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

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

The study of acoustic properties of P205-doped silica fiber

Silica-based optical fibers have been applied to numerous fields. The interactions between acoustic phonons and the optical wave are involved in several of these applications. A significant stimulated scattering mechanism observed is stimulated Brillouin scattering (SBS), resulting in strong backward scattering typically within the optical fiber core. SBS has become one of the significant factors limiting the power transmitted in an optical fiber. Through investigating acoustic properties with temperature and strain effects, novel fibers can be developed by decreasing SBS of high power laser systems for optical remote sensing, or by increasing sensitivity to temperature or strain for distributed fiber-optic sensing systems. This thesis presents measurements and modeling of the P2O5 doping effect on the acoustic damping and temperature sensitivity coefficients of silica fibers. The Brillouin gain spectrum of a highly P2O5-doped fiber is measured at different temperatures. Its thermo-acoustic coefficients (TAC) and thermo-optic coefficients (TOC) are determined. In addition, its acoustic velocity is found to be much less dependent on temperature. We present similar analysis for the P2O5 doping effect on the strain sensitivity coefficients of silica fibers. The strain-optic coefficient (SOC) and the strain-acoustic coefficient (SAC) of bulk P2O5 are determined by investigating the Brillouin gain spectrum of a heavily P2O5-doped fiber and a pure silica fiber at different strains. The Pockels coefficients p11 and p12 for bulk P2O5 are also estimated via Brillouin gain measurements. The experimental data and analysis results are extremely useful for designing optical and acoustic profiles of optical fibers for any applications where Brillouin scattering occurs

Gas-Phase Plasma Synthesis of Free-Standing Silicon Nanoparticles for Future Energy Applications

Silicon nanoparticles (Si-NPs) are considered as possible candidates for a wide spectrum of future technological applications. Research in the last decades has shown that plasmas are one of the most suitable environments for the synthesis of Si-NPs. This review discusses the unique size-dependent features of Si-NPs, and the fundamental mechanisms of nanoparticle formation in plasmas by highlighting major plasma synthesis techniques. In addition, the routes to achieve control on Si-NP morphology and chemistry in plasma environments will be discussed. We will review recent advancements in solar cell and lithium-ion battery applications of gas-phase plasma synthesized Si-NPs by highlighting key results from the literature. We will discuss further technological applications, where gas-phase plasma synthesized Si-NPs can contribute, like water splitting and thermoelectrics.</p