There have been few recent studies demonstrating a definitive association between the transmission of airborne infections and the ventilation of buildings. The severe acute respiratory syndrome (SARS) epidemic in 2003 and current concerns about the risk of an avian influenza (H5N1) pandemic, have made a review of this area timely. We searched the major literature databases between 1960 and 2005, and then screened titles and abstracts, and finally selected 40 original studies based on a set of criteria. We established a review panel comprising medical and engineering experts in the fields of microbiology, medicine, epidemiology, indoor air quality, building ventilation, etc. Most panel members had experience with research into the 2003 SARS epidemic. The panel systematically assessed 40 original studies through both individual assessment and a 2-day face-to-face consensus meeting. Ten of 40 studies reviewed were considered to be conclusive with regard to the association between building ventilation and the transmission of airborne infection. There is strong and sufficient evidence to demonstrate the association between ventilation, air movements in buildings and the transmission/spread of infectious diseases such as measles, tuberculosis, chickenpox, influenza, smallpox and SARS. There is insufficient data to specify and quantify the minimum ventilation requirements in hospitals, schools, offices, homes and isolation rooms in relation to spread of infectious diseases via the airborne route. PRACTICAL IMPLICATION: The strong and sufficient evidence of the association between ventilation, the control of airflow direction in buildings, and the transmission and spread of infectious diseases supports the use of negatively pressurized isolation rooms for patients with these diseases in hospitals, in addition to the use of other engineering control methods. However, the lack of sufficient data on the specification and quantification of the minimum ventilation requirements in hospitals, schools and offices in relation to the spread of airborne infectious diseases, suggest the existence of a knowledge gap. Our study reveals a strong need for a multidisciplinary study in investigating disease outbreaks, and the impact of indoor air environments on the spread of airborne infectious diseases.
P2Y receptors (P2YRs), a family of purinergic G-protein-coupled receptors (GPCRs), are activated by extracellular nucleotides. There are a total of eight distinct functional P2YRs expressed in human, which are subdivided into P2Y1-like receptors and P2Y12-like receptors1. Their ligands are generally charged molecules with relatively low bioavailability and stability in vivo2, which limits our under-standing of this receptor family. P2Y12R regulates platelet activation and thrombus formation3,4, and several antithrombotic drugs targeting P2Y12R—including the prodrugs clopidogrel (Plavix) and prasugrel (Effient) that are metabolized and bind covalently, and the nucleoside analogue ticagrelor (Brilinta) that acts directly on the receptor—have been approved for the prevention of stroke and myocardial infarction. However, limitations of these drugs (for example, a very long half-life of clopidogrel action and a characteristic adverse effect profile of ticagrelor)5,6 suggest that there is an unfulfilled medical need for developing a new generation of P2Y12R inhibitors7,8. Here we report the 2.6 Å resolution crystal structure of human P2Y12R in complex with a non-nucleotide reversible antagonist, AZD1283. The structure reveals a distinct straight conformation of helix V, which sets P2Y12R apart from all other known class A GPCR structures. With AZD1283 bound, the highly conserved disulphide bridge in GPCRs between helix III and extracellular loop 2 is not observed and appears to be dynamic. Along with the details of the AZD1283-binding site, analysis of the extracellular interface reveals an adjacent ligand-binding region and suggests that both pockets could be required for dinucleotide binding. The structure provides essential insights for the development of improved P2Y12R ligands and allosteric modulators as drug candidates.
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