Biomechanical considerations in the pathogenesis of osteoarthritis of the knee

Osteoarthritis is the most common joint disease and a major cause of disability. The knee is the large joint most affected. While chronological age is the single most important risk factor of osteoarthritis, the pathogenesis of knee osteoarthritis in the young patient is predominantly related to an unfavorable biomechanical environment at the joint. This results in mechanical demand that exceeds the ability of a joint to repair and maintain itself, predisposing the articular cartilage to premature degeneration. This review examines the available basic science, preclinical and clinical evidence regarding several such unfavorable biomechanical conditions about the knee: malalignment, loss of meniscal tissue, cartilage defects and joint instability or laxity

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Nerve guidance conduit design based on self-rolling tubes.

The current gold standard in peripheral nerve repair is nerve autografts for bridging gaps larger than a centimeter. However, autografts are associated with a low availability and the loss of function at the donor site. Nerve guidance conduits (NGCs) made of biocompatible and biodegradable materials reflect suitable alternatives. Clinically approved NGCs comprise either wraps that are rolled around the loose ends of the nerve or steady-state tubes; however, both lack internal guidance structures. Here, we established self-rolling NGCs to allow for gentle encapsulation of nerve cells together with supportive microenvironments, such as (1) an inner tube wall coating with a bioactive spider silk film, (2) an inner tube wall lining using an anisotropic spider silk non-woven mat, or (3) a luminal filler using an anisotropic collagen cryogel. Neuronal cells adhered and differentiated inside the modified tubes and formed neurites, which were oriented along the guidance structures provided by the spider silk non-woven mat or by the fibrillary structure of the collagen cryogel. Thus, our size-adaptable NGCs provide several features useful for peripheral nerve repair, and distinct combinations of the used elements might support and enhance the clinical outcome

Enhanced Antibacterial Activity of Se Nanoparticles Upon Coating with Recombinant Spider Silk Protein eADF4(kappa 16)

Purpose: Selenium nanoparticles (Se NPs) are promising antibacterial agents to tackle the growing problem of antimicrobial resistance. The aim of this study was to fabricate Se NPs with a net positive charge to enhance their antibacterial efficacy. Methods: Se NPs were coated with a positively charged protein--recombinant spider silk protein eADF4([kappa] 16)--to give them a net positive surface charge. Their cytotoxicity and antibacterial activity were investigated, with negatively charged polyvinyl alcohol coated Se NPs as a control. Besides, these eADF4([kappa] 16)-coated Se NPs were immobilized on the spider silk films, and the antibacterial activity of these films was investigated. Results: Compared to the negatively charged polyvinyl alcohol coated Se NPs, the positively charged eADF4([kappa] 16)-coated Se NPs demonstrated a much higher bactericidal efficacy against the Gram-negative bacteria E. coli, with a minimum bactericidal concentration (MBC) approximately 50 times lower than that of negatively charged Se NPs. Cytotoxicity testing showed that the eADF4([kappa] 16)-coated Se NPs are safe to both Balb/3T3 mouse embryo fibroblasts and HaCaT human skin keratinocytes up to 31 [micro]g/mL, which is much higher than the MBC of these particles against E. coli (8 [+ or -] 1 [micro]g/mL). In addition, antibacterial coatings were created by immobilising the eADF4([kappa] 16)-coated Se NPs on positively charged spider silk films and these were shown to retain good bactericidal efficacy and overcome the issue of low particle stability in culture broth. It was found that these Se NPs needed to be released from the film surface in order to exert their antibacterial effects and this release can be regulated by the surface charge of the film, such as the change of the spider silk protein used. Conclusion: Overall, eADF4([kappa] 16)-coated Se NPs are promising new antibacterial agents against life-threatening bacteria

Transperineal ultrasound in the assessment of haemorrhoids and haemorrhoidectomy: a pilot study

Background: The purpose of the study was the measurement of the anal cushion area using static transperineal ultrasound in a group of patients with symptomatic grade III and IV haemorrhoids about to undergo haemorrhoidectomy and compare them with a group of age-matched normals and the measured area following haemorrhoidectomy. Methods: Transperineal sonography was performed using a linear transducer measuring the anal cushion area by subtracting the measured luminal diameter of the undisturbed anal canal from the inner border of the internal anal sphincter. Measures were made 6 weeks following haemorrhoidectomy. Results: Comparisons were made between 22 normals and 36 patients with haemorrhoids (31 evaluable post-operatively). The median area of normals was 0.78 cm², that of pre-operative patients 2.25 cm² and that of post-operative cases 1.20 cm². There was a significant difference between pre- and post-operative cases with cushion areas of normal patients being significantly lower than post-operative cases. Variance of measurement in all 3 groups was negligible. Conclusion: Static transperineal sonography measuring the anal cushion area is reproducible and shows marked differences between normals and patients with symptomatic haemorrhoids. There is a marked effect on measured area resultant from haemorrhoidectomy

Intra-observer and interobserver reliability of the 'Pico' computed tomography method for quantification of glenoid bone defect in anterior shoulder instability

Objective To evaluate the intra-observer and interobserver reliability of the \u2018Pico\u2019 computed tomography (CT) method of quantifying glenoid bone defects in anterior glenohumeral instability. Materials and methods Forty patients with unilateral anterior shoulder instability underwent CT scanning of both shoulders. Images were processed in multiplanar reconstruction (MPR) to provide an en face view of the glenoid. In accordance with the Pico method, a circle was drawn on the inferior part of the healthy glenoid and transferred to the injured glenoid. The surface of the missing part of the circle was measured, and the size of the glenoid bone defect was expressed as a percentage of the entire circle. Each measurement was performed three times by one observer and once by a second observer. Intra-observer and interobserver reliability were analyzed using intraclass correlation coefficients (ICCs), 95% confidence intervals (CIs), and standard errors of measurement (SEMs). Results Analysis of intra-observer reliability showed ICC values of 0.94 (95% CI=0.89\u20130.96; SEM=1.1%) for single measurement, and 0.98 (95% CI=0.96\u20130.99; SEM=1.0%) for average measurement. Analysis of interobserver reliability showed ICC values of 0.90 (95% CI=0.82\u20130.95; SEM=1.0%) for single measurement, and 0.95 (95% CI= 0.90\u20130.97; SEM=1.0%) for average measurement. Conclusion Measurement of glenoid bone defect in anterior shoulder instability can be assessed with the Pico method, based on en face images of the glenoid processed in MPR, with a very good intra-observer and interobserver reliability