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The 2019 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was held in Paris, France, and was attended by rheumatologists, dermatologists, representatives of biopharmaceutical companies, and patients. As in previous years, GRAPPA members held a symposium for trainees to discuss their research in psoriatic disease with experts in the field. Other subjects featured during the annual meeting included a composites workshop to review continuous composite measures; the GRAPPA-Collaborative Research Network's third annual meeting; the need for a precision medicine approach to the treatment of psoriatic disease; updates from working groups in International Dermatology Outcome Measures and Outcome Measures in Rheumatology; a debate on the effectiveness of methotrexate in the treatment of psoriatic arthritis (PsA); updating recommendations for optimal treatment approaches for patients with PsA; an update on GRAPPA's research and educational projects; and the GRAPPA ultrasound (US) working group's goal to optimize the evaluation of enthesitis in patients with PsA using US through the development of a diagnostic US enthesitis tool. In this Prologue, we introduce the papers that summarize that meeting.Given the high risk of healthcare worker (HCW) infection with COVID-19 during aerosol-generating medical procedures, the use of a box barrier during intubation for protection of HCWs has been examined. Previous simulation work has demonstrated its efficacy in protecting HCWs from cough-expelled droplets. Our objective was to assess its ability to protect HCWs against aerosols generated during aerosol-generating medical procedures. We used a battery-powered vapouriser to assess movement of vapour with (1) no barrier; (2) a box barrier; and (3) a box barrier and a plastic sheet covering the box and patient's body. We visualised the trajectory of vapour and saw that the vapour remained within the barrier space when the box barrier and plastic sheet were used. This is in contrast to the box barrier alone, where vapour diffused towards the feet of the patient and throughout the room, and to no barrier where the vapour immediately diffused to the laryngoscopist. This demonstrates that the box with the plastic sheet has the potential to limit the spread of aerosols towards the laryngoscopist, and thus may play a role in protecting HCWs during aerosol-generating medical procedures. This is of particular importance in the care of patients with suspected COVID-19.Objective To determine if age is a factor in a patients' likelihood of breaching the 4 hour time target to admission/discharge in emergency departments (EDs) within NHS Scotland. Methods We used data from the Information Service Division Scotland to analyse all ED attendances in Scotland between January 2015 and September 2018 (n=5 596 642). We assessed the likelihood of time to admission/discharge being within 4 hours, 8 hours and 12 hours for all age categories (reference category 20 to 24 years). Univariable logistic regressions were carried out for sex, Scottish Index of Multiple Deprivation level and both major (potentially life threatening) and minor (not immediately life threatening) incidences. Results The likelihood of breaching the 4-hour target increased linearly with age from 15 to 19 years upward. Patients ≥85 years were significantly (p less then 0.001) more likely to have breached than patients aged 20 to 24 years (OR 3.80, 95% CI 3.73 to 3.86). When considering major incidents, patients aged ≥85 years were more likely to have breached than those aged 20 to 24 years (OR 2.05, 95% CI 2.01 to 2.09, p less then 0.001). https://www.selleckchem.com/products/d-ap5.html The same was true of minor incidents (OR 2.85, 95% CI 2.73 to 2.98, p less then 0.001). Conclusions Older age is associated with a higher probability of breaching waiting time targets in a linear fashion within NHS Scotland, which is consistent with previous single hospital or regional studies. This association may be due to the higher proportion of elderly patients being admitted or a more systemic issue, but regardless, the elderly are being put more at risk.Pyrrolo[2,1-c][1,4]benzodiazepine dimer (PBD) is a DNA-minor groove alkylating agent with broad antitumor properties currently under development as a highly potent cytotoxic antibody-drug conjugate warhead against a variety of oncology targets. During a routine assessment of reversible CYP inhibition, it was found that PBD is a reversible inhibitor of CYP2C8 (IC50 = 1.1 µM) but not CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 (IC50 >10 µM). In contrast, PBD is a classic time-dependent inhibitor (TDI) of CYP3A4, with >30-fold shift in IC50 following a 30 min pre-incubation in the presence of NADPH. All other CYP isoforms tested did not show evidence for TDI, but potent inhibition of CYP2B6 (IC50 = 1.5 µM) was observed following a 30-minute pre-incubation both in the absence and presence of NADPH, an unexpected observation given the fact that no CYP2B6 inhibition was observed in the direct reversible inhibition assay up to 10 µM of PBD. No other CYP isoforms were susceptible to this apparent non-NADPH depvery unique in vitro CYP inhibition profile of PBD as a potent reversible CYP2C8 inhibitor, a NADPH dependent CYP3A TDI inhibitor and a NADPH independent CYP2B6 TDI inhibitor, and inhibition can occur through distinct mechanisms reversible drug-enzyme binding, enzyme inactivation via bioactivation, and enzyme inactivation by covalent binding via chemical reactions. Our results suggest that, for compounds with reactive functional moieties, false positives can be reported when the conventional TDI assay is utilized.OATP1B3 is a drug transporter expressed at the basolateral membrane of human hepatocytes. Along with other transporters, including OATP1B1, NTCP, and OCT1, it is responsible for the uptake of endo- and xenobiotics into hepatocytes. Our previous studies demonstrated that OATP1B3 can form hetero-oligomers, with OATP1B1 in HEK293 cells and with NTCP in both HEK293 cells and frozen human liver sections. To further characterize the hetero-oligomerization of OATP1B3, we investigated OCT1 as a potential interacting partner and determined the functional consequences of OATP1B3 hetero-oligomerization. We demonstrated interactions between OATP1B3 and OCT1 by co-immunoprecipitation with an anti-OATP1B3 antibody from human hepatocytes. In addition, we visualized the interaction using the Proximity Ligation Assay in both HEK293 cells and in frozen human liver sections. We investigated the functional consequences of OATP1B3 hetero-oligomerization by measuring the OATP1B3 plasma membrane expression and the uptake of the OATP1B3 selective substrate cholecystokinin-8 (CCK-8) in the absence and presence of OATP1B1, NTCP and OCT1.