3,N4-Etheno-5-methylcytosine blocks TET1-3 oxidation but is repaired by ALKBH2, 3 and FTO.

5-Methyldeoxycytidine (5mC) is a major epigenetic marker that regulates cellular functions in mammals. Endogenous lipid peroxidation can convert 5mC into 3,N4-etheno-5-methylcytosine (ϵ5mC). ϵ5mC is structurally similar to the mutagenic analog 3,N4-ethenocytosine (ϵC), which is repaired by AlkB family enzymes in the direct reversal repair (DRR) pathway and excised by DNA glycosylases in the base excision repair (BER) pathway. However, the repair of ϵ5mC has not been reported. Here, we examined the activities against ϵ5mC by DRR and BER enzymes and TET1-3, enzymes that modify the 5-methyl group in 5mC. We found that the etheno modification of 5mC blocks oxidation by TET1-3. Conversely, three human homologs in the AlkB family, ALKBH2, 3 and FTO were able to repair ϵ5mC to 5mC, which was subsequently modified by TET1 to 5-hydroxymethylcytosine. We also demonstrated that ALKBH2 likely repairs ϵ5mC in MEF cells. Another homolog, ALKBH5, could not repair ϵ5mC. Also, ϵ5mC is not a substrate for BER glycosylases SMUG1, AAG, or TDG. These findings indicate DRR committed by ALKBH2, 3 and FTO could reduce the detrimental effects of ϵ5mC in genetics and epigenetics and may work together with TET enzymes to modulate epigenetic regulations.

The Vehicle Seating Intervention Trial: Cross-Over Randomized Controlled Trial to Evaluate the Impact of 2 Car Seat Configurations on Spinal Posture.

Driving posture can lead to musculoskeletal pain. Most work focuses on the lower back; therefore, we know little about automobile seat design and neck posture. This study evaluated an automobile driver seat that individualized upper back support to improve head and neck posture. Specifically, we examined the system's impact on anterior head translation with secondary outcomes of spine posture and perceptions of comfort/well-being compared with a control. Forty participants were block randomized to experience either the activated or deactivated version of the same seating system first. Participants completed two 30-minute simulated driving trials, separated by washout, with continuous measures of anterior head translation, spine posture, and pelvis orientation. Perceptions of comfort/well-being were assessed by survey and open-ended questions immediately following each condition. Small, but statistically significant decreases in anterior head translation and posterior pelvic tilt occurred with the activated seat system. Participants reported lower satisfaction with the activated seat system. Order of the 2 seat conditions affected differences in pelvis orientation and participant perceptions of comfort/well-being. An anthropometric-based seat system targeting upper back support can significantly affect head and pelvic posture but not satisfaction during simulated driving. Future work should examine long-term impacts of these posture changes on health outcomes.

Induced leg length inequality affects pelvis orientation during upright standing immediately following a sit-to-stand transfer: a pre-post measurement study.

BACKGROUND: Leg length inequality (LLI) greater than 20 mm has been associated with low back pain (LBP) and its correction is clinically recommended. Much less is known about the biomechanical effects that LLI below 15 mm has on pelvis orientation. METHODS: Twenty-two adult participants (8 female) aged between 18 and 30 years without LBP were enrolled in the study and completed a series of sit-to-stand trials with no heel-lift (0 mm baseline) and heel-lifts of varying heights (5, 9 and 12 mm) placed in their right shoe. Three-dimensional kinematic data were obtained from the lower extremities, pelvis and thorax. Additional kinematic data were obtained from the left and right sides of the pelvis. The global orientation of the whole pelvis and relative orientation between the left and right sides of the pelvis were obtained in upright standing immediately upon completion of the sit-to-stand movement. Repeated measures ANOVAs were used to detect differences in sample means across the different levels of heel-lift (0, 5, 9, and 12 mm). The tests for within-subject effects determined overall significant differences between the means at the different levels of heel-lift induced LLI. Partial Eta-Squared was used to express the size for the main effect of heel-lift height. For each level of heel-lift, the estimated marginal mean and 95% confidence interval (95%CI) values of pelvis angles were illustrated graphically. RESULTS: Left frontal plane rotation of the pelvis increased (p = 0.001), that is, the left side of the pelvis was lower than the right side of the pelvis, and anterior tilt of the pelvis decreased (p = 0.020) with a heel-lift height (applied on the right) as low as 5 mm. A significant main effect of heel-lift was only observed for the norm of rotations about all three axes for relative-pelvis orientation (p = 0.034). Post-hoc analyses did not reveal any statistically significant differences between the heel-lifts and the 0 mm baseline (p≥0.072). CONCLUSION: These findings suggest that correcting leg length inequality below the recommended threshold of 20 mm may influence pelvic orientation. Future work can investigate the effects of the altered orientations on spine loading and the clinical effects of corrections to minor leg length inequality.

Experience influences kinematic motor synergies: an Uncontrolled manifold approach to simulated Nordic skiing.

Motor synergies are defined as central nervous system mechanisms which adjust participating degrees of freedom to ensure dynamic stability (control) of certain performance variables and have been identified during many motor tasks. The potential for synergistic control of individual segments during full-body tasks is often overlooked. Thus, this study compared individual differences in the potential stabilization of multiple performance variables on the basis of experience during a full-body sport activity. Normalized time series of synergy indices from Uncontrolled Manifold analyses on experienced (n = 9) and inexperienced (n = 19) participants were analysed using statistical parametric mapping during simulated Nordic skiing. Regardless of experience, hand, upper arm, and whole-body centre of mass (COM) kinematics were found to be stabilized by kinematic motor synergies. Only experienced Nordic skiers stabilized trunk COM position at all, while trunk COM velocity was stabilized for a longer duration than inexperienced participants. However, inexperienced participants stabilized hand velocity for a greater duration overall and to a greater magnitude during early pull phase than the experienced skiers. That motor synergies for hand and trunk COM velocity differed between experience groups suggests potential utility for these performance variables as indicators of motor skill development for full-body tasks such as Nordic skiing.

Can we enable individuals to reach further down without rounding their backs before beginning a lift? Examining the influence of starting foot and trunk position on reach depth.

There is disagreement regarding the efficacy of 'safe' lifting recommendations for reducing low back disorder risk. These recommendations commonly focus on minimising lumbar spine flexion, which limits the range of allowable starting lift positions for that person. This study evaluated whether starting postural adaptations could allow a person to reach down further without rounding their lumbar spine before beginning a lift. Reach displacement was measured as participants performed a series of maximal reach tasks under different combinations of stance width, foot orientation and trunk inclination, with their lumbar spine motion restricted. There were no interactions between any of the three postural adaptations or any effect of stance width or trunk inclination. Seventy-nine percent of participants achieved their greatest reach displacement with their feet externally rotated, which contributed to a 4 cm greater reach displacement compared to a neutral foot orientation (p < 0.001).Practitioner summary: This study examined whether aspects of initial posture could influence the ability to adhere to 'safe' lifting recommendations across a range of lift heights. As a component of lifting (re)training interventions, practitioners should consider starting lift posture adaptations (e.g. manipulating foot external rotation) to improve capacity to adhere to recommendations.

Characteristics of Forces at the Clinician-Patient and Patient-Table Interfaces During Thoracic Spinal Manipulation in Asymptomatic Adults Are Consistent With Deformable Body Models.

Investigating all forces exerted on the patient's body during high-velocity, low-amplitude spinal manipulative therapy (SMT) remains fundamental to elucidate how these may contribute to SMT's effects. Previous conflicting findings preclude our understanding of the relationship between SMT forces acting at the clinician-patient and patient-table interfaces. This study aimed to quantify forces at the clinician-participant and participant-table interfaces during thoracic SMT in asymptnomatic adults. An experienced clinician provided a posterior to anterior SMT centered to T7 transverse processes using predetermined force-time characteristics to 40 asymptomatic volunteers (20 females; average age = 27.2 [4.9] y). Forces at the clinician-participant interface were recorded by triaxial load cells; whereas, forces at the participant-table interface were recorded by the force-sensing table technology. Preload force, total peak force, time to peak, and loading rate at each interface were analyzed descriptively. Total peak vertical forces at the clinician-participant interface averaged 532 (71) N while total peak forces at the participant-table interface averaged 658 (33) N. Forces at the participant-table interface were, on average, 1.27 (0.25) times larger than the ones at the clinician-participant interface. Larger forces at the participant-table interface compared with the ones at the clinician-participant interface during thoracic SMT are consistent with mathematical models developed to investigate thoracic impact simulating a dynamic force-deflection response.

Spinal mobility in radiographic axial spondyloarthritis: criterion concurrent validity of classic and novel measurements.

BACKGROUND: Limitations in spinal mobility are a characteristic feature of Axial Spondyloarthritis. Current clinical measurements of spinal mobility have shown low criterion-concurrent validity. This study sought to evaluate criterion-concurrent validity for a clinically feasible measurement method of measuring spine mobility using tri-axial accelerometers. METHODS: Fifteen radiographic-Spondyloarthritis patients were recruited for this study. Two postural reference radiographs, followed by three trials in forward, left and right lateral bending were taken. For all trials, three measurements were collected: tape (Original Schober's, Modified Schober's, Modified-Modified Schober's, Lateral Spinal Flexion Test and Domjan Test), followed immediately by synchronized radiograph and accelerometer measurements at end range of forward and bilateral lateral flexion. The criterion-concurrent validity of all measurement methods was compared to the radiographic measures using Pearson's correlation coefficients. A Bland-Altman analysis was conducted to assess agreement. RESULTS: In forward bending, the accelerometer method (r = 0.590, p = 0.010) had a stronger correlation to the radiographic measures than all tape measures. In lateral bending, the Lateral Spinal Flexion tape measure (r = 0.743, p = 0.001) correlated stronger than the accelerometer method (r = 0.556, p = 0.016). The Domjan test of bilateral bending (r = 0.708, p = 0.002) had a stronger correlation to the radiographic measure than the accelerometer method. CONCLUSIONS: Accelerometer measures demonstrated superior criterion-concurrent validity compared to current tape measures of spinal mobility in forward bending. While a moderate correlation exists between accelerometer and radiographs in lateral bending, the Lateral Spinal Flexion Test and Domjan Test were found to have the best criterion-concurrent validity of all tests examined in this study.

Effect of Drop-Piece High-Velocity, Low-Amplitude Manipulation to the Midfoot of Asymptomatic Adult Sprinters on Performance During a Unilateral Horizontal Drop-Jump Test: A Feasibility Investigation.

OBJECTIVE: The purpose of this study was to investigate the feasibility of measuring the immediate effects of drop-piece high-velocity, low-amplitude (DP-HVLA) manipulation to the midfoot region on jump distance in competitive adult sprinters during a standardized unilateral horizontal drop-jump (U-HDJ) test. METHODS: Seven asymptomatic competitive adult sprinters (4 women) were recruited for this study. Testing was conducted on the dominant leg. Participants completed a 10-minute self-selected warm-up, followed by a 6-jump familiarization period with the U-HDJ test. All participants completed 3 U-HDJ trials before and after receiving DP-HVLA chiropractic manipulation to the joints of the midfoot assessed as being hypomobile by a licensed sports chiropractor. The primary outcome of the U-HDJ test was horizontal displacement, measured using an optoelectronic motion-capture system. Mean, SD, and 95% confidence intervals were determined for the posttreatment change in jump distance. A single-sample t test with α = 0.05 assessed the posttreatment change in jumping distance. RESULTS: We were able to measure immediate effects. The preliminary findings showed an increase in jump distance after DP-HVLA manipulation to the midfoot region (mean = 0.06 m, SD = 0.05 m; P = .014; 95% confidence interval, 0.02-0.11; effect size = 1.30). CONCLUSION: This study demonstrates that it was feasible to measure immediate improvement in performance after DP-HVLA chiropractic manipulation in a clinical assessment with correlation to sprinting performance in a population of elite sprinters. As this was a feasibility study, the small sample size, overlapping confidence intervals, and specific niche population limit the extrapolation of these findings.

A Kinematic Comparison Between Sit-to-Stand Movements and Individual Cycles of the 5-Cycle Sit-to-Stand Test.

OBJECTIVE: The 5-cycle sit-to-stand (5XSTS) test is frequently used to test physical function for different clinical populations, with time to complete as the measured outcome. This study evaluated the similarity of kinematics between a single cycle of the STS movement and individual cycles of the 5XSTS test. METHODS: Lower extremity, pelvis, and thorax kinematic data were monitored as 20 participants (aged 18-40) completed 5 trials of the STS movement and 1 trial of the 5XSTS test. Correlations and root mean squared differences assessed the temporal and spatial similarities in kinematic patterns of sagittal plane joint angles at the ankles, knees, hips, and spine between single cycles of the STS movement and individual cycles of the 5XSTS test. Peak joint angles were obtained along with discrete angles at the start, seat off, and end of the movement. RESULTS: Temporal and spatial similarity of kinematics for the ankles and hips were reduced over cycles 2 to 5 of the 5XSTS. Increased hip flexion was observed at the start of cycles 2 to 5 of the 5XSTS test. Increased knee and hip flexion were observed at the end of cycles 1 to 4 of the 5XSTS test. CONCLUSIONS: Temporal patterns of sagittal plane joint angles captured in the first cycle of the 5XSTS represented those adopted for an isolated STS movement. Different initial conditions for cycles 2 to 5 of the 5XSTS 58 may have reduced temporal and spatial similarity of sagittal plane joint angles of the ankles and hips.

The Impact of Moderate and High Intensity Cardiovascular Exertion on Sub-Elite Soccer Referee's Cognitive Performance: A Lab-Based Study.

Soccer referees represent a specialized population who are required to perform decisional or perceptual tasks during physical exertion. Recent studies have demonstrated that submaximal acute exercise has a positive impact on cognitive performance. However, less is known about the impact of more strenuous exertion on cognitive performance. This study assessed the effect of moderate and maximal intensity exercise exertion on a cognitive performance in sub-elite soccer referees. Twelve experienced soccer referees (4 female, 8 male) were recruited. Data were collected on 2 separate days. Baseline fitness level was assessed by a standardized aerobic capacity test (VO2max Test) on Day 1, along with practice trials of the Stroop Color Word Test (Stroop Test) for evaluating cognitive performance. On Day 2, cognitive performance was assessed before, during, and after an incremental intensity exercise protocol based on the Fédération International de Football Association (FIFA) referee fitness test. Relative to results obtained at rest performance on the Stroop Test improved at moderate exertion and at maximal exertion during the modified FIFA fitness test (F = 18.97, p = .005). Mean time to completion (in seconds) of the interference Stroop task significantly improved (p < .05) between rest and moderate exertion [-3.0 ± 3.0 seconds] and between rest and maximal exertion [-4.8 ± 2.6 seconds]. In summary, we observed that cognitive performance was found to improve when sub-elite soccer referees performed moderate and maximal exercise relative to results obtained at rest. It is possible that referees focus their attention to improve goal-oriented processing in the brain during physical exertion.

Spine loading during laboratory-simulated fireground operations - inter-individual variation and method of load quantification.

Spine loading data are needed to design low-back health-preserving ergonomic interventions for firefighters. Study objectives were to quantify spine loads during simulated fireground operations using simple (polynomial) and advanced (EMG-assisted musculoskeletal model) methods and to describe the variation in spine loads between performers (N = 20). Spine compression forces differed by as much as 5.5 times bodyweight between individuals performing identical tasks. Anteroposterior and mediolateral shear forces varied by as much 3.2 and 2.1 times bodyweight between individuals performing the same tasks, respectively. Large variations in spine load magnitudes were documented regardless of whether simple or advanced quantification methods were used. Results suggest that low-back loading demands on the fireground would vary widely depending on the physical characteristics of individual firefighters, movement strategies employed, and tasks performed. Thus, personalised ergonomic interventions are warranted to regulate spine loading and load tolerance in firefighters. Practitioner summary: Even when performing the same work, the associated spine loading demands will vary widely across people due to differences in their body sizes, shapes, and movement strategies. Therefore, personalised interventions are needed to regulate spine loading and load tolerance in workers (e.g. obesity prevention, physical capacity-building exercise, and movement [re]training).

Procedure Selection and Patient Positioning Influence Spine Kinematics During High-Velocity, Low-Amplitude Spinal Manipulation Applied to the Low Back.

OBJECTIVES: This investigation compared indirect 3-dimensional angular kinematics (position, velocity, and acceleration) of the lumbar spine for 2 different high-velocity, low-amplitude (HVLA) spinal manipulation procedures (lumbar spinous pull or push), and altered initial patient lower limb posture. METHODS: Twenty-four participants underwent 6 HVLA procedures directed toward the presumed L4 vertebra, reflecting each combination of 2 variants of a spinal manipulation application technique (spinous pull and push) and 3 initial hip flexion angles (0°, 45°, and 90°) applied using a right lateral recumbent patient position. All contact forces and moments between the patient and the external environment, as well as 3-dimensional kinematics of the patient's pelvis and thorax, were recorded. Lumbar spine angular positions, velocities, and accelerations were analyzed within the preload and impulse stages of each HVLA trial. RESULTS: Lumbar spine left axial rotation was greater for the pull HVLA. The pull HVLA also generated a greater maximum (leftward) and lower minimum (rightward) axial rotation velocity and deceleration and greater leftward and rightward lateral bend velocities, acceleration, and deceleration components. Not flexing the hip produced the greatest amount of extension, as well as the lowest axial rotation and maximum axial rotation acceleration during the impulse. CONCLUSIONS: This investigation provides basic kinematic information for clinicians to understand the similarities and differences between 2 HVLA side-lying manipulations in the lumbar spine. Use of these findings and novel technology can drive future research initiatives that can both affect clinical decision making and influence teaching environments surrounding spinal manipulative therapy skill acquisition.

The biomechanical demands of manual scaling on the shoulders & neck of dental hygienists.

The purpose of this study was to evaluate the postural and muscular demands placed on the shoulders and neck of dental hygienists when performing a simulated manual scaling task. Nineteen healthy female dental hygienists performed 30-min of simulated manual scaling on a manikin head in a laboratory setting. Surface electromyography was used to monitor muscle activity from several neck and shoulder muscles, and neck and arm elevation kinematics were evaluated using motion capture. The simulated scaling task resulted in a large range of neck and arm elevation angles and excessive low-level muscular demands in the neck extensor and scapular stabilising muscles. The physical demands varied depending on the working position of the hygienists relative to the manikin head. These findings are valuable in guiding future ergonomics interventions aimed at reducing the physical exposures of dental hygiene work. Practitioner Summary: Given that this study evaluates the physical demands of manual scaling, a procedure that is fundamental to dental hygiene work, the findings are valuable to identify ergonomics interventions to reduce the prevalence of work-related injuries, disability and the potential for early retirement among this occupational group.

Development of a Linked Segment Model to Derive Patient Low Back Reaction Forces and Moments During High-Velocity Low-Amplitude Spinal Manipulation.

OBJECTIVE: The purpose of this paper is to present the experimental setup, the development, and implementation of a new scalable model capable of efficiently handling data required to determine low back kinetics during high-velocity low-amplitude spinal manipulation (HVLA-SM). METHODS: The model was implemented in Visual3D software. All contact forces and moments between the patient and the external environment (2 clinician hand contact forces, 1 contact force between the patient and the treatment table), the patient upper body kinematics, and inertial properties were used as input. Spine kinetics and kinematics were determined from a single HVLA-SM applied to one healthy participant in a right side-lying posture to demonstrate the model's utility. The net applied force was used to separate the spine kinetic and kinematic time-series data from the HVLA-SM into preload as well as early and late impulse phases. RESULTS: Time-series data obtained from the HVLA-SM procedure showed that the participant's spine underwent left axial rotation, combined with extension, and a reduction in left lateral bending during the procedure. All components of the reaction force, as well as the axial twist and flexion/extension reaction moments demonstrated a sinusoidal pattern during the early and late impulse phases. During the early impulse phase, the participant's spine experienced a leftward axial twisting moment of 37.0 Nm followed by a rightward moment of -45.8 Nm. The lateral bend reaction moment exhibited a bimodal pattern during the early and late impulse phases. CONCLUSION: This model was the first attempt to directly measure all contact forces acting on the participant/patient's upper body, and integrate them with spine kinematic data to determine patient low back reaction forces and moments during HVLA-SM in a side-lying posture. Advantages of this model include the brevity of data collection (<1 hour), and adaptability for different patient anthropometries and clinician-patient contacts.

Working position influences the biomechanical demands on the lower back during dental hygiene.

This investigation monitored the biomechanical demands on the lower back during simulated dental hygiene work. A total of 19 female, registered dental hygienists performed 30 continuous minutes of manual scaling (plaque removal) of a manikin's teeth while seated. We monitored the working location and orientation of the dental hygienists, with respect to the manikin, along with their spine kinematics, spine extensor muscle activities and seat pressure, throughout the 30 min. A clock representation was used to express the working location. The location significantly influenced the dental hygienists' pelvic orientation with respect to the manikin, spine posture, erector muscle activity and pressure distribution. Findings from this study suggest that the prevalence of lower back pain amongst dental hygienists may be directly related to low-level tonic activity of the spine's extensor musculature, and the combined flexed and axially rotated spine postures. Practitioner Summary: Low back pain (LBP) is prevalent in dental hygienists, yet occupational demand on the low back has not been investigated. Posture, muscle activity and seat pressure were monitored. Combined spine rotation and flexion, and tonic activity of the extensor musculature may be related to LBP in dental hygienists.

Comparison of 2 methods of measuring spine angular kinematics during dynamic flexion movements: skin-mounted markers compared with markers affixed to rigid bodies.

OBJECTIVE: The purpose of this study was to compare the spine flexion angle time histories computed with the 2 described techniques (dot product [DP] and a modified joint coordinate system [JCS] approaches) that used vector algebra and used skin-mounted markers to the spine flexion angles derived using local coordinate systems constructed from rigid bodies affixed to the pelvis and thorax during spine flexion movements. METHODS: Discrepancies between the simplified marker setup and a criterion standard (CS) method for measuring spine kinematics were quantified. Sixteen participants performed full forward spine flexion. Three-dimensional kinematic data were obtained from markers affixed bilaterally over the greater trochanters, iliac crests, and 10th ribs. Time varying spine flexion angles were derived from the 3-, and 2-dimensional marker data using a DP and a modified JCS approach. Criterion standard spine kinematics were obtained from clusters of markers adhered to 2 rigid fins that were affixed over the pelvis and trunk. The DP and JCS methods were compared with the CS by computing root mean squared differences and correlations during the spine flexion trials. Descriptive measurements of missing kinematic data were also obtained. RESULTS: On average, root mean squared differences were 30.1% lower for the JCS method of deriving spine flexion angles. Correlations were also higher for the JCS method by 2.5%, compared with the DP method. CONCLUSION: The findings suggest that the adapted JCS method is superior to the DP method for deriving spine flexion angles. This is especially true when only 2-dimensional coordinate data are available.

Restricting lumbar spine flexion redistributes and changes total mechanical energy expenditure during lifting.

Minimizing lumbar spine flexion during lifting requires greater lower extremity joint motion. However, the effects of these kinematic changes on lumbar and lower extremity joint kinetics are unknown. Further, it is unclear whether the distribution of biomechanical demands throughout the lumbar spine and lower extremity during lumbar spine flexion restricted lifting are modulated by task factors like lift origin height and object mass. This study examined the influence of restricting lumbar spine flexion during lifting on the distribution of biomechanical demands, operationalized as mechanical energy expenditure (MEE), across the lumbar spine and lower extremity joints during lifting tasks. Twenty participants performed a series of lifting tasks that varied by lift origin height, object mass and presence or absence of lumbar spine motion restricting harness. MEE was quantified for the lumbar spine and lower extremity joints and summed across all joints to represent the total MEE. Distributions of MEE were compared across combinations of the three task factors. Total MEE was greater when lifting with restricted spine motion (p < 0.001). MEE was redistributed away from the lumbar spine and predominantly to the hips in the spine restricted conditions (p < 0.001). The nature and magnitude of this effect was modulated by lift origin height for the lumbar spine (p < 0.001) and hips (p < 0.001). Findings demonstrated that biomechanical demands can be shifted from the lumbar spine to the lower extremity when lifting with restricted spine flexion, which might help mitigate overuse injuries through coordinative variability.

A systematic review and meta analysis of measurement properties for the flexion relaxation ratio in people with and without non specific spine pain.

This review sought to identify, critically appraise, compare, and summarize the literature on the reliability, discriminative validity and responsiveness of the flexion relaxation ratio (FRR) in adults (≥ 18 years old) with or without spine pain (any duration), in either a clinical or research context. The review protocol was registered on Open Science Framework ( https://doi.org/10.17605/OSF.IO/27EDF ) and follows COSMIN, PRISMA, and PRESS guidelines. Six databases were searched from inception to June 1, 2022. The search string was developed by content experts and a health services librarian. Two pairs of reviewers independently completed titles/abstracts and full text screening for inclusion, data extraction, and risk of bias assessment (COSMIN RoB Toolkit). At all stages, discrepancies were resolved through consensus meetings. Data were pooled where possible with a three-level random effects meta-analyses and a modified GRADE assessment was used for the summary of findings. Following duplicate removal, 728 titles/abstracts and 219 full texts were screened with 23 included in this review. We found, with moderate certainty of evidence, that the cervical FRR has high test-retest reliability and lumbar FRR has moderate to high test-retest reliability, and with high certainty of evidence that the cervical and lumbar FRR can discriminate between healthy and clinical groups (standardized mean difference - 1.16 [95% CI - 2.00, - 0.32] and - 1.21 [- 1.84, - 0.58] respectively). There was not enough evidence to summarize findings for thoracic FRR discriminative validity or the standard error of measurement for the FRR. Several studies used FRR assuming responsiveness, but no studies were designed in a way that could confirm responsiveness. The evidence supports adequate reliability of FRR for the cervical and lumbar spine, and discriminative validity for the cervical and lumbar spine only. Improvements in study design and reporting are needed to strengthen the evidence base to determine the remaining measurement properties of this outcome.

An international consensus on gaps in mechanisms of forced-based manipulation research: findings from a nominal group technique.

Force-Based Manipulation (FBM) including light touch, pressure, massage, mobilization, thrust manipulation, and needling techniques are utilized across several disciplines to provide clinical analgesia. These commonly used techniques demonstrate the ability to improve pain-related outcomes; however, mechanisms behind why analgesia occurs with these hands-on interventions has been understudied. Neurological, neuroimmune, biomechanical, neurovascular, neurotransmitter, and contextual factor interactions have been proposed to influence response; however, the specific relationships to clinical pain outcomes has not been well established. The purpose of this study was to identify gaps present within mechanism-based research as it relates to FBM. An international multidisciplinary nominal group technique (NGT) was performed and identified 37 proposed gaps across eight domains. Twenty-three of these gaps met consensus across domains supporting the complex multisystem mechanistic response to FBM. The strength of support for gaps within the biomechanical domain had less overall support than the others. Gaps assessing the influence of contextual factors had strong support as did those associating mechanisms with clinical outcomes (translational studies). The importance of literature investigating how FBM differs with individuals of different pain phenotypes (pain mechanism phenotypes and clinical phenotypes) was also presented aligning with other analgesic techniques trending toward patient-specific pain management (precision medicine) through the use of pain phenotyping.