Background Tennessee women experience the 12th highest breast cancer mortality in the United States. We examined the geographic differences in breast cancer incidence in Tennessee between Appalachian and non-Appalachian counties from 2005 to 2015. Methods We used ArcGIS 10.7 geospatial analysis and logistic regression on the Tennessee Cancer Registry incidence data for adult women aged ≥ 18 years (N = 59,287) who were diagnosed with breast cancer from 2005 to 2015 to evaluate distribution patterns by Appalachian county designation. The Tennessee Cancer Registry is a population-based, central cancer registry serving the citizens of Tennessee and was established by Tennessee law to collect and monitor cancer incidence. The main outcome was breast cancer stage at diagnosis. Independent variables were age, race, marital status, type of health insurance, and county of residence. Results Majority of the sample were White (85.5%), married (58.6%), aged ≥ 70 (31.3%) and diagnosed with an early stage breast cancer (69.6%). More than half of the women had public health insurance (54.2%), followed by private health insurance coverage (44.4%). Over half of the women resided in non-Appalachian counties, whereas 47.6% were in the Appalachian counties. We observed a significant association among breast cancer patients with respect to marital status and type of health insurance coverage (p =  < 0.0001). While the logistic regression did not show a significant result between county of residence and breast cancer incidence, the spatial analysis revealed geographic differences between Appalachian and non-Appalachian counties. The highest incidence rates of 997.49–1164.59/100,000 were reported in 6 Appalachian counties (Anderson, Blount, Knox, Rhea, Roane, and Van Buren) compared to 3 non-Appalachian counties (Fayette, Marshall, and Williamson). Conclusions There is a need to expand resources in Appalachian Tennessee to enhance breast cancer screening and early detection. Using geospatial techniques can further elucidate disparities that may be overlooked in conventional linear analyses to improve women’s cancer health and associated outcomes.

Novel synthetic cannabinoids are appearing in recreational drug markets worldwide. Pharmacological characterization of these new drugs is needed to inform clinicians, toxicologists, and policy makers who monitor public health. [1-(5-Fluoropentyl)-1H-indol-3-yl](1-naphthyl)methanone (AM-2201) is an abused synthetic cannabinoid that was initially created as a research tool for investigating the endocannabinoid system. Here we measured the pharmacodynamic effects of AM-2201 in rats, and simultaneously determined plasma pharmacokinetics for the parent drug and its metabolites. Male Sprague-Dawley rats were fitted with surgically implanted temperature transponders and indwelling jugular catheters under pentobarbital anesthesia. One week later, rats received subcutaneous injection of AM-2201 (0.1, 0.3, and 1.0 mg/kg) or its vehicle, and serial blood specimens were withdrawn via catheters. Core temperatures and catalepsy were measured just prior to each blood withdrawal, and plasma was assayed for drug and metabolites using liquid chromatography-tandem mass spectrometry. We found that AM-2201 produced dose-related hypothermia and catalepsy that peaked at 2 hours and lasted up to 8 hours. AM-2201 plasma concentrations rose linearly with increasing dose and ranged from 0.14 to 67.9 mg/l. Concentrations of three metabolites, AM-2201 N-(4-hydroxypentyl) (#0.17 mg/l), naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) N-(5-hydroxypentyl) (#1.14 mg/l), and JWH-018 N-pentanoic acid (#0.88 mg/l) were detectable but much lower. Peak AM-2201, JWH-018 N-(5-hydroxypentyl), and JWH-018 N-pentanoic acid concentrations occurred at 1.3, 2.4, and 6.5 hours, respectively. Concentrations of AM-2201, JWH-018 N-(5-hydroxypentyl), and JWH-018 N-pentanoic acid were negatively correlated with body temperature, but, given the low concentrations of metabolites detected, AM-2201 is likely the major contributor to pharmacodynamic effects under our experimental conditions.

AM-2201 is a popular synthetic cannabinoid first synthesized in 2000. AM-2201 pharmacokinetic and pharmacodynamic data are scarce, requiring further investigation. We developed a sensitive method for quantifying AM-2201 and 13 metabolites in plasma to provide a tool to further metabolic, pharmacokinetic and pharmacodynamic studies. Analysis was performed by liquid chromatography-tandem mass spectrometry. Chromatographic separation was performed by gradient elution on a biphenyl column with 0.1% formic acid in water/0.1% formic acid in acetonitrile:methanol 50:50 (v/v) mobile phase. Sample preparation (75 μL) consisted of an enzymatic hydrolysis and a supported liquid extraction. The method was validated with human plasma with a 0.025 or 0.050 – 50 μg/L working range, and cross-validated for rat plasma. Analytical recovery was 88.8 – 110.1% of target concentration, and intra- (n = 30) and inter-day (n = 30) imprecision <11.9% coefficient of variation. Method recoveries and matrix effects ranged from 58.4 – 84.4% and −62.1 to −15.6%, respectively. AM-2201 and metabolites were stable (±20%) at room temperature for 24 h, at 4°C for 72 h, and after three freeze-thaw cycles, and for 72 h in the autosampler after extraction. The method was developed for pharmacodynamic and pharmacokinetic studies with controlled administration in rats but is applicable for pre-clinical and clinical research and forensic investigations. Rat plasma specimen analysis following subcutaneous AM-2201 administration demonstrated the suitability of the method. AM-2201, JWH-018 N-(5-hydroxypentyl), and JWH-018 N-pentanoic acid concentrations were 4.8±1.0, 0.15±0.03, and 0.34±0.07 μg/L, respectively, 8h after AM-2201 administration at 0.3 mg/kg (n = 5).