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Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent airflow limitation, progressive dyspnea, and peripheral muscle dysfunction, significantly impairing functional capacity and quality of life. Although the combined implementation of aerobic and resistance exercises is recommended in pulmonary rehabilitation programs, early-onset ventilatory limitation in individuals with COPD often hinders tolerance to high exercise intensities. This limitation increases the need for alternative exercise approaches targeting peripheral muscle adaptations. Low-load blood flow restriction training (LL-BFRT), which enables improvements in muscle strength with low mechanical loads, has emerged as a potential option for this patient population. However, evidence regarding the effects of LL-BFRT in individuals with COPD-particularly on upper extremity muscles-remains limited.
The aim of this study is to comparatively investigate the effects of LL-BFRT and sham-BFRT, both administered in addition to an aerobic exercise program in individuals diagnosed with stage II and III COPD, on upper extremity muscle strength, upper extremity functional capacity, activities of daily living performance, quality of life, functional exercise capacity, muscle oxygenation, and respiratory parameters. The study is designed as a randomized controlled, single-blind, quasi-experimental interventional trial.
The expected outcomes are that LL-BFRT may enhance upper extremity muscle strength and functional capacity, improve activities of daily living and quality of life, and increase exercise tolerance due to its applicability at low mechanical loads. Furthermore, findings related to muscle oxygenation and respiratory parameters are anticipated to provide clinical evidence regarding the physiological effects of LL-BFRT on peripheral muscle adaptations. These results are expected to guide the integration of LL-BFRT as an alternative and safe approach in upper extremity exercise prescription within pulmonary rehabilitation programs, support clinical decision-making processes, and establish a scientific foundation for future research.
Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable, and treatable disease characterized by persistent respiratory symptoms and irreversible airflow limitation resulting from airway and/or alveolar abnormalities, usually caused by prolonged exposure to noxious particles or gases (1). COPD represents one of the leading causes of mortality among chronic respiratory diseases and is recognized as a major global health problem, affecting approximately 10% of the adult population, with an increasing incidence associated with population aging. According to the 2017 Global Burden of Disease (GBD) Study, the global mortality rate attributable to COPD was 41.9 deaths per 100,000 population, accounting for 5.7% of all-cause mortality. The mortality rate was reported as 46.7 per 100,000 in men and 37.0 per 100,000 in women (2).
The progressive and persistent airflow limitation in COPD, together with reduced parenchymal elasticity, increases ventilatory demand and imposes an excessive load on the respiratory muscles. Hyperinflation further reduces the effective contractile range of these muscles, creating a vicious cycle in which mechanoreceptor stimulation enhances ventilatory drive and exacerbates dyspnea. Increased dyspnea and impaired respiratory muscle function limit the performance of activities of daily living (ADLs), leading to substantial reductions in physical performance (3).
Skeletal muscle dysfunction is a frequent systemic manifestation of COPD. Reductions in peripheral muscle strength involving the upper and lower extremities as well as the trunk significantly limit exercise capacity and functional performance, negatively affecting overall health status. Importantly, impaired muscle strength has been identified as a strong predictor of morbidity, mortality, disability, and exacerbation risk, independent of the degree of airway obstruction (4).
During upper extremity activities, individuals with COPD frequently experience marked dyspnea and dynamic hyperinflation, which significantly restrict functional independence and highlight the clinical importance of upper extremity functional capacity (5). Compared with healthy peers, individuals with COPD demonstrate reduced performance during upper limb activities and report substantial difficulty. This limitation is partly attributable to altered respiratory mechanics, as upper extremity muscles also function as accessory respiratory muscles. Consequently, dyspnea intensifies during upper limb activity, often leading to premature termination of exercise (6).
Given the dyspnea-inducing nature of upper extremity use and its negative impact on activity tolerance, preserving and improving upper extremity function constitutes a critical rehabilitation target in COPD. Indeed, as emphasized in the most recent joint official statement by the American Thoracic Society (ATS) and the European Respiratory Society (ERS), the inclusion of upper extremity exercise training in pulmonary rehabilitation programs is strongly supported for individuals with COPD (7).
Pulmonary rehabilitation programs commonly incorporate aerobic modalities such as arm ergometry, as well as resistance-based approaches using multi-station systems, elastic bands, or free weights to target upper extremity function (8). Although aerobic exercise forms the cornerstone of pulmonary rehabilitation, its effects on muscle strength and mass are considered limited. Therefore, combined aerobic and resistance exercise approaches are recommended to more effectively address peripheral muscle dysfunction (9).
However, whether currently tolerated training intensities-often limited by ventilatory constraints-are sufficient to optimally target peripheral muscle dysfunction remains controversial. Both the ATS and ERS have highlighted the need for innovative rehabilitation strategies capable of targeting peripheral muscle dysfunction at lower mechanical loads (10). Traditional moderate-to-high intensity resistance training may be effective but is often poorly tolerated in individuals with COPD due to dyspnea, early fatigue, and ventilatory limitation, thereby limiting adherence and long-term participation (11).
In this context, low-load blood flow restriction training (LL-BFRT) has emerged as a promising alternative. Despite the use of low mechanical loads, LL-BFRT induces localized ischemia and increased metabolic stress, leading to significant gains in muscle strength and hypertrophy. This method may represent a viable option for individuals with COPD who are unable to tolerate high mechanical loads (12).
Although evidence supporting LL-BFRT primarily derives from studies conducted in healthy individuals and predominantly targeting lower extremity muscles (12-14), data regarding its application to upper extremity muscles in individuals with COPD remain limited. Considering that upper limb activities impose greater ventilatory demand and trigger dyspnea earlier, the potential advantages of LL-BFRT in this region warrant investigation. This research gap underscores the necessity of evaluating the effectiveness of LL-BFRT-based upper extremity resistance training in COPD.
Aim of the Study The aim of this study is to comparatively investigate the effects of LL-BFRT and sham-BFRT, administered in addition to an aerobic exercise program, on upper extremity muscle strength, upper extremity functional capacity, performance of activities of daily living, quality of life, functional exercise capacity, muscle oxygenation, and pulmonary function parameters in individuals diagnosed with stage II and III COPD.
Interventions Participants in both groups will undergo an exercise program twice weekly for 8 weeks.
Both groups will perform upper extremity aerobic exercise using an arm cycle ergometer. Each session will begin with a 5-minute warm-up at 0 Watts, followed by 20 minutes of aerobic exercise at 60-70% of age-predicted maximum heart rate. Initial resistance will be set between 35-50 Watts and maintained within this range according to individual exercise tolerance. Dyspnea will be monitored using the Modified Borg Scale. A 5-minute cool-down at 0 Watts will follow the aerobic phase.
Intervention Group (LL-BFRT) In addition to aerobic exercise, participants in the intervention group will receive LL-BFRT. A pneumatic cuff will be placed proximally on the upper extremity. Occlusion pressure will be set at 30-40% of arterial occlusion pressure (AOP). Resistance will be set at 30% of one-repetition maximum (1RM). Exercises will follow a standardized 4-set protocol (30-15-15-15 repetitions) with 45-second inter-set rest periods, during which cuff pressure will be maintained.
Targeted muscle groups will include the biceps brachii, triceps brachii, and anterior deltoid. After completion of each exercise, cuff pressure will be released for a 5-minute reperfusion period before proceeding to the next exercise. Dyspnea will be closely monitored using the Modified Borg Scale, and exercise will be terminated if dyspnea reaches ≥6, indicating exercise intolerance.
Control Group (Sham-BFRT) Participants in the control group will receive the same aerobic exercise protocol and identical resistance exercise structure. However, cuff pressure during sham-BFRT will be set at a level insufficient to produce therapeutic blood flow restriction.
Assessments Demographic data including age, sex, height, and weight will be recorded. Body mass index (BMI) will be calculated. Smoking history will be documented in pack-years. Disease duration and COPD stage (according to GOLD classification) will be determined from medical records. Oxygen therapy and inhaled treatment use will be recorded. Exacerbation frequency, defined as the number of exacerbations and hospital admissions within the past 12 months, will also be documented.
This study is expected to provide evidence regarding the clinical efficacy and physiological mechanisms of LL-BFRT in improving upper extremity function in individuals with COPD and to inform exercise prescription within pulmonary rehabilitation programs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention Group | Experimental | Participants will receive an 8-week upper extremity aerobic exercise program combined with low-load blood flow restriction training targeting upper extremity muscles. |
|
| Control Group | Sham Comparator | Participants will receive the same 8-week upper extremity aerobic exercise program combined with sham blood flow restriction training with non-therapeutic cuff pressure. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low-Load Blood Flow Restriction Training (LL-BFRT) + Aerobic Exercise | Other | Participants will undergo an 8-week upper extremity aerobic exercise program combined with low-load blood flow restriction training (LL-BFRT). The aerobic exercise will be performed using an arm cycle ergometer at 60-70% of age-predicted maximum heart rate for 20 minutes, preceded and followed by 5 minutes of unloaded cycling. In addition, LL-BFRT will be applied to the proximal upper extremity with a pneumatic cuff at 30-40% of arterial occlusion pressure. Resistance exercises will be performed at 30% of one-repetition maximum (1RM) using a 4-set protocol (30-15-15-15 repetitions) with 45-second inter-set rest periods while maintaining cuff pressure. Target muscles include the biceps brachii, triceps brachii, and anterior deltoid. |
| Measure | Description | Time Frame |
|---|---|---|
| Upper Extremity Functional Capacity | Upper extremity functional capacity and endurance will be assessed using the 6-Minute Pegboard & Ring Test (6-PBRT). During the test, participants will be seated in front of a pegboard and instructed to use both hands simultaneously to transfer as many rings as possible from two lower pegboards positioned at shoulder level to two upper pegboards located 20 cm above, and then back to the lower boards. The test duration is 6 minutes. Prior to the actual test, participants will be allowed to practice by transferring a few rings to familiarize themselves with the procedure. During the test, the physiotherapist will provide standardized verbal encouragement every minute to motivate the participant. At the end of the 6 minutes, the total number of rings transferred throughout the test will be recorded as the final score (16). | Pre- and post-intervention (week 8). |
| Measure | Description | Time Frame |
|---|---|---|
| Pulmonary Function Assessment | Pulmonary function will be assessed using spirometric measurements. Spirometry is a standard pulmonary function test that evaluates lung volume and airflow rates. During the test, participants will be instructed to exhale forcefully and completely to achieve maximal lung emptying. Parameters including Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC), and the FEV1/FVC ratio will be recorded. In addition, post-bronchodilator FEV1/FVC < 0.70 will be used for diagnosis and classification in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (18). |
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Inclusion Criteria:
Individuals aged 40-80 years with stage 2 and 3 COPD diagnosed according to GOLD criteria
Exclusion Criteria:
Uncontrolled hypertension
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zeynal Yasacı, Doctor Lecturer | Contact | +905075409791 | zeynal.yasaci@inonu.edu.tr | |
| Emine Tonak | Contact | +905372994319 | eminetonak4006@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Malatya Education and Research Hospital | Recruiting | Malatya | Battalgazi | Turkey (Türkiye) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28557670 | Background | Crum EM, O'Connor WJ, Van Loo L, Valckx M, Stannard SR. Validity and reliability of the Moxy oxygen monitor during incremental cycling exercise. Eur J Sport Sci. 2017 Sep;17(8):1037-1043. doi: 10.1080/17461391.2017.1330899. Epub 2017 May 30. | |
| 38555101 | Background | Huang CT, Ruan SY, Tsai YJ, Chien JY, Yu CJ. Lung fluid content during 6MWT in patients with COPD with and without comorbid heart failure. BMJ Open Respir Res. 2024 Mar 30;11(1):e002000. doi: 10.1136/bmjresp-2023-002000. |
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Participant data will be securely stored by the investigators and may be shared with authorized personnel if deemed necessary, in accordance with applicable privacy regulations.
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Participants will be randomly assigned to one of two parallel groups: (1) an intervention group receiving aerobic exercise combined with low-load blood flow restriction training (LL-BFRT), or (2) a control group receiving aerobic exercise combined with sham blood flow restriction training (sham-BFRT). Both groups will follow the same exercise frequency, duration, and protocol structure over an 8-week period. Outcomes will be compared between groups to determine the additional effects of LL-BFRT on upper extremity muscle strength, functional capacity, and related clinical parameters in individuals with stage II-III COPD.
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This study is designed as a single-blind randomized controlled trial. Participants will be blinded to group allocation. Both the intervention (LL-BFRT) and control (sham-BFRT) groups will receive identical exercise protocols in terms of frequency, duration, targeted muscle groups, and set-repetition structure. In the sham-BFRT group, cuff pressure will be applied at a level insufficient to produce therapeutic blood flow restriction. Participants will not be informed whether the applied cuff pressure represents an active or sham intervention
|
| Sham Low-Load Blood Flow Restriction Training (LL-BFRT) + Aerobic Exercise | Other | Participants will undergo the same 8-week upper extremity aerobic exercise program as the intervention group. Aerobic exercise will be performed using an arm cycle ergometer at 60-70% of age-predicted maximum heart rate for 20 minutes, preceded and followed by 5 minutes of unloaded cycling. In addition, sham blood flow restriction training will be applied with a pneumatic cuff placed proximally on the upper extremity. The cuff pressure will be set at a level insufficient to produce therapeutic blood flow restriction. The exercise structure, sets, repetitions, and muscle groups targeted will be identical to the intervention group. |
|
| Pre- and post-intervention (week 8). |
| Muscle Strength Assestment | Muscle strength of the biceps brachii, triceps brachii, and anterior deltoid muscles will be assessed using a Hand-Held Dynamometer (HHD). Measurements will be performed in standardized seated positions at specific joint angles. Biceps brachii strength will be measured with the elbow flexed at 90° and the forearm in supination (19). Triceps brachii strength will be measured during maximal isometric elbow extension, and anterior deltoid strength during shoulder flexion at 90°. Three measurements will be taken for each muscle group and the highest value will be recorded for analysis. | Pre-post ıntervention (week 8) |
| Activity Of Daily Living Assestment | Activities of daily living will be evaluated using the Londrina Activities of Daily Living (Londrina ADL) Scale. This protocol includes five activities involving upper and lower extremity movements as well as trunk flexion, inclination, and rotation. Participants will sit in front of a table and transfer ten objects of different weights (250 g, 500 g, and 1 kg) from one side of the table to the other using both hands and then return them to the initial position. Participants will also walk three consecutive times over a 6-meter distance as part of the protocol. The total time required to complete all activities will be recorded as the outcome measure. | Pre-post ıntervention (week 8) |
| Quality Of Life Assestment | Quality of life will be assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ is a disease-specific quality of life instrument consisting of 50 items and three domains. The Symptoms domain evaluates the frequency and severity of respiratory symptoms; the Activity domain assesses the impact of respiratory problems on daily activities; and the Impacts domain measures the psychosocial and functional effects of the disease on the individual's life. Response options for the items range between 2 and 5 points, and each item is weighted according to its predefined scoring algorithm during calculation (23). | Pre-post ıntervention (week 8) |
| Functional Capacity | Functional capacity will be assessed using the 6-Minute Walk Test (6MWT). Participants will be instructed to walk as far as possible for 6 minutes, and standardized verbal encouragement will be provided every minute throughout the test. Participants will be allowed to rest as needed; however, they will be encouraged to resume walking as soon as possible. Individuals requiring long-term oxygen therapy or those with resting hypoxemia may receive their usual oxygen flow during the test. Oxygen saturation will be continuously monitored using pulse oximetry (SpO₂) via a finger probe throughout the test. At the end of the test, the total walking distance will be recorded (24). | Pre-post ıntervention (week 8) |
| Muscle Oxygenation Measurement | Muscle oxygenation will be assessed using the Moxy Monitor, a portable device based on near-infrared spectroscopy technology. The device emits light waves into the tissue and detects scattered light using photodetectors placed at different distances from the light source. The detected signal is analyzed using an algorithm based on the Beer-Lambert law to determine oxygenated and deoxygenated hemoglobin levels, allowing the calculation of total hemoglobin (THb) and muscle oxygen saturation (SmO₂). Since light entering larger microvessels is assumed to be fully absorbed, the detected signal mainly originates from capillaries; therefore, the measurements reflect local muscle oxygenation and microvascular oxygen utilization. | Pre-post ıntervention (week 8) |
| 18500580 | Background | Liang WM, Chen JJ, Chang CH, Chen HW, Chen SL, Hang LW, Wang JD. An empirical comparison of the WHOQOL-BREF and the SGRQ among patients with COPD. Qual Life Res. 2008 Jun;17(5):793-800. doi: 10.1007/s11136-008-9326-5. Epub 2008 May 24. |
| 33324483 | Background | Deshpande C, Alaparthi GK, Krishnan S, Chakravarthy Bairapareddy K, Ramakrishna A, Acharya V. Comparison of Londrina activities of daily living protocol and Glittre ADL test on cardio-pulmonary response in patients with COPD: a cross-sectional study. Multidiscip Respir Med. 2020 Dec 4;15(1):694. doi: 10.4081/mrm.2020.694. eCollection 2020 Jan 28. |
| 34501883 | Background | Chamorro C, Arancibia M, Trigo B, Arias-Poblete L, Jerez-Mayorga D. Absolute Reliability and Concurrent Validity of Hand-Held Dynamometry in Shoulder Rotator Strength Assessment: Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2021 Sep 3;18(17):9293. doi: 10.3390/ijerph18179293. |
| 24244095 | Background | Johanson ME, Lateva ZC, Jaramillo J, Kiratli BJ, McGill KC. Triceps Brachii in Incomplete Tetraplegia: EMG and Dynamometer Evaluation of Residual Motor Resources and Capacity for Strengthening. Top Spinal Cord Inj Rehabil. 2013 Fall;19(4):300-10. doi: 10.1310/sci1904-300. |
| 41233773 | Background | Yesilyaprak SS, Ozden F. An acute bout of foam rolling of the biceps brachii does not affect upper extremity sensorimotor function: a randomized trial. BMC Musculoskelet Disord. 2025 Nov 13;26(1):1044. doi: 10.1186/s12891-025-09173-y. |
| 19931443 | Background | Arne M, Lisspers K, Stallberg B, Boman G, Hedenstrom H, Janson C, Emtner M. How often is diagnosis of COPD confirmed with spirometry? Respir Med. 2010 Apr;104(4):550-6. doi: 10.1016/j.rmed.2009.10.023. |
| 38739486 | Background | Oncu H, Calik-Kutukcu E, Vardar Yagli N, Inal-Ince D, Saglam M, Unal F, Aksoy S. Reliability and validity of the 6-minute pegboard and ring test for functional exercise capacity in patients with breast cancer. Physiother Theory Pract. 2025 Mar;41(3):643-655. doi: 10.1080/09593985.2024.2353260. Epub 2024 May 13. |
| 33985406 | Background | Calik-Kutukcu E, Tekerlek H, Bozdemir-Ozel C, Karaduz BN, Cakmak A, Inal-Ince D, Saglam M, Vardar-Yagli N, Sonbahar-Ulu H, Firat M, Arikan H, Kaya SB, Karakaya G. Validity and reliability of 6-minute pegboard and ring test in patients with asthma. J Asthma. 2022 Jul;59(7):1387-1395. doi: 10.1080/02770903.2021.1930040. Epub 2021 May 31. |
| 24381380 | Background | Janaudis-Ferreira T, Hill K, Goldstein RS, Wadell K, Brooks D. Relationship and responsiveness of three upper-limb tests in patients with chronic obstructive pulmonary disease. Physiother Can. 2013 Winter;65(1):40-3. doi: 10.3138/ptc.2011-49. |
| 38541735 | Background | Fabero-Garrido R, Gragera-Vela M, Del Corral T, Hernandez-Martin M, Plaza-Manzano G, Lopez-de-Uralde-Villanueva I. Effects of Low-Load Blood Flow Restriction Training on Muscle Anabolism Biomarkers and Thrombotic Biomarkers Compared with Traditional Training in Healthy Adults Older Than 60 Years: Systematic Review and Meta-Analysis. Life (Basel). 2024 Mar 20;14(3):411. doi: 10.3390/life14030411. |
| 39678440 | Background | Lin Q, Zhang Y, Qin J, Wu F. Effects of Low-Load Blood Flow Restriction Training on Muscle Volume After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis. Orthop J Sports Med. 2024 Dec 13;12(12):23259671241301731. doi: 10.1177/23259671241301731. eCollection 2024 Dec. |
| 38129116 | Background | Kohlbrenner D, Kuhn M, Manettas A, Aregger C, Peterer M, Greco N, Sievi NA, Clarenbach C. Low-load blood flow restriction strength training in patients with COPD: a randomised single-blind pilot study. Thorax. 2024 Mar 15;79(4):340-348. doi: 10.1136/thorax-2023-220546. |
| 37716519 | Background | Pancera S, Lopomo NF, Porta R, Sanniti A, Buraschi R, Bianchi LNC. Effects of Combined Endurance and Resistance Eccentric Training on Muscle Function and Functional Performance in Patients With Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial. Arch Phys Med Rehabil. 2024 Mar;105(3):470-479. doi: 10.1016/j.apmr.2023.09.004. Epub 2023 Sep 15. |
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| 38410717 | Background | Gloeckl R, Pitta F, Nyberg A. Optimising upper-limb exercise in patients with COPD: another step towards personalised pulmonary rehabilitation? ERJ Open Res. 2024 Feb 26;10(1):01012-2023. doi: 10.1183/23120541.01012-2023. eCollection 2024 Jan. |
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| 28128970 | Background | Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DM, Lopez Varela MV, Nishimura M, Roche N, Rodriguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med. 2017 Mar 1;195(5):557-582. doi: 10.1164/rccm.201701-0218PP. |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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