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1.
J Biomech ; 163: 111917, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38184906

ABSTRACT

After stroke, deficits in paretic single limb stance (SLS) are commonly observed and affect walking performance. During SLS, the hip abductor musculature is critical in providing vertical support and regulating balance. Although disrupted paretic hip abduction torque production has been identified in individuals post-stroke, interpretation of previous results is limited due to the discrepancies in weight-bearing conditions. Using a novel perturbation-based assessment that could induce SLS by removing the support surface underneath one limb, we aim to investigate whether deficits in hip abduction torque production, vertical body support, and balance regulation remain detectable during SLS when controlling for weight-bearing, and whether these measures are associated with gait performance. Our results showed that during the perturbation-induced SLS, individuals post-stroke had lower hip abduction torque, less vertical stiffness, and increased frontal plane angular impulse at the paretic limb compared to the non-paretic limb, while no differences were found between the paretic limb and healthy controls. In addition, vertical stiffness during perturbation-induced SLS was positively correlated with single support duration during gait at the paretic limb and predicted self-selected and fast walking speeds in individuals post-stroke. The findings indicate that reduced paretic hip abduction torque during SLS likely affects vertical support and balance control. Enhancing SLS hip abduction torque production could be an important rehabilitation target to improve walking function for individuals post-stroke.


Subject(s)
Gait Disorders, Neurologic , Stroke Rehabilitation , Stroke , Humans , Gait/physiology , Stroke/complications , Walking/physiology , Hip , Biomechanical Phenomena , Paresis
2.
BJU Int ; 133(4): 460-473, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38031657

ABSTRACT

OBJECTIVES: To describe the health-related quality of life (HRQoL) of patients in a prospective 12-month observational cohort study of new bladder cancer diagnoses and compare with national cancer and general population surveys. PATIENTS AND METHODS: A prospective UK study in patients with new bladder cancer diagnoses at 13 NHS Trusts. The HRQoL data were collected at 3, 6, 9 and 12 months. Questionnaires used included: the EuroQoL five Dimensions (EQ-5D), European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-30-item core, EORTC QLQ-24-item non-muscle-invasive bladder cancer, and EORTC QLQ-30-item muscle-invasive bladder cancer. Results were compared with the Cancer Quality of Life Survey and Health Survey for England. RESULTS: A total of 349 patients were recruited, 296 (85%) completed the first (baseline) and 233 (67%) the final survey. The patients underwent transurethral resection of bladder tumour (TURBT) ± intravesical therapy (238 patients, 80%), radical cystectomy/radiotherapy (51, 17%) or palliation (seven, 2%). At baseline, patients needing radical treatment reported worse HRQoL including lower social function (74.2 vs 83.8, P = 0.002), increased fatigue (31.5 vs 26.1, P = 0.03) and more future worries (39.2 vs 29.4, P = 0.005) than patients who underwent TURBT. Post-treatment surveys showed no change/improvements for patients who underwent TURBT but deterioration for the radically treated cohort. At final survey, reports were similar to baseline, regardless of treatment. Radically treated patients continued to report poorer HRQoL including issues with body image (23.4 vs 12.5, P = 0.007) and male sexual function (75.8 vs 40.4, P < 0.001) compared to those who underwent TURBT. Radically treated patients reported lower EQ-5D utility scores and more problems with usual activities than the general population. DISCUSSION: Patients undergoing TURBT can be reassured regarding HRQoL following treatment. However, those requiring radical treatment report greater changes in HRQoL with the need for appropriate clinical and supportive care to minimise the impact of treatments.


Subject(s)
Quality of Life , Urinary Bladder Neoplasms , Humans , Male , Prospective Studies , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/pathology , Surveys and Questionnaires , Longitudinal Studies
3.
MethodsX ; 11: 102399, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37830002

ABSTRACT

Assessment of protective arm reactions associated with forward falls are typically performed by dropping research participants from a height onto a landing surface. The impact velocity is generally modulated by controlling the total height of the fall. This contrasts with an actual fall where the fall velocity is dependent on several factors in addition to fall height and not likely predictable at the onset of the fall. A counterweight and pulley system can be used to modulate the fall velocity in simulated forward falls in a manner that is not predictable to study participants, enhancing experimental validity. However, predicting the fall velocity based on participant height and weight and counterweight mass is not straightforward. In this article, the design of the FALL simulator For Injury prevention Training and assessment (FALL FIT) system is described. A dynamic model of the FALL FIT and counterweight system is developed and model parameters are fit using nonlinear optimization and experimental data. The fitted model enables prediction of fall velocity as a function of participant height and weight and counterweight load. The method can be used to provide controllable perturbations thereby elucidating the control strategy used when protecting the body from injury in a forward fall, how the control strategy changes because of aging or dysfunction or as a method for progressive protective arm reaction training.•Construction of device to simulate forward falls with controllable impact velocity using material that are commercially available is described•A dynamic model of the FALL FIT is developed to estimate the impact velocity of a simulated forward fall using participant height and counterweight load•The dynamic model is validated using data from 3 previous studies.

4.
Sci Rep ; 13(1): 9461, 2023 06 10.
Article in English | MEDLINE | ID: mdl-37301848

ABSTRACT

Acetabular labral tears have shown to be difficult to diagnose and manage in an active and competitive athletic population. The goal of this study was to compare NCAA Division 1 collegiate athletes undergoing operative and non-operative management of their labral injuries by assessing ability to return to competition and secondarily evaluate days lost from sport. A retrospective cohort analysis was conducted on Division 1 collegiate athletes from 2005 to 2020, incorporating all varsity university sports. Records showing MRI confirmed diagnosis were included in the cohort, as well as all pertinent clinical data. Data revealed 10/18 (55%) of individuals managed conservatively versus 23/29 (79%) surgically (p-value = 0.0834) were able to return to sport following treatment. Of those athletes, 22 surgical patients experienced a mean of 324 days ± 223 days lost from sport and nine conservatively managed patients experienced a mean of 27 days ± 70 lost days (p-value < 0.001) Seven of nine conservatively managed patients were able to continue competition while undergoing treatment. Findings suggest no statistical significance regarding operative vs non-operative management of acetabular labral tears. The majority of athletes returning to sport and treated conservatively were able to resume competition during treatment. Therefore, treatment of these injuries should be individualized based on athlete's symptoms.


Subject(s)
Athletic Injuries , Sports , Humans , Retrospective Studies , Athletic Injuries/diagnostic imaging , Athletic Injuries/surgery , Athletes , Cohort Studies
5.
Foot Ankle Int ; 44(7): 579-586, 2023 07.
Article in English | MEDLINE | ID: mdl-37212175

ABSTRACT

BACKGROUND: Arthroscopic ankle arthrodesis (AAA) is a successful treatment for end-stage ankle arthritis. A significant early complication of AAA is symptomatic nonunion. Published nonunion rates range from 8% to 13%. Longer term, there is concern that it predisposes to subtalar joint (STJ) fusion. To better understand these risks, we undertook a retrospective investigation of primary AAA. METHODS: All adult AAA cases conducted at our institution over a 10-year period were reviewed. A total of 284 eligible AAA cases in 271 patients were analyzed. The primary outcome measure was radiographic union. Secondary outcome measures included reoperative rate, postoperative complications and subsequent STJ fusion. Univariate and multivariate logistic regression analysis was performed to identify nonunion risk factors. RESULTS: The overall nonunion rate was 7.7%. Smoking (odds ratio [OR] 4.76 [1.67, 13.6], P = .004) and previous triple fusion (OR 40.29 [9.46, 171.62], P < .001) were independent risk factors on univariate analysis. Only prior triple fusion persisted as a major risk factor associated with nonunion on multivariate analysis (OR 18.3 [3.4, 99.7], P < .001). Seventy percent of patients with a previous triple fusion went on to develop nonunion compared to 5.5% of those without. Increasing age, obesity, surgical grade, diabetes, postoperative weightbearing plan, steroid use, and inflammatory arthropathy were not significant risk factors. The leading cause of reoperation was hardware removal (18%). There were 5 superficial (1.8%) and 4 deep (1.4%) infections. Eleven (4.2%) required subsequent STJ fusion. The "survivorship" of STJ post AAA was 98%, 85%, and 74% at 2, 5, and 9 years, respectively. CONCLUSION: As the largest study of AAA in the literature, our findings suggest prior triple fusion is a major independent risk factor for AAA nonunion. These patients should be counseled of this high risk and may benefit from alternative surgical options. LEVEL OF EVIDENCE: Level III, retrospective cohort study.


Subject(s)
Ankle , Arthritis , Adult , Humans , Retrospective Studies , Treatment Outcome , Arthritis/surgery , Arthritis/etiology , Ankle Joint/diagnostic imaging , Ankle Joint/surgery , Arthrodesis/adverse effects
6.
bioRxiv ; 2023 Apr 12.
Article in English | MEDLINE | ID: mdl-37090545

ABSTRACT

Background: After stroke, deficits in paretic single limb stance (SLS) are commonly observed and affect walking performance. During SLS, the hip abductor musculature is critical in providing vertical support and regulating balance. Although disrupted paretic hip abduction torque production has been identified in individuals post-stroke, interpretation of previous results is limited due to the discrepancies in weight-bearing conditions. Objective: To investigate whether deficits in hip abduction torque production, vertical body support, and balance regulation remain during SLS when controlling for weight-bearing using a perturbation-based assessment, and whether these measures are associated with gait performance. Methods: We compared hip abduction torque, vertical stiffness, and frontal plane angular impulse between individuals post-stroke and healthy controls when SLS was induced by removing the support surface underneath one limb. We also tested for correlations between vertical stiffness and angular impulse during perturbation-induced SLS and gait parameters during overground walking. Results: During the perturbation-induced SLS, lower hip abduction torque, less vertical stiffness, and increased frontal plane angular impulse were observed at the paretic limb compared to the non-paretic limb, while no differences were found between the paretic limb and healthy controls. Vertical stiffness during perturbation-induced SLS was positively correlated with single support duration during gait at the paretic limb and predicted self-selected and fast walking speeds in individuals post-stroke. Conclusions: Reduced paretic hip abduction torque during SLS likely affects vertical support and balance control. Enhancing SLS hip abduction torque production could be an important rehabilitation target to improve walking function for individuals post-stroke.

7.
Sports Biomech ; : 1-15, 2023 Apr 10.
Article in English | MEDLINE | ID: mdl-37038313

ABSTRACT

Preparatory lower-limb loading conditions may affect the jump-to-reach performance of soccer goalkeepers. This study investigated the effect of pre-jump lower-limb loading/unloading during bilateral knee flexion-extension movements on sideways jump-to-reach performance in 18 male collegiate soccer goalkeepers. Participants performed the two-choice (high and low targets) reaction-time single-leg jump-to-reach task under two conditions: without preparatory movements (no-prep) and with continuous alternating knee extension and flexion movements (prep). The 'go' cue was provided with different preparatory loading conditions during the pre-jump knee extension and flexion phases. Performance was assessed using three-dimensional kinematic data and ground reaction forces. A significant main effect of the preparatory condition was observed for the jump take-off time. Pairwise comparisons revealed that the jump take-off time was 3.4-4.4% faster when initiated during the knee flexion phase than the no-prep condition and the extension phase (p ≤ .028). Increasing lower-limb loading and downward body movement with knee flexion appeared to facilitate effective loading to take-off to reach the high target and faster downward-directed take-off to reach the low target, respectively. Pre-jump knee flexion movement could be utilised by soccer goalkeepers to facilitate faster take-off to maximise their chances of saving shots within the reach of single-leg side-jumping.

8.
J Biomech ; 150: 111515, 2023 03.
Article in English | MEDLINE | ID: mdl-36867953

ABSTRACT

Protective arm reactions have been shown to be an important injury avoidance mechanism in unavoidable falls. Protective arm reactions have been shown to be modulated with fall height, however it is not clear if they are modulated with impact velocity. The aim of this study was to determine if protective arm reactions are modulated in response to a forward fall with an initially unpredictable impact velocity. Forward falls were evoked via sudden release of a standing pendulum support frame with adjustable counterweight to control fall acceleration and impact velocity. Thirteen younger adults (1 female) participated in this study. Counterweight load explained more than 89% of the variation of impact velocity. Angular velocity at impact decreased (p < 0.001), drop duration increased from 601 ms to 816 ms (p < 0.001), and the maximum vertical ground reaction force decreased from 64%BW to 46%BW (p < 0.001) between the small and large counterweight. Elbow angle at impact (129 degrees extension), triceps (119 ms) and biceps (98 ms) pre-impact time, and co-activation (57%) were not significantly affected by counterweight load (p-values > 0.08). Average triceps and biceps EMG amplitude decreased from 0.26 V/V to 0.19 V/V (p = 0.004) and 0.24 V/V to 0.11 V/V (p = 0.002) with increasing counterweight respectively. Protective arm reactions were modulated with fall velocity by reducing EMG amplitude with decreasing impact velocity. This demonstrates a neuromotor control strategy for managing evolving fall conditions. Future work is needed to further understand how the CNS deals with additional unpredictability (e.g., fall direction, perturbation magnitude, etc.) when deploying protective arm reactions.


Subject(s)
Elbow Joint , Muscle, Skeletal , Animals , Female , Muscle, Skeletal/physiology , Movement/physiology , Elbow Joint/physiology , Forelimb , Biomechanical Phenomena
9.
Arch Phys Med Rehabil ; 104(2): 169-178, 2023 02.
Article in English | MEDLINE | ID: mdl-36087806

ABSTRACT

OBJECTIVE: To investigate the effect of 16-week home-based physical therapy interventions on gait and muscle strength. DESIGN: A single-blinded randomized controlled trial. SETTING: General community. PARTICIPANTS: Thirty-four older adults (N=34) post hip fracture were randomly assigned to either experimental group (a specific multi-component intervention group [PUSH], n=17, 10 women, age=78.6±7.3 years, 112.1±39.8 days post-fracture) or active control (a non-specific multi-component intervention group [PULSE], n=17, 11 women, age=77.8±7.8 years, 118.2±37.5 days post-fracture). INTERVENTION: PUSH and PULSE groups received 32-40 sessions of specific or non-specific multi-component home-based physical therapy, respectively. Training in the PUSH group focused on lower extremity strength, endurance, balance, and function for community ambulation, while the PULSE group received active movement and transcutaneous electrical nerve stimulation on extremities. MAIN OUTCOME MEASURES: Gait characteristics, and ankle and knee muscle strength were measured at baseline and 16 weeks. Cognitive testing of Trail Making Test (Part A: TMT-A; Part-B: TMT-B) was measured at baseline. RESULTS: At 16 weeks, both groups demonstrated significant increases in usual (P<.05) and fast (P<.05) walking speed, while there was no significant difference in increases between the groups. There was only 1 significant change in lower limb muscle strength over time (non-fractured side) between the groups, such that PUSH did better (mean: 4.33%, 95% confidence interval:1.43%-7.23%). The increase in usual and fast walking speed correlated with the baseline Trail-making Test-B score (r=-0.371, P=.037) and improved muscle strength in the fractured limb (r=0.446, P=.001), respectively. CONCLUSION: Gait speed improved in both home-based multicomponent physical therapy programs in older adults after hip fracture surgery. Muscle strength of the non-fractured limb improved in the group receiving specific physical therapy training. Specific interventions targeting modifiable factors such as muscle strength and cognitive performance may assist gait recovery after hip fracture surgery.


Subject(s)
Hip Fractures , Humans , Female , Aged , Aged, 80 and over , Hip Fractures/rehabilitation , Gait/physiology , Walking , Physical Therapy Modalities/psychology , Muscle Strength
10.
Sci Rep ; 12(1): 19104, 2022 11 09.
Article in English | MEDLINE | ID: mdl-36352032

ABSTRACT

Decreased loading of the paretic lower limb and impaired weight transfer between limbs negatively impact balance control and forward progression during gait in individuals post-stroke. However, the biomechanical and neuromuscular control mechanisms underlying such impaired limb loading remain unclear, partly due to their tendency of avoiding bearing weight on the paretic limb during voluntary movement. Thus, an approach that forces individuals to more fully and rapidly load the paretic limb has been developed. The primary purpose of this study was to compare the neuromechanical responses at the ankle and knee during externally induced limb loading in people with chronic stroke versus able-bodied controls, and determine whether energy absorption capacity, measured during induced limb loading of the paretic limb, was associated with walking characteristics in individuals post-stroke. Results revealed reduced rate of energy absorption and dorsiflexion velocity at the ankle joint during induced limb loading in both the paretic and non-paretic side in individuals post-stroke compared to healthy controls. The co-contraction index was higher in the paretic ankle and knee joints compared to the non-paretic side. In addition, the rate of energy absorption at the paretic ankle joint during the induced limb loading was positively correlated with maximum walking speed and negatively correlated with double limb support duration. These findings demonstrated that deficits in ankle dorsiflexion velocity may limit the mechanical energy absorption capacity of the joint and thereby affect the lower limb loading process during gait following stroke.


Subject(s)
Stroke Rehabilitation , Stroke , Humans , Stroke Rehabilitation/methods , Biomechanical Phenomena/physiology , Gait/physiology , Walking/physiology , Stroke/complications , Ankle Joint , Lower Extremity
11.
Front Sports Act Living ; 4: 1015394, 2022.
Article in English | MEDLINE | ID: mdl-36275443

ABSTRACT

Since the mid-2000s, perturbation-based balance training has been gaining interest as an efficient and effective way to prevent falls in older adults. It has been suggested that this task-specific training approach may present a paradigm shift in fall prevention. In this review, we discuss key concepts and common issues and questions regarding perturbation-based balance training. In doing so, we aim to provide a comprehensive synthesis of the current evidence on the mechanisms, feasibility and efficacy of perturbation-based balance training for researchers and practitioners. We address this in two sections: "Principles and Mechanisms" and "Implementation in Practice." In the first section, definitions, task-specificity, adaptation and retention mechanisms and the dose-response relationship are discussed. In the second section, issues related to safety, anxiety, evidence in clinical populations (e.g., Parkinson's disease, stroke), technology and training devices are discussed. Perturbation-based balance training is a promising approach to fall prevention. However, several fundamental and applied aspects of the approach need to be further investigated before it can be widely implemented in clinical practice.

12.
Int J Comput Assist Radiol Surg ; 17(10): 1823-1835, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35672594

ABSTRACT

PURPOSE: We aim to develop quantitative performance metrics and a deep learning model to objectively assess surgery skills between the novice and the expert surgeons for arthroscopic rotator cuff surgery. These proposed metrics can be used to give the surgeon an objective and a quantitative self-assessment platform. METHODS: Ten shoulder arthroscopic rotator cuff surgeries were performed by two novices, and fourteen were performed by two expert surgeons. These surgeries were statistically analyzed. Two existing evaluation systems: Basic Arthroscopic Knee Skill Scoring System (BAKSSS) and the Arthroscopic Surgical Skill Evaluation Tool (ASSET), were used to validate our proposed metrics. In addition, a deep learning-based model called Automated Arthroscopic Video Evaluation Tool (AAVET) was developed toward automating quantitative assessments. RESULTS: The results revealed that novice surgeons used surgical tools approximately 10% less effectively and identified and stopped bleeding less swiftly. Our results showed a notable difference in the performance score between the experts and novices, and our metrics successfully identified these at the task level. Moreover, the F1-scores of each class are found as 78%, 87%, and 77% for classifying cases with no-tool, electrocautery, and shaver tool, respectively. CONCLUSION: We have constructed quantitative metrics that identified differences in the performances of expert and novice surgeons. Our ultimate goal is to validate metrics further and incorporate these into our virtual rotator cuff surgery simulator (ViRCAST), which has been under development. The initial results from AAVET show that the capability of the toolbox can be extended to create a fully automated performance evaluation platform.


Subject(s)
Rotator Cuff Injuries , Surgeons , Arthroscopy/methods , Humans , Rotator Cuff/surgery , Rotator Cuff Injuries/diagnosis , Rotator Cuff Injuries/surgery , Shoulder , Treatment Outcome
13.
Kans J Med ; 15: 208-211, 2022.
Article in English | MEDLINE | ID: mdl-35762003

ABSTRACT

Introduction: There are few data addressing rodeo injury outcomes, though injury incidence has been well described. The purpose of this study was to describe rodeo-related injury patterns and outcomes. Methods: A 10-year retrospective case series was performed of patients injured in rodeo events and who were treated at an ACS-verified level I trauma center. Data regarding demographics, injury characteristics, and outcomes were summarized. Results: Seventy patients were identified. Half were injured by direct contact with rodeo stock and 34 by falls. Head injuries were most common, occurring in 38 (54.3%). Twenty injuries (28.6%) required surgery. Sixty-nine patients (98.6%) were discharged to home. There was one death. Conclusions: Head injuries were the most common injury among this cohort. Apart from one fatality, immediate outcomes after injury were good, with most patients dismissed home. Improved data collection at the time of admission may help to evaluate the success of current safety equipment use.

14.
MethodsX ; 9: 101702, 2022.
Article in English | MEDLINE | ID: mdl-35518921

ABSTRACT

The use of the hands and arms is an important protective mechanism in avoiding fall-related injury. The aim of this study was to evaluate the test-retest reliability of fall dynamics and evokd protective arm response kinematics and kinetics in forward falls simulated using the FALL simulator For Injury prevention Training and assessment system (FALL FIT). Fall FIT allows experimental control of the fall height and acceleration of the body during a forward fall. Two falls were simulated starting from 4 initial lean angles in Experiment 1 and with 4 different fall accelerations in Experiment 2. Fourteen younger adults (25.1±3.5 years) and 13 older adults (71.3±3.7 years) participated in Experiment 1 and 13 younger adults (31.8±5.7 years) participated in Experiment 2. Intraclass correlation coefficients (ICC) were used to the evaluate absolute agreement of single measures at each condition and averages across conditions. Average measures of fall dynamics and evoked kinematics and kinetics exhibited excellent reliability (ICC(A,4)>0.86). The reliability of single measures (ICC(A,1) > 0.59) was good to excellent, although 18% of single measures had a reliability (ICC(A,1)) between 0.00 and 0.57. The FALL FIT was shown to have good to excellent reliability for most measures. FALL FIT can produce a wide range of fall dynamics through modulation of initial lean angle and body acceleration. Additionally, the range of fall velocities and evoked kinematics and kinetics are consistent with previous fall research.•The FALL FIT can be used to gain further insight into the control of protective arm reactions and may provide a therapeutic tool to assess and train protective arm reactions.

15.
Foot Ankle Int ; 43(5): 694-702, 2022 05.
Article in English | MEDLINE | ID: mdl-35081798

ABSTRACT

BACKGROUND: Telemedicine offers convenient and affordable health care, overcoming the logistical challenges of face-to-face encounters. Clinicians increasingly relied on telemedicine during the global pandemic. To assess the ongoing role for telemedicine in orthopaedics, we prospectively analyzed the failure rate, safety and patient-reported experience of telephone consultations for 12 months. METHODS: 265 telephone Foot/Ankle consultations were conducted in April 2020 and were prospectively analyzed over 12 months. The primary outcome measure was the rate of failed telephone consultations. A consultation was deemed unacceptable if the patient did not answer, if the clinician could not reach a conclusion or if any outcome changed over 12 months. Secondary outcome measures included patient-reported satisfaction and time saved by avoiding a face-to-face visit. RESULTS: A clinical decision was reached in 84% of follow-up telephone consultations and 64% of new patient consultations (P = 0.001). Sixty-six percent were managed with nonoperative therapies, 16% were discharged, and 11% were added to the waiting list for surgery. The reasons for failing to achieve a clinical decision included failure to contact the patient (12.8%), inappropriate discharge with subsequent rereferral (1.9%), and insufficient clinical information (1.5%). Overall, 84.7% of patients reported that the telephone consultation was highly useful and 71.9% would recommend it to a friend or family member. Patients reported a mean time saving of 120 minutes. CONCLUSION: Based on our experience, we provide recommended criteria for the safe and practical use of telephone consultations and suggest versatile patient care pathways into which a telephone consultation can be incorporated. LEVEL OF EVIDENCE: Level IV, prospective cohort series (noncomparative).


Subject(s)
COVID-19 , Orthopedic Procedures , Orthopedics , Ankle/surgery , Follow-Up Studies , Humans , Patient Reported Outcome Measures , Prospective Studies , Referral and Consultation , Telephone
16.
Hum Mol Genet ; 31(5): 748-760, 2022 03 03.
Article in English | MEDLINE | ID: mdl-34559225

ABSTRACT

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy clinically characterized by weakness in the facial, shoulder girdle and upper a muscles. FSHD is caused by chromatin relaxation of the D4Z4 macrosatellite repeat, mostly by a repeat contraction, facilitating ectopic expression of DUX4 in skeletal muscle. Genetic diagnosis for FSHD is generally based on the sizing and haplotyping of the D4Z4 repeat on chromosome 4 by Southern blotting (SB), molecular combing or single-molecule optical mapping, which is usually straight forward but can be complicated by atypical rearrangements of the D4Z4 repeat. One of these rearrangements is a D4Z4 proximally extended deletion (DPED) allele, where not only the D4Z4 repeat is partially deleted, but also sequences immediately proximal to the repeat are lost, which can impede accurate diagnosis in all genetic methods. Previously, we identified several DPED alleles in FSHD and estimated the size of the proximal deletions by a complex pulsed-field gel electrophoresis and SB strategy. Here, using the next-generation sequencing, we have defined the breakpoint junctions of these DPED alleles at the base pair resolution in 12 FSHD families and 4 control individuals facilitating a PCR-based diagnosis of these DPED alleles. Our resultsshow that half of the DPED alleles are derivates of an ancient founder allele. For some DPED alleles, we found that genetic elements are deleted such as DUX4c, FRG2, DBE-T and myogenic enhancers necessitating re-evaluation of their role in FSHD pathogenesis.


Subject(s)
Muscular Dystrophy, Facioscapulohumeral , Alleles , Chromatin , Chromosomes, Human, Pair 4/genetics , Founder Effect , Humans , Muscular Dystrophy, Facioscapulohumeral/genetics , Muscular Dystrophy, Facioscapulohumeral/metabolism
17.
Hum Mov Sci ; 81: 102914, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34923206

ABSTRACT

Fall related injuries in older adults are a major healthcare concern. During a fall, the hands and arms play an important role in minimizing trauma from ground impact. Although older adults are able to orient the hands and arms into a protective orientation after falling and prior to ground impact, an inability to avoid increased body impact occurs with age. Previous investigations have generally studied rapid arm movements in the pre-impact phase or absorbing energy in the post-impact phase. There are no known studies that have directly examined both the pre-impact and post-impact phase in sequence in a forward fall. The aim of this study was to identify age-related biomechanical and neuromuscular changes in evoked arm reactions in response to forward falls that may increase fall injury risk. Fourteen younger and 15 older adults participated. Falls were simulated while standing with torso and legs restrained via a moving pendulum system from 4 different initial lean angles. While there was not a significant age-related difference in the amount of energy absorbed post-impact (p = 0.68), older adults exhibited an 11% smaller maximum vertical ground reaction force when normalized to body weight (p = 0.031), and 8 degrees less elbow extension at impact (p = 0.045). A significant interaction between age and initial lean angle (p = 0.024), indicated that older adults required 54%, 54%, 41%, and 57% greater elbow angular displacement after impact at the low, medium, medium-high, and high initial lean angles compared to younger adults. These results suggested older adults may be at greater risk of increased body impact due to increased elbow flexion angular displacement after impact when the hands and arms are able to contact the ground first. Both groups exhibited robust modulation to the initial lean angle with no observed age-related differences in the initial onset timing or amplitude of muscle activation levels. There were no significant age-related differences in the EMG timing, amplitude or co-activation of muscle activation preceding impact or following impact indicating comparable neuromotor response patterns between older and younger adults. These results suggest that aging changes in muscular elements may be more implicated in the observed differences than changes in neuromuscular capacity. Future work is needed to test the efficacy of different modalities (e.g. instruction, strength, power, perturbation training, fall landing techniques) aimed at reducing fall injury risk.


Subject(s)
Accidental Falls , Hand , Accidental Falls/prevention & control , Aged , Biomechanical Phenomena , Humans , Kinetics , Movement
18.
J Osteopath Med ; 122(2): 85-94, 2021 Nov 18.
Article in English | MEDLINE | ID: mdl-34787381

ABSTRACT

CONTEXT: Movement and loading asymmetry are associated with an increased risk of musculoskeletal injury, disease progression, and suboptimal recovery. Osteopathic structural screening can be utilized to determine areas of somatic dysfunction that could contribute to movement and loading asymmetry. Osteopathic manipulation treatments (OMTs) targeting identified somatic dysfunctions can correct structural asymmetries and malalignment, restoring the ability for proper compensation of stresses throughout the body. Little is currently known about the ability for OMTs to reduce gait asymmetries, thereby reducing the risk of injury, accelerated disease progression, and suboptimal recovery. OBJECTIVES: To demonstrate whether osteopathic screening and treatment could alter movement and loading asymmetry during treadmill walking. METHODS: Forty-two healthy adults (20 males, 22 females) between the ages of 18 and 35 were recruited for this prospective intervention. Standardized osteopathic screening exams were completed by a single physician for each participant, and osteopathic manipulation was performed targeting somatic dysfunctions identified in the screening exam. Three-dimensional (3-D) biomechanical assessments, including the collection of motion capture and force plate data, were performed prior to and following osteopathic manipulation to quantify gait mechanics. Motion capture and loading data were processed utilizing Qualisys Track Manager and Visual 3D software, respectively. Asymmetry in the following temporal, kinetic, and kinematic measures was quantified utilizing a limb symmetry index (LSI): peak vertical ground reaction force, the impulse of the vertical ground reaction force, peak knee flexion angle, step length, stride length, and stance time. A 2-way repeated-measures analysis of variance model was utilized to evaluate the effects of time (pre/post manipulation) and sex (male/female) on each measure of gait asymmetry. RESULTS: Gait asymmetry in the peak vertical ground reaction force (-0.6%, p=0.025) and the impulse of the vertical ground reaction force (-0.3%, p=0.026) was reduced in males following osteopathic manipulation. There was no difference in gait asymmetry between time points in females. Osteopathic manipulation did not impact asymmetry in peak knee flexion angle, step length, stride length, or stance time. Among the participants, 59.5% (25) followed the common compensatory pattern, whereas 40.5% (17) followed the uncommon compensatory pattern. One third (33.3%, 14) of the participants showed decompensation at the occipitoatlantal (OA) junction, whereas 26.2% (11), one third (33.3%, 14), and 26.2% (11) showed decompensation at the cervicothoracic (CT), thoracolumbar (TL), and lumbosacral (LS) junctions, respectively. Somatic dysfunction at the sacrum, L5, right innominate, and left innominate occurred in 88.1% (37), 69.0% (29), 97.6% (41), and 97.6% (41) of the participants, respectively. CONCLUSIONS: Correcting somatic dysfunction can influence gait asymmetry in males; the sex-specificity of the observed effects of osteopathic manipulation on gait asymmetry is worthy of further investigation. Osteopathic structural examinations and treatment of somatic dysfunctions may improve gait symmetry even in asymptomatic individuals. These findings encourage larger-scale investigations on the use of OMT to optimize gait, prevent injury and the progression of disease, and aid in recovery after surgery.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Manipulation, Osteopathic , Adolescent , Adult , Anterior Cruciate Ligament Injuries/surgery , Female , Gait , Humans , Knee Joint/surgery , Male , Prospective Studies , Young Adult
20.
PLoS Genet ; 17(8): e1009737, 2021 08.
Article in English | MEDLINE | ID: mdl-34375333

ABSTRACT

Ultradian glucocorticoid rhythms are highly conserved across mammalian species, however, their functional significance is not yet fully understood. Here we demonstrate that pulsatile corticosterone replacement in adrenalectomised rats induces a dynamic pattern of glucocorticoid receptor (GR) binding at ~3,000 genomic sites in liver at the pulse peak, subsequently not found during the pulse nadir. In contrast, constant corticosterone replacement induced prolonged binding at the majority of these sites. Additionally, each pattern further induced markedly different transcriptional responses. During pulsatile treatment, intragenic occupancy by active RNA polymerase II exhibited pulsatile dynamics with transient changes in enrichment, either decreased or increased depending on the gene, which mostly returned to baseline during the inter-pulse interval. In contrast, constant corticosterone exposure induced prolonged effects on RNA polymerase II occupancy at the majority of gene targets, thus acting as a sustained regulatory signal for both transactivation and repression of glucocorticoid target genes. The nett effect of these differences were consequently seen in the liver transcriptome as RNA-seq analysis indicated that despite the same overall amount of corticosterone infused, twice the number of transcripts were regulated by constant corticosterone infusion, when compared to pulsatile. Target genes that were found to be differentially regulated in a pattern-dependent manner were enriched in functional pathways including carbohydrate, cholesterol, glucose and fat metabolism as well as inflammation, suggesting a functional role for dysregulated glucocorticoid rhythms in the development of metabolic dysfunction.


Subject(s)
Corticosterone/pharmacology , Liver/pathology , Receptors, Glucocorticoid/metabolism , Animals , Gene Expression/genetics , Gene Expression Profiling/methods , Gene Expression Regulation/genetics , Glucocorticoids/metabolism , Liver/metabolism , Male , Periodicity , Protein Transport/genetics , RNA Polymerase II/genetics , RNA, Messenger/genetics , Rats , Rats, Sprague-Dawley , Receptors, Glucocorticoid/physiology , Transcriptional Activation/genetics , Transcriptome/genetics
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