The primary objective of this project was to determine the a4b2* nicotinic acetylcholine receptor (nAChR) occupancy in human brain of a single low dose of varenicline (0.5 mg), and to explore the relationship between receptor occupancy by varenicline and tobacco withdrawal symptoms (*denoting other putative nAChR subunits). Otherwise healthy smokers (n ¼ 9) underwent two positron emission tomography (PET) sessions with the selective a4b2* radioligand 2-FA. For the PET sessions, participants received either a low dose of varenicline (0.5 mg) or matching placebo pill (double-blind, random order) before imaging. For both sessions, participants received bolus plus continuous infusions of 2-FA, were scanned for 1 h after allowing the radiotracer to reach a steady state, smoked to satiety, and were scanned for 2 more hours. We estimated the fractional receptor occupancy by a single dose of varenicline (0.5 mg) and the corresponding varenicline dissociation constant (K V ), along with the effect of low-dose varenicline, pill placebo, and smoking-to-satiety on withdrawal rating scales. The data are compatible with 100% occupancy of a4b2* nAChRs by a single dose of varenicline, with a 90% lower confidence limit of 89% occupancy for the thalamus and brainstem. The corresponding 90% upper limit on effective K V with respect to plasma varenicline was 0.49 nM. Smoking to satiety, but not low-dose varenicline, significantly reduced withdrawal symptoms. Our findings demonstrate that low-dose varenicline results in saturation of a4b2* nAChRs in the thalamus and brainstem without reducing withdrawal symptoms.

The United States Latino population is growing at a rapid pace and is set to reach nearly 30% by 2050. The demand for culturally and linguistically competent health care is increasing in lockstep with this growth; however, the supply of doctors with skills and experience suited for this care is lagging. In particular, there is a major shortage of Latino Spanish-speaking physicians, and the gap between demand and supply is widening. The implementation of the Affordable Care Act (ACA) has increased the capacity of the US healthcare system to care for the growing Latino Spanish-speaking population, through health insurance exchanges, increased funding for safety net institutions, and efforts to improve efficiency and coordination of care, particularly with Accountable Care Organizations and the Hospital Readmissions Reduction Program. With these policies in mind, the authors discuss how the value of Latino Spanish-speaking physicians to the healthcare system has increased under the environment of the ACA. In addition, the authors highlight key efforts to increase the supply of this physician population, including the implementation of the Deferred Action for Childhood Arrivals Act, premedical pipeline programs, and academic medicine and medical school education initiatives to increase Latino representation among physicians.