Nicotinic Receptors Underlying Nicotine Dependence: Evidence from Transgenic Mouse Models.

Nicotine underlies the reinforcing properties of tobacco cigarettes and e-cigarettes. After inhalation and absorption, nicotine binds to various nicotinic acetylcholine receptor (nAChR) subtypes localized on the pre- and postsynaptic membranes of cells, which subsequently leads to the modulation of cellular function and neurotransmitter signaling. In this chapter, we begin by briefly reviewing the current understanding of nicotine's actions on nAChRs and highlight considerations regarding nAChR subtype localization and pharmacodynamics. Thereafter, we discuss the seminal discoveries derived from genetically modified mouse models, which have greatly contributed to our understanding of nicotine's effects on the reward-related mesolimbic pathway and the aversion-related habenulo-interpeduncular pathway. Thereafter, emerging areas of research focusing on modulation of nAChR expression and/or function are considered. Taken together, these discoveries have provided a foundational understanding of various genetic, neurobiological, and behavioral factors underlying the motivation to use nicotine and related dependence processes, which are thereby advancing drug discovery efforts to promote long-term abstinence

Social Relationships and Mortality Risk: A Meta-analytic Review

In a meta-analysis, Julianne Holt-Lunstad and colleagues find that individuals' social relationships have as much influence on mortality risk as other well-established risk factors for mortality, such as smoking

THE PSYCHOANALTIC VISION

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THE PSYCHOANALYTIC VISION

16,5 X 24,5 C

Troubled men: the psychology emotional conflicts, and therapy of men/ Fine

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Patient function, long-term survival, and use of surgery in patients with kidney cancer

BackgroundBeyond age and comorbidity, functionality can shape the long-term survival potential of patients with cancer. Accordingly, herein the authors compared mortality and receipt of cancer-directed surgery according to patient function among older adults with kidney cancer.MethodsUsing Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2000 through 2009, the authors studied 28,326 elderly subjects with primary kidney cancer. Patient function was quantified using function-related indicators, claims indicative of dysfunction and disability. Adjusting for patient and cancer characteristics, competing risk regression was used to assess the relationship between function-related indicator count and cause-specific mortality and then generalized estimating equations were used to quantify the probability of surgery.ResultsA total of 13,619 adult patients (48.1%) with at least 1 function-related indicator were identified. A higher indicator category was associated with older age, greater comorbidity, female sex, unmarried status, lower socioeconomic status, and higher stage of disease (P<.001). Compared with patients with an indicator count of 0, those with an indicator count of 1 (hazard ratio, 1.10; 95% confidence interval [95% CI], 1.04-1.16) and ≥2 (hazard ratio, 1.46; 95% CI, 1.39-1.53) were found to have higher other-cause mortality. Conversely, kidney cancer mortality varied minimally with patient function. Patients with ≥ 2 indicators received cancer-directed surgery less often than those without disability (odds ratio, 0.61; 95% CI, 0.56-0.66), although treatment probabilities remained high for patients with locoregional disease and low for those with metastatic cancer.ConclusionsAmong older adults with kidney cancer, functional health stands as a significant predictor of long-term survival. However, receipt of cancer-directed surgery appears largely determined by cancer stage. Patient function should be considered more heavily when determining treatment for older adults with kidney cancer. Cancer 2016;122:3776-3784. © 2016 American Cancer Society