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In 2019 artist Layla Khoo created and installed a participatory artwork at Nunnington Hall, a property owned by the National Trust, UK. The artwork, named Change in Attitudes, was a response to the taxidermy collection of hunting trophies displayed on site, all shot and collected by the last owner of the house, Colonel Ronald Fife. The work sought to encourage visitors to consider their thoughts on this difficult part of the collection, both in its historical context and in light of current societal norms, by inviting them to participate with the artwork through choice-making. This case study first analyzes the impact of this work on visitor engagement at the site, both in the participation methods intended by the artist and in the unexpected participation methods employed by the visitors as the installation evolved. The questions raised by this case study are then considered, as well as the research currently under way which seeks to answer them.

In 2019 artist Layla Khoo created and installed a participatory artwork at Nunnington Hall, a property owned by the National Trust, UK. The artwork, named Change in Attitudes, was a response to the taxidermy collection of hunting trophies displayed on site, all shot and collected by the last owner of the house, Colonel Ronald Fife. The work sought to encourage visitors to consider their thoughts on this difficult part of the collection, both in its historical context and in light of current societal norms, by inviting them to participate with the artwork through choice-making. This case study first analyzes the impact of this work on visitor engagement at the site, both in the participation methods intended by the artist and in the unexpected participation methods employed by the visitors as the installation evolved. The questions raised by this case study are then considered, as well as the research currently under way which seeks to answer them.

Abstract Context The effects of COVID-19 on the thyroid axis remain uncertain. Recent evidence has been conflicting, with both thyrotoxicosis and suppression of thyroid function reported. Objective We aimed to detail the acute effects of COVID-19 on thyroid function and determine if these effects persisted on recovery from COVID-19. Design A cohort observational study was conducted. Participants and Setting Adult patients admitted to Imperial College Healthcare National Health Service Trust, London, UK, with suspected COVID-19 between March 9 to April 22, 2020, were included, excluding those with preexisting thyroid disease and those missing either free thyroxine (FT4) or thyrotropin (TSH) measurements. Of 456 patients, 334 had COVID-19 and 122 did not. Main Outcome Measures TSH and FT4 measurements were recorded at admission, and where available, in 2019 and at COVID-19 follow-up. Results Most patients (86.6%) presenting with COVID-19 were euthyroid, with none presenting with overt thyrotoxicosis. Patients with COVID-19 had a lower admission TSH and FT4 compared to those without COVID-19. In the COVID-19 patients with matching baseline thyroid function tests from 2019 (n = 185 for TSH and 104 for FT4), TSH and FT4 both were reduced at admission compared to baseline. In a complete case analysis of COVID-19 patients with TSH measurements at follow-up, admission, and baseline (n = 55), TSH was seen to recover to baseline at follow-up. Conclusions Most patients with COVID-19 present with euthyroidism. We observed mild reductions in TSH and FT4 in keeping with a nonthyroidal illness syndrome. Furthermore, in survivors of COVID-19, thyroid function tests at follow-up returned to baseline.

Background Bisphenol A (BPA) is an exogenous endocrine disruptor mimicking hormones closely associated with health complications, such as cancer progression. BPA is also related to an increase in the prevalence of obesity-related diseases due to its obesogenic action. Bombesin-like receptor 3 (BRS3) is an important factor that should be considered in the adipogenic gene network, as depletion of this gene alters adiposity. Methods Therefore, the present study aimed to investigate the messenger ribonucleic acid (mRNA) expression of BRS3 in human liver THLE-2 cells post-BPA treatment by real-time polymerase chain reaction. The effects of BPA on the levels of pro-inflammatory proteins, interleukin 6 (IL6) and CC motif chemokine ligand 2 (CCL2), in conditioned media of BPA-treated THLE-2 cells and deoxyribonucleic acid (DNA) synthesis in replicating BPA-treated THLE-2 cells during the cell cycle were also examined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. Results The study found that the mRNA expression of BRS3 was increased in THLE-2 cells treated with BPA. The study also showed that the expression levels of IL6 and CCL2 reached an optimum level in the conditioned media of BPA-treated THLE-2 cells after 48 h of treatment. Subsequently, the DNA synthesis analysis showed that bromodeoxyuridine/propidium iodide (BrdU/PI) stained positive cells were decreased in BPA-treated THLE-2 cells at 72 h of treatment. Conclusion The study demonstrates that BRS3 expression induced by BPA is likely associated with reduced cell proliferation by inhibiting DNA synthesis and inducing cellular inflammation in liver cells.

Bisphenol (BP) A is an exogenous endocrine disruptor that mimics hormones closely associated with health complications, e.g., obesity and cancers. The present study aimed to evaluate the effects of BPA on human liver cells and tissue. The peroxisome proliferator-activated receptor (PPAR)-γ expression profile across tumour samples and paired normal tissue was first analysed using GEPIA. Subsequently, BPA-treated liver THLE-2 cell viability was evaluated using an MTT assay. Clusterin, PPARα and PPARγ gene expression in BPA-treated THLE-2 cells was assessed using GEPIA before validating the gene expression using real-time PCR and analysing overall survival using TCGA data in GEPIA. Cytoplasmic lipid accumulation was examined in BPA-treated THLE-2 cells using Oil Red O staining, and liver tissue was examined using haematoxylin and eosin staining. Finally, cytochrome P450 (CYP) gene expression was assessed in BPA-treated THLE-2 cells using real-time PCR. PPARγ is likely the primary nuclear receptor protein involved in lipid accumulation in THLE-2 cells following BPA treatment and is associated with liver disease. THLE-2 cells exposed to BPA showed a decrease in viability and lipid accumulation after 48 h treatment. Higher PPARγ gene expression was significantly associated with survival of patients with liver cancer, with an average survival time of <80 months. Haematoxylin and eosin-stained sections showed notable disruption of the liver architecture in tissue exposed to BPA. Downregulated CYP1A1 and CYP1B1 gene expression implied that BPA-treated THLE-2 cells decreased capacity for carcinogen metabolism, while upregulated CYP2S1 gene expression exerted minimal cytotoxicity. The present study revealed that BPA served as a carcinogen, enhanced tumorigenesis susceptibility and may induce other types of liver disease.

IntroductionThere is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19.Methods and analysisPANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid). Eligibility criteria: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18–49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial.Ethics and disseminationEthical approval granted by South Central–Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals.Trial registration numberISRCTN30448031; EudraCT number: 2021-005748-31.

Background Our previous study investigated the levels of soluble growth factors in the conditioned media of bone marrow-derived mesenchymal stem cells (BMSCs) pre-treated with thiazolidinedione solutions. The present study aimed to investigate the complex intracellular proteins extracted from BMSCs pre-treated with pioglitazone and/or rosiglitazone using proteomics. Methods The proliferative effect of the identified protein on MCF-7 cells that interacted non-adhesively with BMSCs pre-treated with pioglitazone and/or rosiglitazone was evaluated using cell culture inserts and conditioned media. The mRNA expression of proliferation and lipid accumulation markers was also evaluated in the interacted MCF-7 cells by reverse transcription-quantitative PCR. Finally, the correlation between the identified protein and fibroblast growth factor 4 (FGF-4) protein in the conditioned media of the pre-treated BMSCs was evaluated by ELISA. Results The present study identified vimentin as the specific protein among the complex intracellular proteins that likely plays a role in MCF-7 cell proliferation when the breast cancer cells interacted non-adhesively with BMSCs pre-treated with a combination of pioglitazone and rosiglitazone. The inhibition of this protein promoted the proliferation of MCF-7 cells when the breast cancer cells interacted with pre-treated BMSCs. Gene expression analysis indicated that pre-treatment of BMSCs with a combination of pioglitazone and rosiglitazone decreased the mRNA expression of Ki67 and proliferating cell nuclear antigen in MCF-7 cells. The pre-treatment did not induce mRNA expression of PPARγ, which is a sign of lipid accumulation. The level of vimentin protein was also associated with the FGF-4 protein expression level in the conditioned media of the pre-treated BMSCs. Bioinformatics analysis revealed that vimentin regulated the expression of FGF-4 through its interaction with SRY-box 2 and POU class 5 homeobox 1. Conclusions The present study identified a novel intracellular protein that may represent the promising target in pre-treated BMSCs to decrease the proliferation of breast cancer MCF-7 cells for human health and wellness.

Bisphenol (BP) A is an exogenous endocrine disruptor that mimics hormones closely associated with health complications, e.g., obesity and cancers. The present study aimed to evaluate the effects of BPA on human liver cells and tissue. The peroxisome proliferator-activated receptor (PPAR)-y expression profile across tumour samples and paired normal tissue was first analysed using GEPIA. Subsequently, BPA-treated liver THLE-2 cell viability was evaluated using an MTT assay. Clusterin, PPAR[alpha] and PPAR[gamma] gene expression in BPA-treated THLE-2 cells was assessed using GEPIA before validating the gene expression using real-time PCR and analysing overall survival using TCGA data in GEPIA. Cytoplasmic lipid accumulation was examined in BPA-treated THLE-2 cells using Oil Red O staining, and liver tissue was examined using haematoxylin and eosin staining. Finally, cytochrome P450 (CYP) gene expression was assessed in BPA-treated THLE-2 cells using real-time PCR. PPAR[gamma] is likely the primary nuclear receptor protein involved in lipid accumulation in THLE-2 cells following BPA treatment and is associated with liver disease. THLE-2 cells exposed to BPA showed a decrease in viability and lipid accumulation after 48 h treatment. Higher PPAR[gamma] gene expression was significantly associated with survival of patients with liver cancer, with an average survival time of <80 months. Haematoxylin and eosin-stained sections showed notable disruption of the liver architecture in tissue exposed to BPA. Downregulated CYP1A1 and CYP1B1 gene expression implied that BPA-treated THLE-2 cells decreased capacity for carcinogen metabolism, while upregulated CYP2S1 gene expression exerted minimal cytotoxicity. The present study revealed that BPA served as a carcinogen, enhanced tumorigenesis susceptibility and may induce other types of liver disease. Key words: bisphenol A, carcinogen, lipid accumulation, clusterin, peroxisome proliferator-activated receptor, cytochrome P450, gene expression, liver cells, liver tissue

Context: The effects of COVID-19 on the thyroid axis remain uncertain. Recent evidence has been conflicting, with both thyrotoxicosis and suppression of thyroid function reported. Objective: We aimed to detail the acute effects of COVID-19 on thyroid function and determine if these effects persisted upon recovery from COVID-19. Design: Cohort observational study. Participants and Setting: Adult patients admitted to Imperial College Healthcare National Health Service Trust, London, UK with suspected COVID-19 between March 9 to April 22, 2020 were included, excluding those with pre-existing thyroid disease and those missing either free thyroxine (FT4) or TSH measurements. Of 456 patients, 334 had COVID-19 and 122 did not. Main Outcome Measures: TSH and FT4 measurements at admission, and where available, those taken in 2019 and at COVID-19 follow-up. Results: Most patients (86·6%) presenting with COVID-19 were euthyroid, with none presenting with overt thyrotoxicosis. Patients with COVID-19 had a lower admission TSH and FT4 compared to those without COVID-19. In the COVID-19 patients with matching baseline thyroid function tests from 2019 (n=185 for TSH and 104 for FT4), both TSH and FT4 were reduced at admission compared to baseline. In a complete cases analysis of COVID-19 patients with TSH measurements at follow-up, admission and baseline (n=55), TSH was seen to recover to baseline at follow-up. Conclusions: Most patients with COVID-19 present with euthyroidism. We observed mild reductions in TSH and FT4 in keeping with a non-thyroidal illness syndrome. Furthermore, in survivors of COVID-19, thyroid function tests at follow-up returned to baseline.