Ubiquinol Reduces Muscle Wasting but Not Fatigue in Tumor-Bearing Mice

Purpose: Fatigue is the most common and distressing symptom reported by cancer patients during and after treatment. Tumor growth increases oxidative stress and cytokine production, which causes skeletal muscle wasting and cardiac dysfunction. The purpose of this study was to determine whether treatment with the antioxidant ubiquinol improves muscle mass, cardiac function, and behavioral measures of fatigue in tumor-bearing mice. Method: Adult female mice were inoculated with colon26 tumor cells. Half the control and tumor-bearing mice were administered ubiquinol (500 mg/kg/day) in their drinking water. Voluntary wheel running (i.e., voluntary running activity [VRA]) and grip strength were measured at Days 0, 8, 14, and 17 of tumor growth. Cardiac function was measured using echocardiography on Day 18 or 19. Biomarkers of inflammation, protein degradation, and oxidative stress were measured in serum and heart and gastrocnemius tissue. Results: VRA and grip strength progressively declined in tumor-bearing mice. Muscle mass and myocardial diastolic function were decreased, and expression of proinflammatory cytokines was increased in serum and muscle and heart tissue on Day 19 of tumor growth. Oxidative stress was present only in the heart, while biomarkers of protein degradation were increased only in the gastrocnemius muscle. Ubiquinol increased muscle mass in the tumor-bearing and control animals but had no effect on the expression of biomarkers of inflammation, protein degradation, or oxidative stress or on behavioral measures of fatigue

Effect of Perceived Stress on Cytokine Production in Healthy College Students

Chronic psychological stress impairs antibody synthesis following influenza vaccination. Chronic stress also increases circulating levels of proinflammatory cytokines and glucocorticoids in elders and caregivers, which can impair antibody synthesis. The purpose of this study was to determine whether psychological stress increases ex vivo cytokine production or decreases glucocorticoid sensitivity (GCS) of peripheral blood leukocytes from healthy college students. A convenience sample of Reserve Officer Training Corps (ROTC) students completed the Perceived Stress Scale (PSS). Whole blood was incubated in the presence of influenza vaccine and dexamethasone to evaluate production of interleukin-6 (IL-6), interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). Multiple regression models controlling for age, gender, and grade point average revealed a negative relationship between PSS and GCS for vaccine-stimulated production of IL-1β, IL-6, and TNF-α. These data increase our understanding of the complex relationship between chronic stress and immune function

Web-Based Skin Cancer Prevention Training for Massage Therapists: Protocol for the Massage Therapists Skin Health Awareness, Referral, and Education Study

Background: Skin cancer, the most common cancer in the United States, is costly and potentially deadly. Its burden can be reduced by early detection and prevention activities. The scope of skin cancer requires going beyond traditional health care providers to promote risk reduction. Partnering with the nonbiomedical workforce, such as massage therapists (MTs), may reach more individuals at risk. MTs see much of their clients' skin and are amenable to performing skin cancer risk reduction activities during massage appointments. Objective: The objective of this study is to describe the Massage Therapists Skin Health Awareness, Referral, and Education protocol, presenting an overview of our systematic approach to developing rigorous e-training for MTs to enable them to be partners in skin cancer risk reduction. We also describe procedures for usability and feasibility testing of the training. Methods: We developed an integrated electronic learning system that includes electronic training (e-training) technology, simulated client interactions, online data collection instruments, and in-person assessment of MTs' application of their training. Results: A total of 20 participants nationally scored the e-training as high for usability and satisfaction. We have screened an additional 77 MTs in Arizona for interest and eligibility, and currently have 37 enrolled participants, of whom 32 have completed the Web-based training. Conclusions: The structured and rigorous development approach for this skin cancer risk reduction and brief behavioral intervention e-training for MTs begins to fill a gap in skin cancer risk reduction research. Iterative usability testing of our asynchronous Web-based training resulted in positive participant response. Our e-training approach offers greater learner accessibility, increased convenience, and greater scalability than the few existing programs and has the potential to reach many MTs nationally.Arizona Biomedical Research Centre through the Arizona Department of Health Services [ABRC/ADHS16-162518]; National Institutes of Health-National Cancer Institute (NIH-NCI) Cancer Center Support Grant [P30 CA023074]open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing: Pathway Analysis Among African American Women

Background: Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking. Objectives: We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1β production. Methods: A candidate gene study using a prospective cohort design was used. We collected blood samples at 28–32 weeks of gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN single-nucleotide polymorphism (SNP) rs2637988 was genotyped, and lipopolysaccharide-stimulated IL-1Ra and IL-1β production was quantified. Medical record review determined timing of birth. Results: Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = .21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [−0.05, 0.13]). Women with GG genotype showed less inhibition of IL-1β production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = .93, p = .03). Greater IL-1β production at 28–32 weeks of pregnancy was marginally associated with earlier birth (b* = .21, p = .05). Discussion: Women with GG genotype may be at risk for earlier birth because of diminished IL-1β inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions

Adapting a conceptual framework to engage diverse stakeholders in genomic/precision medicine research

Introduction: Genomic/precision medicine offers a remarkable opportunity to improve health and address health disparities. Genomic medicine is the study of genes and their interaction with health. Precision medicine is an approach to disease prevention and treatment that considers individual variability in genes, environ- ment and lifestyle. Conclusions from studies lacking diversity may hinder general- izability as genomic variation occurs within and between populations. Historical factors, such as medical mistrust, ethical issues related to decision making, and data sharing pose complex challenges that may further widen inequities in genomic/ precision medicine if not appropriately addressed. Although few biomedical studies integrate priorities of community partners into their conceptual framework, effective implementation of genomic/precision medicine research calls for the involvement of diverse stakeholders to expand traditional unidirectional models of engagement in clinical research towards authentic bidirectional collaboration. Methods: A multipronged approach was used integrating an evidence-based literature review and best practices in developing and evaluating the engagement of diverse stakeholders in genomic and precision medicine research. This was combined with expert consensus building to adapt a conceptual model from a community engagement framework to addressing genomics to be scalable to engagement science, which is challenging to genomic/precision medicine research. Results: The final enhanced conceptual framework is composed of four overarching dimensions now inclusive of domains in trust, exploitation, discrimination, privacy risk, stigmatization, prior harms/injustices, failure to recognize coexisting governments, intersectionality and research transformation. This conceptual framework proposes effective participant research engagement strategies for upstream relationship building, distinct from downstream recruitment strategies in which the goal is enrolment. Conclusion: To further shape the evolution of genomic/precision medicine research, it is important to leverage existing partnerships, engage participants beyond recruitment and embrace diverse perspectives. Patient or Public Contribution: In preparation of this manuscript, the perspectives of the community partners on the impact of engaging in genomic/precision medicine research beyond research participation were integrated into this conceptual framework from various guided listening sessions held in diverse communitie

Effects of Menthol Flavor Cigarettes or Total Urinary Menthol on Biomarkers of Nicotine and Carcinogenic Exposure and Behavioral Measures

Introduction: The effects of either menthol flavor cigarettes or total urinary menthol on nicotine dependence, biomarkers of addictive and carcinogenic exposure, and behavioral measures may inform differences and similarities of these two approaches. Methods: Stratified recruitment by cigarette (menthol flavor or regular) and race (African American and white) yielded a balanced sample of 136 adult smokers in a 36-hour inpatient protocol. Exposure measures assessed during 24-hour data collection included urinary menthol, total NNAL [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol], 10 polycyclic aromatic hydrocarbon metabolites, baseline plasma cotinine, plasma nicotine pre- and post-smoking, exhaled carbon monoxide pre- and post-smoking, and cigarette puff volumes. The latter three were measured at four specified timepoints throughout the day. Results: There were no significant differences between menthol flavor and regular cigarette smokers in measures of nicotine dependence, biomarkers of addictive and carcinogenic exposures, or behavioral measures. Significant race × cigarette type interaction effects were found for two biomarkers: plasma nicotine and 3-hydroxyphenanthrene. Total urinary menthol was significantly associated with higher levels of nearly all dependent variables including puff volume, exhaled carbon monoxide, plasma nicotine and cotinine, NNAL, and polycyclic aromatic hydrocarbons. The significant effects of total urinary menthol were sustained after adjusting for menthol flavor and regular cigarette type and other covariates (eg, number of cigarettes per day, baseline cotinine, and baseline nicotine). Conclusions: Urinary menthol is an independent predictive biomarker for nicotine dependence, addictive and carcinogenic exposure, and behaviors

Mental health, sexual identity, and interpersonal violence: Findings from the Australian longitudinal Women’s health study

Background: We examined the relationships among experiences of interpersonal violence, mental health, and sexual identity in a national sample of young adult women in Australia. Methods: We used existing data from the third (2003) wave of young adult women (aged 25- 30) in the Australian Longitudinal Study on Women's Health (ALSWH). We conducted bivariate analyses and fit multiple and logistic regression models to test experiences of six types of interpersonal violence (physical abuse, severe physical abuse, emotional abuse, sexual abuse, harassment, and being in a violent relationship), and the number of types of violence experienced, as predictors of mental health. We compared types and number of types of violence across sexual identity subgroups. Results: Experiences of interpersonal violence varied significantly by sexual identity. Controlling for demographic characteristics, compared to exclusively heterosexual women, mainly heterosexual and bisexual women were significantly more likely to report physical, sexual, and emotional abuse. Mainly heterosexual and lesbian women were more likely to report severe physical abuse. Mainly heterosexual women were more than three times as likely to have been in a violent relationship in the past three years, and all three sexual minority subgroups were two to three times as likely to have experienced harassment. Bisexual women reported significantly higher levels of depression than any of the other sexual identity groups and scored lower on mental health than did exclusively heterosexual women. In linear regression models, interpersonal violence strongly predicted poorer mental health for lesbian and bisexual women. Notably, mental health indicators were similar for exclusively heterosexual and sexual minority women who did not report interpersonal violence. Experiencing multiple types of interpersonal violence was the strongest predictor of stress, anxiety and depression. Conclusions: Interpersonal violence is a key contributor to mental health disparities, especially among women who identify as mainly heterosexual or bisexual. More research is needed that examines within-group differences to determine which subgroups are at greatest risk for various types of interpersonal violence. Such information is critical to the development of effective prevention and intervention strategies.Gay and Lesbian Medical Association's Lesbian Health Fund in the United States; Australian Government Department of HealthOpen Access Journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Health Status, Health Service Use, and Satisfaction According to Sexual Identity of Young Australian Women

Objectives: To compare physical and mental health status, health service use and satisfaction amongst young Australian women of varying sexual identity; and to explore associations of all of these variables with satisfaction with their general practitioner (GP). Methods: Data are from the youngest cohort of women in the Australian Longitudinal Study on Women‘s Health surveyed in 2003. The sample included women aged 25-30 who identified as exclusively heterosexual (n=8,083, 91.3%), mainly heterosexual (n=568, 6.4%), bisexual (n=100, 1.1%), or lesbian (n=99, 1.1%). Univariate analyses compared self-reported mental health, physical health, access to GP services and satisfaction across the four sexual identity groups. Linear regression, controlling for education, income and residence, was used to identify factors associated with GP satisfaction. Results: Sexual minority women (lesbian, bisexual and mainly heterosexual) were significantly more likely than were heterosexual women to report poorer mental health and to have more frequently used health services; depression was strongly associated with mental health services use. Bisexual and mainly heterosexual women were most likely to report poorer general health, abnormal Pap tests, STI, UTI, Hepatitis B or C, and asthma. Lesbians were most likely to have never had a Pap test or 2 be under-screened. All sexual minority women had lower continuity of GP care and lower satisfaction with that care than heterosexual women. Conclusions: Underlying social determinants of physical and mental health disparities experienced by sexual minority women require exploration, including the possible effects of discrimination and marginalization on higher levels of risk taking. Lower continuity of care and lower satisfaction with GP services also need further investigation