Asymmetric Synthesis and Biological Screening of Quinoxaline-Containing Synthetic Lipoxin A4 Mimetics (QNX-sLXms).

Failure to resolve inflammation underlies many prevalent pathologies. Recent insights have identified lipid mediators, typified by lipoxins (LXs), as drivers of inflammation resolution, suggesting potential therapeutic benefit. We report the asymmetric preparation of novel quinoxaline-containing synthetic-LXA4-mimetics (QNX-sLXms). Eight novel compounds were screened for their impact on inflammatory responses. Structure-activity relationship (SAR) studies showed that (R)-6 (also referred to as AT-02-CT) was the most efficacious and potent anti-inflammatory compound of those tested. (R)-6 significantly attenuated lipopolysaccharide (LPS)- and tumor-necrosis-factor-α (TNF-α)-induced NF-κB activity in monocytes and vascular smooth muscle cells. The molecular target of (R)-6 was investigated. (R)-6 activated the endogenous LX receptor formyl peptide receptor 2 (ALX/FPR2). The anti-inflammatory properties of (R)-6 were further investigated in vivo in murine models of acute inflammation. Consistent with in vitro observations, (R)-6 attenuated inflammatory responses. These results support the therapeutic potential of the lead QNX-sLXm (R)-6 in the context of novel inflammatory regulators.

Guaranteed clean.

Patients' anxiety about hospital hygiene led nurses in Cumbriato devise reassuring welcome cards.

Incident reporting in one UK accident and emergency department.

Greater focus is needed on improving patient safety in modern healthcare systems and the first step to achieving this is to reliably identify the safety issues arising in healthcare. Research has shown the accident and emergency (A&E) department to be a particularly problematic environment where safety is a concern due to various factors, such as the range, nature and urgency of presenting conditions and the high turnover of patients. As in all healthcare environments clinical incident reporting in A&E is an important tool for detecting safety issues which can result in identifying solutions, learning from error and enhancing patient safety. This tool must be responsive and flexible to the local circumstances and work for the department to support the clinical governance agenda. In this paper, we describe the local processes for reporting and reviewing clinical incidents in one A&E department in a London teaching hospital and report recent changes to the system within the department. We used the historical data recorded on the Trust incident database as a representation of the information that would be available to the department in order to identify the high risk areas. In this paper, we evaluate the internal processes, the information available on the database and make recommendations to assist the emergency department in their internal processes. These will strengthen the internal review and staff feedback system so that the department can learn from incidents in a consistent manner. The process was reviewed by detailed examination of the centrally held electronic record (Datix database) of all incidents reported in a one year period. The nature of the incident and the level and accuracy of information provided in the incident reports was evaluated. There were positive aspects to the established system including evidence of positive changes made as a result of the reporting process, new initiatives to feedback to staff, and evolution of the programme for reporting and discussing the incidents internally. There appeared to be a mismatch between the recorded events and the category allocated to the incident in the historical record. In addition the database did not contain complete information for every incident, contributory factors were rarely recorded and relatively large numbers of incidents were recorded as "other" in the type of incident. There was also observed difficulty in updating the system as there is at least a months time lag between reporting or an incident and discussion/resolution of issues at the local departmental clinical risk management committee meetings. We used Leape's model for assessing the reporting system as a whole and found the system in the department to be relatively safe, fairly easy to use and moderately effective. Recommendations as a result of this study include the introduction of an electronic reporting system, limiting the number of staff who categorise the incidents--using clear definitions for classifications including a structured framework for contributory factors, and a process that allows incidents to be updated on the database locally after the discussion. This research may have implications for the incident reporting process in other specialities as well as in other hospitals.