Amyloid Oligomers as Blood Biomarkers in the Diagnosis of Alzheimer’s Disease

Oligomeric forms of the peptide, β-amyloid, (Aβ) are known to be toxic to human and rodent neurones, and have been identified as possible causative agents in the loss of cognitive function in Alzheimer’s Disease (AD). An ELISA assay has been developed capable of detecting oligomeric forms of Aβ in biological fluids, but not detecting monomeric species. The ELISA has been validated with a number of synthetic variant sequences of Aβ and the effects of known inhibitors of Aβ oligomer formation. Significantly raised levels of oligomers were detected in sera samples from AD patients, compared to age-matched control sera

Binary Polyhydroxyalkanoate Systems for Soft Tissue Engineering

Progress in tissue engineering is dependent on the availability of suitable biomaterials. In an effort to overcome the brittleness of poly(3-hydroxybutyrate), P(3HB), a natural biodegradable polyester, and widen its biomedical applications, plasticising of P(3HB) with oligomeric substances of related structure has been studied. A biosynthesised medium-chain-length polyhydroxyalkanoate (mcl-PHA) copolymer, the plasticizer precursor, was obtained using vegetable waste frying oil as a sole carbon source. The mcl-PHA was transformed into an oligomeric derivative by acid hydrolysis. The plasticising effect of the oligomeric mcl-PHA on P(3HB) was studied via characterisation of thermal and mechanical properties of the blends in the course of ageing at ambient conditions. Addition of oligomeric mcl-PHA to P(3HB) resulted in softer and more flexible materials based entirely on PHAs. It was shown that the oligomeric mcl-PHA transformed highly crystalline P(3HB) into materials with a dominant amorphous phase when the content of oligomeric mcl-PHA exceeded 10wt%. In vitro biocompatibility studies of the new binary PHA materials showed high viability and proliferation of C2C12 myoblast cells. Thus, the proposed approach for P(3HB) plasticisation has the potential for the generation of more pliable biomaterials based on P(3HB) which can find application in unique soft tissue engineering applications where a balance between stiffness, tensile strength and ductility is required

Current methodologies and approaches for the formation of core–sheath polymer fibers for biomedical applications

The application of polymer fibers has rocketed to unimaginable heights in recent years and occupies every corner of our day-to-day life, from knitted protective textile clothes to buzzing smartphone electronics. Polymer fibers could be obtained from natural and synthetic polymers at a length scale from the nanometer to micrometer range. These fibers could be formed into different configurations such as single, core–sheath, hollow, blended, or composite according to human needs. Of these several conformations of fibers, core–sheath polymer fibers are an interesting class of materials, which shows superior physical, chemical, and biological properties. In core–sheath fiber structures, one of the components called a core is fully surrounded by the second component known as a sheath. In this format, different polymers can be applied as a sheath over a solid core of another polymer, thus resulting in a variety of modified properties while maintaining the major fiber property. After a brief introduction to core–sheath fibers, this review paper focuses on the development of the electrospinning process to manufacture core–sheath fibers followed by illustrating the current methodology and approaches to form them on a larger scale, suitable for industrial manufacturing and exploitation. Finally, the paper reviews the applications of the core–sheath fibers, in particular, recent studies of core–sheath polymer fibers in tissue engineering (nerve, vascular grafts, cardiomyocytes, bone, tendons, sutures, and wound healing), growth factors and other bioactive component release, and drug delivery. Therefore, core–sheath structures are a revolutionary development in the field of science and technology, becoming a backbone to many emerging technologies and novel opportunities

Does venous thromboembolism prophylaxis affect the risk of venous thromboembolism and adverse events following primary hip and knee replacement?:A retrospective cohort study

BACKGROUND: The optimum chemical venous thromboembolism (VTE) prophylactic agents following total hip and knee replacement (THR and TKR) remain unknown. NICE recommends multiple agents, including direct oral anticoagulants (DOACs), low-molecular weight heparin (LMWH), and aspirin. We assessed whether VTE prophylaxis affected the risk of VTE and adverse events following primary THR and TKR. MATERIALS AND METHODS: We reviewed 982 elective primary THRs (59%) and TKRs (41%) at a large tertiary centre during 2018. The primary outcome was any VTE (DVT and/or PE) within 90-days. Secondary outcomes were adverse events within 90-days (major bleeding and wound complications). The association between VTE prophylaxis and outcomes was assessed. RESULTS: The overall prevalence of VTE and adverse events were 2.7% (n = 27) and 15.2% (n = 136) respectively. The most common agents used were DOAC ± LMWH (50.7%, n = 498), followed by aspirin ± LMWH (35.5%, n = 349) and LMWH alone (4.7%, n = 46). The risk of VTE (aspirin ± LMWH = 3.7%, DOAC = 2.0%, LMWH = 2.2%) was not significantly different between agents (p = 0.294). The risk of any adverse event was significantly higher (p < 0.001) with aspirin ± LMWH (16.1%; n = 56) and LMWH (28.3%; n = 13) compared with DOACs ± LMWH (7.0%; n = 35) in TKRs only, there was no differences between agents for adverse events in THRs (p = 0.644). CONCLUSIONS: Choice of thromboprophylaxis did not influence the risk of VTE following primary THR and TKR. DOACs (+/− LMWH) were associated with the lowest risk of adverse events. Large multicentre trials are still needed to assess the efficacy and safety of these agents following THR and TKR

Boron nitride nanoscrolls: structure, synthesis, and applications

This is the author accepted manuscriptBoron nitride nanoscrolls (BNS) are open-ended, one-dimensional (1D) nanostructures made by the process of rolling boron nitride nanosheets (BNNS) into a scroll-like morphology. BNS offer a high surface area to volume ratio and possess many unique properties (similar to carbon nanotubes (CNT), carbon nanoscrolls (CNS) and boron nitride nanotubes (BNT)) such as high resistance to oxidation, chemical stability, increased lubrication, high-temperature resistance, electrical insulation, the ability to cap molecules inside and at the ends,and a wide band gap regardless of chirality. Despite these attractive featuresand properties well suited for applications in biotechnology, energy storage, and electronics, the true potential of boron nitride, and BNS as the next ‘miracle material’ is yet to be fully explored. In this critical review, we assess, for the first time, various studies published on the formation, structural and dynamic characteristics of BNS, potential routes for BNS synthesis, and the toxicology of BNS. Finally, the future perspectives of BNS are discussed in view of its unique and exceptional candidacy for many (real-world) applications

The effect of surgeon caseload on the relative revision rate of cemented and cementless Unicompartmental Knee Replacements:An analysis from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man

Background: Unicompartmental knee replacement (UKR) offers substantial benefits compared with total knee replacement (TKR) but is associated with higher revision rates. Data from registries suggest that revision rates for cementless UKR implants are lower than those for cemented implants. It is not known how much of this difference is due to the implant or to other factors, such as a greater proportion of high-volume surgeons using cementless implants. We aimed to determine the effect of surgeon caseload on the revision rate of matched cemented and cementless UKRs. Methods: From a group of 40,522 Oxford (Zimmer Biomet) UKR implants (30,814 cemented, 9,708 cementless) recorded in the National Joint Registry, 14,814 (7,407 cemented, 7,407 cementless) were propensity-score matched. Surgeons were categorized into 3 groups: low volume ( Results: The 10-year survival rates for unmatched cementless and cemented UKR implants were 93.3% (95% confidence interval [CI] = 89.8% to 95.7%) and 89.1% (95% CI = 88.6% to 89.6%), respectively, with the difference being significant (hazard ratio [HR] = 0.59; p Conclusions: Cementless fixation decreased the revision rate by about a quarter, whatever the surgeon caseload. Caseload had a profound effect on implant survival. Low-volume surgeons had a high revision rate with cemented or cementless fixation and therefore should consider either stopping or doing more UKR procedures. High-volume surgeons performing cementless UKR demonstrated a 10-year survival rate of 97.5%, which was similar to that reported in registries for the best-performing TKRs. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.</p

A matched comparison of revision rates of cemented Oxford Unicompartmental Knee Replacements with Single and Twin Peg femoral components, based on data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man

Background and purpose — Registries report high revision rates after unicompartmental knee replacement (UKR) due, in part, to aseptic loosing. In an attempt to improve Oxford UKR femoral component fixation a new design was introduced with a Twin rather than a Single peg. We used the National Joint Registry (NJR) to compare the 5-year outcomes of the Single and Twin Peg cemented Oxford UKRs. Patients and methods — We performed a retrospective observational study using NJR data on propensity score matched Single and Twin Peg UKRs (matched for patient, implant and surgical factors). Data on 2,834 Single Peg and 2,834 Twin Peg were analyzed. Cumulative implant survival was calculated using the Kaplan–Meier method and comparisons between groups performed using Cox regression models. Results — In the matched cohort, the mean follow up for both Single and Twin Peg UKRs was 3.3 (SD 2) and 3.4 years (SD 2) respectively. The 5-year cumulative implant survival rates for Single Peg and Twin Peg were 94.8% (95% CI 93.6–95.8) and 96.2% (CI 95.1–97.1) respectively. Implant revision rates were statistically significantly lower in the Twin Peg (hazard ratio [HR)] = 0.74; p = 0.04). The revision rate for femoral component aseptic loosening decreased significantly (p = 0.03) from 0.4% (n = 11) with the Single Peg to 0.1% (n = 3) with the Twin Peg. The revision rate for pain decreased significantly (p = 0.01) from 0.8% (n = 23) with the Single Peg to 0.3% (n = 9) with the Twin Peg. No other reasons for revision had significant differences in revision rates. Interpretation — The revision rate for the cemented Twin Peg Oxford UKR was 26% less than the Single Peg Oxford UKR. This was mainly because the revision rates for femoral loosening and pain more than halved. This suggests that the Twin Peg component should be used in preference to the Single Peg design.</p

New surgical instrumentation reduces the revision rate of Unicompartmental Knee Replacement:A propensity score matched comparison of 15,906 knees from the National Joint Registry

Background Unicompartmental knee replacement (UKR) offers advantages over total knee replacement but has higher revision rates. New instrumentation known as Microplasty was introduced to address this. The aim was to compare the revision rates of UKRs implanted with Microplasty and traditional instrumentation (Non-Microplasty). Methods National Joint Registry (NJR) data was used to propensity score match 15,906 UKRs (7953 Microplasty and 7953 Non-Microplasty) for important patient, implant and surgical factors. Implant survival rates were determined using the Kaplan–Meier method and compared using Cox regression models in a multilevel model. Results The five-year implant survival for Microplasty and Non-Microplasty UKRs were 96.7% (95% CI: 96.0%–97.2%) and 94.5% (CI: 93.8–95.1%), respectively. The revision rate for Microplasty UKR was significantly lower than that of Non-Microplasty UKRs (hazard ratio [HR] = 0.77, p = 0.008). Compared with Non-Microplasty UKRs, the revision rate of Microplasty UKRs implanted during the year after the introduction of Microplasty was lower, but the difference was not significant (HR: 0.86, CI: 0.67–1.10, p = 0.23), whereas for those implanted more than a year after introduction, the difference was significant (HR: 0.69, CI: 0.54–0.89, p = 0.004). Conclusion The use of Microplasty instrumentation has resulted in an improved five-year UKR survival. Microplasty UKR implanted during the first year after introduction had a small, non-significant decrease in revision rate. As the revision rate did not increase, this suggests that there is no adverse learning curve effect. Microplasty UKRs implanted after this transition period had a revision rate 31% lower than the Non-Microplasty group. Level of evidence II.</p