PURPOSE Psychotropic drug consumption as a proxy measure of mental health problems during a disability pension process has only been studied among awarded applicants. This study examined psychotropic drug purchase trajectories among awarded and rejected disability pension applicants. Analyses were conducted in different diagnostic and sociodemographic groups. METHODS A representative 70% sample of Finnish adults applying for disability pension due to a mental disorder in 2009-2011 (N = 18,087) was followed for 4 years in 3-month periods both before and after the pension decision. Register data on purchased drugs measured in defined daily doses (DDDs), gender, age, occupational class, unemployment history, and diagnostic group were used. The DDD levels and trends were analyzed using growth curve models. RESULTS Psychotropic drug purchases increased before the pension decision and decreased gradually thereafter among both awarded and rejected applicants. The average DDD level was higher for rejected than awarded applicants before the decision but lower thereafter. The high pre-decision level for rejected applicants was explicit with a lower socioeconomic status. The pre-decision increase in DDDs was steeper for awarded applicants. Changes in DDDs before and after the decision were most prominent for depression, bipolar disorders, schizophrenia, and anxiety disorders. CONCLUSION Awarded and rejected disability pension applicants differed partly in their trajectories of psychotropic drug consumption. For awarded applicants, the steep rise of consumption prior to the award possibly reflects worsening occupational capacity. Early high consumption for rejected applicants signals long running mental health problems and calls for earlier support.BACKGROUND Frail elderly women with nonmetastatic hormone receptor-positive breast cancer often receive primary endocrine therapy. Limited data are available on the outcomes associated with this population and treatment approach. CRT0066101 purchase METHODS We selected patients with an initial primary diagnosis of stage I-III ER-positive breast cancer from 2001 to 2015 in Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Patients were excluded if they received surgery, radiation, chemotherapy, or other targeted drug treatment including anti-HER2 agents. Two Cox proportional-hazards models were constructed to determine the predictors of breast cancer-specific survival and overall survival after a cancer diagnosis. RESULTS A total of 552 patients were identified, with 82.1% of the patients being 80 years or older and 81.7% of patients being non-Hispanic White. PR positive (OR 1.77; 95% CI 1.09-2.85; p = 0.025) and tumor size larger than 50 mm (OR 1.99; 95% CI 1.05-3.75; p = 0.035) were associated with higher adherence to endocrine therapy. In the multivariable Cox analyses, patients who were adherent of endocrine therapy had significantly worse survival (HR 1.40; 95% CI 1.17-1.69; p  less then  0.001). The other two factors associated with worse survival were larger tumor size and more comorbidities. The competing risk model demonstrated no statistically significant difference between patients who were adherent to endocrine therapy and those who were not in terms of risk of dying from breast cancer. CONCLUSION In elderly women with localized ER-positive breast cancer, there were no statistically significant differences in breast cancer-specific or overall mortality between those who were adherent to endocrine therapy and those who were not.Bitter taste receptors (T2Rs) are GPCRs involved in detection of bitter compounds by type 2 taste cells of the tongue, but are also expressed in other tissues throughout the body, including the airways, gastrointestinal tract, and brain. These T2Rs can be activated by several bacterial products and regulate innate immune responses in several cell types. Expression of T2Rs has been demonstrated in immune cells like neutrophils; however, the molecular details of their signaling are unknown. We examined mechanisms of T2R signaling in primary human monocyte-derived unprimed (M0) macrophages (M[Formula see text]s) using live cell imaging techniques. Known bitter compounds and bacterial T2R agonists activated low-level calcium signals through a pertussis toxin (PTX)-sensitive, phospholipase C-dependent, and inositol trisphosphate receptor-dependent calcium release pathway. These calcium signals activated low-level nitric oxide (NO) production via endothelial and neuronal NO synthase (NOS) isoforms. NO production increased cellular cGMP and enhanced acute phagocytosis ~ threefold over 30-60 min via protein kinase G. In parallel with calcium elevation, T2R activation lowered cAMP, also through a PTX-sensitive pathway. The cAMP decrease also contributed to enhanced phagocytosis. Moreover, a co-culture model with airway epithelial cells demonstrated that NO produced by epithelial cells can also acutely enhance M[Formula see text] phagocytosis. Together, these data define M[Formula see text] T2R signal transduction and support an immune recognition role for T2Rs in M[Formula see text] cell physiology.Risk of relapse is a major challenge in the treatment of substance use disorders. Several types of learning and memory mechanisms are involved in substance use and have implications for relapse. Associative memories form between the effects of drugs and the surrounding environmental stimuli, and exposure to these stimuli during abstinence causes stress and triggers drug craving, which can lead to relapse. Understanding the neural underpinnings of how these associations are formed and maintained will inform future advances in treatment practices. A large body of research has expanded our knowledge of how associative memories are acquired and consolidated, how they are updated through reactivation and reconsolidation, and how competing extinction memories are formed. This review will focus on the vast literature examining the mechanisms of cocaine Pavlovian associative memories with an emphasis on the molecular memory mechanisms and circuits involved in the consolidation, reconsolidation, and extinction of these memories.