Determination of 3D spinal kinematics without defining a local vertebral coordinate system

In this paper a method is presented to calculate Euler's angles of rotation of a body segment during locomotion without a priori defining the location of the center of rotation, and without defining a local vertebral coordinate system. The method was applied to in vivo spinal kinematics. In this method, the orientation of each segment is identified by a set of three markers. The orientation of the axes of rotation is calculated based on the average position of the markers during one stride cycle. Some restrictions and assumptions should be made. The approach is viable only when the average orientation of the anatomical axes of rotation of each spinal segment during a stride cycle coincides with the three axes of the laboratory coordinate system. Furthermore, the rotations should be symmetrical with respect to both sides of the plane of symmetry of the spinal segment, and the subject should move parallel to one axis of the laboratory coordinate system. Since in experimental conditions these assumptions will only be met approximately, errors will be introduced in the calculated angles of rotation. The magnitude of the introduced errors was investigated in a computer simulation experiment. Since the maximal errors did not exceed 0.7° in a range of misalignments up to 10° between the two coordinate systems, the approach proved to be a valid method for the estimation of spinal kinematics.     

A demonstration of the validity of a 3-D video motion analysis method for measuring finger flexion and extension

This study demonstrates the validity of using 3-D video motion analysis to measure hand motion. Several researchers have devised ingenious methods to study normal and abnormal hand movements. Although very helpful, these earlier studies are static representations of a dynamic phenomenon. Despite the many studies of hand motion using scientifically impeccable techniques, little is known about digital motion, and there are still few researchers investigating dynamic three-dimensional motion of the hand. Results from a three-camera video motion analysis system were compared to those from the “gold standard”, 2-D lateral view fluoroscopy. We used these two methods to record hand motion simultaneously during unrestricted flexion and extension of the index finger of the dominant hand in 6 neurologically normal, healthy volunteers. After collection and post-processing, the waveforms of the PIP, DIP and MCP joint angles were compared using the adjusted coefficient of multiple determination (R²_a, or CMD). The mean CMD values for the MCP, PIP and DIP joint angle waveforms were 0.96, 0.98 and 0.94, respectively, suggesting a close similarity between motion of comparable joints analyzed by the 2-D and 3-D methods. This shows that the method of 3-D motion analysis is capable of accurately quantifying digital joint motion.

It is anticipated that 3-D motion analysis, in addition to being used as a research tool, will also have clinical applications such as surgical planning in neuromuscular disorders and the documentation of abnormal motion in many other pathological hand conditions.     

The pregnant “waddle”: An evaluation of torso kinematics in pregnancy

Although pregnant women are anecdotally said to “waddle” during gait, researchers have not quantified the kinematics of these gait alterations. The purpose of this study was to examine the effects of pregnancy on thoracic and pelvic kinematics during gait.     

Lumbar spine angles and intervertebral disc characteristics with end-range positions in three planes of motion in healthy people using upright MRI

Understanding changes in lumbar spine (LS) angles and intervertebral disc (IVD) behavior in end-range positions in healthy subjects can provide a basis for developing more specific LS models and comparing people with spine pathology. The purposes of this study are to quantify 3D LS angles and changes in IVD characteristics with end-range positions in 3 planes of motion using upright MRI in healthy people, and to determine which intervertebral segments contribute most in each plane of movement. Thirteen people (average age = 24.4 years, range 18–51 years; 9 females; BMI = 22.4 ± 1.8 kg/m²) with no history of low back pain were scanned in an upright MRI in standing, sitting flexion, sitting axial rotation (left, right), prone on elbows, prone extension, and standing lateral bending (left, right). Global and local intervertebral LS angles were measured. Anterior-posterior length of the IVD and location of the nucleus pulposus was measured. For the sagittal plane, lower LS segments contribute most to change in position, and the location of the nucleus pulposus migrated from a more posterior position in sitting flexion to a more anterior position in end-range extension. For lateral bending, the upper LS contributes most to end-range positions. Small degrees of intervertebral rotation (1–2°) across all levels were observed for axial plane positions. There were no systematic changes in IVD characteristics for axial or coronal plane positions.     

Optimization of compressive loading parameters to mimic in vivo cervical spine kinematics in vitro

The human cervical spine supports substantial compressive load in vivo. However, the traditional in vitro testing methods rarely include compressive loads, especially in investigations of multi-segment cervical spine constructs. Previously, a systematic comparison was performed between the standard pure moment with no compressive loading and published compressive loading techniques (follower load – FL, axial load – AL, and combined load – CL). The systematic comparison was structured a priori using a statistical design of experiments and the desirability function approach, which was chosen based on the goal of determining the optimal compressive loading parameters necessary to mimic the segmental contribution patterns exhibited in vivo. The optimized set of compressive loading parameters resulted in in vitro segmental rotations that were within one standard deviation and 10% of average percent error of the in vivo mean throughout the entire motion path. As hypothesized, the values for the optimized independent variables of FL and AL varied dynamically throughout the motion path. FL was not necessary at the extremes of the flexion–extension (FE) motion path but peaked through the neutral position, whereas, a large negative value of AL was necessary in extension and increased linearly to a large positive value in flexion. Although further validation is required, the long-term goal is to develop a “physiologic” in vitro testing method, which will be valuable for evaluating adjacent segment effect following spinal fusion surgery, disc arthroplasty instrumentation testing and design, as well as mechanobiology experiments where correct kinematics and arthrokinematics are critical.     

Effect of age and sex on lumbar lordosis and the range of motion. A systematic review and meta-analysis

Lumbar lordosis (LL) and the range of motion (RoM) are important physiological measurements when initiating any diagnosis and treatment plan for patients with low back pain. Numerous studies reported differences in LL and the RoM due to age and sex. However, these findings remain contradictory. A systematic review and meta-analysis were performed to synthesize mean values and the differences in LL and the RoM because of age and sex. The quality assessment tool for quantitative studies was applied to assess the methodological quality of the studies included.We identified 2372 papers through electronic (2309) and physical (63) searches. We assessed 218 full-text studies reporting measurements of LL or the RoM. In total, 65 studies were included, and a normative database for LL and the RoM is provided as supplementary material. Among these, 11 were included in the meta-analysis. LL and the RoM displayed non-monotonic variations with significant age and sex differences. Young females showed a significantly greater LL and the range of extension (RoE), whereas young males exhibited a greater range of flexion (RoF). Sex differences in the range of lateral bending (RoLB) were small but were significant for the axial rotation (RoAR). For the RoF, RoE and RoLB, differences because of age were significant among most of the age groups in both sexes, whereas for the RoAR, differences were significant only between the 20s vs the 30s-40s (males) and 40s vs 50s (females).Significant differences because of age/sex were identified. However, the age-dependent reduction in LL and the RoM was non-monotonic and differed in both sexes. These findings will help to better distinguish between functional deficits caused by spinal disorders and natural factors/conditions related to age and sex.     

Orientation and location of the finite helical axis of the equine forelimb joints

To reduce anatomically unrealistic limb postures in a virtual musculoskeletal model of a horse's forelimb, accurate knowledge on forelimb joint constraints is essential. The aim of this cadaver study is to report all orientation and position changes of the finite helical axes (FHA) as a function of joint angle for different equine forelimb joints. Five horse cadaver forelimbs with standardized cuts at the midlevel of each segment were used. Bone pins with reflective marker triads were drilled into the forelimb bones. Unless joint angles were anatomically coupled, each joint was manually moved independently in all three rotational degrees of freedom (flexion–extension, abduction–adduction, internal–external rotation). The 3D coordinates of the marker triads were recorded using a six infra-red camera system. The FHA and its orientational and positional properties were calculated and expressed against joint angle over the entire range of motion using a finite helical axis method. When coupled, joint angles and FHA were expressed in function of flexion–extension angle. Flexion–extension movement was substantial in all forelimb joints, the shoulder allowed additional considerable motion in all three rotational degrees of freedoms. The position of the FHA was constant in the fetlock and elbow and a constant orientation of the FHA was found in the shoulder. Orientation and position changes of the FHA over the entire range of motion were observed in the carpus and the interphalangeal joints. We report FHA position and orientation changes as a function of flexion–extension angle to allow for inclusion in a musculoskeletal model of a horse to minimize calculation errors caused by incorrect location of the FHA.     

Database for three dimensional structures of pepsin-like enzymes using the internal coordinate system

A database for 3D structures of pepsin-like enzymes has been created on the basis of a novel approach using the Internal Coordinate System (ICS). It allows rapid comparison of multiple structures of pepsin-like enzymes without the need for preliminary calculations. Atomic displacements measured by this approach are very close to those estimated by the superposition procedures widely employed in comparing three-dimensional structures of proteins. Any new structure of pepsin-like enzyme converted to the ICS automatically becomes superimposed with all structures in a database. The ICS approach can be used for any class of enzymes and is especially efficient for families containing a large number of homologous structures.     

Passive stiffness of hindlimb muscles in anurans with distinct locomotor specializations

Anurans (frogs and toads) have been shown to have relatively compliant skeletal muscles. Using a meta-analysis of published data we have found that muscle stiffness is negatively correlated with joint range of motion when examined across mammalian, anuran and bird species. Given this trend across a broad phylogenetic sample, we examined whether the relationship held true within anurans. We identified four species that differ in preferred locomotor mode and hence joint range of motion (Lithobates catesbeianus, Rhinella marina, Xenopus laevis and Kassina senegalensis) and hypothesized that smaller in vivo angles (more flexed) at the knee and ankle joint would be associated with more compliant extensor muscles. We measured passive muscle tension during cyclical stretching (20%) around L₀ (sarcomere lengths of 2.2 μm) in fiber bundles extracted from cruralis and plantaris muscles. We found no relationship between muscle stiffness and range of motion for either muscle–joint complex. There were no differences in the passive properties of the cruralis muscle among the four species, but the plantaris muscles of the Xenopus and Kassina were significantly stiffer than those of the other two species. Our results suggest that in anurans the stiffness of muscle fibers is a relatively minor contributor to stiffness at the level of joints and that variation in other anatomical properties including muscle–tendon architecture and joint mechanics as well as active control likely contribute more significantly to range of motion during locomotion.     

Reliability and sources of variability of 3D kinematics and electromyography measurements to assess newly-acquired gait in toddlers with typical development and unilateral cerebral palsy

The aim was to 1) determine intersession and intertrial reliability and 2) assess three sources of variability (intersubject, intersession and intertrial) of lower limb kinematic and electromyographic (EMG) variables during gait in toddlers with typical development (TD) and unilateral cerebral palsy (UCP) (age <3 years, independent walking experience ≤6 months). Gait kinematics and surface EMG were recorded in 30 toddlers (19 TD and 11 UCP), during two, 3D-motion capture sessions. Standard error of measurement (SEM) between trials (gait cycles) of the same session and between sessions was calculated to assess reliability. Standard deviations (SD) between subjects, sessions and trials were calculated to estimate sources of variability. Sixty-four percent of kinematic SEM-values were acceptable (2°-5°). Frontal plane measurements were most reliable (SEM 2°-4.6°). In toddlers with UCP, EMG variables were most reliable for affected side, distal muscles. Intrinsic (intertrial and intersubject) variability was high, reflecting both motor immaturity and the high variability of toddler gait patterns. In toddlers with UCP, variability was amplified by motor impairment and delayed motor development. 3D gait analysis and surface EMG are partially reliable tools to study individual gait patterns in toddlers in clinical practice and research, although some variables must be interpreted with caution.     

Discovery of benzenesulfonamide derivatives as potent PI3K/mTOR dual inhibitors with in vivo efficacies against hepatocellular carcinoma

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is related to cellular activities. Abnormalities of this signaling pathway were discovered in various cancers, including hepatocellular carcinoma (HCC). The PI3K/mTOR dual inhibitors were proposed to have enhanced antitumor efficacies by targeting multiple points of the signaling pathway. We synthesized a series of propynyl-substituted benzenesulfonamide derivatives as PI3K/mTOR dual inhibitors. Compound 7k (NSC781406) was identified as a highly potent dual inhibitor, which exhibited potent tumor growth inhibition in the hepatocellular carcinoma BEL-7404 xenograft model. Compound 7k may be a potential therapeutic drug candidate for HCC.     

Comparison of three S‐β‐CDs with different degrees of substitution for the chiral separation of 12 drugs in capillary electrophoresis

Three kinds of sulfated β‐cyclodextrin (S‐β‐CD), including a single isomer, heptakis‐6‐sulfato‐β‐cyclodextrin (HS‐β‐CD), degree of substitution (DS) of 7, which was synthesized in our laboratory and another two commercialized randomly substituted mixtures, a sulfated β‐cyclodextrin with DS of 7 to 11, as well as a highly sulfated‐β‐cyclodextrin with DS of 12 to 15, were used for the enantioresolution of 12 drugs (the β‐blockers, phenethylamines, and anticholinergic agents) in capillary electrophoresis. The enantioseparation under varying concentrations of S‐β‐CD and background electrolyte pH were systematically investigated and compared. Based on the experimental results, the effect of the nature of S‐β‐CD and analyte structure on the enantioseparation is discussed.     

Union of Geometric Constraint-Based Simulations with Molecular Dynamics for Protein Structure Prediction

Although proteins are a fundamental unit in biology, the mechanism by which proteins fold into their native state is not well understood. In this work, we explore the assembly of secondary structure units via geometric constraint-based simulations and the effect of refinement of assembled structures using reservoir replica exchange molecular dynamics. Our approach uses two crucial features of these methods: i), geometric simulations speed up the search for nativelike topologies as there are no energy barriers to overcome; and ii), molecular dynamics identifies the low free energy structures and further refines these structures toward the actual native conformation. We use eight α-, β-, and α/β-proteins to test our method. The geometric simulations of our test set result in an average RMSD from native of 3.7 Å and this further reduces to 2.7 Å after refinement. We also explore the question of robustness of assembly for inaccurate (shifted and shortened) secondary structure. We find that the RMSD from native is highly dependent on the accuracy of secondary structure input, and even slightly shifting the location of secondary structure along the amino acid sequence can lead to a rapid decrease in RMSD to native due to incorrect packing.     

Site-specific inhibition of photophosphorylation in isolated spinach chloroplasts by HgCl2. II. Evidence for three sites of energy conservation associated with non-cyclic electron transport

Energy transfer inhibition by HgCl₂ has been demonstrated to be selective for certain System I partial reactions. On the basis of different HgCl₂ effects on the System I reactions, reduced 2,6-dichlorophenolindophenol → methylviologen, diaminodurene → methylviologen and N-phenazine methosulfate cyclic, two sites of energy conservation associated with System I are proposed. Furthermore, these sites are in parallel with each other, in series with the site closely associated with Photosystem II and are shared between non-cyclic and cyclic electron transport.     

An investigation of the flexion relaxation ratio in adults with and without a history of self-reported low back pain and transient sitting-induced pain

It is unknown whether the presence of sitting-induced pain or a clinical history of low back pain (LBP) changes spine function outcomes such as the flexion relaxation ratio (FRR). The purpose of this investigation was to determine whether sitting-induced pain or a history of non-specific LBP results in a different FRR. Forty-seven participants were instrumented with surface electromyography over erector spinae at L1, and accelerometers at L1 and S2. Standing maximum lumbar flexion trials were taken preceding and following a 1-hour sitting trial. Pain ratings during sitting and history of LBP were used to group participants for analysis. FRR values taken after the sitting exposures were compared between those that did and did not develop pain during sitting. Baseline FRR values were compared participants with and without a history of LBP. No significant differences in FRR were found for either pain groups (p = 0.11) or clinical history (p = 0.85). Lack of differences may be due to participants not currently experiencing a clinical episode of pain when the ratio was measured and/or because 1-hour sitting exposure was not long enough to induce pain modulation. The findings suggest that neither sitting-induced pain development or clinical history need to be controlled to prevent confounding of FRR.     

Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based,propensity score analysis

BackgroundThis study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis.MethodsData on newly diagnosed metastatic PrCA cases (stage IV, N = 7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) comparing men who underwent definitive local therapy of the primary tumor to those who did not.ResultsAfter adjusting for sociodemographic and tumor attributes, having RP after diagnosis with metastatic PrCA was associated with 73% (HR = 0.27, 95% CI: 0.20–0.38) lower risk of all-cause mortality and 72% (HR = 0.28, 95% CI: 0.20–0.39) reduced risk of death from PrCA. Having BT also was associated with 57% (HR = 0.43, 95% CI: 0.31–0.59) and 54% (HR = 0.46, 95% CI: 0.33–0.64) lower risk of all-cause and PrCA-specific mortality. Similar results were observed in propensity score-adjusted analysis as well as when stratified by age and extent of tumor metastasis.ConclusionsThese findings suggest that definitive local therapy improves survival in men with metastatic PrCA at diagnosis. Future work should consider comorbidities, diet, physical activity and smoking status.     

Reference database of the gait cycle for young healthy Tunisian adults

BackgroundQuantified gait analysis is a rising technology used increasingly to assess motor disorders. Normal reference data are required in order to evaluate patients, but there are no reference data available for the Tunisian healthy population.AimTo assess the features of normal Tunisian gait pattern, and examine the intrinsic reliability of spatio-temporal, kinematic and kinetic parameters within a new specific reference database.MethodsEighteen healthy active-young adults (age: 23.30 ± 2.54 years, height: 1.78 ± 0.04 m and, weight: 70.00 ± 4.80 kg) have participated to five trials of step gait where the dominant lower limb were recorded. Two over the five trials were randomly selected to be further analyzed. Twenty-three spatio-temporal, kinematic and kinetic parameters determined from 3-dimensional gait analysis. The intrinsic reliability was examined for each variable and our results were compared with those available in the literature.ResultsTwelve over 23 parameters have an excellent intrinsic reliability (P > 0.05, ICC > 0.9 and SEM < 5% of the grand mean). There are similarities with other studies (P < 0.05) but we noticed the existence of some specificity (the height of hip extension peak and the low cadence of gait) that could characterize the Tunisian population.ConclusionA specific reference database of the gait cycle has been established for healthy Tunisian active-young adults and excellent inter-trial reliability may be observed for different variables.     

Development of a novel MATLAB-based framework for implementing mechanical joint stability constraints within OpenSim musculoskeletal models

The Static Optimization (SO) solver in OpenSim estimates muscle activations and forces that only equilibrate applied moments. In this study, SO was enhanced through an open-access MATLAB interface, where calculated muscle activations can additionally satisfy crucial mechanical stability requirements. This Stability-Constrained SO (SCSO) is applicable to many OpenSim models and can potentially produce more biofidelic results than SO alone, especially when antagonistic muscle co-contraction is required to stabilize body joints. This hypothesis was tested using existing models and experimental data in the literature. Muscle activations were calculated by SO and SCSO for a spine model during two series of static trials (i.e. simulation 1 and 2), and also for a lower limb model (supplementary material 2). In simulation 1, symmetric and asymmetric flexion postures were compared, while in simulation 2, various external load heights were compared, where increases in load height did not change the external lumbar flexion moment, but necessitated higher EMG activations. During the tasks in simulation 1, the predicted muscle activations by SCSO demonstrated less average deviation from the EMG data (6.8% −7.5%) compared to those from SO (10.2%). In simulation 2, SO predicts constant muscle activations and forces, while SCSO predicts increases in the average activations of back and abdominal muscles that better match experimental data. Although the SCSO results are sensitive to some parameters (e.g. musculotendon stiffness), when considering the strategy of the central nervous system in distributing muscle forces and in activating antagonistic muscles, the assigned activations by SCSO are more biofidelic than SO.