An In Vivo Experimental Validation of a Computational Model of Human Foot

Reliable computational foot models offer an alternative means to enhance knowledge on the biomechanics of human foot.Model validation is one of the most critical aspects of the entire foot modeling and analysis process.This paper presents an invivo experiment combining motion capture system and plantar pressure measure platform to validate a three-dimensional finiteelement model of human foot.The Magnetic Resonance Imaging(MRI)slices for the foot modeling and the experimental datafor validation were both collected from the same volunteer subject.The validated components included the comparison of staticmodel predictions of plantar force,plantar pressure and foot surface deformation during six loading conditions,to equivalentmeasured data.During the whole experiment,foot surface deformation,plantar force and plantar pressure were recorded simultaneouslyduring six different loaded standing conditions.The predictions of the current FE model were in good agreementwith these experimental results.     

A Coupling Analysis of the Biomechanical Functions of Human Foot Complex during Locomotion

This study represents a functional analysis of the human foot complex based on in-vivo gait measurements, finite element (FE) modeling and biological coupling theory, with the objective of achieving a comprehensive understanding of the impact attenuation and energy absorption functions of the human foot complex. A simplified heel pad FE model comprising reticular fiber structure and fat cells was constructed based on the foot pad Magnetic Resonance (MR) images. The model was then used to investigate the foot pad behaviors under impact during locomotion. Three-dimensional (3D) gait measurement and a 3D FE foot model comprising 29 bones, 85 ligaments and the plantar soft tissues were used to investigate the foot arch and plantar fascia deformations in mid-stance phase. The heel pad simulation results show that the pad model with fat cells (coupling model) has much stronger capacity in impact attenuation and energy storage than the model without fat cells (structure model). Furthermore, the FE simulation reproduced the deformations of the foot arch structure and the plantar fascia extension observed in the gait measurements, which reinforces the postulation that the foot arch structure also plays an important role in energy absorption during locomotion. Finally, the coupling mechanism of the human foot functions in impact attenuation and energy absorption was proposed.     

A unified theory for the energy cost of legged locomotion

Small animals are remarkably efficient climbers but comparatively poor runners, a well-established phenomenon in locomotor energetics that drives size-related differences in locomotor ecology yet remains poorly understood. Here, I derive the energy cost of legged locomotion from two complementary components of muscle metabolism, Activation–Relaxation and Cross-bridge cycling. A mathematical model incorporating these costs explains observed patterns of locomotor cost both within and between species, across a broad range of animals (insects to ungulates), for a wide range of substrate slopes including level running and vertical climbing. This ARC model unifies work- and force-based models for locomotor cost and integrates whole-organism locomotor cost with cellular muscle physiology, creating a predictive framework for investigating evolutionary and ecological pressures shaping limb design and ranging behaviour.     

Segmental Kinematic Coupling of the Human Spinal Column during Locomotion

As one of the most important daily motor activities, human locomotion has been investigated intensively in recent decades. The locomotor functions and mechanics of human lower limbs have become relatively well understood. However, so far our understanding of the motions and functional contributions of the human spine during locomotion is still very poor and simultaneous in-vivo limb and spinal column motion data are scarce. The objective of this study is to investigate the delicate in-vivo kinematic coupling between different functional regions of the human spinal column during locomotion as a stepping stone to explore the locomotor function of the human spine complex. A novel infrared reflective marker cluster system was constrncted using stereophotogrammetry techniques to record the 3D in-vivo geometric shape of the spinal column and the segmental position and orientation of each functional spinal region simultaneously. Gait measurements of normal walking were conducted. The preliminary results show that the spinal column shape changes periodically in the frontal plane during locomotion. The segmental motions of different spinal functional regions appear to be strongly coupled, indicating some synergistic strategy may be employed by the human spinal column to facilitate locomotion. In contrast to traditional medical imaging-based methods, the proposed technique can be used to investigate the dynamic characteristics of the spinal column, hence providing more insight into the functional biomechanics of the human spine.     

Localization of Human Mesenchymal Stem Cells from Umbilical Cord Blood and Their Role in Repair of Diabetic Foot Ulcers in Rats

The aim of this study is to explore the localization of human mesenchymal stem cells from umbilical cord matrix (hMSCs-UC) and the role of these cells in the repair of foot ulcerate tissue in diabetic foot ulcers in rats. A diabetic rat model was established by administering Streptozotocin. Diabetic foot ulceration was defined as non-healing or delayed-healing of empyrosis on the dorsal hind foot after 14 weeks. hMSCs-UC were delivered through the left femoral artery. We evaluated the localization of hMSCs-UC and their role in tissue repair in diabetic foot ulcers by histological analysis, PCR, and immunohistochemical staining. A model for diabetes was established in 54 out of 60 rats (90% success rate) and 27 of these rats were treated with hMSCs-UC. The area of ulceration was significantly and progressively reduced at 7 and 14 days following treatment with hMSCs-UC. This gross observation was strongly supported by the histological changes, including newly developed blood vessels and proliferation of inflammatory cells at 3 days post-treatment, significant increase in granulation tissue at 7 days post-treatment and squamous epithelium or stratified squamous epithelium at 14 days post-treatment. Importantly, human leukocyte antigen type-I (HLA-1) was confirmed in ulcerated tissue by RT-PCR. The expression of cytokeratin 19 was significantly increased in diabetic model rats, with no detectable change in cytokeratin 10. Additionally, both collagens I and III increased in model rats treated with hMSCs-UC, but the ratio of collagen I/III was less significant in treated rats compared with control rats. These results suggest that hMSCs-UC specifically localize to the target ulcerated tissue and may promote the epithelialization of ulcerated tissue by stimulating the release of cytokeratin 19 from keratinocytes and extracellular matrix formation.     

The Calculation of Frequency-Shift Functions for Chains of Coupled Oscillators, with Application to a Network Model of the Lamprey Locomotor Pattern Generator

Chains of coupled limit-cycle oscillators are considered, in which the coupling is assumed to be weak and only between adjacent oscillators. For such a system the change in frequency of an oscillator due to the coupling can be expressed, up to first order in thecoupling strength, by functions that depend only on the phase difference between the coupled oscillators. In this article a numerical algorithm is developed for the evaluation of these functions (the H-functions) in terms of a single oscillator and the interactions between coupled oscillators. The technique is applied to a connectionist model for the locomotor pattern generator in the lamprey spinal cord.An H-function so derived is compared to a function derived empirically(the C-function) from simulations of the same system. The phase lagsthat develop between adjacent oscillators in a simulated chain are compared with those predicted theoretically, and it is shown that coupling thatis functionally strong is nonetheless weak enough to behave as predicted.     

Development and validation of a human biomechanical model for rib fracture and thorax injuries in blunt impact

From 1990 to approximately 50,000–120,000 people die annually of road traffic accidents in China. Traffic accidents are the main cause of death of Chinese adults aged 15–45 years. This study aimed to determine the biomechanical response and injury tolerance of the human body in traffic accidents. The subject was a 35-year-old male with a height of 170 cm, weight of 70 kg and Chinese characteristics at the 50th percentile. Geometry was generated by computed tomography and magnetic resonance imaging. A human-body biomechanical model was then developed. The model featured in great detail the main anatomical characteristics of skeletal tissues, soft tissues and internal organs, including the head, neck, shoulder, thoracic cage, abdomen, spine, pelvis, pleurae and lungs, heart, aorta, arms, legs, and other muscle tissues and skeletons. The material properties of all tissues in the human body model were obtained from the literature. Material properties were developed in the LS-DYNA code to simulate the mechanical behaviour of the biological tissues in the human body. The model was validated against cadaver responses to frontal and side impact. The predicted model response reasonably agreed with the experimental data, and the model can further be used to evaluate thoracic injury in real-world crashes. We believe that the transportation industry can use numerical models in the future to simultaneously reduce physical testing and improve automotive safety.     

A hexapedal jointed-leg model for insect locomotion in the horizontal plane

We develop a simple model for insect locomotion in the horizontal (ground) plane. As in earlier work by Seipel et al. (Biol Cybern 91(0):76–90, 2004) we employ six actuated legs that also contain passive springs, but the legs, with “hip” and ‘knee’ joints, better represent insect morphology. Actuation is provided via preferred angle inputs at each joint, corresponding to zero torques in the hip and knee springs. The inputs are determined from estimates of foot forces in the cockroach Blaberus discoidalis via an inverse problem. The head–thorax–body is modeled as a single rigid body, and leg masses, inertia and joint dissipation are ignored. The resulting three degree-of-freedom dynamical system, subject to feedforward joint inputs, exhibits stable periodic gaits that compare well with observations over the insect’s typical speed range. The model’s response to impulsive perturbations also matches that of freely-running cockroaches (Jindrich and Full, J Exp Biol 205:2803–2823, 2002), and stability is maintained in the face of random foot touchdowns representative of real insects. We believe that this model will allow incorporation of realistic muscle models driven by a central pattern generator in place of the joint actuators, and that it will ultimately permit the study of proprioceptive feedback pathways involving leg force and joint angle sensing.     

Validation of a full body finite element model (THUMS) for running-type impacts to the lower extremity

The purpose of this study was to determine whether modifying an existing, highly biofidelic full body finite element model [total human model for safety (THUMS)] would produce valid amplitude and temporal shock wave characteristics as it travels proximally through the lower extremity. Modifying an existing model may be more feasible than developing a new model, in terms of cost, labour and expertise. The THUMS shoe was modified to more closely simulate the material properties of a heel pad. Relative errors in force and acceleration data from experimental human pendulum impacts and simulated THUMS impacts were 22% and 54%, respectively, across the time history studied. The THUMS peak acceleration was attenuated by 57.5% and took 19.7 ms to travel proximally along the lower extremity. Although refinements may be necessary to improve force and acceleration timing, the modified THUMS represented, to a certain extent, shock wave propagation and attenuation demonstrated by living humans under controlled impact conditions.     

A Mathematical Model of Uterine Dynamics and its Application to Human Parturition

We have developed a simple mathematical model with three physiologically significant states to describe the changes in intrauterine pressure associated with a contraction during human parturition. The myometrium is modelled as a set of smooth muscle cells, each of which is in one of three states (quiescent, contracted, refractory) at a given time. These states are occupied according to a cycle governed by three temporal parameters. The solutions of the equations describing the model show an oscillatory behavior for particular values of these parameters, which is very similar to the time dependant development of intrauterine pressure during labor. Due to its non-linear terms, our model could lead to chaotic oscillations (in the mathematical sense), whose clinical counterpart may occur in cases of dystocia. Despite its simplicity, this model appears to be a useful guide to further investigations of the oscillatory behavior of the myometrium, or other smooth muscles, in normal and pathological situations.     

Evaluating The Effect of Establishing Protocol for Self- Care Practice of Diabetic Foot Patients Regarding Their Needs,Concerns and Medication Use: A quasi-experimental study

BackgroundThe practice of diabetic self-care plays a significant role in maintaining and preventing diabetic foot complications, but low commitment to self-care practices is common. This study evaluates the effect of establishing protocol for self-care practice of diabetic foot patients according to their needs, concerns, and medication use. A quasi-experimental research (pre-test and post-test) design was used in outpatient clinics at Benha University Hospital, Egypt. The study included 100 adult patients diagnosed with diabetes (types I and II) for at least six months. The findings revealed that 79% suffered from burning or tingling in legs or feet; 74% complained of presence of redness of lower limb, legs or foot pain with activity, and loss of lower extremity sensation; and 80% had changes in skin colour or skin lesions. A comparison between the group pre- and post-intervention (protocol) showed that post-intervention patient foot care knowledge and self-care practice scores were higher. Also, 72% of the participants obtained good knowledge related to foot care post- protocol intervention compared to 37% pre- intervention. Based on the findings, the establishing intervention protocol fosters self-care practice and knowledge regarding needs, concerns, and medication use among diabetic foot patients. Therefore, this protocol can be applied in health practice and research in order to prevent diabetic foot ulcer, and thereby foot amputation.     

一个基于熵的指数精细定位人类复杂性状位点

近来,一个基于熵的指数被提出用来对人类复杂性状位点进行连锁不平衡定位．这个熵指数比较了患病个体与正常个体或极端样本之间标记基因频率的熵和条件熵．本文基于熵理论,提出了另一个备选指数．这个新的指数比较患病个体与正常个体之间标记基因型频率的熵和条件熵．计算机模拟结果表明本文提出的新指数平行于之前的熵指数．而基于遗传性血色病（hereditary haemochromatosis,HH）数据的分析表明了这个新指数能有效对人类复杂性状位点进行精细定位．     

A fully coupled framework for in silico investigation of in-stent restenosis

Finite element analysis (FEA) can be implemented along with Agent-based model (ABM) to investigate the biomechanical and mechanobiological mechanisms of pathophysiological processes. However, traditional ABM-FEA approaches are often partially coupled and lack the feedback responses from biological analysis. To overcome this problem, a fully coupled ABM-FEA framework is developed in this paper by linking the macro-scale and cell-scale modules bi-directionally. Numerical studies of the in-stent restenosis process are conducted using the proposed approach and comparisons are made between the two types of frameworks. A reduction in lumen loss rate, which is possibly caused by the time-varying stresses, is observed in the fully coupled simulations. The re-endothelialisation process is also simulated under different frameworks and the simulation results show strong inhibition of endothelial cells to vascular restenosis. The proposed method is proved to be effective to explain the biomechanical-mechanobiological coupling characteristics of the restenosis problem and can be utilized for stent design and optimization.     

Human stomach alcohol and aldehyde dehydrogenases (ALDH): A genetic model proposed for ALDH III isozymes

Isozyme phenotypes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) from human gastroendoscopic as well as surgical gastric biopsies were determined by starch gel electrophoresis and agarose isoelectric focusing. γγ ADH isozymes were expressed predominantly in the mucosal layer of the stomach, whereas ββ isozymes were in the muscular layer. In the 56 gastroendoscopic mucosal biopsies examined, the homozygous ADH₃ 1-1 phenotype was found in 75% of the samples, and the heterozygous ADH₃ 2-1 phenotype in 25%. Accordingly, the gene frequencies of the allelesADH ₃ ¹ andADH ₃ ² were calculated to be 0.88 and 0.12, respectively. Using a modified agarose isoelectric focusing procedure, gastric ALDH I, ALDH II, and up to five ALDH III forms could be clearly resolved. The ALDH III isozymes accounted for more than 80% of the total ALDH activities in gastric mucosa and exhibitedK _m values in the millimolar range for propionaldehyde atpH 9.0. Forty-five percent of the 55 gastroendoscopic biopsies studied lacked ALDH I isozyme. The complex gastric ALDH III isozyme phenotypes seen in these biopsies fall into three patterns. They can be interpreted by a genetic hypothesis, based on a dimeric molecule, in which there are two separate genes,ALDH _3a andALDH _3b, with theALDH _3b locus exhibiting polymorphism. The homozygous phenotypes ALDH_3b 1-1 and ALDH_3b 2-2 were found to be 4 and 76%, respectively, and the heterozygous ALDH_3b 2-1 phenotype 20%, of the total. Therefore, the allele frequencies forALDH _3b ¹ andALDH _3b ² were calculated to be 0.14 and 0.86, respectively. Several lines of biochemical evidence consistent with this genetic model are discussed. This work was supported by grants from the National Science Council, Republic of China, and the Institute of Biomedical Sciences, Academia Sinica.     

Complementation of Yeast Genes with Human Genes as an Experimental Platform for Functional Testing of Human Genetic Variants

While the pace of discovery of human genetic variants in tumors, patients, and diverse populations has rapidly accelerated, deciphering their functional consequence has become rate-limiting. Using cross-species complementation, model organisms like the budding yeast, Saccharomyces cerevisiae, can be utilized to fill this gap and serve as a platform for testing human genetic variants. To this end, we performed two parallel screens, a one-to-one complementation screen for essential yeast genes implicated in chromosome instability and a pool-to-pool screen that queried all possible essential yeast genes for rescue of lethality by all possible human homologs. Our work identified 65 human cDNAs that can replace the null allele of essential yeast genes, including the nonorthologous pair yRFT1/hSEC61A1. We chose four human cDNAs (hLIG1, hSSRP1, hPPP1CA, and hPPP1CC) for which their yeast gene counterparts function in chromosome stability and assayed in yeast 35 tumor-specific missense mutations for growth defects and sensitivity to DNA-damaging agents. This resulted in a set of human–yeast gene complementation pairs that allow human genetic variants to be readily characterized in yeast, and a prioritized list of somatic mutations that could contribute to chromosome instability in human tumors. These data establish the utility of this cross-species experimental approach.     

Controlling Epithelial Polarity: A Human Enteroid Model for Host-Pathogen Interactions

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A Mathematical Formulation for 3D Quasi-Static Multibody Models of Diarthrodial Joints

This study describes a genera] set of equations for quasi-static analysis of three-dimensional multibody systems, with a particular emphasis on modeling of diarthrodial joints. The model includes articular contact, muscle forces, tendons and tendon pulleys, ligaments, and the wrapping of soft tissue structures around bone and cartilage surfaces. The general set of equations governing this problem are derived using a consistent notation for all types of links, which can be converted conveniently into efficient computer codes. The computational efficiency of the model is enhanced by the use of analytical Jacobians, particularly in the analysis of articular surface contact and wrapping of soft tissue structures around bone and cartilage surfaces. The usefulness of the multibody model is demonstrated by modeling the patellofemoral joint of six cadaver knees, using cadaver-specific data for the articular surface and bone geometries, as well as tendon and ligament insertions and muscle lines of actions. Good accuracy was observed when comparing the model patellar kinematic predictions to experimental data (mean ± stand, dev. error in translation: 0.63 ± 1.19 mm, 0.10 ± 0.71 mm, -0.29 ± 0.84 mm along medial, proximal, and anterior directions, respectively; in rotation: -1.41 ± 1.71°, 0.27 ±2.38°, -1.13 ± 1.83° in flexion, tilt and rotation, respectively). The accuracy which can be achieved with this type of model, and the computational efficiency of the algorithm employed in this study may serve in many applications such as computer-aided surgical planning, and real-time computer-assisted surgery in the operating room.     

Sentinel Human Health Indicators: A Model for Assessing Human Health Status of Vulnerable Communities

The presence of toxic substances in the Great Lakes (GL) continues to be a significant concern. Eleven of the most persistent and ubiquitous substances were identified as “critical Great Lakes pollutants” by the International Joint Commission (IJC). In some areas of the GL these toxic substances bioaccumulate in sediment and organisms, biomagnify in food webs, and persist at high levels. The Agency for Toxic Substances and Disease Registry (ATSDR) Great Lakes Human Health Effects Research Program (GLHHERP) characterizes contaminant exposures via GL fish consumption and investigates the potential for short- and long-term adverse health effects. The program has identified a set of eight indicators to determine risk. The GLHHERP findings indicate: (1) vulnerable populations are still being exposed to persistent toxic substances (2) body burden levels are two to four times higher than in the general U.S. population, (3) women and minorities are less knowledgeable about fish advisories than other segments of the population, (4) the presence of neurodevelopmental deficits in newborns, and cognitive deficits in children and adults, and (5) disturbances in reproductive parameters have been demonstrated in adults. The public health implications of these findings and the need for intervention strategies are discussed.     

一种新的B链C端去四肽胰岛素的研制方法

报道了将单体胰岛素前体(MIP)经胰蛋白酶和羧肽酶B两步连续酶切获得B链C端去四肽胰岛素(DTI)的方法。MIP由甲醇酵母表达,最高发酵表达量达到150mg/L。发酵液中MIP通过疏水层析,分子筛初步纯化后直接进行酶切,在胰蛋白酶酶切3h后加入抑制剂paminobenzamidine处理15min,然后直接加入羧肽酶B酶切6h,再通过反相柱纯化即可得到纯品DTI,从分子筛到最后DTI,总纯化得率达到77%。按中国药典小白鼠惊厥法测定得DTI的生物活力为22IU/mg,是胰岛素的80%,在Superdex G-75分子筛上测定DTI的解离聚合曲线,证明其是单体。     

Assessment of Human Health Risk for an Area Impacted by a Large-Scale Metallurgical Refinery Complex in Hunan,China

Due to accelerated urbanization and reform of industrial structure in China, polluting industries in major cities have been closed or relocated. Consequently, large numbers of industrial sites were generated and the contaminated soils on and around these sites may pose risks to humans. This case study presents an estimation of human health risks for an area that is mainly impacted through air dispersion and deposition from a large-scale metallurgical refinery complex in Zhuzhou city, Hunan Province, China. Carcinogenic and non-carcinogenic risks posed by the contaminants were estimated under future industrial and residential land use scenarios. The result shows that adverse health effects may occur primarily through ingestion of soils contaminated with As, Cd, and Pb. The total carcinogenic risks of multiple contaminants for a large area exceed the acceptable risk level of 1 × 10^?5, and several localized hotspots, where the total hazard index exceeds 1 were identified. Soils in the Tongda site pose the highest carcinogenic risks and non-carcinogenic hazards. It is concluded that potential human health risks exist under the proposed redevelopment scenarios, and development of risk-based remediation strategies is recommended.