Bradley E. Aouizerat

Abstract

OBJECTIVES: Factors that determine disease severity in nonalcoholic fatty liver disease (NAFLD) are unclear, but exercise is a recommended treatment. We evaluated the association between physical activity intensity and histological severity of NAFLD.METHODS: We conducted a retrospective analysis of adults with biopsy-proven NAFLD enrolled in the NASH CRN (Nonalcoholic Steatohepatitis Clinical Research Network). Using self-reported time spent in physical activity, we classified participants as inactive or as meeting the US guidelines for either moderate or vigorous exercise. Histology was reviewed by a central pathology committee. Frequency and odds of steatohepatitis (NASH) and advanced fibrosis were compared between subjects who either met or did not meet exercise recommendations, and by the total amount of exercise per week.RESULTS: A total of 813 adults (males=302, females=511) with NAFLD were included, with a mean age of 48 years. Neither moderate-intensity exercise nor total exercise per week was associated with NASH or stage of fibrosis. Meeting vigorous recommendations was associated with a decreased adjusted odds of having NASH (odds ratio (OR): 0.65 (0.43-0.98)). Doubling the recommended time spent in vigorous exercise, as is suggested for achieving additional health benefits, was associated with a decreased adjusted odds of advanced fibrosis (OR: 0.53 (0.29-0.97)).CONCLUSIONS: These data support an association of vigorous but not moderate or total exercise with the severity of NAFLD. Optimal doses of exercise by duration and intensity for the prevention or treatment of NASH have not been established; however, intensity may be more important than duration or total volume.

Abstract

Study Objectives: To examine how self-reported ratings of sleep disturbance changed from the time of the simulation visit to four months after the completion of radiation therapy (RT) and to investigate whether specific patient, disease, and symptom characteristics predicted the initial levels of sleep disturbance and/or characteristics of the trajectories of sleep disturbance. Design: Prospective longitudinal study. Setting: Two radiation therapy centers. Patients: Patients (n = 82) who underwent primary or adjuvant RT for prostate cancer. Measurements and Results: Changes in self-reported sleep disturbance were measured using the General Sleep Disturbance Scale (GSDS). Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale. Trait and state anxiety were measured using the Spielberger State-Trait Anxiety Inventory. Hierarchical linear modeling was used to answer the study aims. Self-reported sleep disturbance increased during the course of RT and then decreased following the completion of RT. Predictors of higher levels of sleep disturbance included younger age, higher levels of trait anxiety, higher levels of depressive symptoms, and higher levels of sleep disturbance at the initiation of RT. Conclusions: Sleep disturbance is a significant problem in patients with prostate cancer who undergo RT. Younger men with co-occurring depression and anxiety may be at greatest risk for sleep disturbance during RT.

Abstract

Objective: The findings from several studies suggest that palliative care patients with advanced cancer experience multiple symptoms, and that these symptoms may be related to demographic and clinical factors as well as to patient outcomes. However, no systematic review has summarized the findings from studies that assessed multiple symptoms, predictors, and outcomes in these patients. The purposes of this review, focused on palliative care patients with advanced cancer, are to: 1) describe the relationships among multiple symptoms; 2) describe the predictors of multiple symptoms; and 3) describe the relationships between multiple symptoms and patient outcomes. Method: Comprehensive literature searches were completed using the following databases: PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsychInfo. The key words: cancer or advanced cancer or neoplasm, AND palliative care or terminal care or hospice or end-of-life, AND symptoms or multiple symptoms or symptom clusters were combined.Results: Twenty-two studies met the inclusion criteria and examined at least one of our purposes. The majority of these studies were descriptive and used one of four common symptom assessment scales. Fifty-six different signs and symptoms were evaluated across various dimensions (i.e., prevalence, severity, distress, frequency, control). Pain, dyspnea, and nausea were the only symptoms measured in all 22 studies. Relationships among concurrent symptoms were examined in nine studies. Relationships among symptoms and predictors (i.e., demographics, cancer type, healthcare delivery environment) were examined in seven studies. Relationships among symptoms and outcomes (i.e., functional status, psychological status, quality-of-life, survival time) were examined in 14 studies. Significant methodological variation was found among these studies.Significance of results: It is difficult to draw conclusions about the relationships among multiple symptoms, predictors, and outcomes due to the heterogeneity of these studies. Future research is needed to determine which symptoms and symptom dimensions to assess in order to better understand how multiple symptoms relate to each other as well to as predictors and outcomes in palliative care patients with advanced cancer.

Abstract

Though pursuit of host genetic factors that influence the pathogenesis of HIV began over two decades ago, progress has been slow. Initial genome-level searches for variations associated with HIV-related traits have yielded interesting candidates, but less in the way of novel pathways to be exploited for therapeutic targets. More recent genome-wide association studies (GWAS) that include different phenotypes, novel designs, and that have examined different population characteristics suggest novel targets and affirm the utility of additional searches. Recent findings from these GWAS are reviewed, new directions for research are identified, and the promise of systems biology to yield novel insights is discussed.

Abstract

Symptom burden has been identified as a predictor of medication adherence, but little is known about which symptoms are most strongly implicated. This study examines self-reported medical adherence in relation to demographic, clinical, and symptom characteristics among 302 adults living with HIV. Only 12% reported missing medication during the 3-day assessment, but 75% gave at least one reason for missing it in the previous month. Poor adherence was associated with higher viral load and greater symptom burden. Trouble sleeping and difficulty concentrating were strongly associated with poor adherence. Given that " forgetting" was the most common reason for missing medication and nearly one third reported sleeping through dose time, future research should examine the influence of sleep disturbance on adherence. Effective management of common symptoms, such as sleep disturbance, fatigue, and gastrointestinal side-effects of medications may result in better adherence, as well as improved clinical outcomes and quality of life.

Abstract

Acetylation is increasingly recognized as an important metabolic regulatory posttranslational protein modification, yet the metabolic consequence of mitochondrial protein hyperacetylation is unknown. We find that high-fat diet (HFD) feeding induces hepatic mitochondrial protein hyperacetylation in mice and downregulation of the major mitochondrial protein deacetylase SIRT3. Mice lacking SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance, hyperlipidemia, and steatohepatitis compared to wild-type (WT) mice. The lipogenic enzyme stearoyl-CoA desaturase 1 is highly induced in SIRT3KO mice, and its deletion rescues both WT and SIRT3KO mice from HFD-induced hepatic steatosis and insulin resistance. We further identify a single nucleotide polymorphism in the human SIRT3 gene that is suggestive of a genetic association with the metabolic syndrome. This polymorphism encodes a point mutation in the SIRT3 protein, which reduces its overall enzymatic efficiency. Our findings show that loss of SIRT3 and dysregulation of mitochondrial protein acetylation contribute to the metabolic syndrome.

Abstract

Background: Little is known about the relationships between sleep parameters and fatigue in patients at the initiation of radiation therapy (RT). Objectives: The objectives of this study were to describe values for nocturnal sleep/rest, daytime wake/activity, and circadian activity rhythm parameters measured using actigraphy and to evaluate the relationships between these objective parameters and subjective ratings of sleep disturbance and fatigue severity, in a sample of patients at the initiation of RT. Methods: Patients (n = 185) with breast, prostate, lung, or brain cancer completed self-report measures for sleep disturbance (ie, Pittsburgh Sleep Quality Index, General Sleep Disturbance Scale) and fatigue (Lee Fatigue Scale) and wore wrist actigraphs for a total of 48 hours prior to beginning RT. Actigraphy data were analyzed using the Cole-Kripke algorithm. Spearman rank correlations were calculated between variables. Results: Approximately 30% to 50% of patients experienced sleep disturbance, depending on whether clinically significant cutoffs for the subjective or objective measures were used to calculate occurrence rates. In addition, these patients reported moderate levels of fatigue. Only a limited number of significant correlations were found between the subjective and objective measures of sleep disturbance. Significant positive correlations were found between the subjective, but not the objective measures of sleep disturbance and fatigue. Conclusions: A significant percentage of oncology patients experience significant disturbances in sleep-wake circadian activity rhythms at the initiation of RT. The disturbances occur in both sleep initiation and sleep maintenance. Implications for Practice: Patients need to be assessed at the initiation of RT for sleep disturbance, so appropriate treatment is initiated.

Abstract

Purpose/Objectives: To describe the percentages of men with and without changes in sexual function from the beginning to end of radiation therapy and evaluate for differences in demographic and clinical characteristics, mood states, and quality of life (QOL) among patients who did and did not experience changes in sexual function. Design: Descriptive, longitudinal. Setting: Two radiation therapy departments in northern California. Sample: 70 men with prostate cancer who underwent primary or adjuvant radiation therapy. Methods: Self-report questionnaires, medical record reviews, and repeated measures analysis of variance. Main Research Variables: Changes in sexual function; depression, anxiety, and QOL. Findings: Patients were categorized into one of four sex groups (No Problem X 2, Problem-No Problem, No Problem-Problem, and Problem X 2) based on their responses to "Is your sexuality impacted by your illness?" at the beginning and end of radiation therapy. About 50% had a problem with sexual function either at the beginning or end of radiation therapy. Overall, men without sexual problems at both the beginning and end of radiation therapy had significantly less anxiety and depression and higher QOL scores than patients who developed a problem at the end and patients who had a problem at both time points. Conclusions: Changes in sexual function during the course of radiation therapy affect patients' mood and QOL. Implications for Nursing: Clinicians should evaluate the effects of radiation therapy on sexual function and monitor patients with prostate cancer for depression and anxiety as well as for changes in QOL.

Abstract

UNLABELLED: The rising incidence of obesity and diabetes coincides with a marked increase in fructose consumption. Fructose consumption is higher in individuals with nonalcoholic fatty liver disease (NAFLD) than in age-matched and body mass index (BMI)-matched controls. Because fructose elicits metabolic perturbations that may be hepatotoxic, we investigated the relationship between fructose consumption and disease severity in NAFLD. We studied 427 adults enrolled in the NASH Clinical Research Network for whom Block food questionnaire data were collected within 3 months of a liver biopsy. Fructose consumption was estimated based on reporting (frequency x amount) of Kool-aid, fruit juices, and nondietary soda intake, expressed as servings per week, and classified into none, minimum to moderate (<7 servings/week), and daily (> or =7 servings/week). The association of fructose intake with metabolic and histological features of NAFLD was analyzed using multiple linear and ordinal logistic regression analyses with and without controlling for other confounding factors. Increased fructose consumption was univariately associated with decreased age (P < 0.0001), male sex (P < 0.0001), hypertriglyceridemia (P < 0.04), low high-density lipoprotein (HDL) cholesterol (<0.0001), decreased serum glucose (P < 0.001), increased calorie intake (P < 0.0001), and hyperuricemia (P < 0.0001). After controlling for age, sex, BMI, and total calorie intake, daily fructose consumption was associated with lower steatosis grade and higher fibrosis stage (P < 0.05 for each). In older adults (age > or = 48 years), daily fructose consumption was associated with increased hepatic inflammation (P < 0.05) and hepatocyte ballooning (P = 0.05).CONCLUSION: In patients with NAFLD, daily fructose ingestion is associated with reduced hepatic steatosis but increased fibrosis. These results identify a readily modifiable environmental risk factor that may ameliorate disease progression in patients with NAFLD.