758 research outputs found
Do individual differences in sociosexuality represent genetic or environmentally contingent strategies? Evidence from the Australian twin registry.
Advanced g-mps-pmma bone cements: Influence of graphene silanisation on fatigue performance, thermal properties and biocompatibility
The incorporation of well-dispersed graphene (G) powder to polymethyl methacrylate(PMMA) bone cement has been demonstrated as a promising solution to improving its mechanicalperformance. However, two crucial aspects limit the effectiveness of G as a reinforcing agent: (1)the poor dispersion and (2) the lack of strong interfacial bonds between G and the matrix of thebone cement. This work reports a successful functionalisation route to promote the homogenousdispersion of G via silanisation using 3-methacryloxypropyltrimethoxy silane (MPS). Furthermore,the effects of the silanisation on the mechanical, thermal and biocompatibility properties of bonecements are presented. In comparison with unsilanised G, the incorporation of silanised G (G_MPS1and G_MPS2) increased the bending strength by 17%, bending modulus by 15% and deflection atfailure by 17%. The most impressive results were obtained for the mechanical properties underfatigue loading, where the incorporation of G_MPS doubled the Fatigue Performance Index (I) valueof unsilanised G-bone cement—meaning a 900% increase over the I value of the cement without G.Additionally, to ensure that the silanisation did not have a negative influence on other fundamentalproperties of bone cement, it was demonstrated that the thermal properties and biocompatibilitywere not negatively impacted—allowing its potential clinical progression
Development of calcium phosphate cement for the augmentation of traumatically fractured porcine specimens using vertebroplasty
AbstractThe study aim was to develop and apply an experimental technique to determine the biomechanical effect of polymethylmethacrylate (PMMA) and calcium phosphate (CaP) cement on the stiffness and strength of augmented vertebrae following traumatic fracture. Twelve burst type fractures were generated in porcine three-vertebra segments. The specimens were randomly split into two groups (n=6), imaged using microCT and tested under axial loading. The two groups of fractured specimens underwent a vertebroplasty procedure, one group was augmented with CaP cement designed and developed at Queen's University Belfast. The other group was augmented with PMMA cement (WHW Plastics, Hull, UK). The specimens were imaged and re-tested . An intact single vertebra specimen group (n=12) was also imaged and tested under axial loading. A significant decrease (p<0.01) was found between the stiffness of the fractured and intact groups, demonstrating that the fractures generated were sufficiently severe, to adversely affect mechanical behaviour. Significant increase (p<0.01) in failure load was found for the specimen group augmented with the PMMA cement compared to the pre-augmentation group, conversely, no significant increase (p<0.01) was found in the failure load of the specimens augmented with CaP cement, this is attributed to the significantly (p<0.05) lower volume of CaP cement that was successfully injected into the fracture, compared to the PMMA cement. The effect of the percentage of cement fracture fill, cement modulus on the specimen stiffness and ultimate failure load could be investigated further by using the methods developed within this study to test a more injectable CaP cement
Operative and Radiographic Acetabular Component Orientation in Total Hip Replacement: Influence of Pelvic Orientation and Surgical Positioning Technique
Orthopaedic surgeons often experience a mismatch between perceived intra-operative and radiographic acetabular cup orientation. This research aimed to assess the impact of pelvic orientation and surgical positioning technique on operative and radiographic cup orientation. Radiographic orientations for two surgical approaches were computationally simulated: a mechanical alignment guide and a transverse acetabular ligament approach, both in combination with different pelvic orientations. Positional errors were defined as the difference between the target radiographic orientation and that achieved. The transverse acetabular ligament method demonstrated smaller positional errors for radiographic version; 4.0° ± 2.9° as compared to 9.4° ± 7.3° for the mechanical alignment guide method. However, both methods resulted in similar errors in radiographic inclination. Multiple regression analysis showed that intraoperative pelvic rotation about the anterior-posterior axis was a strong predictor for these errors (B TAL = −0.893, B MAG = −0.951, p < 0.01). Application of the transverse acetabular ligament method can reduce errors in radiographic version. However, if the orthopaedic surgeon is referencing off the theatre floor to control inclination when operating in lateral decubitus, this is only reliable if the pelvic sagittal plane is horizontal. There is currently no readily available method for ensuring that this is the case during total hip replacement surgery. </p
Evaluating a new generation of wearable high-density diffuse optical tomography (HD-DOT) technology via retinotopic mapping in the adult brain
We investigated the performance of a novel HD-DOT system by replicating a series of classic visual stimulation paradigms. Haemodynamic response functions and cortical activation maps replicated the results obtained with larger fibre-based systems
DNA vaccination for cervical cancer; a novel technology platform of RALA mediated gene delivery via polymeric microneedles.
Systemic RALA/iNOS nanoparticles; a potent gene therapy for metastatic breast cancer coupled as a biomarker of treatment
This study aimed to determine the therapeutic benefit of a nanoparticular formulation for the delivery of inducible nitric oxide synthase (iNOS) gene therapy in a model of breast cancer metastasis. Nanoparticles comprising a cationic peptide vector, RALA, and plasmid DNA were formulated and characterized using a range of physiochemical analyses. Nanoparticles complexed using iNOS plasmids and RALA approximated 60Â nm in diameter with a charge of 25Â mV. A vector neutralization assay, performed to determine the immunogenicity of nanoparticles in immunocompetent C57BL/6 mice, revealed that no vector neutralization was evident. Nanoparticles harboring iNOS plasmids (constitutively active cytomegalovirus [CMV]-driven or transcriptionally regulated human osteocalcin [hOC]-driven) evoked iNOS protein expression and nitrite accumulation and impaired clonogenicity in the highly aggressive MDA-MB-231 human breast cancer model. Micrometastases of MDA-MB-231-luc-D3H1 cells were established in female BALB/c SCID mice by intracardiac delivery. Nanoparticulate RALA/CMV-iNOS or RALA/hOC-iNOS increased median survival in mice bearing micrometastases by 27% compared with controls and also provoked elevated blood nitrite levels. Additionally, iNOS gene therapy sensitized MDA-MB-231-luc-D3H1 tumors to docetaxel treatment. Studies demonstrated that systemically delivered RALA-iNOS nanoparticles have therapeutic potential for the treatment of metastatic breast cancer. Furthermore, detection of nitrite levels in the blood serves as a reliable biomarker of treatment. Keywords: nonviral gene therapy, nitric oxide, nanoparticle, breast cancer, metastasi
Synthesis and characterisation of a nucleotide based pro-drug formulated with a peptide into a nano-chemotherapy for colorectal cancer
Recent studies in colorectal cancer patients (CRC) have shown that increased resistance to thymidylate synthase (TS) inhibitors such as 5-fluorouracil (5-FU), reduce the efficacy of standard of care (SoC) treatment regimens. The nucleotide pool cleanser dUTPase is highly expressed in CRC and is an attractive target for potentiating anticancer activity of chemotherapy. The purpose of the current work was to investigate the activity of P1, P4-di(2',5'-dideoxy-5'-selenouridinyl)-tetraphosphate (P4-SedU2), a selenium-modified symmetrically capped dinucleoside with prodrug capabilities that is specifically activated by dUTPase. Using mechanochemistry, P4-SedU2 and the corresponding selenothymidine analogue P4-SeT2 were prepared with a yield of 19% and 30% respectively. The phosphate functionality facilitated complexation with the amphipathic cell-penetrating peptide RALA to produce nanoparticles (NPs). These NPs were designed to deliver P4-SedU2 intracellularly and thereby maximise in vivo activity. The NPs demonstrated effective anti-cancer activity and selectivity in the HCT116 CRC cell line, a cell line that overexpresses dUTPase; compared to HT29 CRC cells and NCTC-929 fibroblast cells which have reduced levels of dUTPase expression. In vivo studies in BALB/c SCID mice revealed no significant toxicity with respect to weight or organ histology. Pharmacokinetic analysis of blood serum showed that RALA facilitates effective delivery and rapid internalisation into surrounding tissues with NPs eliciting lower plasma Cmax than the equivalent injection of free P4-SedU2, translating the in vitro findings. Tumour growth delay studies have demonstrated significant inhibition of growth dynamics with the tumour doubling time extended by >2weeks. These studies demonstrate the functionality and action of a new pro-drug nucleotide for CRC. </p
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