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Differences in brain structure and theta burst stimulation-induced plasticity implicate the corticomotor system in loss of function after musculoskeletal injury.
Flanagan, SD, Proessl, F, Dunn-Lewis, C, Sterczala, AJ, Connaboy, C, Canino, MC, Beethe, AZ, Eagle, SR, Szivak, TK, Onate, JA, et al
Journal of neurophysiology. 2021;(4):1006-1021
Abstract
Traumatic musculoskeletal injury (MSI) may involve changes in corticomotor structure and function, but direct evidence is needed. To determine the corticomotor basis of MSI, we examined interactions among skeletomotor function, corticospinal excitability, corticomotor structure (cortical thickness and white matter microstructure), and intermittent theta burst stimulation (iTBS)-induced plasticity. Nine women with unilateral anterior cruciate ligament rupture (ACL) 3.2 ± 1.1 yr prior to the study and 11 matched controls (CON) completed an MRI session followed by an offline plasticity-probing protocol using a randomized, sham-controlled, double-blind, cross-over study design. iTBS was applied to the injured (ACL) or nondominant (CON) motor cortex leg representation (M1LEG) with plasticity assessed based on changes in skeletomotor function and corticospinal excitability compared with sham iTBS. The results showed persistent loss of function in the injured quadriceps, compensatory adaptations in the uninjured quadriceps and both hamstrings, and injury-specific increases in corticospinal excitability. Injury was associated with lateralized reductions in paracentral lobule thickness, greater centrality of nonleg corticomotor regions, and increased primary somatosensory cortex leg area inefficiency and eccentricity. Individual responses to iTBS were consistent with the principles of homeostatic metaplasticity; corresponded to injury-related differences in skeletomotor function, corticospinal excitability, and corticomotor structure; and suggested that corticomotor adaptations involve both hemispheres. Moreover, iTBS normalized skeletomotor function and corticospinal excitability in ACL. The results of this investigation directly confirm corticomotor involvement in chronic loss of function after traumatic MSI, emphasize the sensitivity of the corticomotor system to skeletomotor events and behaviors, and raise the possibility that brain-targeted therapies could improve recovery.NEW & NOTEWORTHY Traumatic musculoskeletal injuries may involve adaptive changes in the brain that contribute to loss of function. Our combination of neuroimaging and theta burst transcranial magnetic stimulation (iTBS) revealed distinct patterns of iTBS-induced plasticity that normalized differences in muscle and brain function evident years after unilateral knee ligament rupture. Individual responses to iTBS corresponded to injury-specific differences in brain structure and physiological activity, depended on skeletomotor deficit severity, and suggested that corticomotor adaptations involve both hemispheres.
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Active site variants in STT3A cause a dominant type I congenital disorder of glycosylation with neuromusculoskeletal findings.
Wilson, MP, Garanto, A, Pinto E Vairo, F, Ng, BG, Ranatunga, WK, Ventouratou, M, Baerenfaenger, M, Huijben, K, Thiel, C, Ashikov, A, et al
American journal of human genetics. 2021;(11):2130-2144
Abstract
Congenital disorders of glycosylation (CDGs) form a group of rare diseases characterized by hypoglycosylation. We here report the identification of 16 individuals from nine families who have either inherited or de novo heterozygous missense variants in STT3A, leading to an autosomal-dominant CDG. STT3A encodes the catalytic subunit of the STT3A-containing oligosaccharyltransferase (OST) complex, essential for protein N-glycosylation. Affected individuals presented with variable skeletal anomalies, short stature, macrocephaly, and dysmorphic features; half had intellectual disability. Additional features included increased muscle tone and muscle cramps. Modeling of the variants in the 3D structure of the OST complex indicated that all variants are located in the catalytic site of STT3A, suggesting a direct mechanistic link to the transfer of oligosaccharides onto nascent glycoproteins. Indeed, expression of STT3A at mRNA and steady-state protein level in fibroblasts was normal, while glycosylation was abnormal. In S. cerevisiae, expression of STT3 containing variants homologous to those in affected individuals induced defective glycosylation of carboxypeptidase Y in a wild-type yeast strain and expression of the same mutants in the STT3 hypomorphic stt3-7 yeast strain worsened the already observed glycosylation defect. These data support a dominant pathomechanism underlying the glycosylation defect. Recessive mutations in STT3A have previously been described to lead to a CDG. We present here a dominant form of STT3A-CDG that, because of the presence of abnormal transferrin glycoforms, is unusual among dominant type I CDGs.
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Musculoskeletal MR Imaging Applications at Ultra-High (7T) Field Strength.
Menon, RG, Chang, G, Regatte, RR
Magnetic resonance imaging clinics of North America. 2021;(1):117-127
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Abstract
Regulatory approval of ultrahigh field (UHF) MR imaging scanners for clinical use has opened new opportunities for musculoskeletal imaging applications. UHF MR imaging has unique advantages in terms of signal-to-noise ratio, contrast-to-noise ratio, spectral resolution, and multinuclear applications, thus providing unique information not available at lower field strengths. But UHF also comes with a set of technical challenges that are yet to be resolved and may not be suitable for all imaging applications. This review focuses on the latest research in musculoskeletal MR imaging applications at UHF including morphologic imaging, T2, T2∗, and T1ρ mapping, chemical exchange saturation transfer, sodium imaging, and phosphorus spectroscopy imaging applications.
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Beneficial, adverse, and spiraling health-promotion effects: Evidence from a longitudinal randomized controlled trial of working at sit-stand desks.
Konradt, U, Heblich, F, Krys, S, Garbers, Y, Otte, KP
Journal of occupational health psychology. 2020;(1):68-81
Abstract
In a 6-month longitudinal randomized field experiment, we examined how using height-adjustable sit-stand desks could have beneficial, adverse, and spiraling effects on people's musculoskeletal and psychovegetative complaints, and on positive (vitality and vigilance) and negative psychological symptoms, namely, stressor uncontrollability (i.e., perceived uncontrollability of workload), psychological tension, and mental tiredness. A total of 127 employees in various, mostly sedentary, occupations were randomly assigned to either the intervention or the control group. Variables were assessed monthly for 6 months on a self-reported basis. Bayesian structural equation modeling showed that the intervention produced large inhibiting between-subjects effects for musculoskeletal problems in the neck, back, and shoulders (β ranged between -.26 and -.21). Within-subject analyses revealed that the intervention produced large inhibiting effect sizes for intensity (g = 3.06) and prevalence of musculoskeletal (g = 1.19) and psychovegetative complaints (g between 0.76 and 1.57). For negative psychological symptoms (i.e., psychological tension and mental tiredness), participants in the intervention group showed a steeper decrease than participants in the control group (g between 2.34 and 3.74). For positive indicators (i.e., vitality and vigilance), the intervention produced large promoting effects for participants in the intervention group compared with participants in the control group (g between 0.70 and 1.65). There was no change in stressor uncontrollability between the two groups. Finally, findings suggest that sit-stand desks can be effective in improving occupational health by weakening a downward-spiraling effect. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
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PET/MR Imaging in Musculoskeletal Precision Imaging - Third wave after X-Ray and MR.
Hancin, EC, Borja, AJ, Nikpanah, M, Raynor, WY, Haldar, D, Werner, TJ, Morris, MA, Saboury, B, Alavi, A, Gholamrezanezhad, A
PET clinics. 2020;(4):521-534
Abstract
18F-Fluorodeoxyglucose PET has been used to evaluate a wide array of inflammatory and neoplastic pathologies. MR imaging has great soft tissue resolution and high accuracy for detection of edema. Combining PET with MR imaging offers substantial advantages in musculoskeletal imaging. Specifically, evidence demonstrates the potential of imaging of bone marrow, soft tissue, and synovia by PET/MR imaging. Because of inherent limitations of 1H-MR to image cortical bone, there are some challenges; however, the use of 18F-sodium fluoride for PET/MR imaging could change the landscape. This article reviews the literature regarding PET/MR imaging in identification and management of many musculoskeletal diseases.
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Contrast-Enhanced Ultrasound for Musculoskeletal Applications: A World Federation for Ultrasound in Medicine and Biology Position Paper.
Fischer, C, Krix, M, Weber, MA, Loizides, A, Gruber, H, Jung, EM, Klauser, A, Radzina, M, Dietrich, CF
Ultrasound in medicine & biology. 2020;(6):1279-1295
Abstract
This World Federation for Ultrasound in Medicine and Biology position paper reviews the diagnostic potential of ultrasound contrast agents for clinical decision-making and provides general advice for optimal contrast-enhanced ultrasound performance in musculoskeletal issues. In this domain, contrast-enhanced ultrasound performance has increasingly been investigated with promising results, but still lacks everyday clinical application and standardized techniques; therefore, experts summarized current knowledge according to published evidence and best personal experience. The goal was to intensify and standardize the use and administration of ultrasound contrast agents to facilitate correct diagnoses and ultimately to improve the management and outcomes of patients.
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Epidemiology of the association between serum 25-hydroxyvitamin D levels and musculoskeletal conditions among elderly individuals: a literature review.
Arima, K, Mizukami, S, Nishimura, T, Tomita, Y, Nakashima, H, Abe, Y, Aoyagi, K
Journal of physiological anthropology. 2020;(1):38
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Abstract
BACKGROUND Vitamin D deficiency is associated with osteoporosis, fracture, muscle weakness, falls, and osteoarthritis in adults. Elderly individuals are more likely to present with poor musculoskeletal conditions. Recently, several epidemiological studies have assessed the correlation between serum 25-hydroxyvitamin D (25(OH)D) levels and musculoskeletal conditions in elderly individuals. MAIN TEXT Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Numerous studies have shown a positive association between serum 25(OH)D levels and bone mineral density. Only a few studies have reported an association between serum 25(OH)D levels and quantitative ultrasound (QUS) parameters. Low serum 25(OH)D level may be a risk factor for hip fracture. However, data on the association between vitamin D deficiency and the incidence of non-hip fracture are contrasting. Falls are a major cause of mortality and morbidity in older adults. Several prospective population-based cohort studies have shown that low 25(OH)D levels are associated with an increased risk of falls. Reduced muscle strength and physical performance are risk factors for adverse events, including disability, institutionalization, and mortality. The role of vitamin D in musculoskeletal functionality (muscle weakness and physical performance) among elderly individuals is still controversial. Osteoarthritis (OA) is the most common form of arthritis and is a leading cause of disability among older adults. Data on the association between serum 25(OH)D levels and OA are contrasting. CONCLUSION Some studies have shown that vitamin D deficiency may be a risk factor for poor musculoskeletal conditions, such as osteoporosis, fracture, muscle weakness, falls, and osteoarthritis in adults. However, other studies did not find an association between serum 25(OH)D levels and musculoskeletal conditions.
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Effect of different exercise training intensities on musculoskeletal and neuropathic pain in inactive individuals with type 2 diabetes - Preliminary randomised controlled trial.
Cox, ER, Gajanand, T, Burton, NW, Coombes, JS, Coombes, BK
Diabetes research and clinical practice. 2020;:108168
Abstract
AIMS: People with type 2 diabetes (T2D) have a greater prevalence of musculoskeletal and neuropathic pain. This exploratory analysis investigated whether exercise of different intensities leads to changes in self-reported musculoskeletal pain or symptoms of diabetic neuropathy in inactive individuals with type 2 diabetes. METHODS Thirty-two inactive adults with T2D (59% male, mean age 58.7 ± 9.1yrs, median HbA1c 7.8%) were randomised to usual care (CON), supervised combined aerobic and resistance moderate-intensity continuous training (C-MICT), or supervised combined high-intensity interval training (C-HIIT). At baseline and 8-weeks, musculoskeletal and neuropathic pain were evaluated using a modified Nordic Musculoskeletal Questionnaire and the Neuropathy Total Symptom Score-6 respectively. Quantitative sensory testing was used to determine thermal, mechanical and vibration detection thresholds, as well as pain pressure thresholds. Adverse events were recorded throughout the intervention. RESULTS Compared to CON, reduction in musculoskeletal pain intensity was significantly greater for C-HIIT (MD -5.4, 95% CI [-10.6 to -0.2], p = 0.04) and non-significantly greater for C-MICT (MD -5.9 [-12.4 to 0.7], p = 0.08). Changes in neuropathy symptoms were not different between C-HIIT and CON (MD 1.0 [-0.9 to 2.8], p = 0.31), or C-MICT and CON (MD 0.2 [-3.1 to 3.6], p = 0.89). No differences in sensory function were observed between groups. Similar rates of adverse events were seen in both exercise interventions (19 C-HIIT; 17 C-MICT), all but one of which were mild. CONCLUSIONS Preliminary data suggests 8-weeks of high-intensity combined aerobic and resistance exercise may be safely prescribed for inactive individuals with T2D and may reduce musculoskeletal pain but not neuropathic symptoms. TRIAL REGISTRATION ACTRN12615000475549.
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Applications of Photobiomodulation Therapy to Musculoskeletal Disorders and Osteoarthritis with Particular Relevance to Canada.
Gendron, DJ, Hamblin, MR
Photobiomodulation, photomedicine, and laser surgery. 2019;(7):408-420
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Abstract
Background: Musculoskeletal disorders caused by osteoarthritis (MSDs/OA) are a growing problem in the modern industrialized society in Canada. Overall aging of the general population and a progressive lack of exercise contribute to this alarming increase. Moreover, a range of chronic conditions including cardiovascular and mental diseases show significantly higher comorbidity with MSDs/OA. Conventional medical treatment for MSDs/OA includes nonsteroidal anti-inflammatory drugs and opiate pain killers. These drugs have major drawbacks such as a relative lack of efficacy, potential for addiction, and even death (Vioxx scandal). Photobiomodulation (PBM) was discovered over 50 years ago but has still not attained widespread acceptance by the medical community. This is partly due to uncertainty about the precise molecular mechanisms of action and a bewildering array of different wavelengths and dosimetric parameters employed in reported studies. Objective: The goal of this review was to survey literature reports of PBM, also known as low-level laser therapy used for treatment of MSDs/OA, concentrating on the growth over time, different wavelengths employed, and application to different joints. Methods: We searched the PubMed database for publication of study on PBM to treat the most common joints. Results: We show that the field of PBM to treat MSDs/OA is expanding exponentially over the past 20 years. A trend has emerged over time for more power to achieve better effective treatments, and the understanding of the physiological effect of safe parameters has improved. There is, however, no consensus on the best set of parameters to treat a specific patient indication. Conclusions: Finally, we highlight gaps in our knowledge and the barriers to further clinical trials. We suggest that the growing body of evidence indicating efficacy, and the almost total lack of side effects, should encourage continued clinical research to support clinical applications where better rehabilitation treatments are much needed.
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Top-Ten Tips for Dual-Energy CT in MSK Radiology.
Walstra, FE, Hickle, J, Duggan, P, Alsharhan, R, Murray, N, Mallinson, P, Munk, P, Ouellette, H
Seminars in musculoskeletal radiology. 2019;(4):392-404
Abstract
Dual-energy computed tomography (DECT) has the potential to detect musculoskeletal pathology with greater sensitivity than conventional CT alone at no additional radiation dose to the patient. It therefore has the potential to reduce the need for further diagnostic imaging or procedures (e.g., joint aspirations in the case of gout or magnetic resonance imaging to confirm undisplaced fractures).DECT is a well-established technique for the detection of gout arthropathy. Multiple newer applications have shown clinical potential including bone marrow edema detection and metal artifact reduction. Collagen analysis, bone marrow lesion detection, and iodine mapping in CT arthrography are areas of possible future application and development.This article outlines 10 tips on the use of DECT imaging of the musculoskeletal system, explaining the technique and indications with practical suggestions to help guide the radiologist.