Hormones and breast and endometrial cancers: preventive strategies and future research.

A number of hormonal approaches for prevention of endometrial and breast cancers have been proposed. Because of the hormonal responsiveness of both tumors, much attention has focused on effects of exogenous hormone use. Although estrogens in hormone replacement therapy increase the risk of endometrial cancer, the disease is substantially reduced by long-term use of oral contraceptives. The issues with breast cancer are more complex, mainly because of a variety of unresolved effects. Long-term estrogen use is associated with some increase in breast cancer risk, and certain patterns of oral contraceptives appear to predispose to early-onset disease. With respect to estrogens, preventive approaches for both tumors would include use for as limited periods of time as possible. Addition of a progestin appears to lower estrogen-associated endometrial disease, but its effect on breast cancer risk remains less clear. Additional studies on effects of detailed usage parameters should provide useful insights into etiologic mechanisms. Other preventive approaches for endometrial cancer that may work through hormonal mechanisms include staying thin, being physically active, and maintaining a vegetarian diet. Breast cancer risk may possibly be reduced by extended periods of breastfeeding, restriction of intake of alcoholic beverages, remaining thin later in life, and being physically active. Additional research is needed to clarify the biologic mechanisms of these associations. The bridging of epidemiology with the biologic sciences should clarify many unresolved issues and lead to better preventive approaches

A Test of Interventions to Increase Adherence to Hypertensive Medical Regimens

Low rates of adherence to hypertensive therapy limit patients' securing the full benefits of treatment. While some factors related to adherence have been identified, research on the effectiveness of interventions to increase adherence levels is sparse. The present study was designed to assess the impact of a series of different interventions on a group of some 400 patients, all under the care of private physicians in a small community. A factorial design was employed to deliver four, sequential educational interventions, about four months apart, to randomly selected sub-groups. Interviews before and after each intervention provided information concerning self-reported adherence, health status, health beliefs, and personal characteristics. Pertinent medical records and pharmacy data were also obtained. The first intervention—printed material—did not significantly affect adherence. The second and fourth interventions—nurse telephone calls and social support—each increased medication taking and the third intervention—self-monitoring—led to better weight control. There was no cumulative impact of the interventions and different aspects of regimens were not signiticantly related to one another.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67164/2/10.1177_109019818100800303.pd

Psychiatric symptoms and expression of glucocorticoid receptor gene in cocaine users: A longitudinal study

Background Chronic cocaine users (CU) display reduced peripheral expression of the glucocorticoid receptor gene (NR3C1), which is potentially involved in stress-related psychiatric symptoms frequently occurring in CU. However, it is unknown whether psychiatric symptoms and lower NR3C1 expression are related to each other and whether reduction of drug consumption reverse them. Method At baseline, NR3C1 mRNA expression was measured in 68 recreational CU, 30 dependent CU, and 68 stimulant-naïve controls. Additionally, the Revised Symptom Checklist (SCL-90R) and the Barratt Impulsiveness Scale (BIS) were assessed. At a one-year follow-up, the association between change in NR3C1 expression and psychiatric symptoms was examined in 48 stimulant-naïve controls, 19 CU who increased and 19 CU who decreased their consumption. At both test sessions, cocaine concentrations in hair samples were determined. Mixed-effects models were used to investigate how changes in drug use intensity affect severity of psychiatric symptoms and NR3C1 expression over time. Results At baseline, recreational and dependent CU displayed elevated impulsivity and considerable symptom burden across most of the SCL-90R subscales. Time-group interaction effects were found for several impulsivity scores, SCL-90R Global Severity Index, Paranoid Thoughts, and Depression subscales as well as for NR3C1 expression. Pairwise comparisons showed that decreasing CU specifically improved in these SCL-90R subscales, while their NR3C1 expression was adapted. Finally, changes in NR3C1 expression were negatively correlated with changes in impulsivity but not SCL-90R scores. Conclusion Our findings suggest that NR3C1 expression changes and some psychiatric symptoms are reversible upon reduction of cocaine intake, thus favouring abstinence-oriented treatment approaches

Effect of Injector Exit Geometry on Atomization of a Liquid-Liquid Double Swirl Coaxial Injector using Non-Invasive Laser, Optical, and X-ray Techniques

The spray characteristics of a liquid-liquid double swirl coaxial injector were studied using non-invasive optical, laser, and X-ray diagnostics. Phase Doppler interferometry was used to characterize droplet statistics and non-dimensional droplet parameters over a range of inlet conditions and for various fluids allowing for a study on the role of fluid properties on atomization. Based on the atomization statistics and observed trends from high-speed images, a description of breakup regimes over a range of Reynolds and Weber numbers was created. Next, X-ray computed tomography scans revealed that the spray cone was distinctively non-uniform and comprised of several pockets of increased mass concentration which varied with injection pressure. Finally, a parametric study of injector exit geometry demonstrated that spray breakup time, breakup type, and sheet stability could be controlled with exit geometry. Implications for these data on injector stability and atomization efficiency are discussed considering the desired performance characteristics of liquid-liquid rocket injectors

Disentangling craving‐ and valence‐related brain responses to smoking cues in individuals with nicotine use disorder

Tobacco smoking is one of the leading causes of preventable death and disease worldwide. Most smokers want to quit, but relapse rates are high. To improve current smoking cessation treatments, a better understanding of the underlying mechanisms of nicotine dependence and related craving behaviour is needed. Studies on cue-driven cigarette craving have been a particularly useful tool for investigating the neural mechanisms of drug craving. Here, functional neuroimaging studies in humans have identified a core network of craving-related brain responses to smoking cues that comprises of amygdala, anterior cingulate cortex, orbitofrontal cortex, posterior cingulate cortex and ventral striatum. However, most functional Magnetic Resonance Imaging (fMRI) cue-reactivity studies do not adjust their stimuli for emotional valence, a factor assumed to confound craving-related brain responses to smoking cues. Here, we investigated the influence of emotional valence on key addiction brain areas by disentangling craving- and valence-related brain responses with parametric modulators in 32 smokers. For one of the suggested key regions for addiction, the amygdala, we observed significantly stronger brain responses to the valence aspect of the presented images than to the craving aspect. Our results emphasize the need for carefully selecting stimulus material for cue-reactivity paradigms, in particular with respect to emotional valence. Further, they can help designing future research on teasing apart the diverse psychological dimensions that comprise nicotine dependence and, therefore, can lead to a more precise mapping of craving-associated brain areas, an important step towards more tailored smoking cessation treatments. Keywords: craving; cue-reactivity; functional Magnetic Resonance Imaging; neuroimaging; nicotine use disorder; smoking

Human tissue monitoring and specimen banking: opportunities for exposure assessment, risk assessment, and epidemiologic research

A symposium on Human Tissue Monitoring and Specimen Banking: Opportunities for Exposure Assessment, Risk Assessment, and Epidemiologic Research was held from 30 March to 1 April 1993 in Research Triangle Park, North Carolina. There were 117 registered participants from 18 states and 5 foreign countries. The first 2 days featured 21 invited speakers from the U.S. Environmental Protection Agency, the Centers for Disease Control and Prevention, the National Institute of Environmental Health Sciences, various other government agencies, and universities in the United States, Canada, Germany, and Norway. The speakers provided a state-of-the-art overview of human exposure assessment techniques (especially applications of biological markers) and their relevance to human tissue specimen banking. Issues relevant to large-scale specimen banking were discussed, including program design, sample design, data collection, tissue collection, and ethical ramifications. The final group of presentations concerned practical experiences of major specimen banking and human tissue monitoring programs in the United States and Europe. The symposium addressed the utility and research opportunities afforded by specimen banking programs for future research needs in the areas of human exposure assessment, risk assessment, and environmental epidemiology. The third day of the symposium consisted of a small workshop convened to discuss and develop recommendations to the U.S. Environmental Protection Agency regarding applications and utility of large-scale specimen banking, biological monitoring, and biological markers for risk assessment activities

Design and Fabrication of Oxygen/RP-2 Multi-Element Oxidizer-Rich Staged Combustion Thrust Chamber Injectors

As part of the Combustion Stability Tool Development project funded by the Air Force Space and Missile Systems Center, the NASA Marshall Space Flight Center was contracted to assemble and hot-fire test a multi-element integrated test article demonstrating combustion characteristics of an oxygen/hydrocarbon propellant oxidizer-rich staged-combustion engine thrust chamber. Such a test article simulates flow through the main injectors of oxygen/kerosene oxidizer-rich staged combustion engines such as the Russian RD-180 or NK-33 engines, or future U.S.-built engine systems such as the Aerojet-Rocketdyne AR-1 engine or the Hydrocarbon Boost program demonstration engine. On the current project, several configurations of new main injectors were considered for the thrust chamber assembly of the integrated test article. All the injector elements were of the gas-centered swirl coaxial type, similar to those used on the Russian oxidizer-rich staged-combustion rocket engines. In such elements, oxidizer-rich combustion products from the preburner/turbine exhaust flow through a straight tube, and fuel exiting from the combustion chamber and nozzle regenerative cooling circuits is injected near the exit of the oxidizer tube through tangentially oriented orifices that impart a swirl motion such that the fuel flows along the wall of the oxidizer tube in a thin film. In some elements there is an orifice at the inlet to the oxidizer tube, and in some elements there is a sleeve or "shield" inside the oxidizer tube where the fuel enters. In the current project, several variations of element geometries were created, including element size (i.e., number of elements or pattern density), the distance from the exit of the sleeve to the injector face, the width of the gap between the oxidizer tube inner wall and the outer wall of the sleeve, and excluding the sleeve entirely. This paper discusses the design rationale for each of these element variations, including hydraulic, structural, thermal, combustion performance, and combustion stability considerations. This paper also discusses the fabrication and assembly of the injector components, including the injector body/interpropellant plate, the additive manufactured GRCop-84 faceplate, and the pieces that make up the injector elements including the oxidizer tube, an inlet to the oxidizer tube, and a facenut that includes the fuel tangential inlets and forms the initial recessed volume where oxidizer and fuel first interact. Hot-fire test results of these main injector designs in an integrated test article that includes an oxidizer-rich preburner are described in companion papers at this JANNAF meeting

Plasma endocannabinoids in cocaine dependence and their interaction with cocaine craving and metabotropic glutamate receptor 5 density in the human brain

Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N=103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N=92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N=33; controls: N=43). In an additional analysis using$^{11}$C-ABP688 positron emission tomography (PET) in a male subsample (CU: N=18; controls: N=16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence