Alison Montpetit

Telomere Length: A Review of Methods for Measurement

BackgroundThe exciting discovery that telomere shortening is associated with many health conditions and that telomere lengths can be altered in response to social and environmental exposures has underscored the need for methods to accurately and consistently quantify telomere length. ObjectivesThe purpose of this article is to provide a comprehensive summary that compares and contrasts the current technologies used to assess telomere length. DiscussionMultiple methods have been developed for the study of telomeres. These techniques include quantification of telomere length by terminal restriction fragmentation—which was one of the earliest tools used for length assessment—making it the gold standard in telomere biology. Quantitative polymerase chain reaction provides the advantage of being able to use smaller amounts of DNA, thereby making it amenable to epidemiology studies involving large numbers of people. An alternative method uses fluorescent probes to quantify not only mean telomere lengths but also chromosome-specific telomere lengths; however, the downside of this approach is that it can only be used on mitotically active cells. Additional methods that permit assessment of the length of a subset of chromosome-specific telomeres or the subset of telomeres that demonstrate shortening are also reviewed. ConclusionGiven the increased utility for telomere assessments as a biomarker in physiological, psychological, and biobehavioral research, it is important that investigators become familiar with the methodological nuances of the various procedures used for measuring telomere length. This will ensure that they are empowered to select an optimal assessment approach to meet the needs of their study designs. Gaining a better understanding of the benefits and drawbacks of various measurement techniques is important not only in individual studies, but also to further establish the science of telomere associations with biobehavioral phenomena.

An Integrative Review of Factors Associated with Telomere Length and Implications for Biobehavioral Research

Background:Although telomere shortening occurs as a natural part of aging, there is now a robust body of research that suggests that there is a relationship between psychosocial, environmental, and behavioral factors and changes in telomere length. These factors need to be considered when integrating telomere measurement in biobehavioral research studies. Objectives:This article provides a brief summary of the known facts about telomere biology and an integrative review of current human research studies that assessed relationships between psychosocial, environmental, or behavioral factors and telomere length. Methods:An integrative review was conducted to examine human research studies that focused on psychosocial, environmental, and behavioral factors affecting telomere length and telomerase activity using the electronic databases PubMed/Medline and CINAHL from 2003 to the present. In addition to the known individual factors that are associated with telomere length, the results of the integrative review suggest that perceived stress, childhood adversities, major depressive disorder, educational attainment, physical activity, and sleep duration should also be measured. Discussion:Multiple factors have been shown to affect telomere length. To advance understanding of the role of telomere length in health and disease risk, it will be important to further elucidate the mechanisms that contribute to telomere shortening.

Aberrant ORM (yeast)-like protein isoform 3 (ORMDL3) expression dysregulates ceramide homeostasis in cells and ceramide exacerbates allergic asthma in mice.

BACKGROUND Asthma, a chronic inflammatory condition defined by episodic shortness of breath with expiratory wheezing and cough, is a serious health concern affecting more than 250 million persons. Genome-wide association studies have identified ORM (yeast)-like protein isoform 3 (ORMDL3) as a gene associated with susceptibility to asthma. Although its yeast ortholog is a negative regulator of de novo ceramide biosynthesis, how ORMDL3 contributes to asthma pathogenesis is not known. OBJECTIVES We sought to decipher the molecular mechanism for the pathologic functions of ORMDL3 in asthma and the relationship to its evolutionarily conserved role in regulation of ceramide homeostasis. METHODS We determined the relationship between expression of ORMDL3 and ceramide in epithelial and inflammatory cells and in asthma pathogenesis in mice. RESULTS Although small increases in ORMDL3 expression decrease ceramide levels, remarkably, higher expression in lung epithelial cells and macrophages in vitro and in vivo increased ceramide production, which promoted chronic inflammation, airway hyperresponsiveness, and mucus production during house dust mite-induced allergic asthma. Moreover, nasal administration of the immunosuppressant drug FTY720/fingolimod reduced ORMDL3 expression and ceramide levels and mitigated airway inflammation and hyperreactivity and mucus hypersecretion in house dust mite-challenged mice. CONCLUSIONS Our findings demonstrate that overexpression of ORMDL3 regulates ceramide homeostasis in cells in a complex manner and suggest that local FTY720 administration might be a useful therapeutic intervention for the control of allergic asthma.

Psychoneuroimmunological Relationships in Women With Fibromyalgia

Introduction: The purpose of this pilot study was to characterize the relationships among perceived stress, pain, fatigue, depression, anxiety, biomarkers, and functional status in women with fibromyalgia syndrome (FMS) using a psychoneuroimmunological (PNI) framework. Materials and Method: Using a cross-sectional, correlational design, the authors asked 50 women diagnosed with FMS to complete the Perceived Stress Scale (PSS), Brief Pain Inventory (BPI), Brief Fatigue Inventory (BFI), Center for Epidemiological Studies—Depression scale, State–Trait Anxiety Inventory (STAI), and Functional Impact Questionnaire. The authors analyzed plasma levels of 17 cytokines using a BioPlex® assay and levels of C-reactive protein (CRP) using a high-sensitivity enzyme-linked immunosorbent assay (ELISA). Results: Compared to published guidelines (>3 mg/L reflects high inflammation), CRP levels were elevated in participating women. Perceived stress demonstrated positive correlations with pain, fatigue, depression, anxiety, and functional status and negative correlations with monocyte chemotactic protein (MCP)-1(r = −.30) and interleukin-1 beta (IL-1β; r = −.29). Pain severity correlated with macrophage inflammatory protein (MIP)-1β (r = .29), and pain interference negatively correlated with IL-1β (r = −.30). Fatigue negatively correlated with IL-1β (r = −.32), interleukin-10 (IL-10; r = −.31), and granulocyte colony-stimulating factor (G-CSF; r = −.31). Depressive symptoms correlated with CRP (r = .31). Discussion: Relationships among perceived stress and symptoms supported the PNI framework. Study findings are similar to previous studies showing that cytokines in persons with FMS do not show a consistent pattern. The elevated CRP levels suggest higher levels of generalized inflammation in the sample and provide evidence for continued development of biobehavioral interventions to address both symptoms and their biological markers over time.

A Conceptual Model of Psychoneurological Symptom Cluster Variation in Women with Breast Cancer: Bringing Nursing Research to Personalized Medicine.

Personalized medicine applies knowledge about the patients individual characteristics in relation to health and intervention outcomes, including treatment response and adverse side-effects, to develop a tailored treatment plan. For women with breast cancer, personalized medicine has substantially improved the rate of survival, however, a high proportion of these women report multiple, co-occurring psychoneurological symptoms over the treatment trajectory that adversely affect their quality of life. In a subset of these women, co-occurring symptoms referred to as symptoms clusters, can persist long after treatment has ended. Over the past decade, research from the field of nursing and other health sciences has specifically examined the potential underlying mechanisms of the psychoneurological symptom cluster in women with breast cancer. Recent findings suggest that epigenetic and genomic factors contribute to inter-individual variability in the experience of psychoneurological symptoms during and after breast cancer treatment. While nursing research has been underrepresented in the field of personalized medicine, these studies represent a shared goal; that is, to improve patient outcomes by considering the individuals risk of short- and long-term adverse symptoms. The aim of this paper is to introduce a conceptual model of the individual variations that influence psychoneurological symptoms in women with breast cancer, including perceived stress, hypothalamic-pituitary adrenocortical axis dysfunction, inflammation, as well as epigenetic and genomic factors. The proposed concepts will help bring nursing research and personalized medicine together, in hopes that this hitherto neglected and understudied area of biomedical research convergence may ultimately lead to the development of more targeted clinical nursing strategies in breast cancer patients with psychoneurological symptoms.

Symptom Cluster Research in Women with Breast Cancer: A Comparison of Three Subgrouping Techniques

Aims To examine how symptom cluster subgroups defined by extreme discordant composite scores, cut-off scores, or a median split influence statistical associations with peripheral cytokine levels in women with breast cancer. Background Systemic cytokine dysregulation has been posited as a potential biological mechanism underlying symptom clusters in women with breast cancer. Symptom characteristics may play an important role in identifying cytokines of significant etiological importance, however, there is no consensus regarding the ideal subgrouping technique to use. Design A secondary analysis of data collected from a cross-sectional descriptive study of women with stage I-II breast cancer was used to examine and compare the relationships between peripheral cytokine levels and symptom subgroups defined by extreme discordant composite scores, cut-off scores, or a median split. Methods Participant symptom scores were transformed into a composite score to account for variability in symptom intensity, frequency and interference. Cytokine levels in subgroups defined by composite scores within the highest and lowest 20% were contrasted with those composed from cut-off scores and a median split. Results Subgroups defined by the composite score or cut-off scores resulted in similar statistical relationships with cytokine levels in contrast to the median split technique. The use of a median split for evaluating relationships between symptoms clusters and cytokine levels may increase the risk of a type I error. Conclusion Composite and cut-off scores represent best techniques for defining symptom cluster subgroups in women with breast cancer. Using a consistent approach to defining symptom clusters across studies may assist in identifying relevant biological mechanisms.

A Biobehavioral Perspective on Telomere Length and the Exposome

A major objective of biobehavioral research is defining the mechanisms that underlie linkages among behavior, biology, health, and disease. The genomic revolution has demonstrated the importance of studying the role of the environment in (epi)genetic mechanisms. The idea that interactions between environment and genetics influence health outcomes is a central concept of the exposome, a measure of environmental exposures throughout a lifetime. Research suggests that telomere length (TL) and biologic factors involved in telomere stability may provide an understanding of the effects of gene–environment interaction on disease risk. Telomeres, thus, have become important biomarkers for aging as well as for stress-related disease. However, incorporating telomeres into biobehavioral research requires consideration of several aspects of the exposome. Internal and external modifiable and nonmodifiable exposures have the potential to influence TL. Future research utilizing the concept of the exposome will provide meaningful findings related to exposure sources as well as dosage and duration across the life span that influence telomere biology and disease occurrence. Such findings can be translated into clinical practice and may provide a basis for personalized disease prevention and treatment approaches.

Optimizing safe, comfortable ICU care through multi-professional quality improvement: just DO it

Translating research to the bedside can present significant challenges in the complex ICU environment. In this issue of Critical Care, de Jong and colleagues report on a quality improvement project (NURSE-DO) that led to a decrease in severe pain and serious adverse events during nursing care procedures in their ICU. In this commentary we describe three aspects of this quality improvement study that we think contributed to the overall success of the NURSE-DO project: the hospital environment and culture; multi-professional partnerships; and an evidence-based structured approach.

Nasal NO as a biomarker: Don't say NO to the many challenges of translational medicine

This editorial summarizes the challenges of exhaled breath biomarker research particularly for nasal NO. We also introduce a new focus for Pediatric Pulmonology, a section on Translational Medicine. Pediatr Pulmonol. 2015; 50:100–102.

A Kangaroo and Your Research Toolbox

In a previous article in Biological Research for Nursing, “Beyond the PhD: Putting the Right Tools in Your Research Toolbox,” Downs and Morrison (2011) present rationales for the pursuit of postdoctoral training, enumerate key skills for development during this phase of a research career, and provide an expansive review of funding opportunities, including intra/extramural options at the National Institutes of Health (NIH), National Institute of Nursing Research (NINR), and a wide array of nonprofit foundations. I thank the authors for this great review and think it should be a required reading for all nurses pursuing doctoral studies who wish to follow a research-intensive career trajectory. I, like the authors, had to choose between pursuing a tenure-track faculty position or a postdoctoral fellowship. Because I share the authors’ belief in the importance of postdoctoral training, I ultimately chose that route. The training mechanisms that I have utilized during my postdoctoral journey, however, were not discussed in Downs and Morrison’s article. Thus, I would like to take this opportunity to share my personal perspective on postdoctoral training and describe additional postdoctoral funding mechanisms. I have also provided a framework for planning the postdoctoral training period.