Faculty Bibliography

The purpose of this study was to evaluate for differences in occurrence and severity ratings of sleep disturbance, fatigue, and decreased energy in women who reported breast pain prior to surgery for breast cancer. Of the 390 women who completed self-report measures for each symptom, 28.2% reported pain in their breast prior to surgery. A higher percentage of women in the pain group (i.e., 66.7% versus 53.5%) reported clinically meaningful levels of sleep disturbance. However, no between group differences were found in the severity of sleep disturbance, fatigue, or decreased energy. Findings from this study suggest that sleep disturbance, fatigue, and decreased levels of energy are significant problems for women prior to breast cancer surgery. Future studies need to evaluate for specific characteristics that place women at greater risk for these symptoms as well as the mechanisms that underlie these symptoms.

PURPOSE: Depressive symptoms are common in cancer patients and their family caregivers (FCs). While these symptoms are characterized by substantial interindividual variability, the factors that predict this variability remain largely unknown. This study sought to confirm latent classes of oncology patients and FCs with distinct depressive symptom trajectories and to examine differences in phenotypic and genotypic characteristics among these classes. METHOD: Among 167 oncology outpatients with breast, prostate, lung, or brain cancer and 85 of their FCs, growth mixture modeling (GMM) was used to identify latent classes of individuals based on Center for Epidemiological Studies-Depression (CES-D) scores obtained prior to, during, and for four months following completion of radiation therapy. One hundred four single nucleotide polymorphisms (SNPs) and haplotypes in 15 candidate cytokine genes were interrogated for differences between the two largest latent classes. Multivariate logistic regression analyses assessed effects of phenotypic and genotypic characteristics on class membership. RESULTS: Four latent classes were confirmed: Resilient (56.3%), Subsyndromal (32.5%), Delayed (5.2%), and Peak (6.0%). Participants who were younger, female, non-white, and who reported higher baseline trait and state anxiety were more likely to be in the Subsyndromal, Delayed, or Peak groups. Variation in three cytokine genes (i.e., interleukin 1 receptor 2 [IL1R2], IL10, tumor necrosis factor alpha [TNFA]), age, and performance status predicted membership in the Resilient versus Subsyndromal classes. CONCLUSIONS: Findings confirm the four latent classes of depressive symptom trajectories previously identified in a sample of breast cancer patients. Variations in cytokine genes may influence variability in depressive symptom trajectories.

OBJECTIVE: HIV infection and illicit drug use are each associated with diminished cognitive performance. This study examined the separate and interactive effects of HIV and recent illicit drug use on verbal memory, processing speed, and executive function in the multicenter Women's Interagency HIV Study. METHODS: Participants included 952 HIV-infected and 443 HIV-uninfected women (mean age = 42.8, 64% African-American). Outcome measures included the Hopkins Verbal Learning Test-Revised and the Stroop test. Three drug use groups were compared: recent illicit drug users (cocaine or heroin use in past 6 months, n = 140), former users (lifetime cocaine or heroin use but not in past 6 months, n = 651), and nonusers (no lifetime use of cocaine or heroin, n = 604). RESULTS: The typical pattern of recent drug use was daily or weekly smoking of crack cocaine. HIV infection and recent illicit drug use were each associated with worse verbal learning and memory (P < 0.05). Importantly, there was an interaction between HIV serostatus and recent illicit drug use such that recent illicit drug use (compared with nonuse) negatively impacted verbal learning and memory only in HIV-infected women (P < 0.01). There was no interaction between HIV serostatus and illicit drug use on processing speed or executive function on the Stroop test. CONCLUSIONS: The interaction between HIV serostatus and recent illicit drug use on verbal learning and memory suggests a potential synergistic neurotoxicity that may affect the neural circuitry underlying performance on these tasks.

MicroRNAs (miRs) are epigenetic regulators of messenger RNAs' (mRNA) expression of polypeptides. As such, miRs represent an intriguing mechanism by which gene-environment interactions are hypothesized to occur on the level of epigenetic control over gene expression. In addition to promising findings from in vitro studies indicating that miRs have the potential to function as therapeutic agents in modifying the course of pathophysiologic conditions, recent human studies revealed changes in miR expression patterns in response to behavioral interventions. The authors provide an overview of how miRs are preserved and isolated from other genetic material and describe commonly used methods for measuring miR in the research setting, including Northern blot, polymerase chain reaction, and microarray. The authors also introduce bioinformatic approaches to analysis of high-throughput miR expression and techniques used to create predictive models of miR-mRNA binding to describe possible physiologic pathways affected by specific miRs.

PURPOSE OF THE RESEARCH: Little is known about the relationships between pain, anxiety, and depression in women prior to breast cancer surgery. The purpose of this study was to evaluate for differences in anxiety, depression, and quality of life (QOL) in women who did and did not report the occurrence of breast pain prior to breast cancer surgery. We hypothesized that women with pain would report higher levels of anxiety and depression as well as poorer QOL than women without pain. METHODS AND SAMPLE: A total of 390 women completed self-report measures of pain, anxiety depression, and QOL prior to surgery. KEY RESULTS: Women with preoperative breast pain (28%) were significantly younger, had a lower functional status score, were more likely to be Non-white and to have gone through menopause. Over 37% of the sample reported clinically meaningful levels of depressive symptoms. Almost 70% of the sample reported clinically meaningful levels of anxiety. Patients with preoperative breast pain reported significantly higher depression scores and significantly lower physical well-being scores. No between group differences were found for patients' ratings of state and trait anxiety or total QOL scores. CONCLUSIONS: Our a priori hypotheses were only partially supported. Findings from this study suggest that, regardless of pain status, anxiety and depression are common problems in women prior to breast cancer surgery.

PURPOSE: To introduce current and emerging approaches that are being utilized in the field of genomics so the reader can conceptually evaluate the literature and appreciate how these approaches are advancing our understanding of health-related issues. ORGANIZING CONSTRUCT: Each approach is described and includes information related to how it is advancing research, its potential clinical utility, exemplars of current uses, challenges related to technologies used for these approaches, and when appropriate information related to understanding the evidence base for clinical utilization of each approach is provided. Web-based resources are included for the reader who would like more in-depth information and to provide opportunity to stay up to date with these approaches and their utility. CONCLUSIONS: The chosen approaches-genome sequencing, genome-wide association studies, epigenomics, and gene expression-are extremely valuable approaches for collecting research data to help us better understand the pathophysiology of a variety of health-related conditions, but they are also gaining in utility for clinical assessment and testing purposes. CLINICAL RELEVANCE: Our increased understanding of the molecular underpinnings of disease will assist with better development of screening tests, diagnostic tests, tests that allow us to prognosticate, tests that allow for individualized treatments, and tests to facilitate post-treatment surveillance.

CONTEXT: Sleep disturbance is a problem for oncology patients. OBJECTIVES: To evaluate how sleep disturbance and daytime sleepiness (DS) changed from before to six months following surgery and whether certain characteristics predicted initial levels and/or the trajectories of these parameters. METHODS: Patients (n=396) were enrolled prior to surgery and completed monthly assessments for six months following surgery. The General Sleep Disturbance Scale was used to assess sleep disturbance and DS. Using hierarchical linear modeling, demographic, clinical, symptom, and psychosocial adjustment characteristics were evaluated as predictors of initial levels and trajectories of sleep disturbance and DS. RESULTS: All seven General Sleep Disturbance Scale scores were above the cutoff for clinically meaningful levels of sleep disturbance. Lower performance status; higher comorbidity, attentional fatigue, and physical fatigue; and more severe hot flashes predicted higher preoperative levels of sleep disturbance. Higher levels of education predicted higher sleep disturbance scores over time. Higher levels of depressive symptoms predicted higher preoperative levels of sleep disturbance, which declined over time. Lower performance status; higher body mass index; higher fear of future diagnostic tests; not having had sentinel lymph node biopsy; having had an axillary lymph node dissection; and higher depression, physical fatigue, and attentional fatigue predicted higher DS prior to surgery. Higher levels of education, not working for pay, and not having undergone neo-adjuvant chemotherapy predicted higher DS scores over time. CONCLUSION: Sleep disturbance is a persistent problem for patients with breast cancer. The effects of interventions that can address modifiable risk factors need to be evaluated.

CONTEXT: Fatigue is a prevalent symptom among adults living with HIV. There is increasing evidence that fatigue and energy are related, yet distinct constructs. Although HIV-related fatigue has been well studied, little is known about perceived energy and how it relates to fatigue, individual characteristics, and other symptoms. OBJECTIVES: To describe the experience of perceived energy in adults with HIV and evaluate its relationship to demographic and clinical characteristics as well as symptoms of fatigue, sleep disturbance, anxiety, depression, and daytime function. METHODS: The design was descriptive, comparative, and correlational. The sample of 318 adults with HIV completed a demographic questionnaire; the Memorial Symptom Assessment Scale; and measures of fatigue, sleep disturbance, anxiety, depressive symptoms, and daytime function. Medical records were reviewed for disease and treatment data. Participants who reported a lack of energy were compared with those who did not on demographic, clinical, and symptom variables. Regression models of perceived energy and its interference with daytime function also were evaluated. RESULTS: Perceived lack of energy was highly prevalent (65%) and more strongly related to interference with daytime function than more general measures of fatigue severity, even when controlling for other characteristics and symptoms. Like other aspects of fatigue, lack of energy was associated with sleep disturbance, anxiety, and depressive symptoms. Lack of energy was more strongly related to morning fatigue than to evening fatigue. CONCLUSION: Lack of energy interferes with daytime function and is not just the inverse of fatigue but a distinct perception that differs from fatigue.

BACKGROUND: Mortality rates for cancer are decreasing in patients under 60 and increasing in those over 60 years of age. The reasons for these differences in mortality rates remain poorly understood. One explanation may be that older patients received substandard treatment because of concerns about adverse effects. Given the paucity of research on the multiple dimensions of the symptom experience in older oncology patients, the purpose of this study was to evaluate for differences in ratings of symptom occurrence, severity, frequency, and distress between younger (< 60 years) and older ( >/= 60 years) adults undergoing cancer treatment. We hypothesized that older patients would have significantly lower ratings on four symptom dimensions. METHODS: Data from two studies in the United States and one study in Australia were combined to conduct this analysis. All three studies used the MSAS to evaluate the occurrence, severity, frequency, and distress of 32 symptoms. RESULTS: Data from 593 oncology outpatients receiving active treatment for their cancer (i.e., 44.4% were < 60 years and 55.6% were >/= 60 years of age) were evaluated. Of the 32 MSAS symptoms, after controlling for significant covariates, older patients reported significantly lower occurrence rates for 15 (46.9%) symptoms, lower severity ratings for 6 (18.9%) symptoms, lower frequency ratings for 4 (12.5%) symptoms, and lower distress ratings for 14 (43.8%) symptoms. CONCLUSIONS: This study is the first to evaluate for differences in multiple dimensions of symptom experience in older oncology patients. For almost 50% of the MSAS symptoms, older patients reported significantly lower occurrence rates. While fewer age-related differences were found in ratings of symptom severity, frequency, and distress, a similar pattern was found across all three dimensions. Future research needs to focus on a detailed evaluation of patient and clinical characteristics (i.e., type and dose of treatment) that explain the differences in symptom experience identified in this study.

MicroRNAs are structural components of an epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. Recently, there is significant interest in the application of microRNA as a blood-based biomarker of underlying physiologic conditions, and the therapeutic administration of microRNA inhibitors and mimics. The purpose of this review is to describe the current body of knowledge on microRNA regulation of genes involved in lipid metabolism, and to introduce the role of microRNA in development and progression of atherosclerosis.