Virtual trial to evaluate the robustness of cementless femoral stems to patient and surgical variation

Primary stability is essential for the success of cementless femoral stems. In this study, patient specific finite element (FE) models were used to assess changes in primary stability due to variability in patient anatomy, bone properties and stem alignment for two commonly used cementless femoral stems, Corail® and Summit® (DePuy Synthes, Warsaw, USA). Computed-tomography images of the femur were obtained for 8 males and 8 females. An automated algorithm was used to determine the stem position and size which minimized the endo-cortical space, and then span the plausible surgical envelope of implant positions constrained by the endo-cortical boundary. A total of 1952 models were generated and ran, each with a unique alignment scenario. Peak hip contact and muscle forces for stair climbing were scaled to the donor’s body weight and applied to the model. The primary stability was assessed by comparing the implant micromotion and peri-prosthetic strains to thresholds (150 μm and 7000 µε, respectively) above which fibrous tissue differentiation and bone damage are expected to prevail. Despite the wide range of implant positions included, FE prediction were mostly below the thresholds (medians: Corail®: 20–74 µm and 1150–2884 µε, Summit®: 25–111 µm and 860–3010 µε), but sensitivity of micromotion and interfacial strains varied across femora, with the majority being sensitive (p < 0.0029) to average bone mineral density, cranio-caudal angle, post-implantation anteversion angle and lateral offset of the femur. The results confirm the relationship between implant position and primary stability was highly dependent on the patient and the stem design used.     

Limited predictive ability of surrogate indices of insulin sensitivity/resistance in Asian-Indian men

Insulin resistance is highly prevalent in Asian Indians and contributes to worldwide public health problems, including diabetes and related disorders. Surrogate measurements of insulin sensitivity/resistance are used frequently to study Asian Indians, but these are not formally validated in this population. In this study, we compared the ability of simple surrogate indices to accurately predict insulin sensitivity as determined by the reference glucose clamp method. In this cross-sectional study of Asian-Indian men (n = 70), we used a calibration model to assess the ability of simple surrogate indices for insulin sensitivity [quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment (HOMA2-IR), fasting insulin-to-glucose ratio (FIGR), and fasting insulin (FI)] to predict an insulin sensitivity index derived from the reference glucose clamp method (SI(Clamp)). Predictive accuracy was assessed by both root mean squared error (RMSE) of prediction as well as leave-one-out cross-validation-type RMSE of prediction (CVPE). QUICKI, FIGR, and FI, but not HOMA2-IR, had modest linear correlations with SI(Clamp) (QUICKI: r = 0.36; FIGR: r = -0.36; FI: r = -0.27; P < 0.05). No significant differences were noted among CVPE or RMSE from any of the surrogate indices when compared with QUICKI. Surrogate measurements of insulin sensitivity/resistance such as QUICKI, FIGR, and FI are easily obtainable in large clinical studies, but these may only be useful as secondary outcome measurements in assessing insulin sensitivity/resistance in clinical studies of Asian Indians.     

Development of a surrogate model based on patient weight,bone mass and geometry to predict femoral neck strains and fracture loads

Osteoporosis and related bone fractures are an increasing global burden in our ageing society. Areal bone mineral density assessed through dual energy X-ray absorptiometry (DEXA), the clinically accepted and most used method, is not sufficient to assess fracture risk individually. Finite element (FE) modelling has shown improvements in prediction of fracture risk, better than aBMD from DEXA, but is not practical for widespread clinical use. The aim of this study was to develop an adaptive neural network (ANN)-based surrogate model to predict femoral neck strains and fracture loads obtained from a previously developed population-based FE model. The surrogate model performance was assessed in simulating two loading conditions: the stance phase of gait and a fall.The surrogate model successfully predicted strains estimated by FE (r² = 0.90–0.98 for level gait load case, r² = 0.92–0.96 for the fall load case). Moreover, an ANN model based on three measurements obtainable in clinics (femoral neck length (level gait) or maximum femoral neck diameter (fall), femoral neck bone mass, body weight) was able to give reasonable predictions (r² = 0.84–0.94) for all of the strain metrics and the estimated femoral neck fracture load. Overall, the surrogate model has potential for clinical applications as they are based on simple measures of geometry and bone mass which can be derived from DEXA images, accurately predicting FE model outcomes, with advantages over FE models as they are quicker and easier to perform.     

Generalized n-dimensional biomechanical field analysis using statistical parametric mapping

A variety of biomechanical data are sampled from smooth n-dimensional spatiotemporal fields. These data are usually analyzed discretely, by extracting summary metrics from particular points or regions in the continuum. It has been shown that, in certain situations, such schemes can compromise the spatiotemporal integrity of the original fields. An alternative methodology called statistical parametric mapping (SPM), designed specifically for continuous field analysis, constructs statistical images that lie in the original, biomechanically meaningful sampling space. The current paper demonstrates how SPM can be used to analyze both experimental and simulated biomechanical field data of arbitrary spatiotemporal dimensionality. Firstly, 0-, 1-, 2-, and 3-dimensional spatiotemporal datasets derived from a pedobarographic experiment were analyzed using a common linear model to emphasize that SPM procedures are (practically) identical irrespective of the data's physical dimensionality. Secondly two probabilistic finite element simulation studies were conducted, examining heel pad stress and femoral strain fields, respectively, to demonstrate how SPM can be used to probe the significance of field-wide simulation results in the presence of uncontrollable or induced modeling uncertainty. Results were biomechanically intuitive and suggest that SPM may be suitable for a wide variety of mechanical field applications. SPM's main theoretical advantage is that it avoids problems associated with a priori assumptions regarding the spatiotemporal foci of field signals. SPM's main practical advantage is that a unified framework, encapsulated by a single linear equation, affords comprehensive statistical analyses of smooth scalar fields in arbitrarily bounded n-dimensional spaces.     

Using two palpable measurements improves the subject-specific femoral modeling

Subject-specific musculoskeletal models are essential to biomedical research and clinical applications, such as customized joint replacement, computer-aided surgical planning, gait analysis and automated segmentation. Generating these models from CT or magnetic resonance imaging (MRI) is time and resource intensive, requiring special skills. Therefore, in many studies individual bone models are approximated by scaling a generic template. Thus, the primary goal of this study was to determine a set of clinically available parameters (palpable measures and demographic data) that could improve the prediction of femoral dimensions, as compared to predicting these variables using uniform scaling based on palpable length. Similar to previous non-homogenous anthropometric scaling methods, the non-homogenous scaling method proposed in this study improved the prediction over uniform scaling of five key femoral measures. Homogenous scaling forces all dimensions of an object to be scaled equally, whereas non-homogenous scaling allows the dimensions to be scaled independently. The largest improvement was in femoral depth, where the coefficient of determination (r²) improved from 0.22 (homogenous) to 0.60 (non-homogeneous). In general, the major advantage of this non-homogenous scaling method is its ability to support the accurate and rapid generation of subject-specific femoral models since all parameters can be collected clinically, without imaging or invasive methods.     

EVA: Evaluation of protein structure prediction servers

EVA (http://cubic.bioc.columbia.edu/eva/) is a web server for evaluation of the accuracy of automated protein structure prediction methods. The evaluation is updated automatically each week, to cope with the large number of existing prediction servers and the constant changes in the prediction methods. EVA currently assesses servers for secondary structure prediction, contact prediction, comparative protein structure modelling and threading/fold recognition. Every day, sequences of newly available protein structures in the Protein Data Bank (PDB) are sent to the servers and their predictions are collected. The predictions are then compared to the experimental structures once a week; the results are published on the EVA web pages. Over time, EVA has accumulated prediction results for a large number of proteins, ranging from hundreds to thousands, depending on the prediction method. This large sample assures that methods are compared reliably. As a result, EVA provides useful information to developers as well as users of prediction methods.     

Influence of spermine and nitrogen deficiency on growth and secondary metabolites accumulation in Castilleja tenuiflora Benth. cultured in a RITA® temporary immersion system

The effect of exogenous spermine (SPM) on Castilleja tenuiflora shoots developing under nitrogen deficiency (ND) stress was evaluated. Shoots cultivated in a temporary immersion system were subjected to four experimental treatments: (1) control; (2) exogenous SPM; (3) ND; and (4) ND+SPM. Shoots were longer in the ND+SPM treatment (6.3 ± 0.5 cm) than in the ND treatment (4.2 ± 0.5 cm). The total chlorophyll content was similar in the control and SPM treatments (0.41 µg mg^?1 FM) and the highest values of total phenolic content were detected at 21 days in the ND+SPM treatment (84.1 ± 0.05 GAE g^?1 DM). In the ND+SPM treatment, the phenylalanine ammonia lyase activity increased earlier than in ND treatment, and reached its maximum at day 21 (3.9 ± 0.2 µmol E‐CIN h^?1 mg^?1 protein). Compared with the control, the ND and ND+SPM treatments resulted in increased secondary metabolites contents in both root and aerial parts. The strongest effect was in the roots, where the SPM and ND+SPM treatments both resulted in increased quercetin content (4.3‐fold that in the control). Our results showed that SPM partially counteract the damage caused by ND and results in increased contents of valuable bioactive compounds.     

Effect of aluminum combined with ApoEε4 on Tau phosphorylation and Aβ deposition

BackgroundAluminum is an environmental neurotoxin widely exposed to animals and humans. Studies have shown that Alzheimer's disease (AD) is characterized by abnormally phosphorylated tau and Aβ deposition, aluminum exposure can lead to abnormal phosphorylated tau and Aβ deposition. Numerous epidemiological data and studies have confirmed that ApoEε4 is a risk factor for AD. However, whether there is an interaction effect between aluminum and ApoEε4 has yet to be verified.MethodsSH-SY5Y cells were exposed with AlCl₃ and transfected with ApoEε4 respectively. The experimental groups included the blank control group, the low dose group (200 μM AlCl₃), the medium dose group (400 μM AlCl₃), the high dose group (800 μM AlCl₃), empty plasmid group, ApoEε4 group and 400 μM AlCl₃+ApoEε4 group. The cell viability was determined by CCK-8 kit after transfection for 48 h.The contents of total tau proteins, tau-181, tau-231, tau-262, tau-396 and Aβ42, were determined by ELISA kit. The interaction between AlCl₃ and ApoEε4 was analyzed by factorial design.ResultsWith the increase of aluminum exposure, SH-SY5Y cell viability decreased, and the expression of the total tau, tau-181, tau-231, tau-262, tau-396 and Aβ content increased. The viability of cells transfected with ApoEε4 is significantly lower than control group, and the expressions of total tau, tau-181, tau-231, tau-262, tau-396 and Aβ in ApoEε4 transfected cells were significantly higher than control group. The viability of cells treated with AlCl₃ plus ApoEε4 was lower than those treated with, either AlCl₃, or ApoEε4. The expression of total tau, tau-181, tau-231, tau-262, tau-396 and Aβ in the cells treated with AlCl₃ plus ApoEε4 were significantly higher than those in other groups (p < 0.05). Moreover, analyzing data based on the factorial design, there was existed an interaction between AlCl₃ and ApoEε4 (p < 0.05).ConclusionAl and ApoEε4 gene can cause morphological changes of SH-SY5Y cells, reduce cell activity, and have obvious cytotoxic effects, and increase the phosphorylation levels of tau and the deposition of Aβ increases. In the presence of both Al and ApoEε4 genes, the two factors interact with each other and show a synergistic effect.     

A modelling approach demonstrating micromechanical changes in the tibial cemented interface due to in vivo service

Post-operative changes in trabecular bone morphology at the cement-bone interface can vary depending on time in service. This study aims to investigate how micromotion and bone strains change at the tibial bone-cement interface before and after cementation. This work discusses whether the morphology of the post-mortem interface can be explained by studying changes in these mechanical quantities. Three post-mortem cement-bone interface specimens showing varying levels of bone resorption (minimal, extensive and intermediate) were selected for this study Using image segmentation techniques, masks of the post-mortem bone were dilated to fill up the mould spaces in the cement to obtain the immediately post-operative situation. Finite element (FE) models of the post-mortem and post-operative situation were created from these segmentation masks. Subsequent removal of the cement layer resulted in the pre-operative situation. FE micromotion and bone strains were analyzed for the interdigitated trabecular bone. For all specimens micromotion increased from the post-operative to the post-mortem models (distally, in specimen 1: 0.1 to 0.5 µm; specimen 2: 0.2 to 0.8 µm; specimen 3: 0.27 to 1.62 µm). Similarly bone strains were shown to increase from post-operative to post-mortem (distally, in specimen 1: −185 to −389 µε; specimen 2: −170 to −824 µε; specimen 3: −216 to −1024 µε). Post-mortem interdigitated bone was found to be strain shielded in comparison with supporting bone indicating that failure of bone would occur distal to the interface. These results indicate that stress shielding of interdigitated trabeculae is a plausible explanation for resorption patterns observed in post-mortem specimens.     

儿茶素分光光度法与微量法抗氧化活性研究

为比较微量法和分光光度法的差异,以Trolox为参比物,PG、BHA和BHT为阳性对照品,比较其IC50和TEAC;以儿茶素的抗氧化活性为研究对象,对2种方法的相关性做Paired—samplet t est。发现2种方法所得到的TEAC基本一致,4个标准品和儿茶素的抗氧化活性顺序一致,即：PG〉儿茶素〉BHA〉Trolox〉BHT;2种方法的相关系数r=0．998,显著性P=0．501。研究结果表明,分光光度法操作繁琐费时,用样量大;微量法操作简单快速,用样量小,准确性好,适合对微量天然产物抗氧化活性的评价。     

Pulse arrival time is not an adequate surrogate for pulse transit time as a marker of blood pressure

Pulse transit time (PTT) is a proven, simple to measure, marker of blood pressure (BP) that could potentially permit continuous, noninvasive, and cuff-less BP monitoring (after an initial calibration). However, pulse arrival time (PAT), which is equal to the sum of PTT and the pre-ejection period, is gaining popularity for BP tracking, because it is even simpler to measure. The aim of this study was to evaluate the hypothesis that PAT is an adequate surrogate for PTT as a marker of BP. PAT and PTT were estimated through the aorta using high-fidelity invasive arterial waveforms obtained from six dogs during wide BP changes induced by multiple interventions. These time delays and their reciprocals were evaluated in terms of their ability to predict diastolic, mean, and systolic BP (DBP, MBP, and SBP) per animal. The root mean squared error (RMSE) between the BP parameter predicted via the time delay and the measured BP parameter was specifically used as the evaluation metric. Taking the reciprocals of the time delays tended to reduce the RMSE values. The DBP, MBP, and SBP RMSE values for 1/PAT were 9.8 ± 5.2, 10.4 ± 5.6, and 11.9 ± 6.1 mmHg, whereas the corresponding values for 1/PTT were 5.3 ± 1.2, 4.8 ± 1.0, and 7.5 ± 2.2 mmHg (P < 0.05). Thus tracking BP via PAT was not only markedly worse than via PTT but also unable to meet the FDA BP error limits. In contrast to previous studies, our results quantitatively indicate that PAT is not an adequate surrogate for PTT in terms of detecting challenging BP changes.     

Safety assessment of potential lactic acid bacteria Bifidobacterium longum SPM1205 isolated from healthy Koreans

The safety assessment of Bifidobacterium longum SPM1205 isolated from healthy Koreans and this strain's inhibitory effects on fecal harmful enzymes of intestinal microflora were investigated. The overall safety of this strain was investigated during a feeding trial. Groups of SD rats were orally administered a test strain or commercial reference strain B. longum 1 x 10(9) CFU/kg body weight/day for four weeks. Throughout this time, their feed intake, water intake and live body weight were monitored. Fecal samples were periodically collected to test harmful enzyme activities of intestinal microflora. At the end of the four-week observation period, samples of blood, liver, spleen, kidney, and gut tissues were collected to determine for hematological parameters and histological differences. The results obtained in this experiment demonstrated that four weeks of consumption of this Bifidobacterium strain had no adverse effects on rat's general health status, blood biochemical parameters or histology. Therefore, it is likely to be safe for human use. Fecal harmful enzymes such as beta-glucosidase, beta-glucuronidase, tryptophanase and urease, were effectively inhibited during the administration of the B. longum SPM1205. These results suggested that this B. longum SPM 1205 could be used for humans as a probiotic strain.     

电穿孔介导马尔尼菲青霉转化体系的建立和优化

目的 建立和优化马尔尼菲青霉电穿孔转化体系,为其基因功能研究提供良好平台.方法 直接使用马尔尼菲青霉缺陷株SPM4（pyrG-,niaD-）萌发孢子进行电穿孔转化,并通过改变孢子龄、孢子萌发时间、质粒浓度、电场强度等影响因素对体系进行优化.结果 适合SPM4电穿孔转化条件为：孢子龄为6d,孢子萌发时间为4h,电场强度为5 kV/cm.上述条件下分别使用1 μg环状或线性化质粒DNA转化SPM4,平均可得到21个和13个转化子.结论 马尔尼菲青霉电穿孔转化效率高,重复性好,针对SPM4萌发孢子,环状质粒较线性化质粒电穿孔转化效率高.     

Influence of experimental conditions on visco-hyperelastic properties of skeletal muscle tissue using a Box–Behnken design

The Mechanical characterization of skeletal muscles is strongly dependent on numerous experimental design factors. Nevertheless, significant knowledge gaps remain on the characterization of muscle mechanics and a large number of experiments should be implemented to test the influence of a large number of factors. In this study, we propose a design of experiment method (DOE) to study the parameter sensitivity while minimizing the number of tests. A Box-Behnken design was then implemented to study the influence of strain rate, preconditioning and preloading conditions on visco-hyperelastic mechanical parameters of two rat forearm muscles. The results show that the strain rate affects the visco-hyperelastic parameters for both muscles. These results are consistent with previous work demonstrating that stiffness and viscoelastic contributions increase with strain rate. Thus, DOE has been shown to be a valid method to determine the effect of the experimental conditions on the mechanical behaviour of biological tissues such as skeletal muscle. This method considerably reduces the number of experiments. Indeed, the presented study using 3 parameters at 3 levels would have required at least 54 tests per muscle against 14 for the proposed DOE method.     

ε-聚赖氨酸产生菌TUST-2的分离鉴定

【目的】ε-聚赖氨酸是一种天然氨基酸同聚物,本研究目的为分离筛选新的ε-聚赖氨酸产生菌。【方法】采用一种新的分离方法从土壤中分离ε-PL产生菌。分离方法含3步:(1)富集培养ε-PL耐受菌;(2)通过改进的Nishikawa方法筛选;(3)挑选高浓度ε-PL耐受菌株。【结果】从海南省土样中分离获得ε-聚赖氨酸产生菌TUST-2。分类和形态特征属链霉菌属。16S rDNA序列分析比对结果表明TUST-2属淀粉酶产色链霉菌(Streptomyces diastatochromogenes)。经特征反应分析、水解物分析、红外光谱、1H NMR、13C NMR和MALDI-TOF-MS分析表明TUST-2发酵产物为ε-聚赖氨酸。【结论】根据16S rRNA基因序列比对和形态及生理生化特征表明ε-聚赖氨酸产生菌TUST-2属于淀粉酶产色链霉菌,命名为淀粉酶产色链霉菌TUST-2。     

Alpha-glucosidase inhibitory and antiplasmodial properties of terpenoids from the leaves of Buddleja saligna Willd

In our continuing search for biologically active natural product(s) of plant origin, Buddleja saligna, a South African medicinal plant, was screened in line with its traditional use for antidiabetic (yeast alpha glucosidase inhibitory) and antiplasmodial (against a chloroquine sensitive strain of Plasmodium falciparum (NF54)) activities. The hexane fraction showed the most promising activity with regards to its antidiabetic (IC₅₀?=?260?±?0.112?µg/ml) and antiplasmodial (IC₅₀?=?8.5?±?1.6?µg/ml) activities. Using activity guided fractionation three known terpenoids (betulonic acid, betulone and spinasterol) were isolated from this species for the first time. The compounds displayed varying levels of biological activities (antidiabetic: 27.31?µg/ml?≥?IC₅₀?≥?5.6?µg/ml; antiplasmodial: 14?µg/ml?≥?IC₅₀?≥?2?µg/ml) with very minimal toxicity.     

基于辅助环境变量的土壤有机碳空间插值——以黄土丘陵区小流域为例

利用普通克里格法(OK)、反距离加权法(IDW)、径向基函数法(RBF)、基于土地利用类型修正的普通克里格法(OK_LU)4种插值方法,对黄土丘陵羊圈沟小流域的土壤有机碳含量进行空间插值。预测结果的准确性通过Pearson相关系数(R),平均绝对误差(MAE),均方根误差(RMSE),准确度(AC)来评价。研究结果表明:(1)在前3种常规空间插值方法中,OK对刻画区域土壤有机碳的空间分布趋势效果最佳,其预测MAE值和RMSE值均为最小,Pearson相关系数(R)和准确度(AC)最大,说明其预测结果的准确性最好、预测的极端误差也最小;其次为RBF;IDW预测的效果最差。(2)OK_LU在空间特征表达方面能够更好地反映复杂地形区的局部变异,其插值结果的精度相比OK有一定程度的提高,其平均绝对误差(MAE)从0.900%降到了0.567%,均方根误差(RMSE)从1.101%降到了0.777%,Pearson相关系数(R)从0.4026提高到0.5589,准确度(AC)从0.9081提高到0.9505。综合比较,在黄土丘陵地区,OK_LU能使插值结果的精度有较大提高,是土壤有机碳空间制图的有效途径。     

Muscle endurance time estimation during isometric training using electromyogram and supervised learning

Constant-force isometric muscle training is useful for increasing the maximal strength , rehabilitation and work-fatigue assessment. Earlier studies have shown that muscle fatigue characteristics can be used for evaluating muscle endurance limit. Study Objective: To predict muscle endurance time during isometric task using frequency spectrum characteristics of surface electromyography signals along with analysis of frequency spectrum shape and scale during fatigue accumulation. Method: Thirteen subjects performed isometric lateral raise at 60% MVC of deltoid (lateral) till endurance limit. Time windowed sEMG frequency spectrum was modelled using 2-parameter distributions namely Gamma and Weibull for spectrum analysis and endurance prediction. Results: Gamma distribution provided better spectrum fitting (P < 0.001) than Weibull distribution. Spectrum Distribution demonstrated no change in shape but shifted towards lower frequency with increase of magnitude at characteristic mode frequency. Support Vector Regression based algorithm was developed for endurance time estimation using features derived from fitted frequency spectrum. Time taken till endurance limit for acquired dataset 38.53 ± 17.33 s (Mean ± Standard Deviation) was predicted with error of 0.029 ± 4.19 s . R-square: 0.956, training and test sets RMSE was calculated as 3.96 and 4.29 s respectively. The application of the algorithm suggested that model required 70% of sEMG signal from maximum time of endurance for high prediction accuracy. Conclusion: Endurance Limit prediction algorithm was developed for quantification of endurance time for optimizing isometric training and rehabilitation. Our method could help personalize and change conventional training method of same weight and duration for all subjects with optimized training parameters, based upon individual sEMG activity.     

Genome sequence of Lactobacillus ruminis SPM0211, isolated from a fecal sample from a healthy Korean

Lactobacillus ruminis SPM0211 is a potential probiotic strain that shows antimicrobial activity against emerging pathogens. Here we present the draft genomic sequence of L. ruminis SPM0211, isolated from a fecal sample from a healthy Korean and describe both the common and unique features of this strain.