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

F-18-fluoride-PET for dynamic in vivo monitoring of bone formation in multiple myeloma

Background: Bone disease in multiple myeloma is characterized by reduced bone formation. The gold standard of bone formation is the mineral apposition rate (MAR), an invasive technique reflecting bone formation at a single site. We compared F-18-fluoride-PET with the MAR in myeloma patients. Methods: Bone formation was measured before and after bortezomib treatment by determination of the MAR in iliac bone marrow biopsies and the measurement of F-18-uptake. Results: The inter-and intra-individual variations in F-18-uptake (SUVA50%) were pronounced as 33.50 (range 4.42 to 37.92) and 27.18 (range 4.00 to 31.18), respectively. A significant correlation between the MAR and F-18-uptake was found (r = 0.80, p = 0.017). There was a heterogeneous response after treatment varying from -2.20 to 4.53. Conclusions: Iliac F-18-uptake was associated with the local MAR in myeloma patients. Furthermore, F-18-fluoride-PET demonstrated the heterogeneity of in vivo bone formation, enabling monitoring during treatment

Interventions and decision-making at the end of life: the effect of establishing the terminal illness situation

Background: Mobile learning (m-learning) has becoming very popular in education due to the rapidly advancing technology in our society. The potentials of the mobile applications should be used to enhance the education process. Few mobile applications have been designed to complement the study of physical therapy skills for physiotherapy students. The aim of this study was to investigate whether a mobile application, as a supplement to traditional learning, is useful for physiotherapy students in the acquisition of palpation and ultrasound skills in the shoulder area. Methods: Forty-nine students participated in this single-blinded, randomized controlled study. They were randomly distributed into two groups: experimental, with free access to the mobile application; and control, with access to traditional learning materials on the topic. Objective structured clinical evaluation (OSCE) and multiple-choice questionnaire (MCQ) were used to assess the educational intervention. Then, we also assessed the time taken to get a reliable ultrasound image and to localize a specific shoulder structure by palpation. Results: There was no significant intergroup difference in the acquisition of theoretical knowledge (p = .089). Scores were significantly higher in the experimental group than in the control group for the majority items in the ultrasound assessment; positioning of patient (p < .001), positioning of ultrasound probe (p = 0.007), handling of ultrasound probe (p = .013) and global OSCE (p < .001) and skills in palpation of the shoulder; position of patient (p = .009), direction of palpation contact (p = .021) and global OSCE (p = .034). There were no significant differences in the time required to perform the examination between groups in ultrasound (p = .944) and palpation (p = .393). The results from the post-program survey assessing the global satisfaction with the mobile application were high (8.200 ± .767), on an 11 numeric point rating scale. Conclusion: These results suggest the effectiveness of an m-learning program as a complement to traditional education for developing skills in ultrasound and palpation of the shoulder region in undergraduate physiotherapy students.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by a grant from the Educational Innovation Unit of the University of Granada, Spain (PID 13–86)