Publications by authors named "Robert Maidstone"

Exposure to artificial light-at-night (ALAN) has been linked to cancer risk. Few meta-analyses on this topic have reviewed only breast cancer. This study aimed to systematically review and meta-analyze existing studies on ALAN exposure and cancer incidence, thoroughly evaluating exposure assessment quality.

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Article Synopsis
  • Allergic diseases are a significant global health issue, and this study examines the impact of exposure to artificial light at night (ALAN) on such conditions, with a focus on asthma, allergic rhinitis, and skin allergies.
  • The research included a thorough review of 12 studies, revealing that higher exposure to light at night correlates with increased risks for allergic diseases, particularly asthma and allergic rhinitis, with notable effects seen in younger individuals.
  • The findings suggest that evening chronotype and night shift work also contribute to these risks, indicating that light exposure at night can significantly affect allergic health outcomes.
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Background And Aims: Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common liver disease worldwide. Modern lifestyles have been linked to this rise in prevalence with changes in rhythmic human behaviour emerging as a possible mechanism. We investigated how shift working patterns and chronotype were associated with hepatic fat fraction and NAFLD in 282,303 UK Biobank participants.

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  • Asthma affects the rhythmic regulation of the body's immune response, with findings indicating a heightened circadian pattern in blood immune cells of asthma patients compared to healthy individuals.
  • A study involving blood samples taken every 6 hours from participants revealed that asthma patients have altered immune cell dynamics and enhanced immune responses, particularly peaking in the afternoon.
  • The research also suggests that changes in serum ceramides reflect systemic inflammation in asthma, highlighting a potential link between the lung and blood's circadian rhythms and the effectiveness of steroid treatment at specific times.
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The circadian clock regulates multiple aspects of human physiology including immunity. People have a circadian preference termed chronotype. Those with an evening preference may be better suited to shift work, but also carry higher risk of adverse health.

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The gut microbiota is important for host health and immune system function. Moreover autoimmune diseases, such as rheumatoid arthritis, are associated with significant gut microbiota dysbiosis, although the causes and consequences of this are not fully understood. It has become clear that the composition and metabolic outputs of the microbiome exhibit robust 24 h oscillations, a result of daily variation in timing of food intake as well as rhythmic circadian clock function in the gut.

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Artificial light at night (ALAN) exposure is associated with the disruption of human circadian processes. Through numerous pathophysiological mechanisms such as melatonin dysregulation, it is hypothesised that ALAN exposure is involved in asthma and allergy, mental illness, and cancer outcomes. There are numerous existing studies considering these relationships; however, a critical appraisal of available evidence on health outcomes has not been completed.

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The circadian clock controls the physiological function of tissues through the regulation of thousands of genes in a cell-type-specific manner. The core cellular circadian clock is a transcription-translation negative feedback loop, which can recruit epigenetic regulators to facilitate temporal control of gene expression. Histone methyltransferase, mixed lineage leukemia gene 3 (MLL3) was reported to be required for the maintenance of circadian oscillations in cultured cells.

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  • - Chronic inflammation, such as that seen in rheumatoid arthritis, leads to rhythmic joint inflammation and alters energy metabolism in muscles and the liver at different times of the day.
  • - Research using a mouse model indicates that inflammatory conditions trigger changes in gene expression and fat metabolism, particularly through mechanisms involving EGFR-JAK-STAT3 signaling.
  • - The study found an increase in ceramides and sphingolipid production, especially during the day when inflammation peaks, highlighting a connection between inflammation timing and lipid metabolism issues.
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Introduction: Shift work is associated with lung disease and infections. We therefore investigated the impact of shift work on significant COVID-19 illness.

Methods: 501 000 UK Biobank participants were linked to secondary care SARS-CoV-2 PCR results from Public Health England.

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Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide for which there are no curative therapies. The major challenge in curing infection is eradicating or silencing the covalent closed circular DNA (cccDNA) form of the viral genome. The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the liver transcriptome and yet their role in HBV replication is unknown.

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Introduction: Shift work causes misalignment between internal circadian time and the external light/dark cycle and is associated with metabolic disorders and cancer. Approximately 20% of the working population in industrialised countries work permanent or rotating night shifts, exposing this large population to the risk of circadian misalignment-driven disease. Analysis of the impact of shift work on chronic inflammatory diseases is lacking.

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Background: The circadian clock powerfully regulates inflammation and the clock protein REV-ERBα is known to play a key role as a repressor of the inflammatory response. Asthma is an inflammatory disease of the airways with a strong time of day rhythm. Airway hyper-responsiveness (AHR) is a dominant feature of asthma; however, it is not known if this is under clock control.

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Efficient mitochondrial function is required in tissues with high energy demand such as the heart, and mitochondrial dysfunction is associated with cardiovascular disease. Expression of mitochondrial proteins is tightly regulated in response to internal and external stimuli. Here we identify a novel mechanism regulating mitochondrial content and function, through BUD23-dependent ribosome generation.

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The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time of day, but the mechanisms involved remain undefined. Here we show that loss of the core clock protein BMAL1 in macrophages confers protection against pneumococcal pneumonia.

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Objective: To identify whether renal transplant activity varies in a reproducible manner across the year.

Design: Retrospective cohort study using NHS Blood and Transplant data.

Setting: All renal transplant centres in the UK.

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Pulmonary airway epithelial cells (AECs) form a critical interface between host and environment. We investigated the role of the circadian clock using mice bearing targeted deletion of the circadian gene brain and muscle ARNT-like 1 () in AECs. Pulmonary neutrophil infiltration, biomechanical function, and responses to influenza infection were all disrupted.

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Objective: We applied systems biology approaches to investigate circadian rhythmicity in rheumatoid arthritis (RA).

Methods: We recruited adults (age 16-80 years old) with a clinical diagnosis of RA (active disease [DAS28 > 3.2]).

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The importance of circadian factors in managing patients is poorly understood. We present two retrospective cohort studies showing that lungs reperfused between 4 and 8 AM have a higher incidence (OR 1.12; 95% CI 1.

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The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day.

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