Estimating total knee replacement joint load ratios from kinematics

Accurate prediction of loads acting at the joint in total knee replacement (TKR) patients is key to developing experimental or computational simulations which evaluate implant designs under physiological loading conditions. In vivo joint loads have been measured for a small number of telemetric TKR patients, but in order to assess device performance across the entire patient population, a larger patient cohort is necessary. This study investigates the accuracy of predicting joint loads from joint kinematics. Specifically, the objective of the study was to assess the accuracy of internal–external (I–E) and anterior–posterior (A–P) joint load predictions from I–E and A–P motions under a given compressive load, and to evaluate the repeatability of joint load ratios (I–E torque to compressive force (I–E:C), and A–P force to compressive force (A–P:C)) for a range of compressive loading profiles. A tibiofemoral finite element model was developed and used to simulate deep knee bend, chair-rise and step-up activities for five patients. Root-mean-square (RMS) differences in I–E:C and A–P:C load ratios between telemetric measurements and model predictions were less than 1.10e–3 Nm/N and 0.035 N/N for all activities. I–E:C and A–P:C load ratios were consistently reproduced regardless of the compressive force profile applied (RMS differences less than 0.53e–3 Nm/N and 0.010 N/N, respectively). When error in kinematic measurement was introduced to the model, joint load predictions were forgiving to kinematic measurement error when conformity between femoral and tibial components was low. The prevalence of kinematic data, in conjunction with the analysis presented here, facilitates determining the scope of A–P and I–E joint loading ratios experienced by the TKR population.     

MicroRNA replacement therapy in cancer

Despite the recent progress in cancer management approaches, the mortality rate of cancer is still growing and there are lots of challenges in the clinics in terms of novel therapeutics. MicroRNAs (miRNA) are regulatory small noncoding RNAs and are already confirmed to have a great role in regulating gene expression level by targeting multiple molecules that affect cell physiology and disease development. Recently, miRNAs have been introduced as promising therapeutic targets for cancer treatment. Regulatory potential of tumor suppressor miRNAs, which enables regulation of entire signaling networks within the cells, makes them an interesting option for developing cancer therapeutics. In this regard, over recent decades, scientists have aimed at developing powerful and safe targeting approaches to restore these suppressive miRNAs in cancerous cells. The present review summarizes the function of miRNAs in tumor development and presents recent findings on how miRNAs have served as therapeutic agents against cancer, with a special focus on tumor suppressor miRNAs (mimics). Moreover, the latest investigations on the therapeutic strategies of miRNA delivery have been presented.     

The choice of the femoral center of rotation affects material loss in total knee replacement wear testing – A parametric finite element study of ISO 14243-3

A leading cause of long-term failure of total knee replacements (TKRs) is osteolysis caused by polyethylene wear particles. The current gold standard for preclinical wear testing of TKRs is mechanical knee simulators. The definition of the femoral center of flexion-extension rotation (CoR) has been identified as one possible source of variability within TKR wear tests, since the femoral curvature varies from distal to posterior. The magnitude of the influence on wear due to changes in location of femoral CoR has not been investigated in depth. During this study, a computational framework utilizing finite element analysis for modelling wear of TKRs was developed and used to investigate the influence of the location of femoral CoR on TKR polyethylene wear during standardized displacement controlled testing (ISO 14243-3:2014). The study was carried out using a 40-point Latin Hypercube Design of Experiments approach. Volumetric wear was highly correlated to femoral CoR in both the superior/inferior and anterior/posterior directions, with a stronger relationship in the superior/inferior direction. In addition, wear scars showing linear penetration were examined, with large differences in simulations at the extreme ends of the sampling region. In this study, it was found that variations in the location of the femoral center of rotation can represent a large source of variability in the preclinical testing and evaluation of the wear performance of total knee replacements. This study represents the first attempt at quantifying the effect on wear of different femoral center of rotations across a large sampling space.     

Zinc content of normal human serum and its correlation with some hematic parameters

Numerous studies have demonstrated that several diseases and stress conditions are associated with changes in the levels of zinc in the blood plasma and cellular elements. In this research the association between serum zinc concentrations and other hematic parameters of diagnostic interest has been evaluated. Quantitative determinations of zinc, total plasmatic proteins, albumin, hemoglobin and calculation of mean corpuscular volume were performed on blood samples from 58 males aged 20–61 years. Concentrations measured in our sample are comparable with reference values. Statistically significant correlation coefficients were found between age and albumin (r = - 0.562, P < 0.001), serum zinc and albumin (r = 0.328, P < 0.05), serum zinc and hemoglobin (r = 0.291, P < 0.05), and total plasmatic proteins and albumin (r = 0.463, P < 0.001). These correlation coefficients were significant even after adjustment for age effect. The determination of serum zinc concentration may be useful in the assessment of clinical scenarios. Particularly, it may provide additional information for the diagnosis of specific pathologies, such as hepatic malfunctions. It could also be useful in the identification of different stages of anemia.     

Lipase-catalyzed asymmetric synthesis of naphtho[2,3-c]furan-1(3H)-one derivatives by a one-pot dynamic kinetic resolution/intramolecular Diels–Alder reaction: Total synthesis of (−)-himbacine

One-pot sequential reactions using the acyl moieties installed by enzymatic dynamic kinetic resolution of alcohols have been little investigated. In this work, the acryloyl moiety installed via the lipase/oxovanadium combo-catalyzed dynamic kinetic resolution of a racemic dienol [4-(cyclohex-1-en-1-yl)but-3-en-2-ol or 1-(cyclohex-1-en-1-yl)but-2-en-1-ol] with a (Z)-3-(phenylsulfonyl)acrylate underwent an intramolecular Diels–Alder reaction in a one-pot procedure to produce an optically active naphtho[2,3-c]furan-1(3H)-one derivative (98% ee). This method was successfully applied to the asymmetric total synthesis of (?)-himbacine.     

苏北沿海不同土地利用方式土壤水溶性有机碳含量特征

土壤水溶性有机碳(WSOC)是土壤碳循环最活跃的组成部分之一。土地利用方式的改变可能显著影响土壤有机碳的组成和结构,进而影响到大气与土壤间的碳交换。本研究以苏北沿海地区农田、杨农复合经营、杨树纯林以及草地等4种不同土地利用方式土壤为研究对象,采用TOC-VCPN总有机碳仪测定了4种不同土地方式下土壤WSOC含量的变化。分析了土壤WSOC与土壤总有机碳(TOC)、易氧化碳(ROC)及理化性质的相关关系。结果表明:WSOC和TOC、土壤全氮(TN)、ROC呈显著正相关,与碳氮比、pH、土壤容重呈显著负相关;WSOC的含量随土层的加深而减少,与总有机碳的变化特征一致,在各个土层,不同土地利用方式WSOC含量差异不显著;农田和草地的WSOC含量在0～10cm土层与10～25cm土层之间差异显著(P<0.05),杨农复合经营的WSOC含量在10～25cm土层与25～40cm土层之间差异显著(P<0.05),其他3种类型差异不显著。     

Structural and functional characterization of simvastatin-induced myotoxicity in different skeletal muscles

Background

Statins are the most commonly used drugs for the treatment of hypercholesterolemia. Their most frequent side effect is myotoxicity. To date, it remains unclear whether statins preferentially induce myotoxicity in fast- or in slow-twitch muscles. Therefore, we investigated these effects on fast- (extensor digitorum longus; EDL), slow- (soleus; SOL), and mixed-twitch muscles (diaphragm; DIA) in rats by comparing their contractile and molecular structural properties.

Methods

Simvastatin-induced functional changes were determined by muscle contraction measurements, and drug-induced molecular changes were investigated using Fourier transform infrared (FTIR) and attenuated total reflectance (ATR) FTIR spectroscopy.

Results

With simvastatin administration (30 days, 50 mg/kg), a depression in the force–frequency curves in all muscles was observed, indicating the impairment of muscle contractility; however, the EDL and DIA muscles were affected more severely than the SOL muscle. Spectroscopic findings also showed a decrease in protein, glycogen, nucleic acid, lipid content and an increase in lipid order and lipid dynamics in the simvastatin-treated muscles. The lipid order and dynamics directly affect membrane thickness. Therefore, the kinetics and functions of membrane ion channels were also affected, contributing to the statin-induced impairment of muscle contractility. Furthermore, a reduction in α-helix and β-sheet and an increase in random coil, aggregated and antiparallel β-sheet were observed, indicating the protein denaturation. Spectral studies showed that the extent of molecular structural alterations in the muscles following simvastatin administration was in the order EDL > DIA > SOL.

Conclusions

Simvastatin-induced structural and functional alterations are more profound in the fast-twitch than in the slow-twitch muscles.

General significance

Myotoxic effects of simvastatin are primarily observed in the fast-twitch muscles.     

桂西北喀斯特土壤对生态系统退化的响应

在桂西北喀斯特地区选取玉米 红薯轮作地（KMS）、放牧+冬季火烧草地（KGB）、自然恢复地（KNR）和原生林地（KPF）4种典型生态系统,研究了土壤有机碳、全氮、全磷,微生物生物量碳、氮、磷和土壤结构对生态系统退化的响应.结果表明：KPF土壤有机碳、全氮、全磷和微生物生物量碳、氮、磷均极显著高于其他3种土壤;其他3种土壤中,有机碳和全氮为：KNR > KGB > KMS,但差异不显著;KMS土壤全磷含量（0.87g·kg^-1）分别是KNR和KGB的2.07和9.67倍 (P<0.01);KGB和KNR土壤微生物生物量碳、氮、磷含量均显著大于KMS;KGB中微生物生物量碳显著大于KNR,但二者间微生物生物量氮和磷含量差异不显著.说明减少人为干扰后喀斯特退化生态系统可以缓慢增加土壤有机碳含量,适当放牧和自然恢复都可以作为退化生态系统恢复的方式;土壤微生物生物量对生态系统的变化响应较灵敏,可以作为喀斯特地区土壤养分变化或生态系统退化的一个敏感指标.土壤结构以>0.25 mm水稳性大团聚体为主（>70%）(KMS除外,以2～0.25 mm团聚体为主),并以>2 mm团聚体为主;土壤结构破坏率KMS（51.62%）大于KGB（23.48%）,KNR和KPF较小（分别为9.09%和9.46%）.说明人为干扰或农业耕作破坏了土壤水稳性大团聚体,使其向小粒级转变,土壤结构破坏率增大.对喀斯特地区退化严重的生态系统应减少人为干扰,以自然恢复等保护性措施为主.     

Role of glutathione in ethanol stress tolerance in yeast Pachysolen tannophilus

The effect of glutathione enrichment and depletion on the survival of Pachysolen tannophilus after ethanol stress was investigated. In this work, we verified that both control and glutathione deficient yeast cells were much more oxidized after ethanol stress. Depletion of cellular glutathione enhanced the sensitivity to ethanol and suppressed the adaptation. Incubation of the cell with amino acids constituting glutathione (GIu, Cys, Gly) increased the intracellular glutathione content, and subsequently the cell acquired resistance against ethanol. The level of reactive oxygen species, protein carbonyl, and lipid peroxidation in glutathione enriched groups were also studied. These results strongly suggest that intracellular glutathione plays an important role in the adaptive response in P. tannophilus to ethanol induced oxidative stress.