular morphology was assessed ex vivo via micro-computed tomography of vessels filled with contrast. Results: IACFM had no effect on tissue perfusion when assessed immediately, or at 5, 10, 15 or 20 min following intervention (all p > 0.05). However, IACFM-treated hindlimbs had enhanced tissue perfusion when assessed 1 day following the 4th and 9th (last) treatment sessions (all p < 0.05). IACFM-treated hindlimbs also had greater perfusion when assessed 1 wk following the final treatment session (32 days post-injury) (p < 0.05). Subsequent investigation of microvascular morphology found IACFM to increase the proportion of arteriole-sized blood vessels (5.9 to <41.2 μm) in the tibial third of the ligament (p < 0.05). Conclusions: These findings suggest IACFM alters regional perfusion and vascularity in the vicinity of healing rodent knee MCL injuries. This effect may contribute to the beneficial effect of IACFM observed on the recovery of knee ligament biomechanical properties following injury.Item International Expert Consensus on Instrument-Assisted Soft-Tissue Mobilization Precautions and Contraindications: A Modified Delphi Study(MDPI, 2025-03-15) Cheatham, Scott W.; Baker, Russell T.; Loghmani, M. Terry; Schleip, Robert; Physical Therapy, School of Health and Human SciencesBackground: Instrument-assisted soft-tissue mobilization (IASTM) is a popular myofascial intervention used by healthcare professionals. Despite the growing body of research evidence, there is still a gap in understanding what healthcare professionals consider as treatment precautions or contraindications. To date, no consensus on precautions and contraindications has been established among IASTM experts. The purpose of this modified Delphi survey was to determine IASTM precautions and contraindications among international IASTM experts. Methods: A three-round Delphi study of 24 international IASTM experts was conducted. In round 1, experts chose from a list of 81 medical conditions and treatment considerations that could be a concern for IASTM treatment. Consensus was considered if more than 70% of experts agreed on an item. Round 2 included the updated list of 39 items, and the experts decided if each item should be a precaution, contraindication, or both. The strength of agreement grade scale was used to rank the precautions and contraindications, by the level of expert agreement using grades A-D (e.g., A-strong, B-moderate, C-weak, D-both). Grade D conditions could potentially be both a precaution and contraindication. In round 3, the final list of categories and items was presented to the experts for final approval. Results: All recruited experts (n = 24) participated in the three rounds and the final list of items received 100% approval. Contraindications had the highest number of conditions (n = 16) across the strength of agreement grade categories A-C followed by category D (both) (n = 8). Discussion: This Delphi study was the first survey to document expert consensus on precautions and contraindications based upon the strength of agreement. This study offers a beginner's guide for clinicians to safely implement IASTM by establishing required precautions and contraindications through consensus agreement. Conclusions: This survey should be the first step in a series of planned IASTM studies on precautions and contraindications to establish the best-practice recommendations for the application of IASTM in clinical practice.Item Physical activity completed when young has residual bone benefits at 94 years of age: a within-subject controlled case study(Hylonome, 2014) Warden, Stuart J.; Mantila Roosa, Sara M.; Physical Therapy, School of Health and Human SciencesPhysical activity is recommended for skeletal health because bones adapt to mechanical loading. The young skeleton shows greatest plasticity to physical activity-related mechanical loads, but bones are most at risk of failure later in life. The discrepancy raises the question of whether the skeletal benefits of physical activity completed when young persist with aging. Here we present a unique case wherein the cortical bone benefit of physical activity completed over five decades earlier could be established within an individual aged in their tenth decade of life. Specifically, we compared bone properties at the midshaft humerus between the throwing and nonthrowing arms of a 94-year-old former Major League Baseball player who ceased throwing 55 years earlier. By performing analyses within-subject, the long-term skeletal benefit of physical activity completed when young could be assessed independent of inherited and systemic traits. Also, as the subject threw left-handed during his throwing career, but was right-hand dominant in all other activities throughout life, any lasting skeletal benefits in favor of the throwing arm could not be attributable to simple arm dominance. Analyses indicated that any cortical bone mass, area and thickness benefits of throwing-related physical activity completed when young were lost with aging, possibly due to accelerated intracortical remodeling. In contrast, the subject's throwing (nondominant) arm had greater total cross-sectional area and estimated strength (polar moment of inertia) than in his dominant arm, despite muscle indices favoring the latter. These data indicate that physical activity completed when young can have lasting benefits on bone size and strength, independent of the maintenance of bone mass benefits.Item Musculoskeletal Health Worsened from Carnitine Supplementation and Not Impacted by a Novel Individualized Treadmill Training Protocol(Karger, 2024) Troutman, Ashley D.; Srinivasan, Shruthi; Metzger, Corinne E.; Fallen, Paul B.; Chen, Neal; O’Neill, Kalisha D.; Allen, Matthew R.; Biruete, Annabel; Moe, Sharon M.; Avin, Keith G.; Physical Therapy, School of Health and Human SciencesIntroduction: Chronic kidney disease (CKD) negatively affects musculoskeletal health, leading to reduced mobility, and quality of life. In healthy populations, carnitine supplementation and aerobic exercise have been reported to improve musculoskeletal health. However, there are inconclusive results regarding their effectiveness and safety in CKD. We hypothesized that carnitine supplementation and individualized treadmill exercise would improve musculoskeletal health in CKD. Methods: We used a spontaneously progressive CKD rat model (Cy/+ rat) (n = 11-12/gr): (1) Cy/+ (CKD-Ctrl), (2) CKD-carnitine (CKD-Carn), and (3) CKD-treadmill (CKD-TM). Carnitine (250 mg/kg) was injected daily for 10 weeks. Rats in the treadmill group ran 4 days/week on a 5° incline for 10 weeks progressing from 30 min/day for week one to 40 min/day for week two to 50 min/day for the remaining 8 weeks. At 32 weeks of age, we assessed overall cardiopulmonary fitness, muscle function, bone histology and architecture, and kidney function. Data were analyzed by one-way ANOVA with Tukey's multiple comparisons tests. Results: Moderate to severe CKD was confirmed by biochemistries for blood urea nitrogen (mean 43 ± 5 mg/dL CKD-Ctrl), phosphorus (mean 8 ± 1 mg/dL CKD-Ctrl), parathyroid hormone (PTH; mean 625 ± 185 pg/mL CKD-Ctrl), and serum creatinine (mean 1.1 ± 0.2 mg/mL CKD-Ctrl). Carnitine worsened phosphorous (mean 11 ± 3 mg/dL CKD-Carn; p < 0.0001), PTH (mean 1,738 ± 1,233 pg/mL CKD-Carn; p < 0.0001), creatinine (mean 1 ± 0.3 mg/dL CKD-Carn; p < 0.0001), cortical bone thickness (mean 0.5 ± 0.1 mm CKD-Ctrl, 0.4 ± 0.1 mm CKD-Carn; p < 0.05). Treadmill running significantly improves maximal aerobic capacity when compared to CKD-Ctrl (mean 14 ± 2 min CKD-TM, 10 ± 2 min CKD-Ctrl; p < 0.01). Conclusion: Carnitine supplementation worsened CKD progression, mineral metabolism biochemistries, and cortical porosity and did not have an impact on physical function. Individualized treadmill running improved maximal aerobic capacity but did not have an impact on CKD progression or bone properties. Future studies should seek to better understand carnitine doses in conditions of compromised renal function to prevent toxicity which may result from elevated carnitine levels and to optimize exercise prescriptions for musculoskeletal health.Item Male Lrp5A214V mice maintain high bone mass during dietary calcium restriction by altering the vitamin D endocrine system(Oxford University Press, 2024) Ozgurel, Serra Ucer; Reyes Fernandez, Perla C.; Chanpaisaeng, Krittikan; Fleet, James C.; Physical Therapy, School of Health and Human SciencesEnvironmental factors and genetic variation individually impact bone. However, it is not clear how these factors interact to influence peak bone mass accrual. Here we tested whether genetically programmed high bone formation driven by missense mutations in the Lrp5 gene (Lrp5A214V) altered the sensitivity of mice to an environment of inadequate dietary calcium (Ca) intake. Weanling male Lrp5A214V mice and wildtype littermates (control) were fed AIN-93G diets with 0.125%, 0.25%, 0.5% (reference, basal), or 1% Ca from weaning until 12 weeks of age (ie, during bone growth). Urinary Ca, serum Ca, Ca regulatory hormones (PTH, 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)), bone parameters (μCT, ash), and renal/intestinal gene expression were analyzed. As expected, low dietary Ca intake negatively impacted bones and Lrp5A214V mice had higher bone mass and ash content. Although bones of Lrp5A214V mice have more matrix to mineralize, their bones were not more susceptible to low dietary Ca intake. In control mice, low dietary Ca intake exerted expected effects on serum Ca (decreased), PTH (increased), and 1,25(OH)2D3 (increased) as well as their downstream actions (ie, reducing urinary Ca, increasing markers of intestinal Ca absorption). In contrast, Lrp5A214V mice had elevated serum Ca with a normal PTH response but a blunted 1,25(OH)2D3 response to low dietary Ca that was reflected in the renal 1,25(OH)2D3 producing/degrading enzymes, Cyp27b1 and Cyp24a1. Despite elevated serum Ca in Lrp5A214V mice, urinary Ca was not elevated. Despite an abnormal serum 1,25(OH)2D3 response to low dietary Ca, intestinal markers of Ca absorption (Trpv6, S100g mRNA) were elevated in Lrp5A214V mice and responded to low Ca intake. Collectively, our data indicate that the Lrp5A214V mutation induces changes in Ca homeostasis that permit mice to retain more Ca and support their high bone mass phenotype.Item Asymptomatic female softball pitchers have altered hip morphology and cartilage composition(Springer Nature, 2025-01-25) Warden, Stuart J.; Coburn, Sally L.; Fuchs, Robyn K.; Surowiec, Rachel K.; Carballido-Gamio, Julio; Kemp, Joanne L.; Jalaie, Peter K.; Hanff, David F.; Palmer, Antony J. R.; Fernquest, Scott J.; Crossley, Kay M.; Heerey, Joshua J.; Physical Therapy, School of Health and Human SciencesFew studies have explored hip morphology and cartilage composition in female athletes or the impact of asymmetric repetitive loading, such as occurs during softball pitching. The current cross-sectional study assessed bilateral bony hip morphology on computed tomography imaging in collegiate-level softball pitchers ('Pitch1', n = 25) and cross-country runners ('Run', n = 13). Magnetic resonance imaging was used to assess cartilage relaxation times in a second cohort of pitchers ('Pitch2', n = 10) and non-athletic controls ('Con', n = 4). Pitch1 had 52% greater maximum alpha angle than Run (p < 0.001) and were 21.3 (95% CI 2.4 to 192.0) times more likely to have an alpha angle ≥ 60° within at least one hip. Pitch2 had longer T2 relaxation times in the superior femoral cartilage of the drive leg (same side as the throwing arm) and stride leg than Con (all p < 0.02). The drive leg in Pitch2 had longer T1ρ and T2 relaxation times in the superior femoral cartilage compared to the stride leg (all p ≤ 0.03). Asymptomatic softball pitchers exhibit altered bony hip morphology and cartilage composition compared to cross-country runners and non-athletic controls, respectively. They also exhibit asymmetry in cartilage composition. Further studies with larger sample sizes are warranted and any potential long-term consequences of the changes in terms of symptom and osteoarthritis development requires investigation.Item Dynamic causal modeling of reorganization of memory and language networks in temporal lobe epilepsy(Wiley, 2023-12) Fallahi, Alireza; Hoseini-Tabatabaei, Narges; Eivazi, Fatemeh; Mohammadi Mobarakeh, Neda; Dehghani-Siahaki, Hamed; Alibiglou, Laila; Rostami, Reza; Habibabadi, Jafar Mehvari; Hashemi-Fesharaki, Seyed-Sohrab; Joghataei, Mohammad Taghi; Nazem-Zadeh, Mohammad-Reza; Physical Therapy, School of Health and Human SciencesObjective To evaluate the alterations of language and memory functions using dynamic causal modeling, in order to identify the epileptogenic hemisphere in temporal lobe epilepsy (TLE). Methods Twenty-two patients with left TLE and 13 patients with right TLE underwent functional magnetic resonance imaging (fMRI) during four memory and four language mapping tasks. Dynamic causal modeling (DCM) was employed on fMRI data to examine effective directional connectivity in memory and language networks and the alterations in people with TLE compared to healthy individuals. Results DCM analysis suggested that TLE can influence the memory network more widely compared to the language network. For memory mapping, it demonstrated overall hyperconnectivity from the left hemisphere to the other cranial regions in the picture encoding, and from the right hemisphere to the other cranial regions in the word encoding tasks. On the contrary, overall hypoconnectivity was seen from the brain hemisphere contralateral to the seizure onset in the retrieval tasks. DCM analysis further manifested hypoconnectivity between the brain's hemispheres in the language network in patients with TLE compared to controls. The CANTAB® neuropsychological test revealed a negative correlation for the left TLE and a positive correlation for the right TLE cohorts for the connections extracted by DCM that were significantly different between the left and right TLE cohorts. Interpretation In this study, dynamic causal modeling evidenced the reorganization of language and memory networks in TLE that can be used for a better understanding of the effects of TLE on the brain's cognitive functions.Item Single-cell RNAseq provides insight into altered immune cell populations in human fracture nonunions(Wiley, 2023) Avin, Keith G.; Dominguez, James M., II; Chen, Neal X.; Hato, Takashi; Myslinski, Jered J.; Gao, Hongyu; Liu, Yunlong; McKinley, Todd O.; Brown, Krista M.; Moe, Sharon M.; Natoli, Roman M.; Physical Therapy, School of Health and Human SciencesNonunion describes bone fractures that fail to heal, resulting in the fracture callus failing to fully ossify or, in atrophic cases, not forming altogether. Fracture healing is regulated, in part, by the balance of proinflammatory and anti-inflammatory processes occurring within the bone marrow and surface cell populations. We sought to further understand the role of osteoimmunology (i.e., study of the close relationship between the immune system and bone) by examining immune cell gene expression via single-cell RNA sequencing of intramedullary canal tissue obtained from human patients with femoral nonunions. Intramedullary canal tissue samples obtained by reaming were collected at the time of surgical repair for femur fracture nonunion (n = 5) or from native bone controls when harvesting autologous bone graft (n = 4). Cells within the samples were isolated and analyzed using the Chromium Single-Cell System (10x Genomics Inc.) and Illumina sequencers. Twenty-three distinct cell clusters were identified, with higher cell proportions in the nonunion samples for monocytes and CD14 + dendritic cells (DCs), and lower proportions of T cells, myelocytes, and promyelocytes in nonunion samples. Gene expression differences were identified in each of the cell clusters from cell types associated with osteoimmunology, including CD14 + DC, monocytes, T cells, promyelocytes, and myelocytes. These results provide human-derived gene profiles that can further our understanding of pathways that may be a cause or a consequence of nonunion, providing the clinical rationale to focus on specific components of osteoimmunology. Clinical significance: The novel single-cell approach may lead to clinically relevant diagnostic biomarkers during earlier stages of nonunion development and/or investigation into therapeutic options.Item Examining Mechanisms for Voltage-Sensitive Calcium Channel-Mediated Secretion Events in Bone Cells(Springer, 2023) Reyes Fernandez, Perla C.; Wright, Christian S.; Farach-Carson, Mary C.; Thompson, William R.; Physical Therapy, School of Health and Human SciencesIn addition to their well-described functions in cell excitability, voltage-sensitive calcium channels (VSCCs) serve a critical role in calcium (Ca2+)-mediated secretion of pleiotropic paracrine and endocrine factors, including those produced in bone. Influx of Ca2+ through VSCCs activates intracellular signaling pathways to modulate a variety of cellular processes that include cell proliferation, differentiation, and bone adaptation in response to mechanical stimuli. Less well understood is the role of VSCCs in the control of bone and calcium homeostasis mediated through secreted factors. In this review, we discuss the various functions of VSCCs in skeletal cells as regulators of Ca2+ dynamics and detail how these channels might control the release of bioactive factors from bone cells. Because VSCCs are druggable, a better understanding of the multiple functions of these channels in the skeleton offers the opportunity for developing new therapies to enhance and maintain bone and to improve systemic health.Item Fracture discrimination capability of ulnar flexural rigidity measured via Cortical Bone Mechanics Technology: study protocol for The STRONGER Study(Oxford University Press, 2024-01-04) Warden, Stuart J.; Dick, Andrew; Simon, Janet E.; Manini, Todd M.; Russ, David W.; Lyssikatos, Charalampos; Clark, Leatha A.; Clark, Brian C.; Physical Therapy, School of Health and Human SciencesOsteoporosis is characterized by low bone mass and structural deterioration of bone tissue, which leads to bone fragility (ie, weakness) and an increased risk for fracture. The current standard for assessing bone health and diagnosing osteoporosis is DXA, which quantifies areal BMD, typically at the hip and spine. However, DXA-derived BMD assesses only one component of bone health and is notably limited in evaluating the bone strength, a critical factor in fracture resistance. Although multifrequency vibration analysis can quickly and painlessly assay bone strength, there has been limited success in advancing a device of this nature. Recent progress has resulted in the development of Cortical Bone Mechanics Technology (CBMT), which conducts a dynamic 3-point bending test to assess the flexural rigidity (EI) of ulnar cortical bone. Data indicate that ulnar EI accurately estimates ulnar whole bone strength and provides unique and independent information about cortical bone compared to DXA-derived BMD. Consequently, CBMT has the potential to address a critical unmet need: Better identification of patients with diminished bone strength who are at high risk of experiencing a fragility fracture. However, the clinical utility of CBMT-derived EI has not yet been demonstrated. We have designed a clinical study to assess the accuracy of CBMT-derived ulnar EI in discriminating post-menopausal women who have suffered a fragility fracture from those who have not. These data will be compared to DXA-derived peripheral and central measures of BMD obtained from the same subjects. In this article, we describe the study protocol for this multi-center fracture discrimination study (The STRONGER Study).