Background The surveillance and effector functions of the immune system are critically dependent on the appropriate distribution of immune cells in the body. An acute or short-term stress response induces a rapid and significant redistribution of immune cells among different body compartments. Stress-induced leukocyte redistribution may be a fundamental survival response that directs leukocyte subpopulations to specific target organs during stress, and significantly enhances the speed, efficacy and regulation of an immune response. Immune responses are generally enhanced in compartments (e.g., skin) that are enriched with leukocytes, and suppressed in compartments that are depleted of leukocytes during/following stress. The experiments described here were designed to elucidate the: 1) Time-course, trajectory, and subpopulation-specificity of stress-induced mobilization and trafficking of blood leukocytes. 2) Individual and combined actions of the principal stress hormones, norepinephrine (NE), epinephrine (EPI), and corticosterone (CORT), in mediating mobilization or trafficking of specific leukocyte subpopulations. 3) Effects of stress/stress hormones on adhesion molecule, L-selectin (CD62L), expression by each subpopulation to assess its adhesion / functional / maturation status. Methods Male Sprague Dawley rats were stressed (short-term restraint, 2–120 min), or adrenalectomized and injected with vehicle (VEH), NE, EPI, CORT, or their combinations, and blood was collected for measurement of hormones and flow cytometric quantification of leukocyte subpopulations. Results Acute stress induced an early increase/mobilization of neutrophils, lymphocytes, helper T cells (Th), cytolytic T cells (CTL), and B cells into the blood, followed by a decrease/trafficking of all cell types out of the blood, except neutrophil numbers that continued to increase. CD62L expression was increased on neutrophils, decreased on Th, CTL, and natural killer (NK) cells, and showed a biphasic decrease on monocytes & B cells, suggesting that CD62L is involved in mediating the redistribution effects of stress. Additionally, we observed significant differences in the direction, magnitude, and subpopulation specificity of the effects of each hormone: NE increased leukocyte numbers, most notably CD62L−/+ neutrophils and CD62L− B cells. EPI increased monocyte and neutrophil numbers, most notably CD62L−/+ neutrophils and CD62L− monocytes, but decreased lymphocyte numbers with CD62L−/+ CTL and CD62L+ B cells being especially sensitive. CORT decreased monocyte, lymphocyte, Th, CTL, and B cell numbers with CD62L− and CD62L+ cells being equally affected. Thus, naïve (CD62L+) vs. memory (CD62L−) T cells, classical (CD62L+) vs. non-classical (CD62L−) monocytes, and similarly distinct functional subsets of other leukocyte populations are differentially mobilized into the blood and trafficked to tissues by stress hormones. Conclusion Stress hormones orchestrate a large-scale redistribution of immune cells in the body. NE and EPI mobilize immune ...

A B S T R A C T PurposeNumerous studies have examined the comorbidity of depression with cancer, and some have indicated that depression may be associated with cancer progression or survival. However, few studies have assessed whether changes in depression symptoms are associated with survival. MethodsIn a secondary analysis of a randomized trial of supportive-expressive group therapy, 125 women with metastatic breast cancer (MBC) completed a depression symptom measure (Center for Epidemiologic Studies-Depression Scale [CES-D]) at baseline and were randomly assigned to a treatment group or to a control group that received educational materials. At baseline and three follow-up points, 101 of 125 women completed a depression symptom measure. We used these data in a Cox proportional hazards analysis to examine whether decreasing depression symptoms over the first year of the study (the length of the intervention) would be associated with longer survival. ResultsMedian survival time was 53.6 months for women with decreasing CES-D scores over 1 year and 25.1 months for women with increasing CES-D scores. There was a significant effect of change in CES-D over the first year on survival out to 14 years (P ϭ .007) but no significant interaction between treatment condition and CES-D change on survival. Neither demographic nor medical variables explained this association. ConclusionDecreasing depression symptoms over the first year were associated with longer subsequent survival for women with MBC in this sample. Further research is necessary to confirm this hypothesis in other samples, and causation cannot be assumed based on this analysis. J Clin

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These findings show that better sleep efficiency and less sleep disruption are significant independent prognostic factors in women with advanced breast cancer. Further research is needed to determine whether treating sleep disruption with cognitive behavioral and/or pharmacologic therapy could improve survival in women with advanced breast cancer.

ObjectiveThough most patients wish to discuss end-of-life (EOL) issues, doctors are reluctant to conduct end-of-life conversations. Little is known about the barriers doctors face in conducting effective EOL conversations with diverse patients. This mixed methods study was undertaken to empirically identify barriers faced by doctors (if any) in conducting effective EOL conversations with diverse patients and to determine if the doctors’ age, gender, ethnicity and medical sub-specialty influenced the barriers reported.DesignMixed-methods study of multi-specialty doctors caring for diverse, seriously ill patients in two large academic medical centers at the end of the training; data were collected from 2010 to 2012.OutcomesDoctor-reported barriers to EOL conversations with diverse patients.Results1040 of 1234 potential subjects (84.3%) participated. 29 participants were designated as the development cohort for coding and grounded theory analyses to identify primary barriers. The codes were validated by analyses of responses from 50 randomly drawn subjects from the validation cohort (n= 996 doctors). Qualitative responses from the validation cohort were coded and analyzed using quantitative methods. Only 0.01 % doctors reported no barriers to conducting EOL conversations with patients. 99.99% doctors reported barriers with 85.7% finding it very challenging to conduct EOL conversations with all patients and especially so with patients whose ethnicity was different than their own. Asian-American doctors reported the most struggles (91.3%), followed by African Americans (85.3%), Caucasians (83.5%) and Hispanic Americans (79.3%) in conducting EOL conversations with their patients. The biggest doctor-reported barriers to effective EOL conversations are (i) language and medical interpretation issues, (ii) patient/family religio-spiritual beliefs about death and dying, (iii) doctors’ ignorance of patients’ cultural beliefs, values and practices, (iv) patient/family's cultural differences in truth handling and decision making, (v) patients’ limited health literacy and (vi) patients’ mistrust of doctors and the health care system. The doctors' ethnicity (Chi-Square = 12.77, DF = 4, p = 0.0125) and medical subspecialty (Chi-Square = 19.33, DF = 10, p =0.036) influenced their reported barriers. Friedman’s test used to examine participants relative ranking of the barriers across sub-groups identified significant differences by age group (F statistic = 303.5, DF = 5, p < 0.0001) and medical sub-specialty (F statistic =163.7, DF = 5, p < 0.0001).Conclusions and RelevanceDoctors report struggles with conducting effective EOL conversations with all patients and especially with those whose ethnicity is different from their own. It is vital to identify strategies to mitigate barriers doctors encounter in conducting effective EOL conversations with seriously ill patients and their families.

These results augment the growing literature supporting the use of hypnosis as an adjunctive treatment for medical patients experiencing pain.

PAWSS has excellent psychometric characteristics and predictive value among medically ill hospitalized patients, helping clinicians identify those at risk for complicated AWS and allowing for prevention and timely treatment of complicated AWS.

Women who consume folic acid in early pregnancy reduced their risks for delivering offspring with neural tube defects (NTDs). The underlying process by which folic acid facilitated this risk reduction is unknown. Investigating genetic variation that influences cellular absorption, transport, and metabolism of folate will help fill this data gap. We focused our studies on a candidate gene that is involved in folate transport, the reduced folate carrier 1 (RFC1). Using data from a California population-based case control interview study (1989-1991 birth cohorts), we investigated whether spina bifida risk was influenced by an interaction between a polymorphism of infant RFC1 at nucleotide 80 (A80G) and maternal periconceptional use of vitamins containing folic acid. Allelic variants of RFC1 were determined by genotyping 133 live-born spina bifida case infants and 188 control infants. The percentages of case infants with the A80/A80, G80/G80, and G80/A80 genotypes were 27.2%, 28.0%, and 44.7%, respectively. The percentages of control infants were similar: 26.1%, 29.3%, and 44.7%. Odds ratios of 1.0 (95% confidence interval 0.5-2.0) for the G80/G80 genotype and 1.1 (0.6-2.0) for the G80/A80 genotype were observed relative to the A80/A80 genotype. Among mothers who did not use vitamins, spina bifida risk was 2.4 (0.8-6.9) for infants with genotype G80/G80 compared to those with A80/A80 genotype. Among mothers who did use vitamins, the risk was 0.5 (0.1-3.1) for infants with the G80/G80 genotype. Although this study did not find an increased spina bifida risk for infants who were heterozygous or homozygous for RFC1 A80G, it did reveal modest evidence for a gene-nutrient interaction between infant homozygosity for the RFC1 G80/G80 genotype and maternal periconceptional intake of vitamins containing folic acid on the risk of spina bifida.