Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Political and personal reactions to COVID-19 during initial weeks of social distancing in the United States.

ObjectiveTo examine perceptions, behaviors, and impacts surrounding COVID-19 early in the pandemic response.Materials and methodsA cross-sectional survey of 1,030 U.S. adults was administered on March 31st, 2020. This survey examined attitudes toward media, government, and community responses to COVID-19 by political ideology and sociodemographic factors. Knowledge, anxieties, and impacts of COVID-19 were also assessed.ResultsConservatives were more likely to report that COVID-19 was receiving too much media coverage and people were generally overreacting; liberals were more likely to report the government had not done enough in response to the pandemic. Females and those with lower income experienced more COVID-19 related economic anxieties. Those working and with children at home reported higher social, home, and work disruption. Social distancing behaviors were more common among liberals and were associated with increases in depressive symptoms. General knowledge about COVID-19 was widely exhibited across the sample, however, Black and Hispanic respondents were less likely to correctly answer questions about the availability of a vaccine and modes of transmission.ConclusionsPublic health experts should consider the political climate in crafting messaging that appeals to the values of those across the political spectrum. Research on the COVID-19 pandemic should continue to monitor the effects of social distancing on mental health and among vulnerable populations

Ozone photochemistry during the UK heat wave of August 2003

A wide range of chemical and physical parameters have been observed over the course of a severe Europe-wide air pollution episode in August 2003. Detailed surface observations made at the rural perimeter edge of London, U.K. indicated significantly elevated levels of primary VOCs, ozone (>110ppb), other photochemical by-products such as PAN, HCHO, and higher oxygenates but not NOx. Reactive organic tracers in combination with surface Doppler wind radar and back trajectory analysis have been used to establish that initial rapid morning rises in O3 during the episode were caused by entrainment of air from aloft, polluted on regional scales from mainland Europe. Total VOC reactivity to OH approximately doubled during this episode, with similar distribution between functional groups, but showing a temperature dependant exponentially increasing contribution from biogenic isoprene (max 1.2 ppbV). In addition to entrainment of regional air pollution, ozone formation rates within the U.K. boundary layer on the day of observation have been determined using measured peroxy radicals in combination with other chemical data. Under episodic conditions total peroxy radicals in excess 120pptV were observed in late afternoon with strong correlation to a later and higher peak in ozone when compared to non-episodic conditions. During the daytime under episodic conditions alkyl peroxy radical formation was dominated by PAN thermolysis, whose afternoon lifetime averaged only 18.3 min, but which was sustained at a concentration greater than 750 pptV. Low episodic wind speeds resulted in a relatively small possible spatial footprint for emissions of reactive precursors to PAN, and a strong correlation between isoprene and PAN production rate suggest this species may have contributed to the later afternoon increases seen in surface O3

Delaying surgery for patients with a previous SARS-CoV-2 infection

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