Polyethylene wear simulation models applied to a prosthetic hip joint based on unidirectional articulations.

Ultra-high molecular weight polyethylene (UHMWPE) is commonly used as soft-bearing material in total joint replacements. However, the release of polymeric wear debris is still related to complications leading to aseptic loosening. Recently, a novel hip prosthesis showing reduced wear was developed by the authors of this study, consisting of unidirectional cylindrical articulations instead of the conventional multidirectional ball-and-socket design. This study evaluates four different theoretical wear models applied to this new design. The calculated volumetric wear was compared to experimental results. Although all models provided a good indication of the wear rates for the ball-and-socket prosthesis, they exhibited high discrepancies when predicting the amount of wear of the new unidirectional design. It was observed that the closest agreement with experimental results was obtained by the models that consider the friction-induced molecular orientation phenomenon exhibited by UHMWPE.

Steroids-has the time come to extend their use to AML?

BACKGROUND: In 2018, leukaemia accounted for 2.6% of all new cancers, it being the 13th most common cause of cancer and the 10th most common cause of cancer death. Glucocorticoids are commonly used in lymphoid leukaemia treatment, where they are cytotoxic. The aim of this review is to highlight ongoing research of steroid use in myeloid leukaemias. MAIN TEXT: Glucocorticoids increase infection risks in acute myeloid leukaemia, but with adequate antifungal cover, they can help in hyperleucocytic disease. They also show some benefits in sensitising multidrug-resistant AML cell lines to cytotoxic agents, induce differentiation marker expression and can also induce CD38 expression, making AML cells possible targets of daratumumab. Cardiotonic steroids, like digitalis, are being recognised as sensitising AML cells to the chemotherapeutic effects of many cytotoxic agents, primarily by inhibiting efflux pumps, thus minimising AML resistance. Ecdysteroids enhance sensitivity in multidrug-resistant AML, but also in non-resistant AML cell lines, through pathways including the activation of mitochondrial apoptosis. Their anti-apoptotic effects on non-malignant cell lines help their target specificity. Sensitisation is chemotherapy-specific, enhancing the effects of doxorubicin and tubulin inhibitors but increasing resistance to cisplatinum. SHORT CONCLUSION: Cardiotonic steroids and ecdysteroids both show chemosensitisation to the cytotoxic effects of chemotherapy on AML cell lines. It is likely time to consider clinical trials to assess whether these, as well as traditional glucocorticoids, can contribute to the AML armamentarium, particularly in chemo-resistant disease.

Therapeutic Potential of Ecdysteroids and Steroidal Alkaloids on Solid Cancers.

BACKGROUND: Cancer is the second most common cause of death globally. Common modalities of treatment include surgery, chemotherapy, radiotherapy and lately immunotherapy. Different steroidal agents have also been identified as therapeutics for solid cancers, often as part of chemotherapy regimens. This review will specifically focus on steroidal alkaloids and ecdysteroids, which are different types of steroids originating from plants and arthropods respectively. These have been proven to show anti-cancer effects through several methods, including inhibition of proliferation and increasing apoptosis in cancer cells. Synthetic steroids are also used as chemotherapy adjuvants. By increasing our knowledge and understanding of these compounds, further studies can be carried out which may lead to clinical trials. This may enable a potential alternative to current therapies used as cancer treatment today, and may help improve the standard of care.

Author Correction: Influence of environment on testing of hydraulic sealers.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Antimicrobial and biological activity of leachate from light curable pulp capping materials.

OBJECTIVES: Characterization of a number of pulp capping materials and assessment of the leachate for elemental composition, antimicrobial activity and cell proliferation and expression. METHODOLOGY: Three experimental light curable pulp-capping materials, Theracal and Biodentine were characterized by scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction. The elemental composition of the leachate formed after 24h was assessed by inductively coupled plasma (ICP). The antimicrobial activity of the leachate was determined by the minimum inhibitory concentration (MIC) against multispecies suspensions of Streptococcus mutans ATCC 25175, Streptococcus gordonii ATCC 33478 and Streptococcus sobrinus ATCC 33399. Cell proliferation and cell metabolic function over the material leachate was assessed by an indirect contact test using 3-(4,5 dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The hydration behavior of the test materials varied with Biodentine being the most reactive and releasing the highest amount of calcium ions in solution. All materials tested except the unfilled resin exhibited depletion of phosphate ions from the solution indicating interaction of the materials with the media. Regardless the different material characteristics, there was a similar antimicrobial activity and cellular activity. All the materials exhibited no antimicrobial activity and were initially cytotoxic with cell metabolic function improving after 3days. CONCLUSIONS: The development of light curable tricalcium silicate-based pulp capping materials is important to improve the bonding to the final resin restoration. Testing of both antimicrobial activity and biological behavior is critical for material development. The experimental light curable materials exhibited promising biological properties but require further development to enhance the antimicrobial characteristics.

Male factors in ART outcome prediction.

Paternal influences on reproduction are significant causing about half of the infertile couples to turn to assisted reproductive techniques. Due to the increasing proportion of infertile couples adopting to conceive by in vitro fertilisation (IVF), predicting outcomes is of ever increasing importance. Since pregnancy rates following IVF are still quite low, prognostic information is very helpful in clinical decisions. Although significant research has been done on the maternal influence, male factor infertility is relatively understudied. To date, potential predictors include: method of fertilisation, age, reactive oxygen species, sperm quality parameters and DNA fragmentation. Predictors under investigation which show promising signs, even though there is no clear cut consensus on the predictive value to date include: folate and homocysteine, anti müllerian hormone measurement, environmental factors, body mass index, smoking, male age, stress, some subsets of antisperm antibodies and epigenetic features.

Biocompatibility and characterization of a Kolsterised(®) medical grade cobalt-chromium-molybdenum alloy.

High failure rates of cobalt-chromium-molybdenum (Co-Cr-Mo) metal-on-metal hip prosthesis were reported by various authors, probably due to the alloy's limited hardness and tribological properties. This thus caused the popularity of the alloy in metal-on-metal hip replacements to decrease due to its poor wear properties when compared with other systems such as ceramic-on-ceramic. S-phase surface engineering has become an industry standard when citing surface hardening of austenitic stainless steels. This hardening process allows the austenitic stainless steel to retain its corrosion resistance, while at the same time also improving its hardness and wear resistance. By coupling S-phase surface engineering, using the proprietary Kolsterising(®) treatment from Bodycote Hardiff GmbH, that is currently being used mainly on stainless steel, with Co-Cr-Mo alloys, an improvement in hardness and tribological characteristics is predicted. The objective of this paper is to analyze the biocompatibility of a Kolsterised(®) Co-Cr-Mo alloy, and to characterize the material surface in order to show the advantages gained by using the Kolsterised(®) material relative to the original untreated alloy, and other materials. This work has been performed on 3 fronts including; Material characterization, "In-vitro" corrosion testing, and Biological testing conforming to BS EN ISO 10993-18:2009 - Biological evaluation of medical devices. Using these techniques, the Kolsterised(®) cobalt-chromium-molybdenum alloys were found to have good biocompatibility and an augmented corrosion resistance when compared with the untreated alloy. The Kolsterised(®) samples also showed a 150% increase in surface hardness over the untreated material thus predicting better wear properties.

An extract from Ricinus communis L. leaves possesses cytotoxic properties and induces apoptosis in SK-MEL-28 human melanoma cells.

Plants are an important source of several clinically useful anti-cancer agents. A volatile extract was obtained from Ricinus communis L. (Euphorbiaceae) leaves by standard hydrodistillation and subsequent extraction of the cohobated water in chloroform. GC-MS identified three monoterpenoids: 1,8-cineole, camphor and alpha-pinene, and a sesquiterpenoid: beta-caryophyllene, as the main constituents. The leaf extract is cytotoxic to several human tumour cell lines in a dose-dependent fashion, with IC(50) values ranging between 10-40 microg mL(-1). Apoptosis was shown to be induced in SK-MEL-28 human melanoma cells at a concentration of 20 microg mL(-1), as identified by means of morphological examination, nuclear staining and flow cytometric analysis of DNA content. Translocation of phosphatidyl serine to the cell membrane's external surface and loss of mitochondrial membrane potential were also detected. This study provides further insight into the potential use of mixtures of terpenoids as they occur in nature, as inducers of apoptosis in cancer cells.

Developmental effect of the XmnI site on Ggamma-globin gene expression among newborn Hb F-Malta-I [Ggamma117(G19)His-->Arg, CAT-->CGT] heterozygotes and adult beta+ -Thalassemia homozygotes.

Hb F-Malta-I [Ggamma117(19)His-->Arg, CAT-->CGT] is a stable and benign variant of Hb F found in 1.8% of Maltese newborn. We studied 120 Hb F-Malta-I heterozygotes and four Hb F-Malta-I homozygotes. The mean proportion of Ggamma-F-Malta-I in Hb F was 0.26 +/- 0.03 for the Hb F-Malta-I heterozygotes and 0.58 +/- 0.06 for the Hb F-Malta-I homozygotes. The Hb F-Malta-I allele was shown to occur on a background of the common Mediterranean haplotype Va [+ + - - - - - + + -]. Furthermore, the common Mediterranean haplotypes Va, IIIb [- + + + - + + + + -], I [+ + - - - - - + + +] and II [- + - + + - + + + +] accounted for most (66.2%) of the wild-type alleles among the tested Hb F-Malta-I heterozygotes. Different genotypes at the 5' epsilon HincII, Ggamma and Agamma HindIII, and 3'psibeta HincII sites (but not at the 5' Ggamma XmnI site) were found to be linked to significant variations in the proportion of Ggamma-F-Malta-I and Ggamma-globins in the Hb F of newborn Hb F-Malta-I heterozygotes. Moreover, the 5' Ggamma XmnI site was found to be associated with variations in Hb F and Ggamma-globin levels in a population of adult Maltese beta-thalassemia (thal) homozygotes. This implies that a determinant linked to the XmnI site which effects Ggamma-globin gene expression is active in anemic adults but not in normal infants.