Hip extension, knee flexion paradox: a new mechanism for non-contact ACL injury

Considering that an athlete performs at-risk sports activities countless times throughout the course of his or her career prior to the instance of anterior cruciate ligament (ACL) injury, one may conclude that non-contact ACL injury is a rare event. Nevertheless, the overall number of non-contact ACL injuries, both in the US and worldwide, remains alarming due to the growing number of recreational and professional athletes participating in high-risk activities. To date, numerous non-contact ACL injury mechanisms have been proposed, but none provides a detailed picture of sequence of events leading to injury and the exact cause of this injury remains elusive. In this perspective article, we propose a new conception of non-contact ACL injury mechanism that comprehensively integrates risk factors inside and outside the knee joint. The proposed mechanism is robust in the sense that it is biomechanically justifiable and addresses a number of confounding issues related to ACL injury.     

The application of musculoskeletal modeling to investigate gender bias in non-contact ACL injury rate during single-leg landings

The central tenet of this study was to develop, validate and apply various individualised 3D musculoskeletal models of the human body for application to single-leg landings over increasing vertical heights and horizontal distances. While contributing to an understanding of whether gender differences explain the higher rate of non-contact anterior cruciate ligament (ACL) injuries among females, this study also correlated various musculoskeletal variables significantly impacted by gender, height and/or distance and their interactions with two ACL injury-risk predictor variables; peak vertical ground reaction force (VGRF) and peak proximal tibia anterior shear force (PTASF). Kinematic, kinetic and electromyography data of three male and three female subjects were measured. Results revealed no significant gender differences in the musculoskeletal variables tested except peak VGRF (p = 0.039) and hip axial compressive force (p = 0.032). The quadriceps and the gastrocnemius muscle forces had significant correlations with peak PTASF (r = 0.85, p < 0.05 and r = ? 0.88, p < 0.05, respectively). Furthermore, hamstring muscle force was significantly correlated with peak VGRF (r = ? 0.90, p < 0.05). The ankle flexion angle was significantly correlated with peak PTASF (r = ? 0.82, p < 0.05). Our findings indicate that compared to males, females did not exhibit significantly different muscle forces, or ankle, knee and hip flexion angles during single-leg landings that would explain the gender bias in non-contact ACL injury rate. Our results also suggest that higher quadriceps muscle force increases the risk, while higher hamstring and gastrocnemius muscle forces as well as ankle flexion angle reduce the risk of non-contact ACL injury.     

Development of dynamic knee stability after acute ACL injury.

Recently, a training program that includes perturbation of support surfaces has been shown to allow most active individuals with ACL injury who pass a screening examination to successfully return to high level activities. The purpose of this study was to identify the effect of this rehabilitation program on involved side muscle activation during walking in subjects with acute ACL rupture and to determine if the activation changes were coincident with improved function. Nine subjects with an acute, unilateral ACL injury or rupture of an ACL graft, who met the screening examination criteria, received ten sessions of rehabilitation that included perturbation training. Motion analysis of five self-paced walking trials were performed before and after training. Electromyographic (EMG) data were collected during stance. After training during walking, the vastus lateralis (VL) integral of activity increased, and relationships between muscles were significantly altered. During walking, VL activation variables were dependent on lateral hamstrings (LH) and/or the soleus (SOL) activation, while no relationships were found before training. Function improved after training, and all subjects returned to their pre-injury activities without experiencing instability. The relationships formed between muscles post-training suggests that perturbation training enhances dynamic knee stability by inducing a well-coordinated strategy among muscles that affect tibial translation.     

Sensitivity of medial and lateral knee contact force predictions to frontal plane alignment and contact locations

Musculoskeletal models are increasingly used to estimate medial and lateral knee contact forces, which are difficult to measure in vivo. The sensitivity of contact force predictions to modeling parameters is important to the interpretation and implication of results generated by the model. The purpose of this study was to quantify the sensitivity of knee contact force predictions to simultaneous errors in frontal plane knee alignment and contact locations under different dynamic conditions. We scaled a generic musculoskeletal model for N = 23 subjects’ stature and radiographic knee alignment, then perturbed frontal plane alignment and mediolateral contact locations within experimentally-possible ranges of 10° to −10° and 10 to −10 mm, respectively. The sensitivity of first peak, second peak, and mean medial and lateral knee contact forces to knee adduction angle and contact locations was modeled using linear regression. Medial loads increased, and lateral loads decreased, by between 3% and 6% bodyweight for each degree of varus perturbation. Shifting the medial contact point medially increased medial loads and decreased lateral loads by between 1% and 4% bodyweight per millimeter. This study demonstrates that realistic measurement errors of 5 mm (contact distance) or 5° (frontal plane alignment) could result in a combined 50% BW error in subject specific contact force estimates. We also show that model sensitivity varies between subjects as a result of differences in gait dynamics. These results demonstrate that predicted knee joint contact forces should be considered as a range of possible values determined by model uncertainty.     

The effects of core muscle activation on dynamic trunk position and knee abduction moments: Implications for ACL injury

Anterior cruciate ligament (ACL) injury is one of the most common serious lower-extremity injuries experienced by athletes participating in field and court sports and often occurs during a sudden change in direction or pivot. Both lateral trunk positioning during cutting and peak external knee abduction moments have been associated with ACL injury risk, though it is not known how core muscle activation influences these variables. In this study, the association between core muscle pre-activation and trunk position as well as the association between core muscle pre-activation and peak knee abduction moment during an unanticipated run-to-cut maneuver were investigated in 46 uninjured individuals. Average co-contraction indices and percent differences between muscle pairs were calculated prior to initial contact for internal obliques, external obliques, and L5 extensors using surface electromyography. Outside tilt of the trunk was defined as positive when the trunk was angled away from the cutting direction. No significant associations were found between pre-activations of core muscles and outside tilt of the trunk. Greater average co-contraction index of the L5 extensors was associated with greater peak knee abduction moment (p=0.0107). Increased co-contraction of the L5 extensors before foot contact could influence peak knee abduction moment by stiffening the spine, limiting sagittal plane trunk flexion (a motion pattern previously linked to ACL injury risk) and upper body kinetic energy absorption by the core during weight acceptance.     

Is lower limb muscle synchrony during landing affected by gender? Implications for variations in ACL injury rates.

This study examined whether lower limb muscle synchrony during abrupt landings was affected by gender, thereby predisposing females to a higher incidence of non-contact anterior cruciate ligament (ACL) injuries than males. Seven males and 11 females landed in single-limb stance on a force platform after receiving a chest-height netball pass and decelerating abruptly. Ground reaction force and electromyographic data for rectus femoris, vastus lateralis, vastus medialis, semimembranosus (SM), biceps femoris, and gastrocnemius were sampled (1000 Hz) during landing. Subjects' sagittal plane motion was also filmed (200 Hz). Knee joint reaction forces and sagittal planar net moments of force were estimated using Newtonian equations of motion and inverse dynamics. Tibiofemoral shear forces (F(s)) were obtained and muscle bursts temporally analysed with respect to initial foot-ground contact (IC) and peak F(s) times. Males displayed significantly delayed SM onset relative to IC (113+/-46 ms) compared to females (173+/-54 ms; p=0.03), and significantly delayed SM peak activity relative to peak F(s) (54+/-27 ms) compared to females (77+/-15 ms; p=0.03). Delayed SM activity during landing was suggested to allow peak muscle activity to better coincide with high anterior F(s), thereby acting as an ACL synergist via increased joint compression and posterior tibial drawer. It was concluded that females displayed muscle synchrony less protective of the ACL than males, possibly increasing their susceptibility to non-contact ACL injuries.     

The influence of limb alignment on the gait of above-knee amputees.

Biomechanical gait tests on above-knee amputees were conducted in which the alignment of the prosthesis was changed systematically. An eight-segment biomechanical model of the above-knee amputee was developed to analyse and present the three-dimensional kinematic and kinetic data obtained. The effects of alignment changes on the above-knee amputees' gait were studied in terms of the angular displacements of the lower limbs, ground reactions and intersegmental moments. It was found that following the alignment changes the angular displacement at the hip joint on the prosthetic side showed compensatory actions by the amputee. The ground reaction force was sensitive to alignment changes, and in particular, the changes in the characteristics of the fore-aft component of the ground force could be related to the alignment changes. The antero-posterior intersegmental moments at the prosthetic ankle and knee joints were evidently influenced by alignment.     

Energetic consequences of mechanical loads

In this brief review, we have focussed largely on the well-established, but essentially phenomenological, linear relationship between the energy expenditure of the heart (commonly assessed as the oxygen consumed per beat, oxygen consumption (VO2)) and the pressure-volume-area (PVA, the sum of pressure-volume work and a specified 'potential energy' term). We raise concerns regarding the propriety of ignoring work done during 'passive' ventricular enlargement during diastole as well as the work done against series elasticity during systole. We question the common assumption that the rate of basal metabolism is independent of ventricular volume, given the equally well-established Feng- or stretch-effect. Admittedly, each of these issues is more of conceptual than of quantitative import. We point out that the linearity of the enthalpy-PVA relation is now so well established that observed deviations from linearity are often ignored. Given that a one-dimensional equivalent of the linear VO2-PVA relation exists in papillary muscles, it seems clear that the phenomenon arises at the cellular level, rather than being a property of the intact heart. This leads us to discussion of the classes of crossbridge models that can be applied to the study of cardiac energetics. An admittedly superficial examination of the historical role played by Hooke's Law in theories of muscle contraction foreshadows deeper consideration of the thermodynamic constraints that must, in our opinion, guide the development of any mathematical model. We conclude that a satisfying understanding of the origin of the enthalpy-PVA relation awaits the development of such a model.     

A bit-parallel dynamic programming algorithm suitable for DNA sequence alignment

Myers' elegant and powerful bit-parallel dynamic programming algorithm for approximate string matching has a restriction that the query length should be within the word size of the computer, typically 64. We propose a modification of Myers' algorithm, in which the modification has a restriction not on the query length but on the maximum number of mismatches (substitutions, insertions, or deletions), which should be less than half of the word size. The time complexity is O(m log |Σ|), where m is the query length and |Σ| is the size of the alphabet Σ. Thus, it is particularly suited for sequences on a small alphabet such as DNA sequences. In particular, it is useful in quickly extending a large number of seed alignments against a reference genome for high-throughput short-read data produced by next-generation DNA sequencers.     

The influence of limb alignment and transfemoral amputation technique on muscle capacity during gait

Many factors influence successful outcomes following transfemoral amputation. One factor is surgical technique. In this study, the influence of limb alignment and surgical technique on a muscle’s capacity to generate force was examined using musculoskeletal modeling. Non-amputee and transfemoral amputee models were analyzed while hip adduction, femur length, and reattached muscle wrap position, tension and stabilization technique were systematically varied. With muscle tension preserved, wrap position and femur length had little influence on muscle capacity. However, limb alignment, muscle tension and stabilization technique notably influenced muscle capacity. Overall, myodesis stabilization provided greater muscle balance and function than myoplasty stabilization.     

Population dynamic consequences of allee effects

We take a well-known dynamic model of an isolated, unstructured population and modify this to include a factor that allows for a reduction in fitness due to declining population sizes, often termed an Allee effect. Analysis of the behaviour of this model is carried out on two fronts - determining the equilibrium values and examining the stability of these equilibria. Our results point to the stabilising effect on population dynamics of the Allee effect and an unexpected increase in stability with increased competition due to the interaction between competitive and Allee effects.     

Epiphyseal-based designs for tibial plateau components--I. Stress analysis in the frontal plane

Two-dimensional, finite element studies were conducted of the proximal tibia before and after joint arthroplasty. Equivalent-thickness models projected onto the mid-frontal plane were created for the natural, proximal tibia and for the proximal tibia with four different types of tibial plateau components. All components simulated bony ingrowth fixation, i.e. no cement layer existed between component and bone. In addition, the interface between component and bone was assumed to be intimately connected, representing complete bony ingrowth and a rigid state of fixation. Loads consisted of bi-condylar and uni-condylar forces. Results indicated that conventional plateau designs with central posts or multiple pegs led to higher stress magnitudes in the trabecular bone near the distal ends of the post/pegs and stress shielding at more proximal locations. A design without posts or pegs whose interface geometry mimics the epiphyseal plate minimizes bone stress shielding. An implant consisting of separate components covering each condyle was found effective in limiting component tilting and the consequent tensile stresses caused by non-symmetrical, uni-condylar loading.     

Independent alignment of RNA for dynamic studies using residual dipolar couplings

Molecular motion and dynamics play an essential role in the biological function of many RNAs. An important source of information on biomolecular motion can be found in residual dipolar couplings which contain dynamics information over the entire ms-ps timescale. However, these methods are not fully applicable to RNA because nucleic acid molecules tend to align in a highly collinear manner in different alignment media. As a consequence, information on dynamics that can be obtained with this method is limited. In order to overcome this limitation, we have generated a chimeric RNA containing both the wild type TAR RNA, the target of our investigation of dynamics, as well as the binding site for U1A protein. When U1A protein was bound to the portion of the chimeric RNA containing its binding site, we obtained independent alignment of TAR by exploiting the physical chemical characteristics of this protein. This technique can allow the extraction of new information on RNA dynamics, which is particularly important for time scales not covered by relaxation methods where important RNA motions occur.     

Pattern recognition based on color-coded quantum mechanical surfaces for molecular alignment

A pattern recognition algorithm for the alignment of drug-like molecules has been implemented. The method is based on the calculation of quantum mechanical derived local properties defined on a molecular surface. This approach has been shown to be very useful in attempting to derive generalized, non-atom based representations of molecular structure. The visualization of these surfaces is described together with details of the methodology developed for their use in molecular overlay and similarity calculations. In addition, this paper also introduces an additional local property, the local curvature (C _L), which can be used together with the quantum mechanical properties to describe the local shape. The method is exemplified using some problems representing common tasks encountered in molecular similarity. Figure Molecular surfaces for Lorazepam (left) and Diazepam (right)     

Self-consistently optimized statistical mechanical energy functions for sequence structure alignment.

A quantitative form of the principle of minimal frustration is used to obtain from a database analysis statistical mechanical energy functions and gap parameters for aligning sequences to three-dimensional structures. The analysis that partially takes into account correlations in the energy landscape improves upon the previous approximations of Goldstein et al. (1994, 1995) (Goldstein R, Luthey-Schulten Z, Wolynes P, 1994, Proceedings of the 27th Hawaii International Conference on System Sciences. Los Alamitos, California: IEEE Computer Society Press. pp 306-315; Goldstein R, Luthey-Schulten Z, Wolynes P, 1995, In: Elber R, ed. New developments in theoretical studies of proteins. Singapore: World Scientific). The energy function allows for ordering of alignments based on the compatibility of a sequence to be in a given structure (i.e., lowest energy) and therefore removes the necessity of using percent identity or similarity as scoring parameters. The alignments produced by the energy function on distant homologues with low percent identity (less than 21%) are generally better than those generated with evolutionary information. The lowest energy alignment generated with the energy function for sequences containing prosite signatures but unknown structures is a structure containing the same prosite signature, providing a check on the robustness of the algorithm. Finally, the energy function can make use of known experimental evidence as constraints within the alignment algorithm to aid in finding the correct structural alignment.     

Dynamic mechanical consequences of deep inflation in mice depend on type and degree of lung injury.

In a previous study (Allen G, Lundblad LK, Parsons P, and Bates JH. J Appl Physiol 93: 1709-1715, 2002), our laboratory used deep inflations (DI) in mice to show that recruitment of closed lung units can be a very transient phenomenon in lung injury. The purpose of this study was to investigate how this transience of lung recruitment depends on the nature and degree of acute lung injury. Mice were administered 50 microl of either saline (n = 8), 0.01 M (n = 9) or 0.025 M (n = 8) hydrochloric acid, or 50 microg (n = 10) or 150 microg (n = 6) of LPS and were mechanically ventilated 24-48 h later. At various levels of positive end-expiratory pressure, two DIs were delivered, and forced oscillations were used to obtain a measure of lung stiffness (H) periodically over 7 min. After LPS exposure, pressure-volume curve hysteresis and recovery in H after DI were no different from saline-exposed controls despite 500 times more neutrophils in bronchoalveolar lavage fluid. Pressure-volume hysteresis and recovery in H were increased in acid-exposed mice (P < 0.001) and were correlated with bronchoalveolar lavage fluid protein content (R = 0.81). Positive end-expiratory pressure reduced recovery in H in all groups (P < 0.01) but reduced pressure-volume hysteresis in the acid-injured groups only (P < 0.001). We conclude that the effects of DIs in acute lung injury depend on the degree of lung injury but only to the extent that this injury reflects a disruption of the air-liquid interface.     

Biomechanical construction principles of the human hip joint in frontal plane

The prognosis of hip joint function is only to determine unsatisfactory on the base of the knowledges of anatomy by means of inspection or angles and distances from X-rays as well as on the base of models known for the biomechanic of hip. The term "normal anatomical" hip structure is analysed with respect to functional biomechanical influences on its macroscopic design in frontal plane. It is shown to interpret the macroscopic hip design as result of an effective arrangement of centre of rotation and muscle forces which a minimum on energy needing for its function. A mathematical equation describes the skeleton-muscle-system hip biomechanically. This new connection between angles and distances as well as first easy consequences are proofed on a-p-hip radiographs of 53 normal adults.     

The protective efficacy of magnolol in hind limb ischemia-reperfusion injury

We investigated the protective effects of magnolol, an active antioxidant and free radical scavenger extracted from Magnolia officinalis, in a hind limb ischemic-reperfusion animal model. Adult male Spraque-Dawley rats were subjected to hind limb ischemic insult for 2 hours and were intravenously treated with magnolol at 0.01 mg/kg (n=8), 0.3 mg/kg (n=8) mg/kg or 1 mg/kg (n=8) mg/kg, or vehicle (n=8). At 24 h post-insult, the levels of nitrite/nitrate (NOX), malondialdehyde (MDA) and myeloperoxidase (MPO), as well as the degree of muscle damage, were assessed. Relative to controls, animals treated with magnolol (0.3 and 1 mg/kg) had attenuated muscular inflammation, edema and damage. Magnolol (0.3–1 mg/kg) also effectively reduced postischemic rises in the MDA, NOx and MPO levels (p<0.05, respectively). Magnolol administrated at 0.01 mg/kg, however, failed to protect against the ischemic-perfusion limb injury. In addition, magnolol (0.01–1 mg/kg) did not affect local muscular blood reperfusion or other physiological parameters, including hematocrit, glucose, arterial blood gases and mean arterial blood pressure. Thus, intravenous administration with magnolol at 0.3–1 mg/kg protects against ischemic limb damage in rats. This cytoprotection may be attributed to its antioxidant, anti-nitrosative and anti-inflammatory actions.