FeMn and FeMnAg biodegradable alloys: An in vitro and in vivo investigation.

Iron-based biodegradable metal bone graft substitutes are in their infancy but promise to fill bone defects that arise after incidents such as trauma and revision arthroplasty surgery. Before clinical use however, a better understanding of their in vivo biodegradability, potential cytotoxicity and biocompatibility is required. In addition, these implants must ideally be able to resist infection, a complication of any implant surgery. In this study there was significant in vitro cytotoxicity caused by pure Fe, FeMn, FeMn1Ag and FeMn5Ag on both human foetal osteoblast (hFOB) and mouse pre-osteoblast (MC3T3-E1) cell lines. In vivo experiments on the other hand showed no signs of ill-effect on GAERS rats with the implanted FeMn, FeMn1Ag and FeMn5Ag pins being removed largely uncorroded. All Fe-alloys showed anti-bacterial performance but most markedly so in the Ag-containing alloys, there is significant bacterial resistance in vitro.

Targeting Signalling Pathways in Chronic Wound Healing.

Chronic wounds fail to achieve complete closure and are an economic burden to healthcare systems due to the limited treatment options and constant medical attention. Chronic wounds are characterised by dysregulated signalling pathways. Research has focused on naturally derived compounds, stem-cell-based therapy, small molecule drugs, oligonucleotide delivery nanoparticles, exosomes and peptide-based platforms. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT), Wingless-related integration (Wnt)/ß-catenin, transforming growth factor-ß (TGF-ß), nuclear factor erythroid 2-related factor 2 (Nrf2), Notch and hypoxia-inducible factor 1 (HIF-1) signalling pathways have critical roles in wound healing by modulating the inflammatory, proliferative and remodelling phases. Moreover, several regulators of the signalling pathways were demonstrated to be potential treatment targets. In this review, the current research on targeting signalling pathways under chronic wound conditions will be discussed together with implications for future studies.

A novel hip joint prosthesis with uni-directional articulations for reduced wear.

A novel polymer-on-metal hip joint prosthesis design that makes use of uni-directional articulations was developed and tested in this work. The new implant was tested using two polymer variants, virgin ultra-high molecular weight polyethylene (UHMWPE), and Vitamin E-infused highly crosslinked polyethylene (VEHXPE). The degrees of freedom of the ball-and-socket are reproduced by three cylindrical orthogonally-aligned articulations. This unconventional design leverages on the molecular orientation hardening mechanisms of the polyethylene and increased contact area to minimize wear. An experimental hip joint simulator was used to compare the gravimetric wear of the conventional ball-on-socket and the new implant. The new prosthesis including UHMWPE components produced a 78% reduction in wear, whereas the new prosthesis with VEHXPE components produced a 100% reduction in wear, as no measurable wear was detected. Machining marks on the acetabular cups of the new prosthesis were retained for both polyethylene variants, further demonstrating the low levels of wear exhibited by the new implants. Both polyethylene materials produced particles in the range of 0.1-1.0 µm, which are the most biologically active. Nonetheless, the extremely low wear rates are likely to induce minimal osteolysis effects. Furthermore, the novel design also offers an increase of more than 24% in the range of motion in flexion/extension when compared to a dual-mobility hip implant. A prototype of the prosthesis was implanted into a Thiel-embalmed human cadaver during a mock-surgery, which demonstrated high resistance to dislocation and the possibility of performing a figure of four position.

Application of Machine Learning to Predict Dielectric Properties of In Vivo Biological Tissue.

In this paper we revisited a database with measurements of the dielectric properties of rat muscles. Measurements were performed both in vivo and ex vivo; the latter were performed in tissues with varying levels of hydration. Dielectric property measurements were performed with an open-ended coaxial probe between the frequencies of 500 MHz and 50 GHz at a room temperature of 25 °C. In vivo dielectric properties are more valuable for creating realistic electromagnetic models of biological tissue, but these are more difficult to measure and scarcer in the literature. In this paper, we used machine learning models to predict the in vivo dielectric properties of rat muscle from ex vivo dielectric property measurements for varying levels of hydration. We observed promising results that suggest that our model can make a fair estimation of in vivo properties from ex vivo properties.

First Profile of Phenolic Compounds from Maltese Extra Virgin Olive Oils Using Liquid-Liquid Extraction and Liquid Chromatography-Mass Spectrometry.

This study presents the profile of phenolic extracts from different Extra Virgin Olive Oils (EVOOs) from Malta and is the first study that characterizes the phenolic profile of the Maltese EVOOs Bidni (B) and Malti (M) using liquid-liquid extraction (LLE) and Liquid Chromatography-Mass Spectrometry (LC-MS). The total phenolic content (TPC), ortho diphenolic content (TdPC) and flavonoid content (TFC) were determined using the Folin-Ciocalteau assay, the Arnow's assay and the Aluminium Chloride method respectively. Results show that the B variety had the highest TPC, TdPC and TFC. Using LC-MS analysis, over 30 phenolic compounds were identified belonging to different classes of phenolic compounds.

Axolotl Ambystoma mexicanum extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cells.

Acute myeloid leukemia is the most common form of acute leukemia in adults, constituting about 80% of cases. Although remarkable progress has been made in the therapeutic scenario for patients with acute myeloid leukemia, research and development of new and effective anticancer agents to improve patient outcome and minimize toxicity is needed. In this study, the antitumor activity of axolotl (AXO) Ambystoma mexicanum crude extract was assessed in vitro on the human acute myeloid leukemia HL-60 cell line. The anticancer activity was evaluated in terms of ability to influence proliferative activity, cell viability, cell cycle arrest, and differentiation. Moreover, gene expression analysis was performed to evaluate the genes involved in the regulation of these processes. The AXO crude extract exhibited antiproliferative but not cytotoxic activities on HL-60 cells, with cell cycle arrest in the G0/G1 phase. Furthermore, the AXO-treated HL-60 cells showed an increase in both the percentage of nitroblue tetrazolium positive cells and the expression of CD11b, whereas the proportion of CD14-positive cells did not change, suggesting that extract is able to induce differentiation toward the granulocytic lineage. Finally, the treatment with AXO extract caused upregulation of CEBPA, CEBPB, CEBPE, SPI1, CDKN1A, and CDKN2C, and downregulation of c-MYC. Our data clearly show the potential anticancer activity of Ambystoma mexicanum on HL-60 cells and suggest that it could help develop promising therapeutic agents for the treatment of acute myeloid leukemia.

Anticancer effects of an extract from a local planarian species on human acute myeloid leukemia HL-60 cells in vitro.

Current anti-cancer drugs can cause many undesirable side effects to patients. Thus, there is a constant need to develop alternative therapeutic drugs. Bioactive compounds derived from natural products including animals, plants and microorganisms are being actively studied as sources for anticancer treatments. Freshwater planarians are important models for stem cell research and regeneration. However, to date, no studies on the biological activities of planaria extracts on cancer have been published. The aim of this study was to examine the potential antitumoral activity of the extract from planaria species-Malta (PSM) on human acute myeloid leukemia (AML) HL-60 cells. Antiproliferative activity was studied in terms of proliferation, apoptosis and differentiation. The expression of genes involved in the regulation of these important cellular processes was also analyzed using real-time PCR. PSM extract exhibited a selective cytotoxic effect on HL-60 cells when compared to normal lymphocytes. Furthermore, cell cycle analysis and Annexin V/PI assay showed that the extract induced apoptosis in HL-60 cells. The PSM extract induced myeloid differentiation with HL-60 cells showing a decreased nucleo/cytoplasmic ratio, an increase in nitroblue tetrazolium-positive cells, and CD11b- and CD14-positive cells. Finally, we also found that the PSM extract increased the expression of CEBPA, CEBPB, CEBPE, SPI1, BAX, CDKN1A and CDKN2C; whereas it reduced the expression of c-MYC and BCL2. This is the first study to reveal the antiproliferative, cytotoxic, and differentiation potential of PSM on HL-60 cells and suggests that it may have considerable potential for development as a novel natural product-based anticancer agent against AML.

The effect of alloying elements on the properties of pressed and non-pressed biodegradable Fe-Mn-Ag powder metallurgy alloys.

Current trends in the biodegradable scaffold industry call for powder metallurgy methods in which compression cannot be applied due to the nature of the scaffold template itself and the need to retain the shape of an underlying template throughout the fabrication process. Iron alloys have been shown to be good candidates for biomedical applications where load support is required. Fe-Mn alloys were researched extensively for this purpose. Current research shows that all metallurgical characterisation and corrosion test on Fe-Mn and Fe-Mn-Ag non pre-alloyed powder alloys are performed on alloys which are initially pressed into greens and subsequently sintered. In order to combine the cutting-edge field of biodegradable metallic alloys with scaffold production, metallurgical characterisation of pressed and non-pressed Fe, Fe-Mn and Fe-Mn-Ag sintered elemental powder compacts was carried out in this study. This was performed along with determination of the corrosion rate of the same alloys in in vitro mimicking solutions. These solutions were synthesised to mimic the osteo environment in which the final scaffolds are to be used. Both pressed and non-pressed alloys formed an austenite phase under the right sintering conditions. The corrosion rate of the non-pressed alloy was greater than that of its pressed counterpart. In a potentiodynamic testing scenario, addition of silver to the alloy formed a separate silver phase which galvanically increased the corrosion rate of the pressed alloy. This result wasn't replicated in the non-pressed alloys in which the corrosion rate was seen to remain similar to the non-silver-bearing alloy counterparts.

Kinematic and Kinetic Comparison of Fresh Frozen and Thiel-Embalmed Human Feet for Suitability for Biomechanical Educational and Research Settings.

BACKGROUND: In vitro biomechanical testing of the human foot often involves the use of fresh frozen cadaveric specimens to investigate interventions that would be detrimental to human subjects. The Thiel method is an alternative embalming technique that maintains soft-tissue consistency similar to that of living tissue. However, its suitability for biomechanical testing is unknown. Thus, the aim of this study was to determine whether Thiel-embalmed foot specimens exhibit kinematic and kinetic biomechanical properties similar to those of fresh frozen specimens. METHODS: An observational study design was conducted at a university biomechanics laboratory. Three cadavers had both limbs amputated, with one being fresh frozen and the other preserved by Thiel's embalming. Each foot was tested while undergoing plantarflexion and dorsiflexion in three states: unloaded and under loads of 10 and 20 kg. Their segment kinematics and foot pressure mapping were assessed simultaneously. RESULTS: No statistically significant differences were detected between fresh frozen and Thiel-embalmed sample pairs regarding kinematics and kinetics. CONCLUSIONS: These findings highlight similar kinematic and kinetic properties between fresh frozen and Thiel-embalmed foot specimens, thus possibly enabling these specimens to be interchanged due to the latter specimens' advantage of delayed decomposition. This can open innovative opportunities for the use of these specimens in applications related to the investigation of dynamic foot function in research and education.

The axolotl model for cancer research: a mini-review.

Gastric cancer is the sixth most common cancer worldwide with increased associated morbidity and mortality. Although a multimodality treatment approach is necessary, surgery is still considered as the standard of care. There is a longstanding intercontinental debate between Eastern and Western upper GI surgeons in regards to the proper type of lymphadenectomy that should accompany the resection of the primary tumor. While D2 gastrectomy was performed as the standard procedure in eastern countries, the increased morbidity and mortality attributed initially to the D2 lymphadenectomy by the Medical Research Council (MRC), the Dutch and the Italian randomized control trial without respective survival benefits had led Western surgeons towards a more limited lymphadenectomy. Only 15 years after the conclusion of its accrual, the Dutch trial reported a significant decrease in recurrence rate after D2 procedure and attributed the D2-associated morbidity and mortality to the spleno-pancreatectomy that was routinely performed in the D2 arm of the study. As the D2 lymphadenectomy can be safely and adequately performed while preserving the spleen and/or the pancreas, it has been suggested as the recommended procedure for patients with resectable gastric cancer.

Transoral Endoscopic Thyroidectomy: A Systematic Review of the Practice So Far.

Background and Objectives: Thyroid disease largely affects young females, but the incidence is also increasing among males. In an effort to avoid the scarring of the neck that is synonymous with conventional thyroidectomy, endoscopic techniques have been developed over the years. The transoral endoscopic approach is the latest of these innovations that promises a scarless surgical outcome. This review evaluates whether this technique is safe and feasible in live patients and outlines the outcomes in published literature so far. Database: PubMed, Medline, BioMed Central, Cochrane Library, OVID and Web of Science were systematically searched by using a Medical Subject Heading (MeSH)-optimized search strategy. The selection of papers followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines after setting strict inclusion and exclusion criteria. Sixteen studies were included in the final analysis. Discussion: This systematic review presents cases of 785 patients. Surgeons in 15 of the studies used a completely vestibular approach, whereas those in the remaining 2 used the floor of the mouth for primary access. Conversion to open surgery took place in 1.3%. In total, 4.3% of patients experienced transient laryngeal nerve palsy, whereas 0.1% had permanent recurrent incidences of the condition. Transient hypocalcemia occurred in 7.4% of cases, with no recorded permanent cases. Carbon dioxide embolism occurred in 0.6% of cases, and another 0.6% had a deep-seated neck infection. The complication rates within the review were deemed acceptable and the overall technique feasible. A prospective randomized controlled trial was proposed to compare this technique with conventional thyroidectomy.

WASP (Write a Scientific Paper): Writing a Research Grant - 1, Applying for Funding.

The academic world revolves around research which is both a requisite to achieve a degree, as well as part of the job description of academics. Obtaining a research grant is often essential in order to cover the running costs of a research project. Once a research proposal has been formulated, with the help of supervisors/collaborators, both tangible costs and non-tangible costs can be calculated. These predicted values are essential when applying for a research grant. Different funding opportunities are available from different sources, often both local and international. The latter funding bodies are usually either dedicated to a specific disease or process. It is essential to identify the appropriate funding opportunity according to the funding body's priorities and guidelines so that the grant can then be accordingly formulated. The great majority of funding sources issue competitive calls, so the aim of your application is not to show that the researcher deserves funds, but why the study in question is the one most deserving of the limited funds available. In any funding application, the strengths of the individual researcher/research group and the relevance of the project itself are the main two selling points. However, without a well prepared management plan, applications flounder. This paper will outline how best to target and formulate this approach.

WASP (Write a Scientific Paper): Writing a Research Grant - 2, Drafting the Proposal.

When writing up a grant application, the proposal has to be targeted to the funding source identified and being approached. However, some general rules apply in all cases. Provision of preliminary data may be useful and collaboration with well-known/published colleagues and top centres may also help and may be a prerequisite for some kinds of application. The quality and originality of the science is the main selling point as well as convincing the review board that you/your consortium are the best placed group to do the job. A strong organisational structure showing how the fund will be managed, as well as realistic targeted deliverables and a research timeline will help convince funding bodies/assessment boards of the likelihood that the team can handle the project. Before submission of the grant proposal, a more experienced grant writer should review the proposal. Using a checklist to assess adherence to the funding body's guidelines and grant submission guidelines is essential prior to submission.

The Relationship of Surface Characteristics and Antimicrobial Performance of Pulp Capping Materials.

INTRODUCTION: Pulp capping materials need to be able to protect the pulp but also bond to the overlying restorative materials. Light-curable pulp capping materials bond better to restorative materials and are easier to place than most water-based cements. The aim of this study was to characterize new light-curable tricalcium silicate-based pulp capping materials and compare their surface and antimicrobial properties with clinically available Theracal (Bisco, Schaumburg, IL) and Biodentine (Septodont, Saint-Maur-des-Fossés, France). METHODS: The surface characteristics of 3 light-curable pulp capping materials based on a resin and filled with tricalcium silicate and tantalum oxide radiopacifier and Theracal and Biodentine were assessed by scanning electron microscopy, X-ray diffraction, and contact angle measurement. The radiopacity was measured following ISO 6876 standards. The antimicrobial activity was determined by the direct contact test and the antibiofilm activity by the adenosine triphosphate assay and the confocal laser scanning Live/Dead assay (Invitrogen, Eugene, OR) using a polymicrobial culture. RESULTS: The surface characteristics of the materials varied with the unfilled resin and Biodentine exhibiting a hydrophobic surface. Biodentine showed significantly higher antimicrobial properties in the direct contact test, but this property was absent in the antibiofilm activity tests. The resins filled with tricalcium silicate and Theracal showed higher antimicrobial activity than Biodentine in the adenosine triphosphate and live/dead assays. CONCLUSIONS: The surface characteristics of a material affect its antimicrobial properties. The experimental resin-modified materials exhibited comparable antimicrobial properties with other light-curable pulp capping agents. Further long-term studies on the materials' antimicrobial activity are required to assess whether they can result in better clinical outcomes.

Interfacial Characteristics and Cytocompatibility of Hydraulic Sealer Cements.

INTRODUCTION: The stability and long-term success of root canal obturation depends on the choice of sealer because the sealer bonds to the dentin and stabilizes the solid cone. Furthermore, the sealer needs to be nontoxic because sealer toxicity will certainly lead to treatment failure. The aim of this study was to assess the sealer-dentin interface of 3 hydraulic root canal sealers and to evaluate their cytocompatibility compared with AH Plus (Dentsply DeTrey GmbH, Konstanz, Germany). METHODS: Four dental root canal sealers were assessed. AH Plus, MTA Fillapex (Angelus, Londrina, Brazil), BioRoot RCS (Septodont, Saint-Maur-des-Fossés, France), and Endoseal (Maruchi, Wonju-si, Gangwon-do, South Korea) were characterized using scanning electron microscopy and energy-dispersive spectroscopy. The sealer-tooth interface was assessed by confocal microscopy and scanning electron microscopy, and biocompatibility was measured by assessing the cell metabolic function using direct contact assays and alkaline phosphatase activity. RESULTS: The tricalcium silicate-based sealers presented a different microstructure and elemental composition despite their similar chemistry and classification. BioRoot RCS was free of aluminum, and all sealers presented different radiopacifying elements. The sealer penetration in the dentinal tubules and interfacial characteristics were different. The migration of silicon was evident from sealer to tooth for all sealers containing tricalcium silicate. MTA Fillapex and BioRoot RCS exhibited the best cytocompatibility in both the direct contact test and alkaline phosphatase activity. CONCLUSIONS: The use of hydraulic calcium silicate-based sealers has introduced a different material type to endodontics. These materials are different than other sealers mostly because of their hydraulic nature and their interaction with the environment. Although the sealers tested had a similar chemistry, their cytocompatibility and bonding mechanisms were diverse.