7 research outputs found
Systematic review of studies examining transtibial prosthetic socket pressures with changes in device alignment
Suitable lower-limb prosthetic sockets must provide an adequate distribution of the pressures created from standing and ambulation. A systematic search for articles reporting socket pressure changes in response to device alignment perturbation was carried out, identifying 11 studies. These were then evaluated using the American Academy of Orthotists and Prosthetists guidelines for a state-of-the-science review. Each study used a design where participants acted as their own controls. Results were available for 52 individuals and 5 forms of alignment perturbation. Four studies were rated as having moderate internal and external validity, the remainder were considered to have low validity. Significant limitations in study design, reporting quality and in representation of results and the suitability of calculations of statistical significance were evident across articles. Despite the high inhomogeneity of study designs, moderate evidence supports repeatable changes in pressure distribution for specific induced changes in component alignment. However, there also appears to be a significant individual component to alignment responses. Future studies should aim to include greater detail in the presentation of results to better support later meta-analyses
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
Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk
PURPOSE: Studies of vitamin D pathway genetic variants in relation to cancer risk have been inconsistent. We examined associations between vitamin D-related genetic polymorphisms, plasma 25-hydroxyvitamin D [25(OH)D], and breast cancer risk. METHODS: In a population-based case-control study of 967 incident breast cancer cases and 993 controls, we genotyped 25 polymorphisms encoding the vitamin D receptor (VDR) gene, 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1), and vitamin D binding protein (GC) and measured plasma 25(OH)D. We used multivariable logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: Among CYP24A1 polymorphisms, rs6068816 was associated with a 72% reduction in breast cancer risk (TT vs. CC, OR: 0.28, 95%CI: 0.10–0.76; p(trend)=0.01), but for rs13038432, the 46% decrease included the null value (GG vs. AA, OR: 0.54, 95%CI: 0.17–1.67; p(trend)=0.03). Increased risk that included the null value was noted for CYP24A1 rs3787557 (CC vs. TT, OR: 1.34, 95% CI: 0.92–1.89). The VDR polymorphism, TaqI (rs731236), was associated with a 26% risk reduction (TT vs. CC, OR: 0.74, 95%CI: 0.56–0.98; p(trend)=0.01). For other polymorphisms, ORs were weak and included the null value. The inverse association for plasma 25(OH)D with breast cancer was more pronounced (OR: 0.43, 95%CI: 0.27–0.68) among women with the common allele for CYP24A, rs927650 (p for interaction on a multiplicative scale=0.01). CONCLUSION: Breast cancer risk may be associated with specific vitamin D-related polymorphisms, particularly CYP24A1. Genetic variation in the vitamin D pathway should be considered when designing potential intervention strategies with vitamin D supplementation