In-vivo 3-Dimensional gait symmetry analysis in patients with bilateral total hip arthroplasty

Although three-dimensional (3D) asymmetry has been reported in unilateral THA patients during gait, it is not well understood whether asymmetric hip kinematics during gait persist in bilaterally operated THA patients. The purpose of this study was to compare the in vivo 3D kinematics and component placement between bilateral and unilateral THA patients during gait. Eight bilateral and thirty-three unilateral THA patients were evaluated for both hips during treadmill gait using a validated combination of 3D computer tomography-based modeling and dual fluoroscopic imaging system (DFIS). The in vivo 3D kinematics of the unilateral THA group was first assessed. The magnitudes of kinematics and component placement difference between implanted hips in the bilateral THA group and between the implanted and non-implanted hips in the unilateral THA group were compared. The study results showed asymmetric gait kinematics in the unilateral THA group. Although the magnitude of kinematics differences between sides for both the bilateral and unilateral THA groups did not change significantly for hip rotations (p > 0.05), the bilaterally operated THA group has significantly lower magnitude of hip gait translation difference. Significant reduction in the magnitude of the acetabular cup adduction, stem adduction, and combine hip anteversion and adduction difference was observed in the bilateral THA group (p < 0.05). Our findings demonstrated that despite significant improvements of component placement and reduced magnitude of hip gait translation difference between implanted hips in the bilateral THA group, asymmetric hip kinematic rotations persisted in patients with bilateral THA during gait.     

Inter-joint coordination of kinematics and kinetics before and after total hip arthroplasty compared to asymptomatic subjects

While differences in joint kinematics and kinetics between control subjects and patients before and after total hip arthroplasty (THA) has often been studied, inter-joint coordination has not been fully characterized. We hypothesized that in patients undergoing THA, inter-joint coordination (i) is different from control subjects before surgery, (ii) changes from pre-operative to post-operative, and (iii) remains different from control subjects after surgery. Seventy-eight subjects underwent gait analysis before and ∼1 year after primary unilateral THA. 109 control subjects were age, sex, and BMI matched to the THA group. We selected a representative trial at each subjects’ self-selected walking speed from a motion analysis data repository. To assess kinematic coordination, we constructed sagittal plane hip-knee angle cyclograms, and calculated total, stance, and swing phase plot area (deg²). To assess kinetic coordination, we calculated the support moment (M_S, %wt 1 ht), the time-integral of support moment (M_S impulse, %wt 1 ht 1 t), and the relative contribution of each joint to M_S impulse (%_Hip, %_Knee, %_Ankle). We used t-tests to compare groups. Total and swing-phase cyclogram area was smaller preoperatively, but improved to control values after THA. Swing-phase area was smaller than control values after THA. M_S impulse was larger in THA subjects than controls both before and after surgery. While, the relative contribution of the hip to M_S impulse was not different from control values, the contributions of the knee and ankle were smaller. Inter-joint coordination, as measured by hip-knee angle cyclograms and M_S impulse, may be used to distinguish differences in gait mechanics between osteoarthritis and THA. Future work focusing on coordination among joints may be needed to fully restore gait function.     

Impact of the method of exposure in total hip arthroplasty on the variability of gait in the first 6 months of the postoperative period

Introduction, objectiveGait analysis has provided important information about the variability of gait for patients prior to and after total hip arthroplasty (THA). The objective of this research was to clarify how the method of exposure in total hip arthroplasty affects the variability of gait.Materials and methodGait analysis was performed at 0.8 m/s, 1.0 m/s, and 1.2 m/s on 25 patients with direct-lateral exposure (DL), 22 with antero-lateral exposure (AL) and 25 with posterior exposure (P) during total hip arthroplasty. The control group was represented by 45 healthy subjects of identical age. Gait analysis was performed pre-operatively and 3 and 6 months after the surgery. Gait parameter variability was characterized by the coefficient of variance (CV) of spatial–temporal parameters and by the mean coefficient of variance (MeanCV) of angular parameters.ResultsThe variability of gait tends to reach control values during the first 6 months of the postoperative period in all three patient groups. Six months after THA, in patients operated with DL and AL exposure the variability of gait differs significantly from control values; however, in patients operated with P exposure, the variability of spatial–temporal and angular parameters – except the rotation of pelvis – was similar to that of controls.Discussion, conclusionThe type of surgical technique significantly influences the variability of gait. Difference in the variability of angular parameters predicts gait instability and increased risk of falling after THA without the joint capsule preserved. Joint capsule preservation ensures a recovery of gait variability. It should be taken into account when compiling rehabilitation protocols. Differences related to the method of exposure should be considered when abandoning therapeutic aids.     

Hip kinematics and kinetics in total hip replacement patients stratified by age and functional capacity

To examine functional differences in total hip replacement patients (THR) when stratified either by age or by functional ability as defined by self-selected walking speed. THR patients and a control group underwent three-dimensional motion analysis under self-selected normal and fast walking conditions. Patients were stratified into five age groups for comparison with existing literature. The THR cohort was also stratified into three functional groups determined by their self-selected gait speed (low function <1SD of total cohort’s mean walking speed; high function >1SD; normal function within 1SD). Hip kinematics, ground reaction forces, joint moments and joint powers in all three planes (x-y-z) were analysed. 137 THR and 27 healthy control patients participated. When stratified by age, during normal walking the youngest two age groups walked quicker than the oldest two groups (p < 0.0001) but between-group differences were not consistent across age strata. The differences were diminished under the fast walking condition. When stratified by function, under normal walking conditions, the low function and normal function THR groups had a reduced extension angle (mean = 1.75°, SD = ±7.75, 1.26° ± 7.42, respectively) compared to the control group (−6.07° ± 6.43; p < 0.0001). The low function group had a reduced sagittal plane hip power (0.75 W/kg ± 0.24), reduced flexor (0.60 Nm/kg ± 0.85) and extensor moment (0.51 Nm/kg ± 0.17) compared to controls (p < 0.0001). These differences persisted under the fast walking condition. There were systematic differences between patients when stratified by function, in both walking conditions. Age-related differences were less systematic. Stratifying by biomechanical factors such as gait speed, rather than age, might be more robust for investigating functional differences.     

Four-dimensional model of the lower extremity after total hip arthroplasty

We have developed a four-dimensional (4D) model of the lower extremities after total hip arthroplasty in patients. The model can aid in preventing complications such as dislocation and wearing of the sliding surface. The skeletal structure and implant alignment were obtained from CT data. We applied registration method using CAD data to estimate accurate implant alignment from scattered CT data. The reconstructed three-dimensional (3D) skeletal model was combined with motion capture data that were acquired by an optical tracking system. We displayed the patient's skeletal movement and analyzed several parameters that relate to complications. The patient's skeletal model was superimposed onto video footage that was taken by a synchronized and calibrated digital video camera. For validation of the measurement error in this system, we used open MRI to evaluate the relative movement between skin markers and bones. This system visually represents not only the 3D anatomical structure, but also 4D dynamic functions that include the time sequential transitions of components and their positions. The open MRI results indicated that the average error in hip angle was within 5° for each static posture. This system enables clinicians to analyze patient's motions on the basis of individual differences. We found that our system was an effective tool in providing precise guidance of daily postoperative motions that was individualized for each patient. This system will be applicable for surgical planning, assessment of postoperative activities, and the development of new surgical techniques, materials, and prosthetic designs.     

Contact mechanics of modular metal-on-polyethylene total hip replacement under adverse edge loading conditions

Edge loading can negatively impact the biomechanics and long-term performance of hip replacements. Although edge loading has been widely investigated for hard-on-hard articulations, limited work has been conducted for hard-on-soft combinations. The aim of the present study was to investigate edge loading and its effect on the contact mechanics of a modular metal-on-polyethylene (MoP) total hip replacement (THR). A three-dimensional finite element model was developed based on a modular MoP bearing. Different cup inclination angles and head lateral microseparation were modelled and their effect on the contact mechanics of the modular MoP hip replacement were examined. The results showed that lateral microseparation caused loading of the head on the rim of the cup, which produced substantial increases in the maximum von Mises stress in the polyethylene liner and the maximum contact pressure on both the articulating surface and backside surface of the liner. Plastic deformation of the liner was observed under both standard conditions and microseparation conditions, however, the maximum equivalent plastic strain in the liner under microseparation conditions of 2000 µm was predicted to be approximately six times that under standard conditions. The study has indicated that correct positioning the components to avoid edge loading is likely to be important clinically even for hard-on-soft bearings for THR.     

A new role for the SHATTERPROOF genes during Arabidopsis gynoecium development

Gynoecium development is a complex process which is regulated by key factors that control the spatial formation of the apical, medial and basal parts. SHATTERPROOF1 (SHP1) and SHP2, two closely related MADS-box genes, redundantly control the differentiation of the dehiscence zone and promote the lignification of adjacent cells. Furthermore, SHP1 and SHP2 have shown to play an important role in ovule identity determination. The present work identifies a new function for these two genes in promoting stigma, style and medial tissue development. This new role was discovered by combining the shp1 shp2 double mutant with the aintegumenta (ant) and crabs claw (crc) mutants. In quadruple mutant flowers, the inner whorl is composed of unfused carpels which lack almost completely apical and medial tissues, a phenotype similar to the previously reported fil ant and lug ant double mutants.     

Novel in vitro and in vivo models to study central nervous system infections due to Acanthamoeba spp.

Acanthamoeba granulomatous encephalitis is a serious human infection with fatal consequences. The most distressing aspect of Acanthamoeba granulomatous encephalitis is the limited improvement in mortality. The underlying neurobiology is at present not well understood and treatment options are often of limited efficacy. There is therefore a real need to obtain more knowledge regarding the pathogenesis and pathophysiology of Acanthamoeba granulomatous encephalitis and to develop new chemotherapeutic approaches. However, the difficulties in using mammalian models to study this infection have hindered our search for therapeutic interventions. Recent availability of the blood-brain barrier, in vitro and use of locust as an in vivo model will undoubtedly allow us to investigate disease pathogenesis, mechanisms of parasite traversal across the blood-brain barrier and new drug therapies. It is argued that the models described here can offer several advantages in terms of speed, cost, technical convenience, and ethical acceptance. Furthermore, they are extremely valuable tools to discriminate molecules participating from both sides of the host-parasite interaction and will generate potentially useful leads in the identification of new potential drugs, as well as testing drug toxicity.     

Effect of obesity on inpatient rehabilitation outcomes after total hip arthroplasty

Objective: This study examined whether obesity affected inpatient rehabilitation outcomes after total hip arthroplasty (THA). Research Methods and Procedures: This was a retrospective, comparative study conducted using a computerized medical database derived from THA patients at a university‐affiliated rehabilitation hospital (data from 2002 to 2005). Patients were divided into four brackets based on BMI: non‐obese (<25 kg/m²), overweight (25 to 29.9 kg/m²), moderate obesity (30 to 39.9 kg/m²), and severe obesity (≥40 kg/m²). All patients completed an interdisciplinary inpatient rehabilitation program after THA. Functional independence measure (FIM) scores, length of stay (LOS), FIM efficiency scores (FIM/LOS), hospital charges, and discharge disposition location were collected. Results: FIM scores improved from admission to discharge similarly in all groups (25 to 29.5 points). However, FIM efficiency, LOS, and total charges were curvilinearly related with BMI (all p < 0.05). Total hospital charges were highest in the severely obese group compared with the overweight group (p < 0.05). Non‐homebound discharge disposition rates were lower in non‐obese (13.1%) and severely obese groups (10.5%). Discussion: Elevated BMI does not prevent FIM gains in THA patients during inpatient rehabilitation. However, BMI is related with FIM efficiency, LOS, and hospital charges in a curvilinear fashion. Severely obese patients can achieve physical improvements but at a lower efficiency and greater cost.     

On the roles of Notch, Delta, kuzbanian, and inscuteable during the development of Drosophila embryonic neuroblast lineages

The generation of cellular diversity in the nervous system involves the mechanism of asymmetric cell division. Besides an array of molecules, including the Par protein cassette, a heterotrimeric G protein signalling complex, Inscuteable plays a major role in controlling asymmetric cell division, which ultimately leads to differential activation of the Notch signalling pathway and correct specification of the two daughter cells. In this context, Notch is required to be active in one sibling and inactive in the other. Here, we investigated the requirement of genes previously known to play key roles in sibling cell fate specification such as members of the Notch signalling pathway, e.g., Notch (N), Delta (Dl), and kuzbanian (kuz) and a crucial regulator of asymmetric cell division, inscuteable (insc) throughout lineage progression of 4 neuroblasts (NB1-1, MP2, NB4-2, and NB7-1). Notch-mediated cell fate specification defects were cell-autonomous and were observed in all neuroblast lineages even in cells born from late ganglion mother cells (GMC) within the lineages. We also show that Dl functions non-autonomously during NB lineage progression and clonal cells do not require Dl from within the clone. This suggests that within a NB lineage Dl is dispensable for sibling cell fate specification. Furthermore, we provide evidence that kuz is involved in sibling cell fate specification in the central nervous system. It is cell-autonomously required in the same postmitotic cells which also depend on Notch function. This indicates that KUZ is required to facilitate a functional Notch signal in the Notch-dependent cell for correct cell fate specification. Finally, we show that three neuroblast lineages (NB1-1, NB4-2, and NB7-1) require insc function for sibling cell fate specification in cells born from early GMCs whereas insc is not required in cells born from later GMCs of the same lineages. Thus, there is differential requirement for insc for cell fate specification depending on the stage of lineage progression of NBs.     

Computational analysis of knee joint stability following total knee arthroplasty

The overall objective of this study was to introduce knee joint power as a potential measure to investigate knee joint stability following total knee arthroplasty (TKA). Specific aims were to investigate whether weakened knee joint stabilizers cause abnormal kinematics and how it influences the knee joint kinetic (i.e., power) in response to perturbation.Patient-specific musculoskeletal models were simulated with experimental gait data from six TKA patients (baseline models). Muscle strength and ligament force parameter were reduced by up to 30% to simulate weak knee joint stabilizers (weak models). Two different muscle recruitment criteria were tested to examine whether altered muscle recruitment pattern can mask the influence of weakened stabilizers on the knee joint kinematics and kinetics. Level-walking knee joint kinematics and kinetics were calculated though force-dependent kinematic and inverse dynamic analyses. Bode analysis was then recruited to estimate the knee joint power in response to a simulated perturbation.Weak models resulted in larger anterior-posterior (A-P) displacement and internal-external (I-E) rotation compared to baseline (I-E: 18.4 ± 8.5 vs. 11.6 ± 5.7 (deg), A-P: 9.7 ± 5.6 vs. 5.5 ± 4.1 (mm)). Changes in muscle recruitment criterion however altered the results such that A-P and I-E were not notably different from baseline models. In response to the simulated perturbation, weak models versus baseline models generated a delayed power response with unbounded magnitudes. Perturbed power behavior of the knee remained unaltered regardless of the muscle recruitment criteria.In conclusion, impairment at the knee joint stabilizers may or may not lead to excessive joint motions but it notably affects the knee joint power in response to a perturbation. Whether perturbed knee joint power is associated with the patient-reported outcome requires further investigation.     

Regulation of apoptosis of rbf mutant cells during Drosophila development

Inactivation of the retinoblastoma gene Rb leads to defects in cell proliferation, differentiation, or apoptosis, depending on specific cell or tissue types. To gain insights into the genes that can modulate the consequences of Rb inactivation, we carried out a genetic screen in Drosophila to identify mutations that affected apoptosis induced by inactivation of the Retinoblastoma-family protein (rbf) and identified a mutation that blocked apoptosis induced by rbf. We found this mutation to be a new allele of head involution defective (hid) and showed that hid expression is deregulated in rbf mutant cells in larval imaginal discs. We identified an enhancer that regulates hid expression in response to developmental cues as well as to radiation and demonstrated that this hid enhancer is directly repressed by RBF through an E2F binding site. These observations indicate that apoptosis of rbf mutant cells is mediated by an upregulation of hid. Finally, we showed that bantam, a miRNA that regulates hid translation, is expressed in the interommatidial cells in the larval eye discs and modulates the survival of rbf mutant cells.     

The Him gene inhibits the development of Drosophila flight muscles during metamorphosis

During Drosophila metamorphosis some larval tissues escape the general histolysis and are remodelled to form adult tissues. One example is the dorso-longitudinal muscles (DLMs) of the indirect flight musculature. They are formed by an intriguing process in which residual larval oblique muscles (LOMs) split and fuse with imaginal myoblasts associated with the wing disc. These myoblasts arise in the embryo, but remain undifferentiated throughout embryogenesis and larval life, and thus share characteristics with mammalian satellite cells. However, the mechanisms that maintain the Drosophila myoblasts in an undifferentiated state until needed for LOM remodelling are not understood. Here we show that the Him gene is expressed in these myoblasts, but is undetectable in developing DLM fibres. Consistent with this, we found that Him could inhibit DLM development: it inhibited LOM splitting and resulted in fibre degeneration. We then uncovered a balance between mef2, a positive factor required for proper DLM development, and the inhibitory action of Him. Mef2 suppressed the inhibitory effect of Him on DLM development, while Him could suppress the premature myosin expression induced by mef2 in myoblasts. Furthermore, either decreased Him function or increased mef2 function disrupted DLM development. These findings, together with the co-expression of Him and Mef2 in myoblasts, indicate that Him may antagonise mef2 function during normal DLM development and that Him participates in a balance of signals that controls adult myoblast differentiation and remodelling of these muscle fibres. Lastly, we provide evidence for a link between Notch function and Him and mef2 in this balance.     

Temporal expression and steroidal regulation of piRNA pathway genes (mael, piwi, vasa) during Silurana (Xenopus) tropicalis embryogenesis and early larval development

It has been extensively documented that exposure of amphibians and teleost fish to exogenous steroid hormones like estrogen, androgen, xenoestrogen or steroid biosynthesis inhibitors can impair their gonadal development or induce sex reversal against genotypic sex. However, the molecular pathways underlying sexual development and the effects of sex steroids or other exogenous hormones in these aquatic vertebrates remain elusive. Recently, a germ plasm-associated piRNA (piwi-interacting RNA) pathway has been shown to be a determinant in the development of animal gonadal germline cells. In the current study, we examined whether this piRNA pathway is involved in the regulation of sex steroid hormones in gonadal development. We firstly established developmental expression patterns of three key piRNA pathway genes (mael, piwi and vasa), during Silurana (Xenopus) tropicalis embryogenesis and early larval development. All three genes exhibit high expression at early developmental stages and have significantly decreased expression thereafter, indicating a very active involvement of piRNA pathway at the beginning of embryogenesis. We further examined gene expression changes of those genes in frog larvae exposed to two sex steroid biosynthesis inhibitors, fadrozole and finasteride, both of which are known to result in male-biased or female-biased phenotypes, respectively. We found that fadrozole and finasteride exposures increased the expression of piRNA pathway genes such as mael and vasa at the larval stage when the expression of piRNA pathway genes is programmed to be very low. Therefore, our results indicate that the piRNA pathway is likely a common pathway by which different sex steroid hormones regulate gonadal sex differentiation.     

Septal pore complex morphology in the Agaricomycotina (Basidiomycota) with emphasis on the Cantharellales and Hymenochaetales

The ultrastructure of septa and septum-associated septal pore caps are important taxonomic markers in the Agaricomycotina (Basidiomycota, Fungi). The septal pore caps covering the typical basidiomycetous dolipore septum are divided into three main phenotypically recognized morphotypes: vesicular-tubular (including the vesicular, sacculate, tubular, ampulliform, and globular morphotypes), imperforate, and perforate. Until recently, the septal pore cap-type reflected the higher-order relationships within the Agaricomycotina. However, the new classification of Fungi resulted in many changes including revision of existing and addition of new orders. Therefore, the septal pore cap ultrastructure of more than 325 species as reported in literature was related to this new classification. In addition, the septal pore cap ultrastructures of Rickenella fibula and Cantharellus formosus were examined by transmission electron microscopy. Both fungi have dolipore septa associated with perforate septal pore caps. These results combined with data from the literature show that the septal pore cap-type within orders of the Agaricomycotina is generally monomorphic, except for the Cantharellales and Hymenochaetales.It appears from the fungal phylogeny combined with the septal pore cap ultrastructure that the vesicular-tubular and the imperforate type both may have arisen from endoplasmic reticulum. Thereafter, the imperforate type eventually gave rise to the perforate septal pore cap-type.