The oxylipin analog CS585 prevents platelet activation and thrombosis through activation of the prostacyclin receptor.

Cardiovascular disease remains the primary cause of morbidity and mortality globally. Platelet activation is critical for maintaining hemostasis and preventing the leakage of blood cells from the vessel. There has been a paucity in the development of new drugs to target platelet reactivity. Recently, the oxylipin 12(S)-hydroxy-eicosatrienoic acid (12-HETrE), which is produced in platelets, was shown to limit platelet reactivity by activating the prostacyclin receptor. Here, we demonstrated the synthesis of a novel analog of 12-HETrE, known as CS585. Human blood and mouse models of hemostasis and thrombosis were assessed for the ability of CS585 to attenuate platelet activation and thrombosis without increasing the risk of bleeding. Human platelet activation was assessed using aggregometry, flow cytometry, western blot analysis, total thrombus formation analysis system, microfluidic perfusion chamber, and thromboelastography. Hemostasis, thrombosis, and bleeding assays were performed in mice. CS585 was shown to potently target the prostacyclin receptor on the human platelet, resulting in a highly selective and effective mechanism for the prevention of platelet activation. Furthermore, CS585 was shown to inhibit platelet function in human whole blood ex vivo, prevent thrombosis in both small and large vessels in mouse models, and exhibit long-lasting prevention of clot formation. Finally, CS585 was not observed to perturb coagulation or increase the risk of bleeding in the mouse model. Hence, CS585 represents a new validated target for the treatment of thrombotic diseases without the risk of bleeding or off-target activation observed with other prostaglandin receptor agonists.

Exploring the relationship between strip clubs and rates of sexual violence and violent crime.

AIMS: We examined whether (a) the number of strip clubs per capita and (b) the proportion of clubs with "high-risk characteristics" were significantly associated with rates of sexual violence (SV) and other violent crime at the county level. METHODS: Using large, public data sets, we tested effects across 926 counties (13 U.S. states), controlling for percent below the poverty line and alcohol outlets per capita. RESULTS: We found that rates of strip clubs were significantly associated with violent crime, but not SV, in all but one model (accounting for Saturday hours). Counties with greater proportions of "high-risk" strip clubs (i.e., greater days and hours of operation, drink specials, full-nudity policies, or private rooms) have higher rates of SV. All models, except the full-nudity policy model, demonstrated increased rates of violent crime. CONCLUSIONS: These results provide information for community-level violence prevention and equips stakeholders with information to create safer communities.

Mortality risk in a sample of emergency department patients who use cocaine with alcohol and/or cannabis.

BACKGROUND: Illicit drug use is common among emergency department (ED) patients, yet the association between drug use and subsequent mortality is not well understood. This study examines 36-month mortality rates for a sample of ED patients based on reported use of alcohol, cannabis, and cocaine, both individually and in combination. METHODS: Patients (N = 1669) from 2 urban EDs were surveyed at the time of the visit. The patient survey included the Alcohol Smoking and Substance Involvement Screening Test (ASSIST) and information on physical and mental health, health care utilization, and risk factors associated with substance use. ASSIST scores were used to categorize patients into drug risk groups. Mortality information from the National Death Index was used to calculate mortality rates from 2009 to 2012. A Cox regression model identified associations between drug risk groups and mortality while controlling for patient demographics. RESULTS: The use of cocaine and cannabis both individually and in combination was associated with significantly higher mortality risk compared with other ED patients. CONCLUSIONS: ED patients who use cannabis and cocaine have higher mortality risks than other patients. Further research is necessary to determine whether this result is stable across racial/ethnic groups.