21827 research outputs found
Sort by
The protective role of vitamin D in BNT162b2 vaccine-related acute myocarditis
Get PDFIntroduction: Vaccine-related myocarditis is recognized as a rare but important complication, especially after mass-scale mRNA COVID-19 vaccination. Knowledge regarding how to minimize the risk is limited. As NK cells can mediate acute myocarditis after mRNA COVID-19 vaccination and vitamin D may inhibit NK cells via cytokine modulation, we hypothesize that the myocarditis side effect is related to a hypovitaminosis D – mRNA vaccine – hypercytokinemia – NK cell axis, which is amendable to clinical intervention. Methods: Biochemical, immunophenotypic and genotyping assays were performed to examine vitamin D status and immune profiles in 60 patients who had BNT162b2 vaccine-related acute myocarditis. Results: A high incidence of hypovitaminosis D (73.3%) was observed in these individuals with vaccine-related myocarditis, particularly in those presented with chest pain or intensive care unit (ICU) admission. Moreover, vitamin D level was negatively associated with peak serum cardiac troponin T level during vaccine-related myocarditis. Genotypically, the GC (vitamin D binding protein) rs4588T allele which encoded the GC2 isoform of vitamin D binding protein was a risk allele, whereas the GC1S isoform was protective. Mechanistically, hypovitaminosis D was associated with higher levels of cytokines pivotal for natural killer (NK) cells (particularly interleukin-1β (IL-1β), IL-12, Interferon-γ (IFN-γ), and IL-8) and higher percentage of CD69+ NK cells in blood, which in turn correlated with chest pain presentation. Conclusion: These data support the hypothesis that vitamin D plays a crucial role in mitigating mRNA vaccine-related myocarditis by modulating proinflammatory cytokine milieu and subsequent unfavorable NK cell activation, laying a groundwork for preventive and treatment strategies
Alpha-Lipoic Acid Reduces Neuroinflammation and Oxidative Stress Induced by Dapsone in an Animal Model
Get PDFBackground/Objectives: Chronic treatment with dapsone (DDS) has been linked to adverse reactions involving all organ systems, such as dapsone hypersensitivity syndrome, methemoglobinemia and hemolytic anemia, besides neuroinflammation and neurodegeneration due to iron accumulation and oxidative stress. These effects probably occur due to the presence of its toxic metabolite DDS-NOH, which can generate reactive oxygen species (ROS) and iron overload. In this sense, antioxidant compounds with chelating properties, such as alpha-lipoic acid (ALA), may be an interesting adjuvant therapy strategy in treating or preventing these effects. Thus, the aim of this study was to evaluate the effects of ALA on oxidative and neuroinflammatory changes caused by DDS treatment in the prefrontal cortex and hippocampus of mice. Materials and Methods:Mus musculus male mice that were pre-treated with DDS (40 mg/kg) and post-treated with ALA (25 mg/kg) underwent analyses for oxidative stress, antioxidant capacity, cytokine expression and microglial/astrocytic activity. Results: DDS did not activate macrophages/microglia or astrocytes in the prefrontal cortex but induced their activation in the hippocampus. ALA stimulated a protective microglial profile and reduced astrocyte reactivity, especially in the hippocampus. DDS increased the pro-inflammatory cytokine IL-1β and reduced brain-derived neurotrophic factor (BDNF), effects reversed by ALA. DDS also reduced antioxidant capacity (TEAC, GSH, SOD, CAT) and increased oxidative damage (lipid peroxidation, iron accumulation), while ALA restored antioxidant levels and reduced oxidative stress. Conclusions: ALA was able to reduce the effects of DDS, such as reducing microglial and astrocytic activation, as well as to decrease the levels of pro-inflammatory cytokines and increase BDNF, in addition to increasing antioxidant capacity and reducing oxidative damage caused by iron accumulation. Therefore, ALA is considered a useful and promising therapeutic alternative for the treatment of diseases related to oxidative stress and neuroinflammation
The Influence of Senescent Associated Secretory Phenotype on Glucose Homeostasis in C2C12 Muscle Cells: Insights into Potential p38 Inhibitor Interventions
Get PDFIncreased accumulation of senescent cells with aging is associated with reduced ability of insulin-target tissues to utilize glucose, resulting in increased insulin resistance and glucotoxicity. We investigated the role of the senescent-associated secretory phenotype (SASP) within C2C12, skeletal muscle cells on glucose homeostasis and if such effects could be reduced by blocking pro-inflammatory pathways. C2C12 myotubes were treated with 40% conditioned media from senescent fibroblasts. Indirect glucose uptake and glycogen content were measured. The effect of SASP on the generation of reactive oxygen species [Citation 1] and mitochondrial function was also measured. The experiments above were repeated with a p38 inhibitor. 40% SASP treatment significantly decreased glucose utilization and glycogen storage within myotubes (p < 0.0001). 40% SASP was successful in inducing oxidative stress and increased mitochondrial density, whilst reducing membrane potential following 48 h of incubation (p < 0.0001) and blocking NF-κβ, restored glucose utilization (p < 0.01) despite the presence of SASP. Co-incubation of 40% SASP with an NF-κβ inhibitor eliminates excessive ROS production and restores mitochondrial activity to levels comparable to control treatment (p < 0.0001). This study shows changes in glucose homeostasis in senescent cells is mediated through SASP, and interventions aimed at mitigating pro-inflammatory pathways can potentially improve insulin resistance
Blodgett's (1919) “Ship camouflage” 105 years on: A misperception of dazzle perception revealed and redressed
Get PDFDuring WWI, dazzle camouflage involved painting allied shipping with bold geometric patterns to disrupt the perceptions of enemy submariners. The first experiment to provide quantitative results on this (Blodgett, 1919; MIT Libraries, MA) used scale models and mechanical simulation, and reported enormous perceptual errors for their perceived direction of travel (up to ∼60°), possibly due to a “twist” effect from forced perspective. However, Blodgett's work did not meet modern standards and the organisation of his report complicates evaluation. Here, we produce (i) reformatted and (ii) heavily edited versions of the original report to improve readability, and (iii) provide a critical reappraisal of the work including (iv) a detailed reanalysis of Blodgett's data and (v) a new control experiment on edited images of the original stimuli. After addressing problems with Blodgett's analysis and control experiment, we found results indicating a twist of only about 7°, but a much larger “hysteresis” effect (∼19–23°) where perceived direction was drawn to the horizon regardless of dazzle. This effect combined both constructively and destructively with “twist”, depending on the direction of the target ship. These reappraised findings resolve an apparent conflict with the second quantitative experiment on dazzle ships conducted over a century later using computer displays online (Lovell et al., 2024; Royal Society Open Science). We conclude that Blodgett's approach and data remain of interest today, but his conclusions substantially overestimated the effectiveness of dazzle camouflage in biasing the perceived directions of ships. However, other potential benefits of dazzle, including perceptual variance, await systematic investigation
Socioeconomic status and prescribing of ADHD medications: a study of ICB-level data in England
Get PDFBACKGROUND: Little is known about the impact of healthcare structural changes and socioeconomic indices, such as deprivation, mental health needs, and inequalities, on attention-deficit hyperactivity disorder (ADHD) medication prescribing across different regions in England. OBJECTIVE: The objective was to examine trends in ADHD medication prescribing and explore their association with socioeconomic factors. METHODS: A population-level observational study was conducted using the English Prescribing Dataset (from April 2019 to March 2024) published by the NHS Business Services Authority and the OpenPrescribing platform (Bennett Institute for Applied Data Science, University of Oxford). The study examined trends in five licensed ADHD medications at national, regional and integrated care board (ICB) levels, using linear regression and a generalised additive model to explore the association between socioeconomic factors and prescription rates. FINDINGS: The prescriptions increased significantly from 25.17 items per 1000 population in 2019/20 (pre-COVID-19) to 41.55 items in 2023/24 (post-COVID-19), with an average annual increase of 18% nationally. Methylphenidate remained the most prescribed medication, while lisdexamfetamine showed the highest growth rate (55% annually, 95% CI 40% to 71%, p<0.01). Significant regional variations were observed, with London experiencing the highest annual increase (28%), and the Northeast and Yorkshire the lowest (13%). Socioeconomic factors, including ethnicity and deprivation, were significantly associated with ADHD prescription rates (p<0.05). CONCLUSIONS: Findings reveal a substantial increase in ADHD medication use in England following the COVID-19 pandemic, with significant variations at regional and ICB levels and complex socioeconomic influences. CLINICAL IMPLICATIONS: Findings highlight the need to understand and address drivers of disparities in ADHD care while optimising management strategies across diverse populations
“It’s a Permanent Struggle to Manage It Really”: Psychological Burden and Coping Strategies of Adults Living With Food Allergy
Get PDFFood allergy (FA) is a potentially life-threatening condition which is associated with poor quality of life and psychological distress in patients and caregivers. Although FA is often seen as a condition that affects children, increasing numbers of adults have FA, either as a condition they have grown up with or they were diagnosed as an adult. No recent research has explored the lived experiences of adults with FA and how they manage this condition. In response, this study aimed to qualitatively assess the current lived experiences of adults in the UK with FA, and how they manage this condition. Adults aged 18 years or over, with medically diagnosed FA, living in the UK were recruited through patient organisations and interviewed (n = 22). Data were analysed using template analysis. Two main themes were identified from the data. The first theme explores the influence of FA on the participants’ lives, in particular on their ‘psychological’ and ‘social’ well-being. The second theme unpacks the strategies participants employed to cope with and manage their FA, specifically participants’ deployment of ‘avoidance’, ‘control’, ‘self-monitoring’, and ‘adaptation’ to manage their FA and their anxieties around it. Clearly, FA has a profound, ongoing effect on the lives of adults. Few adults in this study were able to access any support to manage their FA and accompanying anxieties. Ways in which effective support can be made available to adults with FA must be identified and implemented
Virtual Tools and Student Engagement: Insights from Engineering Education
No full textMaximising student engagement in higher education requires more than traditional lecture methods; it requires the integration of interactive virtual tools that foster active learning. With increasing shifts towards blended and online learning environments, there is a growing need for innovative educational technologies to enhance interactivity and student involvement. This study investigates the impact of audience response systems and tools within virtual learning environments (VLEs) on student engagement within a blended learning context. Data were collected from two Engineering modules - a first-year Mathematics module and a final-year Software Project Management module - capturing distinct cohorts and learning objectives. The first-year course focuses on developing foundational analytical skills, while the final-year course emphasises higher-order skills such as critical thinking and problem-solving. Using a mixed-methods approach, this study combines quantitative metrics (participation frequency, interaction types, participation rates, and temporal patterns) with qualitative insights (interaction dynamics) to examine student engagement and how students across these academic levels interact with these virtual tools. Results indicate that platforms, such as Padlet and Kahoot!, can effectively engage students who may be less active in traditional classroom settings, while chat-enabled lectures facilitate immediate feedback and active learning, creating opportunities for deeper engagement. The findings highlight both the strengths and limitations of these tools providing for educators in engineering and related disciplines with insights and strategies for implementing virtual tools to enhance student engagement. By embracing these technologies, educators can create inclusive, interactive experiences adapted to suit the diverse needs and learning preferences of students
Fluorescence spectra of cell markers in the spinal cord for a murine model of amyotrophic lateral sclerosis with heat shock protein overexpression
Get PDFAmyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder with few existing therapies. Fused-in-sarcoma (FUS) gene mutations underlie many cases of ALS worldwide, whereas 70 kDa heat shock protein (HSP70) was shown to be beneficial for neuronal resistance in ALS. In this study, we observed structural changes in the nervous tissue of the spinal cord when FUS and a member of the HSP70 family, HSPA1A, were expressed together. We regarded fluorescent markers of neurons and neuroglial cells in mice with a transgenic FUS model of ALS, comparing them to transgenic animals with HSPA1A overexpression in cells, Hsp70 (in), and in extracellular substance, Hsp70 (out), and to double transgenic mice with both HSPA1A and FUS genes. We revealed the count of neuronal marker NeuN to be significantly decreased in transgenic FUS animals compared to the intact mice from the control group, whereas it increased in double transgenic FUS + Hsp70 (in) animals. The counts of GFAP, astroglial marker, and Iba1, microglial marker, were increased in transgenic FUS mice with a slight but significant decrease in FUS + Hsp70 (in) mice. Overall survival of transgenic FUS animals was less than that of FUS + Hsp70 (in) mice but even higher than the survival of FUS + Hsp70 (out) mice. We consider that HSPA1A in cells of animals with aberrant FUS has a strong impact on their longevity, neuronal survival, and neuroinflammation avoidance. The data from our study outline intracellular HSPA1A as an important target for the development of disease-modifying therapies for FUS-related ALS
Widely FSR tunable high Q-factor microresonators formed at the intersection of straight optical fibers
Get PDFWe present a class of high-Q tunable microresonators formed at the intersection of two straight silica optical fibers, whose free spectral range (FSR) can be widely tuned by fiber rotation. The proposed configuration avoids the limitations of traditional monolithic microresonators that lack FSR tunability required for a wide range of photonic applications. Using small rotation angles (1–15 mrad), we demonstrate a tunability of the FSR from 2 pm to 10 pm, enabled by microscale fiber displacements that reshape the resonator profile over millimeter scales. The proposed approach minimizes mechanical stress, supports miniaturization, and is suitable for integration with MEMS. It paves the way for the fabrication of tunable delay lines, ultralow repetition rate broadband frequency comb generators, and nonlocal optofluidic sensors on a chip
The case for treating all children with myopia control interventions
Get PDFWith the growing rates of myopia across the world and the potentially devastating effect of myopia-associated pathology in later life, should we be treating all children with myopia control interventions? Conversely, interventions are not without side effects such as impact on visual function, increased risk of ocular infection and possible ocular surface effects from long-term applications. The focus of this Point–Counterpoint article is to weigh up whether the risks outweigh the benefits of treating all children with myopia control interventions until there is a way to predict accurately those that will benefit substantially from them. Untreatable retinal pathology is life changing, impacting an individual's ability to work, their independence and their mental health. Therefore, this issue cannot be taken lightly. The focus on healthcare in most countries across the world is shifting towards prevention rather than a ‘cure’ as this is generally more economically viable for already stretched healthcare systems. As retinal pathology associated with myopia typically takes decades to become evident in an individual, the eye care community and regulatory agencies will need to take a stance on this question before there is definitive evidence as to the potential tsunami of myopia-associated visual impairment in their population. Here, Xiangui He and Nicola Logan debate whether the case for treating all children with myopia control interventions is warranted or not
Data sources:
Access Repository Dashboard
Do you manage Aston Publications Explorer? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!