Knee function and neuromuscular adaptations following ACL rupture and reconstruction

In order to alleviate symptoms associated with progressive knee dysfunction and deterioration following anterior cruciate ligament (ACL) injury, patients undergo either conservative non-operative rehabilitative regimens or early reconstructive surgery using the patella tendon (PT) or combined semitendinosus and gracilis tendon (STGT) grafts. Following treatment, ACL deficient (ACLD) and ACL reconstructed (ACLR) patients demonstrate varying levels of knee function with compensatory neuromuscular adaptations thought to be responsible for enhancing the dynamic restraint capabilities in more functional patients. Derivation of the neuromuscular factors that estimate participation restrictions could assist clinicians in developing prognoses and outcome measures for ACLD and ACLR patients. Therefore, the main aim of the present thesis was to identify neuromuscular variables, derived during open and closed kinetic chain tasks, that relate to and predict post ACL injury/ACLR functional outcome. To achieve this, 10 male ACLD subjects together with 27 matched-males who had undergone ACLR (14 PT graft and 13 STGT graft) and 22 matched-control subjects were recruited. In Experiment 1, the Cincinnati Knee Rating System was used to assess knee symptoms and limitations associated with activities of daily living and sports. Three single-leg tests designed to replicate athletic activities were also implemented. Subjective and objective scores were combined to provide an overall knee function score for each subject. The ACLD group was significantly more symptomatic and limited in activities of daily living and sports and they also demonstrated impaired jump and hop performance. Whilst the PT and STGT subjects rated significantly higher than their ACLD counterparts, their average subjective and overall knee function scores were significantly lower compared to the control group. Importantly, graft selection did not significantly influence average subjective, objective or overall knee function scores. In Experiment 2, the effect of ACL injury and ACLR on open kinetic chain isokinetic strength of the quadriceps and hamstrings was assessed in 10o intervals through their operational domain. Antagonist activity of the semitendinosus (ST) and biceps femoris (BF) muscles was also determined during knee extension in 10o intervals between 80 and 10o flexion. Conservatively managed subjects demonstrated significant quadriceps and hamstring weakness with involved limb quadriceps strength deficits transferred to the contralateral limb. Harvesting the central one-third of the PT as an ACL substitute did not inhibit quadriceps strength compared those ACL-insufficient knees in which the extensor mechanism was not used in the reconstruction technique (STGT graft). In contrast, harvesting the flexor mechanism for ACLR caused significant hamstring strength deficits that were not apparent in patients having undergone ACLR using the PT graft. Relatively large amounts of hamstring antagonist activity were evident during knee extension, although ST and BF electromyographic discharge was not influenced by ACL status. Hamstring antagonist activity increased and decreased widely as a function of joint angle with the BF significantly more active than the ST in order to control internal tibial rotation. Kinesthetic joint capsule receptors were thought to be the major source dictating hamstring muscle activity in such a manner that it varied nearly inversely relative to its moment arm. In Experiment 3, lower limb kinematics, kinetics and neuromuscular responses were assessed in ACLD and ACLR subjects during a closed kinetic chain task known to stress the ACL, namely abrupt deceleration when landing from a single-leg hop for distance. For the ACLD group, no significant alterations were evident in joint kinematic parameters. Biceps femoris of the involved limb of the ACLD group was activated significantly later compared to the non-involved limb, supporting the notion that after ACL injury, sensory feedback may be used to build a new internal model depicting the expected conditions during functional activities. The involved limb of the ACLD and ACLR groups demonstrated a significant reduction in vertical ground reaction force during the support phase of landing compared to the non-involved limb. Whilst the magnitude of peak tibial acceleration was not significantly different between test limbs or subject groups, it took significantly longer for the involved limb of the ACLD and ACLR groups to attain constant tibial motion compared to the non-involved limb. Subjects having undergone ACLR using the PT graft demonstrated a stiff knee strategy during landing and, whilst the STGT group also demonstrated trends towards decreased knee flexion during landing, no significant kinematic adaptations at the hip, knee or ankle were identified. Decreased knee flexion was found to significantly attenuate the mechanical advantage of the involved limb hamstrings of the ACLD, PT and STGT groups. Cumulative changes in involved limb hip and knee kinematics of the ACLD and ACLR subjects meant that the ST and BF muscles were significantly elongated when decelerating to improve dynamic restraint. Importantly, ACLR led to a restoration of normal quadriceps and hamstring electromyographic (EMG) synchrony in the involved and contralateral limbs and there was no evidence to suggest that the ACLD subjects adopted a pattern of quadriceps-avoidance. In Experiment 4, the strength of the associations among knee functionality of ACLD and ACLR subjects (Experiment 1) and neuromuscular variables derived from open (Experiment 2) and closed (Experiment 3) kinetic chain movements was determined. Numerous significant moderate to strong correlations were identified with determinants of knee functionality related to the type of ACL treatment and graft selection. Compensatory neuromuscular strategies that enhance function in the ACLD knee included amplified hamstring co-activation, increased hamstring preparatory activity and a greater ability to control tibial motion during dynamic deceleration. Following ACL replacement, the degree of residual strength deficit in the muscle from which the tendon graft was harvested (i.e. quadriceps or hamstrings) become an important prognosticator of knee functionality as did attenuated hamstring co-activation during knee extension within the range utilsed during single-limb deceleration. More functional PT subjects demonstrated enhanced tibial control whilst superior knee functionality in STGT subjects was associated with increased preparatory activity of the quadriceps when landing on the involved limb. Furthermore, by synchronising peak hamstring muscle activity at the time when the ACL graft is most vulnerable to injury, more functional STGT subjects enhanced dynamic restraint by increasing joint compression and posterior tibial drawer. By identifying neuromuscular factors that predict function in ACLD and ACLR subjects, the results of these studies will lead to the development of more specific and effective treatment strategies

Anabolic steroids after total knee arthroplasty. A double blinded prospective pilot study

Background: Total knee arthroplasty is reported to improve the patient’s quality of life and mobility. However loss of mobility and pain prior to surgery often results in disuse atrophy of muscle. As a consequence the baseline functional state prior to surgery may result in poorer outcome “post surgery” and extended rehabilitation may be required. The use of anabolic steroids for performance enhancement and to influence muscle mass is well established. The positive effects of such treatment on bone and muscle could therefore be beneficial in the rehabilitation of elderly patients. The purpose of this study was to investigate the effects of small doses of Nandrolone decanoate on recovery and muscle strength after total knee replacement and to establish the safety of this drug in multimorbid patients. Methods: This study was designed as a prospective double blind randomized investigation. Five patients (treatment group) with a mean age of 66.2 (58-72), average BMI of 30.76 (24.3-35.3) received 50 mg nandrolone decanoate intramuscular bi-weekly for 6 months. The control group (five patients; mean age 65.2, range 59-72; average BMI 31.7, range 21.2-35.2) was injected with saline solution. “Pre-operatively” and “post-operatively” (6 weeks, 3,6,9 and 12 months) all patients were assessed using the knee society score (KSS), isokinetic strength testing and functional tests (a sit-to-stand and timed walking tests). In addition, a bone density scan was used preoperatively and 6 month postoperatively to assess bone mineral density. Results: Whilst the steroid group generally performed better than the placebo group for all of the functional tests, ANOVA failed to reveal any significant differences. The steroid group demonstrated higher levels of quadriceps muscle strength across the postoperative period which reached significance at 3 (p = 0.02), 6 (p = 0.01), and 12 months (p = 0.02). There was a significant difference for the KSS at 6 weeks (p = 0.02), 6 (p = 0.02) and 12 month (p = 0.01). The steroid group demonstrated a reduction in the amount of bone mineral density at both the femur and lumbar spine from “pre-” to “post-surgery”, however, these results did not reach significance (p < 0.05) using one-way ANOVA. Conclusions: This project strongly suggests that the use of anabolic steroids result in an improved outcome as assessed by the KSS and significantly increases extensor strength. No side effects were seen in either the study or control group. Trial Registration Number: Regional Health District: Register No. 03.05 Human Research Ethics Committee University: Clearance Number: 04/03-1

Muscle force contributions to anterior cruciate ligament loading

Anterior cruciate ligament (ACL) injuries are one of the most common knee pathologies sustained during athletic participation and are characterised by long convalescence periods and associated financial burden. Muscles have the ability to increase or decrease the mechanical loads on the ACL, and thus are viable targets for preventative interventions. However, the relationship between muscle forces and ACL loading has been investigated by many different studies, often with differing methods and conclusions. Subsequently, this review aimed to summarise the evidence of the relationship between muscle force and ACL loading. A range of studies were found that investigated muscle and ACL loading during controlled knee flexion, as well as a range of weightbearing tasks such as walking, lunging, sidestep cutting, landing and jumping. The quadriceps and the gastrocnemius were found to increase load on the ACL by inducing anterior shear forces at the tibia, particularly when the knee is extended. The hamstrings and soleus appeared to unload the ACL by generating posterior tibial shear force; however, for the hamstrings, this effect was contingent on the knee being flexed greater than ~ 20° to 30°. The gluteus medius was consistently shown to oppose the knee valgus moment (thus unloading the ACL) to a magnitude greater than any other muscle. Very little evidence was found for other muscle groups with respect to their contribution to the loading or unloading of the ACL. It is recommended that interventions aiming to reduce the risk of ACL injury consider specifically targeting the function of the hamstrings, soleus and gluteus medius

Current ankle sprain prevention and management strategies of netball athletes: a scoping review of the literature and comparison with best-practice recommendations

Background: Ankle sprains are the most commonly reported injury in netball. Approximately four in five netball athletes will sustain an ankle sprain, up to half will go on to sustain recurrent ankle sprains, and nine in ten report perceived ankle instability. Historically, prevention and management strategies of ankle sprains and injuries have been investigated for a variety of sports, however, no literature reviews have investigated these in netball athletes, or compared these with current best-practice within the literature. Therefore, this scoping review aims to understand how netball athletes currently prevent and manage ankle sprains and to compare these approaches with best-practice recommendations. Methods: A literature search was conducted using MEDLINE, CINAHL, and SPORTDiscus databases using keywords to capture studies with data or information related to the prevention and management of ankle sprains and injuries in netball. Results: The search strategy captured 982 studies across all databases, with 30 netball studies included in this scoping review. Studies suggest netball athletes are not commonly referred to health professionals, do not undertake adequate rehabilitation, and almost immediately return to court following an ankle sprain or injury. Current best-practices suggest injury prevention programs and external ankle support effectively reduce ankle sprains and injuries; however, poor compliance and implementation may be a significant barrier. Currently, there is a lack of evidence that netball-specific footwear reduces the risk of ankle sprains. Conclusion: The findings suggest netball athletes do not implement current best-practice prevention and management strategies following an ankle sprain. This is despite evidence of the effectiveness of injury prevention programs, external ankle support, and adequate rehabilitation in reducing ankle sprain rates. Current-best practice prevention and management of ankle sprains should be considered by clinicians, coaches, and athletes to reduce the prevalence and chronicity of ankle sprains in netball

Eliciting a Sensemaking Process from Verbal Protocols of Reverse Engineers

Abstract A process of sensemaking in reverse engineering was elicited from verbal protocols of reverse engineers as they investigated the assembly code of executable programs. Four participants were observed during task performance and verbal protocols were collected and analyzed from two of the participants to determine their problem-solving states and characterize likely transitions between those states. From this analysis, a highlevel process of sensemaking is described which represents hypothesis generation and information-seeking behaviors in reverse engineering within a framework of goal-directed planning. Future work in validation and application of the process is discussed

The SAMI Galaxy Survey: Revising the Fraction of Slow Rotators in IFS Galaxy Surveys

The fraction of galaxies supported by internal rotation compared to galaxies stabilized by internal pressure provides a strong constraint on galaxy formation models. In integral field spectroscopy surveys, this fraction is biased because survey instruments typically only trace the inner parts of the most massive galaxies. We present aperture corrections for the two most widely used stellar kinematic quantities $V/\sigma$ and $\lambda_{R}$. Our demonstration involves integral field data from the SAMI Galaxy Survey and the ATLAS$^{\rm{3D}}$ Survey. We find a tight relation for both $V/\sigma$ and $\lambda_{R}$ when measured in different apertures that can be used as a linear transformation as a function of radius, i.e., a first-order aperture correction. We find that $V/\sigma$ and $\lambda_{R}$ radial growth curves are well approximated by second order polynomials. By only fitting the inner profile (0.5$R_{\rm{e}}$), we successfully recover the profile out to one $R_{\rm{e}}$ if a constraint between the linear and quadratic parameter in the fit is applied. However, the aperture corrections for $V/\sigma$ and $\lambda_{R}$ derived by extrapolating the profiles perform as well as applying a first-order correction. With our aperture-corrected $\lambda_{R}$ measurements, we find that the fraction of slow rotating galaxies increases with stellar mass. For galaxies with $\log M_{*}/M_{\odot}>$ 11, the fraction of slow rotators is $35.9\pm4.3$ percent, but is underestimated if galaxies without coverage beyond one $R_{\rm{e}}$ are not included in the sample ($24.2\pm5.3$ percent). With measurements out to the largest aperture radius the slow rotator fraction is similar as compared to using aperture corrected values ($38.3\pm4.4$ percent). Thus, aperture effects can significantly bias stellar kinematic IFS studies, but this bias can now be removed with the method outlined here.Comment: Accepted for Publication in the Monthly Notices of the Royal Astronomical Society. 16 pages and 11 figures. The key figures of the paper are: 1, 4, 9, and 1

The genetics of virus particle shape in equine influenza A virus

Background Many human strains of influenza A virus produce highly pleomorphic virus particles that at the extremes can be approximated as either spheres of around 100 nm diameter or filaments of similar cross-section but elongated to lengths of many microns. The role filamentous virions play in the virus life cycle remains enigmatic. Objectives/Methods Here, we set out to define the morphology and genetics of virus particle shape in equine influenza A virus, using reverse genetics and microscopy of infected cells. Results and Conclusions The majority of H3N8 strains tested were found to produce filamentous virions, as did the prototype H7N7 A/eq/Prague/56 strain. The exception was the prototype H3N8 isolate, A/eq/Miami/63. Reassortment of equine influenza virus M genes from filamentous and non-filamentous strains into the non-filamentous human virus A/PR/8/34 confirmed that segment 7 is a major determinant of particle shape. Sequence analysis identified three M1 amino acid polymorphisms plausibly associated with determining virion morphology, and the introduction of these changes into viruses confirmed the importance of two: S85N and N231D. However, while either change alone affected filament production, the greatest effect was seen when the polymorphisms were introduced in conjunction. Thus, influenza A viruses from equine hosts also produce filamentous virions, and the major genetic determinants are set by the M1 protein. However, the precise sequence determinants are different to those previously identified in human or porcine viruses

Genetic basis of thermal nociceptive sensitivity and brain weight in a BALB/c reduced complexity cross

Thermal nociception involves the transmission of temperature-related noxious information from the periphery to the CNS and is a heritable trait that could predict transition to persistent pain. Rodent forward genetics complement human studies by controlling genetic complexity and environmental factors, analysis of end point tissue, and validation of variants on appropriate genetic backgrounds. Reduced complexity crosses between nearly identical inbred substrains with robust trait differences can greatly facilitate unbiased discovery of novel genes and variants. We found BALB/cByJ mice showed enhanced sensitivity on the 53.5°C hot plate and mechanical stimulation in the von Frey test compared to BALB/cJ mice and replicated decreased gross brain weight in BALB/cByJ versus BALB/cJ. We then identified a quantitative trait locus (QTL) on chromosome 13 for hot plate sensitivity (LOD = 10.7; p < 0.001; peak = 56 Mb) and a QTL for brain weight on chromosome 5 (LOD = 8.7; p < 0.001). Expression QTL mapping of brain tissues identified H2afy (56.07 Mb) as the top transcript with the strongest association at the hot plate locus (FDR = 0.0002) and spliceome analysis identified differential exon usage within H2afy associated with the same locus. Whole brain proteomics further supported decreased H2AFY expression could underlie enhanced hot plate sensitivity, and identified ACADS as a candidate for reduced brain weight. To summarize, a BALB/c reduced complexity cross combined with multiple-omics approaches facilitated identification of candidate genes underlying thermal nociception and brain weight. These substrains provide a powerful, reciprocal platform for future validation of candidate variants

Single-Leg Squat Performance is Impaired 1 to 2 Years After Hip Arthroscopy

Objective: To evaluate single-leg squat performance 1-2 years after arthroscopy for intra-articular hip pathology compared with control subjects and the nonsurgical limb, and to investigate whether single-leg squat performance on the operated limb was associated with hip muscle strength

The IUPHAR/BPS Guide to PHARMACOLOGY in 2018: updates and expansion to encompass the new guide to IMMUNOPHARMACOLOGY.

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb, www.guidetopharmacology.org) and its precursor IUPHAR-DB, have captured expert-curated interactions between targets and ligands from selected papers in pharmacology and drug discovery since 2003. This resource continues to be developed in conjunction with the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS). As previously described, our unique model of content selection and quality control is based on 96 target-class subcommittees comprising 512 scientists collaborating with in-house curators. This update describes content expansion, new features and interoperability improvements introduced in the 10 releases since August 2015. Our relationship matrix now describes ∼9000 ligands, ∼15 000 binding constants, ∼6000 papers and ∼1700 human proteins. As an important addition, we also introduce our newly funded project for the Guide to IMMUNOPHARMACOLOGY (GtoImmuPdb, www.guidetoimmunopharmacology.org). This has been 'forked' from the well-established GtoPdb data model and expanded into new types of data related to the immune system and inflammatory processes. This includes new ligands, targets, pathways, cell types and diseases for which we are recruiting new IUPHAR expert committees. Designed as an immunopharmacological gateway, it also has an emphasis on potential therapeutic interventions