Evaluation of the flow-dialysis technique for analysis of protein-ligand interactions: an experimental and a monte carlo study

Flow dialysis has found widespread use in determining the dissociation constant (KD) of a protein-ligand interaction or the amount of available binding sites (E0). This method has the potency to measure both these parameters in a single experiment and in this article a method to measure simultaneously the KD and E0 is presented, together with an extensive error analysis of the method. The flow-dialysis technique is experimentally simple to perform. However, a number of practical aspects of this method can have a large impact on the outcome of KD and E0. We have investigated all sources of significant systematic and random errors, using the interaction between mannitol and its transporter from Escherichia coli as a model. Monte Carlo simulations were found to be an excellent tool to assess the impact of these errors on the binding parameters and to define the experimental conditions that allow their most accurate estimation.     

Kinin-mediated inflammation in neurodegenerative disorders

The mediatory role of kinins in both acute and chronic inflammation within nervous tissues has been widely described. Bradykinin, the major representative of these bioactive peptides, is one of a few mediators of inflammation that directly stimulates afferent nerves due to the broad expression of specific kinin receptors in cell types in these tissues. Moreover, kinins may be delivered to a site of injury not only after their production at the endothelium surface but also following their local production through the enzymatic degradation of kininogens at the surface of nerve cells. A strong correlation between inflammatory processes and neurodegeneration has been established. The activation of nerve cells, particularly microglia, in response to injury, trauma or infection initiates a number of reactions in the neuronal neighborhood that can lead to cell death after the prolonged action of inflammatory substances. In recent years, there has been a growing interest in the effects of kinins on neuronal destruction. In these studies, the overexpression of proteins involved in kinin generation or of kinin receptors has been observed in several neurologic disorders including neurodegenerative diseases such Alzheimer's disease and multiple sclerosis as well as disorders associated with a deficiency in cell communication such as epilepsy. This review is focused on recent findings that provide reliable evidence of the mediatory role of kinins in the inflammatory responses associated with different neurological disorders. A deeper understanding of the role of kinins in neurodegenerative diseases is likely to promote the future development of new therapeutic strategies for the control of these disorders. An example of this could be the prospective use of kinin receptor antagonists.     

关节镜清理术治疗前踝撞击征的疗效

目的:探讨踝关节镜对前踝撞击征的诊疗价值。方法:采用关节镜清理术治疗前踝撞击综合征33例,其中男23例,女10例。年龄平均39岁(18～72岁)。左踝16例,右踝17例。病史6个月至20年,有运动损伤史13例,踝关节扭伤病史17例,踝关节骨折史3例。临床表现为踝关节肿胀、疼痛和下蹲活动受限。X线片显示胫骨前唇和距骨骨质增生,MRI显示距骨软骨损伤,踝关节腔内积液。采用局麻关节镜下骨赘磨削,滑膜切除,踝关节清理术。结果:随访33例,平均时间35个月(4个月-6年)。术后踝关节背伸活动功能正常,按照McGuire踝关节评分系统对术前、术后踝关节功能进行评估,术前平均55分,术后平均80分,术后提高了25分。优13例,良15例,可3例,差2例,优良率84.8%。结论:局麻下踝关节镜骨赘切除、滑膜刨削和软骨修整可有效解除踝关节撞击症状,手术创伤小、功能恢复快,效果满意。     

Motion control of musculoskeletal systems with redundancy

Motion control of musculoskeletal systems for functional electrical stimulation (FES) is a challenging problem due to the inherent complexity of the systems. These include being highly nonlinear, strongly coupled, time-varying, time-delayed, and redundant. The redundancy in particular makes it difficult to find an inverse model of the system for control purposes. We have developed a control system for multiple input multiple output (MIMO) redundant musculoskeletal systems with little prior information. The proposed method separates the steady-state properties from the dynamic properties. The dynamic control uses a steady-state inverse model and is implemented with both a PID controller for disturbance rejection and an artificial neural network (ANN) feedforward controller for fast trajectory tracking. A mechanism to control the sum of the muscle excitation levels is also included. To test the performance of the proposed control system, a two degree of freedom ankle–subtalar joint model with eight muscles was used. The simulation results show that separation of steady-state and dynamic control allow small output tracking errors for different reference trajectories such as pseudo-step, sinusoidal and filtered random signals. The proposed control method also demonstrated robustness against system parameter and controller parameter variations. A possible application of this control algorithm is FES control using multiple contact cuff electrodes where mathematical modeling is not feasible and the redundancy makes the control of dynamic movement difficult.     

The influence of joint rigidity on impact efficiency and ball velocity in football kicking

Executing any skill with efficiency is important for performance. In football kicking, conflicting and non-significant results have existed between reducing ankle plantarflexion during foot-ball contact with impact efficiency, making it unclear as to its importance as a coaching instruction. The aims of this study were to first validate a mechanical kicking machine with a non-rigid ankle, and secondly compare a rigid to a non-rigid ankle during the impact phase of football kicking. Measures of foot-ball contact for ten trials per ankle configuration were calculated from data recorded at 4000 Hz and compared. The non-rigid ankle was characterised by initial dorsiflexion followed by plantarflexion for the remainder of impact, and based on similarities to punt and instep kicking, was considered valid. Impact efficiency (foot-to-ball speed ratio) was greater for the rigid ankle (rigid = 1.16 ± 0.02; non-rigid = 1.10 ± 0.01; p < 0.001). The rigid ankle was characterised by significantly greater effective mass and significantly less energy losses. Increasing rigidity allowed a greater portion of mass from the shank to be used during the collision. As the ankle remained in plantarflexion at impact end, stored elastic energy was not converted to ball velocity and was considered lost. Increasing rigidity is beneficial for increasing impact efficiency, and therefore ball velocity.     

Bone remodelling around the tibia due to total ankle replacement: effects of implant material and implant–bone interfacial conditions

Abstract

One of the major causes of implant loosening is due to excessive bone resorption surrounding the implant due to bone remodelling. The objective of the study is to investigate the effects of implant material and implant–bone interface conditions on bone remodelling around tibia bone due to total ankle replacement. Finite element models of intact and implanted ankles were developed using CT scan data sets. Bone remodelling algorithm was used in combination with FE analysis to predict the bone density changes around the ankle joint. Dorsiflexion, neutral, and plantar flexion positions were considered, along with muscle force and ligaments. Implant–bone interfacial conditions were assumed as debonded and bonded to represent non-osseointegration and fully osseointegration at the porous coated surface of the implant. To investigate the effect of implant material, three finite element models having different material combinations of the implant were developed. For model 1, tibial and talar components were made of Co–Cr–Mo, and meniscal bearing was made of UHMWPE. For model 2, tibial and talar components were made of ceramic and meniscal bearing was made of UHMWPE. For model 3, tibial and talar components were made of ceramic and meniscal bearing was made of CFR-PEEK. Changes in implant material showed no significant changes in bone density due to bone remodelling. Therefore, ceramic appears to be a viable alternative to metal and CFR-PEEK can be used in place of UHMWPE. This study also indicates that proper bonding between implant and bone is essential for long-term survival of the prosthetic components.     

Ankle and foot power in gait analysis: Implications for science,technology and clinical assessment

In human gait analysis studies, the entire foot is typically modeled as a single rigid-body segment; however, this neglects power generated/absorbed within the foot. Here we show how treating the entire foot as a rigid body can lead to misunderstandings related to (biological and prosthetic) foot function, and distort our understanding of ankle and muscle-tendon dynamics. We overview various (unconventional) inverse dynamics methods for estimating foot power, partitioning ankle vs. foot contributions, and computing combined anklefoot power. We present two case study examples. The first exemplifies how modeling the foot as a single rigid-body segment causes us to overestimate (and overvalue) muscle-tendon power generated about the biological ankle (in this study by up to 77%), and to misestimate (and misinform on) foot contributions; corroborating findings from previous multi-segment foot modeling studies. The second case study involved an individual with transtibial amputation walking on 8 different prosthetic feet. The results exemplify how assuming a rigid foot can skew comparisons between biological and prosthetic limbs, and lead to incorrect conclusions when comparing different prostheses/interventions. Based on analytical derivations, empirical findings and prior literature we recommend against computing conventional ankle power (between shank-foot). Instead, we recommend using an alternative estimate of power generated about the ankle joint complex (between shank-calcaneus) in conjunction with an estimate of foot power (between calcaneus-ground); or using a combined anklefoot power calculation. We conclude that treating the entire foot as a rigid-body segment is often inappropriate and ill-advised. Including foot power in biomechanical gait analysis is necessary to enhance scientific conclusions, clinical evaluations and technology development.     

带线锚钉修复三角韧带损伤的效果及对患者踝关节功能的影响

目的:研究带线锚钉修复三角韧带损伤在踝关节骨折内固定治疗中的作用及对踝关节功能的影响。方法:回顾性分析2012年9月至2016年8月本院收治的72例裸关节骨折并三角韧带损伤患者并且行切开复位钢板置入内固定,及采取带线锚钉内固定方式修复三角韧带损伤视为观察组;另选取同期在本院进行踝关节骨折内固定治疗但不修复三角韧带的72例患者视为对照组。分析患者治疗前、治疗后1个月、3个月、6个月踝关节功能恢复情况,观察患侧内踝间隙和不良反应。结果:观察组在治疗后1个月、3个月、6个月的AOFAS评分显著高于对照组(P0.05)。观察组在治疗后6个月后的患侧内踝间隙显著小于对照组(P0.05)。结论:带线锚钉修复三角韧带损伤在踝关节骨折内固定治疗中,可明显降低患侧内踝间隙距离,可促进患者踝关节功能恢复,无严重不良反应,值得进一步广泛推广使用。     

Coherent phase microscopy in cell biology: visualization of metabolic states

Visualization of functional properties of individual cells and intracellular organelles still remains an experimental challenge in cell biology. The coherent phase microscopy (CPM) provides a convenient and non-invasive tool for imaging cells and intracellular organelles. In this work, we report results of statistical analysis of CPM images of cyanobacterial cells (Synechocystis sp. PCC 6803) and spores (Bacillus licheniformis). It has been shown that CPM images of cyanobacterial cells and spores are sensitive to variations of their metabolic states. We found a correlation between one of optical parameters of the CPM image (‘phase thicknesses’ Δh) and cell energization. It was demonstrated that the phase thickness Δh decreased after cell treatment with the uncoupler CCCP or inhibitors of electron transport (KCN or DCMU). Statistical analysis of distributions of parameter Δh and cell diameter d demonstrated that a decrease in the phase thickness Δh could not be attributed entirely to a decrease in geometrical sizes of cells. This finding demonstrates that the CPM technique may be a convenient tool for fast and non-invasive diagnosis of metabolic states of individual cells and intracellular organelles.