Biological consequences of Vanadium effects on formation of reactive oxygen species and lipid peroxidation

Lipid peroxidation (LPO), a process that affects human health, can be induced by exposure to vanadium salts and compounds. LPO is often exacerbated by oxidation stress, with some forms of vanadium providing protective effects. The LPO reaction involves the oxidation of the alkene bonds, primarily in polyunsaturated fatty acids, in a chain reaction to form radical and reactive oxygen species (ROS). LPO reactions typically affect cellular membranes through direct effects on membrane structure and function as well as impacting other cellular functions due to increases in ROS. Although LPO effects on mitochondrial function have been studied in detail, other cellular components and organelles are affected. Because vanadium salts and complexes can induce ROS formation both directly and indirectly, the study of LPO arising from increased ROS should include investigations of both processes. This is made more challenging by the range of vanadium species that exist under physiological conditions and the diverse effects of these species. Thus, complex vanadium chemistry requires speciation studies of vanadium to evaluate the direct and indirect effects of the various species that are present during vanadium exposure. Undoubtedly, speciation is important in assessing how vanadium exerts effects in biological systems and is likely the underlying cause for some of the beneficial effects reported in cancerous, diabetic, neurodegenerative conditions and other diseased tissues impacted by LPO processes. Speciation of vanadium, together with investigations of ROS and LPO, should be considered in future biological studies evaluating vanadium effects on the formation of ROS and on LPO in cells, tissues, and organisms as discussed in this review.info:eu-repo/semantics/publishedVersio

Numerical simulations of a non-commutative theory: the scalar model on the fuzzy sphere

We address a detailed non-perturbative numerical study of the scalar theory on the fuzzy sphere. We use a novel algorithm which strongly reduces the correlation problems in the matrix update process, and allows the investigation of different regimes of the model in a precise and reliable way. We study the modes associated to different momenta and the role they play in the ``striped phase'', pointing out a consistent interpretation which is corroborated by our data, and which sheds further light on the results obtained in some previous works. Next, we test a quantitative, non-trivial theoretical prediction for this model, which has been formulated in the literature: The existence of an eigenvalue sector characterised by a precise probability density, and the emergence of the phase transition associated with the opening of a gap around the origin in the eigenvalue distribution. The theoretical predictions are confirmed by our numerical results. Finally, we propose a possible method to detect numerically the non-commutative anomaly predicted in a one-loop perturbative analysis of the model, which is expected to induce a distortion of the dispersion relation on the fuzzy sphere.Comment: 1+36 pages, 18 figures; v2: 1+55 pages, 38 figures: added the study of the eigenvalue distribution, added figures, tables and references, typos corrected; v3: 1+20 pages, 10 eps figures, new results, plots and references added, technical details about the tests at small matrix size skipped, version published in JHE

Don’t turn your back on the symptoms of psychosis : a proof-of-principle, quasi-experimental public health trial to reduce the duration of untreated psychosis in Birmingham, UK

Background: Reducing the duration of untreated psychosis (DUP) is an aspiration of international guidelines for first episode psychosis; however, public health initiatives have met with mixed results. Systematic reviews suggest that greater focus on the sources of delay within care pathways, (which will vary between healthcare settings) is needed to achieve sustainable reductions in DUP (BJP 198: 256-263; 2011). Methods/Design: A quasi-experimental trial, comparing a targeted intervention area with a ‘detection as usual’ area in the same city. A proof-of–principle trial, no a priori assumptions are made regarding effect size; key outcome will be an estimate of the potential effect size for a definitive trial. DUP and number of new cases will be collected over an 18-month period in target and control areas and compared; historical data on DUP collected in both areas over the previous three years, will serve as a benchmark. The intervention will focus on reducing two significant DUP component delays within the overall care pathway: delays within the mental health service and help-seeking delay. Discussion: This pragmatic trial will be the first to target known delays within the care pathway for those with a first episode of psychosis. If successful, this will provide a generalizable methodology that can be implemented in a variety of healthcare contexts with differing sources of delay. Trial registration: http://www.controlled-trials.com/ISRCTN45058713 Keywords: Public mental health campaign, First-episode psychosis, Early detection, Duration of untreated psychosis, Youth mental healt

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

‘Subjective resilience’: using perceptions to quantify household resilience to climate extremes and disasters.

How should we measure a household’s resilience to climate extremes, climate change or other evolving threats? As resilience gathers momentum on the international stage, interest in this question continues to grow. So far, efforts to measure resilience have largely focused on the use of ‘objective’ frameworks and methods of indicator selection. These typically depend on a range of observable socio-economic variables, such as levels of income, the extent of a household’s social capital or its access to social safety nets. Yet while objective methods have their uses, they suffer from well-documented weaknesses. This paper advocates for the use of an alternative but complementary method: the measurement of ‘subjective’ resilience at the household level. The concept of subjective resilience stems from the premise that people have an understanding of the factors that contribute to their ability to anticipate, buffer and adapt to disturbance and change. Subjective household resilience therefore relates to an individual’s cognitive and affective self-evaluation of their household’s capabilities and capacities in responding to risk. We discuss the advantages and limitations of measuring subjective household resilience and highlight its relationships with other concepts such as perceived adaptive capacity, subjective well-being and psychological resilience. We then put forward different options for the design and delivery of survey questions on subjective household resilience. While the approach we describe is focused at the household level, we show how it has the potential to be aggregated to inform sub-national or national resilience metrics and indicators. Lastly, we highlight how subjective methods of resilience assessment could be used to improve policy and decision-making. Above all, we argue that, alongside traditional objective measures and indicators, efforts to measure resilience should take into account subjective aspects of household resilience in order to ensure a more holistic understanding of resilience to climate extremes and disasters

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

Synthesis of Tridentate (PCN) Ligands for the Development of Organometallic Catalysts

Color poster with text, images, charts, photographs, and graphs.Catalysis plays a great role in the world today with one of the most prominent industries being the polymers industry. Linear alpha olefins (LAO’s) are short to long chain carbon molecules whose uses range from plastics to motor oils to synthetic lubricants. This project aims to develop a ligand that can direct a metal complex to selectively catalyze the formation of lucrative short chain linear alpha olefins from ethylene.1-5 The target ligand is a tridentate ligand that uses phosphorous, carbon, and nitrogen to bind to the transition metal of choice and features a benzimidazole backbone. This ligand design is a continuation of research initiated in the Dr. Carney’s group at UWEC.6,7 After synthesis and characterization of this ligand, the obtained organometallic complex is anticipated to function as an effective catalyst. Presented here are the first synthetic steps of this project to obtain the free pre-ligand. This synthesis utilizes a combination of open-to-air and air-sensitive techniques. Future work is planned to complete the synthesis of the metal complex and test the catalytic ability for the selectivity of the desired LAO’s.University of Wisconsin--Eau Claire Office of Research and Sponsored Program