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1.  Environmental Enrichment Alters Splenic Immune Cell Composition and Enhances Secondary Influenza Vaccine Responses in Mice 
Molecular Medicine  2014;20(1):179-190.
Chronic stress has deleterious effects on immune function, which can lead to adverse health outcomes. However, studies investigating the impact of stress reduction interventions on immunity in clinical research have yielded divergent results, potentially stemming from differences in study design and genetic heterogeneity, among other clinical research challenges. To test the hypothesis that reducing glucocorticoid levels enhances certain immune functions, we administered influenza vaccine once (prime) or twice (boost) to mice housed in either standard control caging or environmental enrichment (EE) caging. We have shown that this approach reduces mouse corticosterone production. Compared with controls, EE mice had significantly lower levels of fecal corticosterone metabolites (FCMs) and increased splenic B and T lymphocyte numbers. Corticosterone levels were negatively associated with the numbers of CD19+ (r2 = 0.43, p = 0.0017), CD4+ (r2 = 0.28, p = 0.0154) and CD8+ cells (r2 = 0.20, p = 0.0503). Vaccinated mice showed nonsignificant differences in immunoglobulin G (IgG) titer between caging groups, although EE mice tended to exhibit larger increases in titer from prime to boost than controls; the interaction between the caging group (control versus EE) and vaccine group (prime versus boost) showed a strong statistical trend (cage-group*vaccine-group, F = 4.27, p = 0.0555), suggesting that there may be distinct effects of EE caging on primary versus secondary IgG vaccine responses. Vaccine-stimulated splenocytes from boosted EE mice had a significantly greater frequency of interleukin 5 (IL-5)-secreting cells than boosted controls (mean difference 7.7, IL-5 spot-forming units/106 splenocytes, 95% confidence interval 0.24–135.1, p = 0.0493) and showed a greater increase in the frequency of IL-5–secreting cells from prime to boost. Our results suggest that corticosterone reduction via EE caging was associated with enhanced secondary vaccine responses, but had little effect on primary responses in mice. These findings help identify differences in primary and secondary vaccine responses in relationship to stress mediators that may be relevant in clinical studies.
doi:10.2119/molmed.2013.00158
PMCID: PMC4002849  PMID: 24687160
2.  Positive Affect in the Midst of Distress: Implications for Role Functioning 
Stress has been shown to deplete the self-regulation resources hypothesized to facilitate effective role functioning. However, recent research suggests that positive affect may help to replenish these vital self-regulation resources. Based on revised Stress and Coping theory and the Broaden-and-Build theory of positive emotion, three studies provide evidence of the potential adaptive function of positive affect in the performance of roles for participants experiencing stress. Participants were students (Study 1), caregivers of ill children (Study 2), and individuals recently diagnosed with HIV (Study 3). In cross sectional analyses, using role functioning as an indicator of self-regulation performance, we found that positive affect was significantly correlated with better self regulation performance, independent of the effects of negative affect. The effects were not as strong longitudinally, however, and there was little evidence of a reciprocal association between increases in positive affect and improvements in role functioning over time. The results provide some modest support for hypotheses stemming from the Broaden and Build model of positive emotion and revised Stress and Coping theory, both of which argue for unique adaptive functions of positive affect under stressful conditions.
doi:10.1002/casp.1133
PMCID: PMC3501106  PMID: 23175617
self-control; self-regulation; roles; relationships; positive emotions; affect
3.  Illness Appraisals and Depression in the First Year after HIV Diagnosis 
PLoS ONE  2013;8(10):e78904.
Illness appraisals provide important context to help understand the way individuals cope with chronic illness. In the present study, a qualitative approach to the analysis of HIV diagnosis experience narratives in a sample of 100 people newly diagnosed with HIV revealed five groups that differed in their initial illness appraisals: HIV as Chronic Illness, Concern about Dying, Stigmatization, Threat to Identity, and Other Threats Overshadow HIV. When compared on quantitatively measured depressive mood, the groups differed on level and trajectory over the course of the first year post-diagnosis. Although the experience of living with HIV has changed significantly with the advent of effective Antiretroviral Therapies (ART), there were a number of similarities between the appraisals of this group of participants who were diagnosed post ART and groups who were diagnosed before ART became widely available. Posttest counselors and other HIV service providers should take individual differences in illness appraisals into account in order to help newly HIV-positive clients manage their healthcare and cope adaptively with their diagnosis.
doi:10.1371/journal.pone.0078904
PMCID: PMC3808295  PMID: 24205346
4.  Cortisol Patterns Are Associated with T Cell Activation in HIV 
PLoS ONE  2013;8(7):e63429.
Objective
The level of T cell activation in untreated HIV disease is strongly and independently associated with risk of immunologic and clinical progression. The factors that influence the level of activation, however, are not fully defined. Since endogenous glucocorticoids are important in regulating inflammation, we sought to determine whether less optimal diurnal cortisol patterns are associated with greater T cell activation.
Methods
We studied 128 HIV-infected adults who were not on treatment and had a CD4+ T cell count above 250 cells/µl. We assessed T cell activation by CD38 expression using flow cytometry, and diurnal cortisol was assessed with salivary measurements.
Results
Lower waking cortisol levels correlated with greater T cell immune activation, measured by CD38 mean fluorescent intensity, on CD4+ T cells (r = −0.26, p = 0.006). Participants with lower waking cortisol also showed a trend toward greater activation on CD8+ T cells (r = −0.17, p = 0.08). A greater diurnal decline in cortisol, usually considered a healthy pattern, correlated with less CD4+ (r = 0.24, p = 0.018) and CD8+ (r = 0.24, p = 0.017) activation.
Conclusions
These data suggest that the hypothalamic-pituitary-adrenal (HPA) axis contributes to the regulation of T cell activation in HIV. This may represent an important pathway through which psychological states and the HPA axis influence progression of HIV.
doi:10.1371/journal.pone.0063429
PMCID: PMC3724863  PMID: 23922644
5.  Yoga Breathing for Cancer Chemotherapy–Associated Symptoms and Quality of Life: Results of a Pilot Randomized Controlled Trial 
Abstract
Background
Many debilitating symptoms arise from cancer and its treatment that are often unrelieved by established methods. Pranayama, a series of yogic breathing techniques, may improve cancer-related symptoms and quality of life, but it has not been studied for this purpose.
Objectives
A pilot study was performed to evaluate feasibility and to test the effects of pranayama on cancer-associated symptoms and quality of life.
Design
This was a randomized controlled clinical trial comparing pranayama to usual care.
Setting
The study was conducted at a university medical center.
Subjects
Patients receiving cancer chemotherapy were randomized to receive pranayama immediately or after a waiting period (control group).
Interventions
The pranayama intervention consisted of four breathing techniques taught in weekly classes and practiced at home. The treatment group received pranayama during two consecutive cycles of chemotherapy. The control group received usual care during their first cycle, and received pranayama during their second cycle of chemotherapy.
Outcome measures
Feasibility, cancer-associated symptoms (fatigue, sleep disturbance, anxiety, depression, stress), and quality of life were the outcomes.
Results
Class attendance was nearly 100% in both groups. Sixteen (16) participants were included in the final intent-to-treat analyses. The repeated-measures analyses demonstrated that any increase in pranayama dose, with dose measured in the number of hours practiced in class or at home, resulted in improved symptom and quality-of-life scores. Several of these associations—sleep disturbance (p=0.04), anxiety (p=0.04), and mental quality of life (p=0.05)—reached or approached statistical significance.
Conclusions
Yoga breathing was a feasible intervention among patients with cancer receiving chemotherapy. Pranayama may improve sleep disturbance, anxiety, and mental quality of life. A dose–response relationship was found between pranayama use and improvements in chemotherapy-associated symptoms and quality of life. These findings need to be confirmed in a larger study.
doi:10.1089/acm.2011.0555
PMCID: PMC3353818  PMID: 22525009
6.  Disclosure and Nondisclosure Among People Newly Diagnosed with HIV: An Analysis from a Stress and Coping Perspective 
AIDS Patient Care and STDs  2012;26(3):181-190.
Abstract
Disclosing HIV status to friends, family, and sex partners is often stressful. However, HIV disclosure has been associated with improved physical health, psychological well-being, and improved health behaviors. The aim of this study was to address some of the gaps in the literature regarding the disclosure process by conducting a mixed-methods study of disclosure in people newly diagnosed with HIV and the relationship of disclosure to stigma and social support. The CHAI (Coping, HIV, and Affect Interview) Study was a longitudinal cohort study that followed individuals who were newly diagnosed with HIV. The study took place from October 2004 to June 2008 in the San Francisco Bay Area. This sample includes data from 50 participants who were interviewed 1, 3, and 9 months following diagnosis with HIV. We identified four main approaches to HIV disclosure that revealed distinct differences in how participants appraised disclosure, whether disclosure was experienced as stressful, and whether disclosure or nondisclosure functioned as a way of coping with an HIV diagnosis. Implications of these findings for disclosure counseling are discussed.
doi:10.1089/apc.2011.0282
PMCID: PMC3286804  PMID: 22256856
7.  Acute Low Back Pain and Primary Care: How to Define Recovery and Chronification? 
Spine  2011;36(26):2316-2323.
Study Design
Prospective cohort study
Objective
to establish outcome measures for recovery and chronic pain for studies with patients that present with recent-onset acute low back pain in primary care
Summary of Background Data
Among back pain researchers, no consensus exists about outcome definitions or how to identify primary-care patients as not-recovered from an episode of low back pain. Cut points for outcome scales have mostly been arbitrarily chosen. Theoretical models for establishing minimal important change (MIC) values in studies of patients with low back pain have been proposed and need to be applied to real data.
Methods
In a sample of 521 patients which presented with acute low back pain (<4 weeks) in primary care clinics and were followed for 6 months, scores for pain and disability were compared with ratings on a global perceived effect scale. Using multiple potential “gold standards” as anchors (reference standards), the receiver operating characteristics method was used to determine optimal cut points for different ways of defining non-recovery from acute low back pain.
Results
MIC values and upper limits for pain and disability scores as well as minimal important percent changes are presented for five different definitions of recovery. A previously suggested 30% change from baseline scores does not accurately discriminate between recovered and not recovered patients in patients presenting with acute low back pain in primary care.
Conclusions
Outcome definitions that combine ratings from perceived recovery scales with pain and disability measures provide the highest accuracy in discriminating recovered from non-recovered patients.
doi:10.1097/BRS.0b013e31820c01a6
PMCID: PMC3100452  PMID: 21311400
Acute low back pain; primary care; outcome definitions; minimal important change; receiver operating characteristics
8.  A Positive Affect Intervention for People Experiencing Health-Related Stress: Development and Non-randomized Pilot Test 
Journal of health psychology  2011;17(5):676-692.
In this paper we present background, theoretical rationale, and pilot data on the development of an intervention designed to increase positive affect in people living with serious health-related stress. This proof-of-concept study demonstrated that a multiple-component positive affect intervention is feasible and acceptable for people newly diagnosed with HIV. Retention in the intervention and adherence to home practice were high. Participants reported significant increases in positive affect and significant decreases in negative affect. This positive affect intervention can serve as a template for programs to be developed to help people experiencing health-related and other types of life stress.
doi:10.1177/1359105311425275
PMCID: PMC3498769  PMID: 22021272
positive affect; stress; intervention; feasibility; chronic illness; HIV
9.  The Calm Mouse: An Animal Model of Stress Reduction 
Molecular Medicine  2012;18(1):606-617.
Chronic stress is associated with negative health outcomes and is linked with neuroendocrine changes, deleterious effects on innate and adaptive immunity, and central nervous system neuropathology. Although stress management is commonly advocated clinically, there is insufficient mechanistic understanding of how decreasing stress affects disease pathogenesis. Therefore, we have developed a “calm mouse model” with caging enhancements designed to reduce murine stress. Male BALB/c mice were divided into four groups: control (Cntl), standard caging; calm (Calm), large caging to reduce animal density, a cardboard nest box for shelter, paper nesting material to promote innate nesting behavior, and a polycarbonate tube to mimic tunneling; control exercise (Cntl Ex), standard caging with a running wheel, known to reduce stress; and calm exercise (Calm Ex), calm caging with a running wheel. Calm, Cntl Ex and Calm Ex animals exhibited significantly less corticosterone production than Cntl animals. We also observed changes in spleen mass, and in vitro splenocyte studies demonstrated that Calm Ex animals had innate and adaptive immune responses that were more sensitive to acute handling stress than those in Cntl. Calm animals gained greater body mass than Cntl, although they had similar food intake, and we also observed changes in body composition, using magnetic resonance imaging. Together, our results suggest that the Calm mouse model represents a promising approach to studying the biological effects of stress reduction in the context of health and in conjunction with existing disease models.
doi:10.2119/molmed.2012.00053
PMCID: PMC3388136  PMID: 22398685
10.  Hematopoietic Cell Transplant and Use of Massage for Improved Symptom Management: Results from a Pilot Randomized Control Trial 
Background. Pediatric hematopoietic cell transplant (HCT) is a lifesaving treatment that often results in physical and psychological discomfort. An acupressure-massage intervention may improve symptom management in this setting. Methods. This randomized controlled pilot trial compared a combined massage-acupressure intervention to usual care. Children were offered three practitioner-provided sessions per week throughout hospitalization. Parents were trained to provide additional acupressure as needed. Symptoms were assessed using nurses' reports and two questionnaires, the behavioral affective and somatic experiences scale and the Peds quality of life cancer module. Results. We enrolled 23 children, ages 5 to 18. Children receiving the intervention reported fewer days of mucositis (Hedges' g effect size ES = 0.63), lower overall symptom burden (ES = 0.26), feeling less tired and run-down (ES = 0.86), having fewer moderate/severe symptoms of pain, nausea, and fatigue (ES = 0.62), and less pain (ES = 0.42). The intervention group showed trends toward increasing contentness/serenity (ES = +0.50) and decreasing depression (ES = −0.45), but not decreased anxiety (ES = +0.42). Differences were not statistically significant. Discussion. Feasibility of studying massage-acupressure was established in children undergoing HCT. Larger studies are needed to test the efficacy of such interventions in reducing HCT-associated symptoms in children.
doi:10.1155/2012/450150
PMCID: PMC3292254  PMID: 22454665
11.  Use of Complementary Medicine in Pediatric Patients With Inflammatory Bowel Disease: Results From a Multicenter Survey 
Objectives
We examined the use of complementary and alternative medicine (CAM) at 3 US pediatric medical centers, comparing a group of children with inflammatory bowel disease (IBD) with children presenting with chronic constipation.
Materials and Methods
Surveys were administered by postal mail and at pediatric IBD centers in San Francisco, Houston, and Atlanta from 2001 to 2003. A comparison group consisting of pediatric patients with chronic constipation also was surveyed. Data were analyzed by t tests and by exact tests of contingency tables.
Results
In all, 236 surveys were collected from the IBD group; 126 surveys were collected from the chronic constipation comparison group. CAM therapies were used by 50% in the IBD group and 23% in the chronic constipation group. The overall regional breakdown of CAM use in IBD revealed no differences, although the types of CAM therapy used varied by site. The most commonly used CAM therapies in the IBD group were spiritual interventions (25%) and nutritional supplements (25%). Positive predictors for CAM use in IBD include the patient's self-reported overall health, an increase in the number of side effects associated with allopathic medications, white ethnicity, and parental education beyond high school.
Conclusions
This is the first US study to characterize CAM use in pediatric patients with IBD with another chronic gastrointestinal disorder. CAM use was twice as common with the IBD group compared with the chronic constipation group. Regional variations exist with the types of CAM therapy used. Practitioners should know that half of their pediatric patients with IBD may be using CAM in conjunction with or as an alternative to other treatments and that certain predictors can help identify those using CAM therapies.
doi:10.1097/MPG.0b013e318169330f
PMCID: PMC3250599  PMID: 19172124
Complementary and alternative medicine; Constipation; Inflammatory bowel disease; Survey study

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