Stress in the Patella Following Autologous Chondrocyte Implantation - A Finite Element Study

Bovine patella cartilage shows signs of damage and cell death when subjected to a compressive cyclic load of 6 MPa, which results in a shear stress of 5.6 MPa. The aim of this research was to investigate the effect of activities of daily living (descending stairs, bicycling and deep flexion) on the contact stresses in the patellofemoral compartment following an articular chondrocyte implantation (ACI). A finite element (FE) model of the patellar femoral joint was created and dynamic non-linear analyses were carried out for this purpose. A shear stress of 5.6 MPa was used as the threshold that cartilage can tolerate without resulting in damage. The FE model was verified numerically. Our results show that, for a 70 kg individual at 50% recovery, (i) contact stress in the patella is 11% higher than that in the femur; (ii) shear stress in the host cartilage reaches 4.75 MPa at 50° of flexion; (iii) shear stress in the patella host cartilage is twice that in a healthy cartilage during deep flexion approaching 70°; (iv) maximum shear stress value was 2.75 MPa during cycling at 60% load; (v) stress shielding still occurs through the host cartilage even when the implanted cartilage reaches 97.5% the Young’s modulus of a healthy cartilage. Based on these results, (i) using an exercise bicycle is recommended for rehabilitation; (ii) deep knee flexion should be avoided; (iii) obese people with a BMI of over 42 kg/m2 should not undertake vigorous weight-bearing exercises involving deep knee flexion

Total hip replacement: effect of cement mantle thickness - an integrated computational simulation and in vitro study

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Total Hip Replacement: Tensile Stress in Bone Cement is influenced by Cement Mantle Thickness, Acetabular Size, Bone Quality, and Body Mass Index

Background: High stress developed in the cement mantle of a total hip replacement is reported to contribute to premature failure of acetabular components. We postulate that stress level is influenced by cement mantle thickness, acetabular size, bone quality and body mass index. Methods: Finite element models of reconstructed hemi pelves of different sizes and acetabular diameters (46, 52 and 58 mm) were created from CT-Scan data. We investigated the effects of cement mantle thickness (1, 2, 3 and 4 mm), acetabular size, body mass index (BMI = 20, 25 and 30 kg/m2) and bone quality on stress level developed in the cement mantle. Findings: Peak tensile stresses in the cement mantle increased with a decrease in cement mantle thickness, acetabular size and bone quality and an increase in BMI. Interpretation: Our results indicate that a 4-mm-thick cement mantle is required in small reconstructed acetabulae of ≤ 50-mm diameters, while a 1-mm thick cement mantle can be used on larger reconstructed acetabulae of ≥ 58 mm diameter. Patients with poor bone quality require at least a 4-mm-thick cement mantle to reduce the risk failure caused by high stress level in the cement mantle

Total hip replacement: effects of body mass index, acetabular morphology, and bone quality on stresses developed in cement mantles

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Total hip replacement: improving cement fixation of the acetabular component

The primary aim of this study was to propose fixation techniques that would improve the cement fixation of the acetabular cup. This was done by (1) studying current practice, (2) creating FE models of the reconstructed acetabulum to predict improved fixation techniques, (3) validating the FE models by laboratory investigations and (4) proposing designs of jigs and drill bit that would assist orthopaedic surgeons use the recommended techniques

Stress distribution in the knee joint following a high tibial osteotomy

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Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network. It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented. For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations. We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent. We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines. Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website

A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone

<p>Abstract</p> <p>Background</p> <p>Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA) and curcumin (CCM) are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone.</p> <p>Methods</p> <p>Dose response curves for CCM and DHA were generated for five breast cell lines. Effects of the DHA+ CCM combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of CCM and DHA based on their individual ED₅₀. Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. Gene expression results were validated by RT-PCR, and western blot analysis was performed for potential signaling mediators. Cellular curcumin uptake, with and without DHA, was analyzed via flow cytometry and HPLC.</p> <p>Results</p> <p>CCM+DHA had an antiproliferative effect in SK-BR-3, MDA-MB-231, MDA-MB-361, MCF7 and MCF10AT cells. The effect was synergistic for SK-BR-3 (ER^-PR^-Her2⁺) relative to the two compounds individually. A whole genome microarray approach was used to investigate changes in gene expression for the synergistic effects of CCM+DHA in SK-BR-3 cells lines. CCM+DHA triggered transcript-level responses, in disease-relevant functional categories, that were largely non-overlapping with changes caused by CCM or DHA individually. Genes involved in cell cycle arrest, apoptosis, inhibition of metastasis, and cell adhesion were upregulated, whereas genes involved in cancer development and progression, metastasis, and cell cycle progression were downregulated. Cellular pools of PPARγ and phospho-p53 were increased by CCM+DHA relative to either compound alone. DHA enhanced cellular uptake of CCM in SK-BR-3 cells without significantly enhancing CCM uptake in other cell lines.</p> <p>Conclusions</p> <p>The combination of DHA and CCM is potentially a dietary supplemental treatment for some breast cancers, likely dependent upon molecular phenotype. DHA enhancement of cellular curcumin uptake is one potential mechanism for observed synergy in SK-BR-3 cells; however, transcriptomic data show that the antiproliferation synergy accompanies many signaling events unique to the combined presence of the two compounds.</p

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data