Ensuring due process in the IACUC and animal welfare setting: considerations in developing noncompliance policies and procedures for institutional animal care and use committees and institutional officials.

Every institution that is involved in research with animals is expected to have in place policies and procedures for the management of allegations of noncompliance with the Animal Welfare Act and the U.S. Public Health Service Policy on the Humane Care and Use of Laboratory Animals. We present here a model set of recommendations for institutional animal care and use committees and institutional officials to ensure appropriate consideration of allegations of noncompliance with federal Animal Welfare Act regulations that carry a significant risk or specific threat to animal welfare. This guidance has 3 overarching aims: 1) protecting the welfare of research animals; 2) according fair treatment and due process to an individual accused of noncompliance; and 3) ensuring compliance with federal regulations. Through this guidance, the present work seeks to advance the cause of scientific integrity, animal welfare, and the public trust while recognizing and supporting the critical importance of animal research for the betterment of the health of both humans and animals.-Hansen, B. C., Gografe, S., Pritt, S., Jen, K.-L. C., McWhirter, C. A., Barman, S. M., Comuzzie, A., Greene, M., McNulty, J. A., Michele, D. E., Moaddab, N., Nelson, R. J., Norris, K., Uray, K. D., Banks, R., Westlund, K. N., Yates, B. J., Silverman, J., Hansen, K. D., Redman, B. Ensuring due process in the IACUC and animal welfare setting: considerations in developing noncompliance policies and procedures for institutional animal care and use committees and institutional officials.

Sequential Multiple Assignment Randomized Trial (SMART) to Construct Weight Loss Interventions for African American Adolescents.

The purpose of this study was to develop an adaptive behavioral treatment for African American adolescents with obesity. In a sequential multiple assignment randomized trial, 181 youth ages 12-16 years with primary obesity and their caregiver were first randomized to 3 months of home-based versus office-based delivery of motivational interviewing plus skills building. After 3 months, nonresponders to first phase treatment were rerandomized to continued home-based skills or contingency management. Primary outcome was percent overweight and hypothesized moderators were adolescent executive functioning and depression. There were no significant differences in primary outcome between home-based or office-based delivery or between continued home-based skills or contingency management for nonresponders to first-phase treatment. However, families receiving home-based treatment initially attended significantly more sessions in both phases of the trial, and families receiving contingency management attended more sessions in the second phase. Overall, participants demonstrated decreases in percent overweight over the course of the trial (3%), and adolescent executive functioning moderated this effect such that those with higher functioning lost more weight. More potent behavioral treatments to address the obesity epidemic are necessary, targeting new areas such as executive functioning. Delivering treatment in the home with contingency management may increase session attendance for this population.

Recruitment strategies and the retention of obese urban racial/ethnic minority adolescents in clinical trials: the FIT families project, Michigan, 2010-2014.

INTRODUCTION: The successful recruitment and retention of participants is integral to the translation of research findings. We examined the recruitment and retention rates of racial/ethnic minority adolescents at a center involved in the National Institutes of Health Obesity Research for Behavioral Intervention Trials (ORBIT) initiative by the 3 recruitment strategies used: clinic, informatics, and community. METHODS: During the 9-month study, 186 family dyads, each composed of an obese African American adolescent and a caregiver, enrolled in a 6-month weight-loss intervention, a sequential multiple assignment randomized trial. We compared recruitment and retention rates by recruitment strategy and examined whether recruitment strategy was related to dyad baseline characteristics. RESULTS: Of the 186 enrolled families, 110 (59.1%) were recruited through clinics, 53 (28.5%) through informatics, and 23 (12.4%) through community. Of those recruited through community, 40.4% enrolled in the study, compared with 32.7% through clinics and 8.2% through informatics. Active refusal rate was 3%. Of the 1,036 families identified for the study, 402 passively refused to participate: 290 (45.1%) identified through informatics, 17 (29.8%) through community, and 95 (28.3%) through clinics. Recruitment strategy was not related to the age of the adolescent, adolescent comorbidities, body mass index of the adolescent or caregiver, income or education of the caregiver, or retention rates at 3 months, 7 months, or 9 months. Study retention rate was 87.8%. CONCLUSION: Using multiple recruitment strategies is beneficial when working with racial/ethnic minority adolescents, and each strategy can yield good retention. Research affiliated with health care systems would benefit from the continued specification, refinement, and dissemination of these strategies.

Cardiovascular disease risk factors are elevated in urban minority children enrolled in head start.

BACKGROUND: The prevalence of obesity and overweight persists in the preschool population, despite some prevention and treatment advances, particularly in minorities. Investigating the prevalence of dyslipidemia and the effect of family health may also guide the focus of intervention efforts. METHODS: Anthropometric data were collected from urban minority preschool children (n=161; 42% female) enrolled in USDA Head Start. Blood was collected by finger prick and analyzed with the Cholestech LDX Analyzer (Cholestech Corporation, Hayward, CA). Caregivers provided a self-reported family health history for cardiovascular diseases (CVDs). RESULTS: By BMI percentile, 8% of the children were underweight (UW), 54% healthy weight (HW), 10% overweight (OW), and 28% obese (OB). One of every 5 children had borderline or high-risk levels for total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides based on the National Cholesterol Education Program categories. In OW/OB children only, BMI was positively correlated with TC (r(61)=0.428; p=0.001) and LDL (r(58)=0.395; p=0.005). Child BMI was also associated with family comorbid diseases (r(159)=0.177; p=0.025). UW/HW children with a family history of CVD had significantly higher LDL than UW/HW children without a family history of CVD (p=0.001). Step-wise regression analysis revealed that BMI (p=0.005) plus family history of heart attack (p=0.018) were significant predictors of blood TC levels. CONCLUSION: Continued efforts to treat and prevent elevated weight are urgently needed for minority preschoolers. Attention to CVD screening may be an important target in school, community, and healthcare arenas for minority populations regardless of weight status.

Consumer health information technology in an adult public health primary care clinic: a heart health education feasibility study.

OBJECTIVE: To explore the feasibility and short term outcomes of using an interactive kiosk integrated into office flow to deliver health information in a primary care clinic. METHODS: Fifty-one adults with BMI ≥25 were randomly assigned to use a kiosk with attached devices to receive a six-week healthy eating/weight monitoring (intervention) or general health/BP monitoring (attention-control) program. Outcomes were measured at baseline, 8 weeks (post) and three month follow-up. RESULTS: Participants completed an average of 2.73 weekly sessions, with transportation and time given as limiting factors. They found the kiosk easy to use (97%), liked the touchscreen (94%), and would use the kiosk again (81%). Although there were no differences between groups, the 27 completing all assessments showed reduced weight (p=.02), and decreased systolic (p=.01) and diastolic BP (p<.001) at follow-up. Although healthy eating behaviors increased, the change was not statistically significant. CONCLUSION: Using a kiosk within a clinic setting is a feasible method of providing health information and self-monitoring. Multi-session educational content can provide beneficial short-term outcomes in overweight adults. PRACTICE IMPLICATIONS: A kiosk with attached peripherals in a clinic setting is a viable adjunct to provider education, particularly in medically underserved areas.

Endogenous and diet-induced hypercholesterolemia in nonhuman primates: effects of age, adiposity, and diabetes on lipoprotein profiles.

Nonhuman primates (NHPs) share with humans many features of lipid metabolism and often develop all features of the metabolic syndrome, including hypertriglyceridemia and low high-density lipoprotein cholesterol, and have been used in many studies of potential therapeutics during the preclinical phase. Here we identify for the first time in middle-aged and older rhesus the natural occurrence of hypercholesterolemia, and this hypercholesterolemia develops despite maintenance on a low-cholesterol diet. The aims of this study were to (a) define normal and hypercholesterolemia in rhesus monkeys, (b) determine the factors associated with the development of hypercholesterolemia, (c) compare the lipoprotein profiles in adult rhesus monkeys fed a low-fat/low-cholesterol diet (LFLC) with the profiles of human subjects, and (d) determine the effect of a 16-week high-fat/high-cholesterol (HFHC) diet feeding on total cholesterol and lipoprotein profiles in middle-aged and older monkeys. In our colony, maintained on a constant diet with negligible cholesterol, the mean total cholesterol level in healthy nondiabetic monkeys was 3.7 ± 0.02 mmol/L, with hypercholesterolemia identified as the 95th percentile of the normal cholesterol distribution (≥5.2 mmol/L). Severe hypercholesterolemia developed in the HFHC-fed group; however, despite the high-fat diet composition, unexpectedly, no weight gain occurred in these NHPs. The diet-induced hypercholesterolemia differed significantly in lipoprotein pattern from that of the spontaneous hypercholesterolemia. In summary, despite ingesting only a LFLC, NHPs frequently develop hypercholesterolemia, reflecting lipoprotein patterns similar to human subjects; and this lipid profile of spontaneous hypercholesterolemia differs significantly from the hypercholesterolemia induced by an HFHC diet.

Dietary alpha-cyclodextrin lowers low-density lipoprotein cholesterol and alters plasma fatty acid profile in low-density lipoprotein receptor knockout mice on a high-fat diet.

High dietary intake of saturated fat and cholesterol, and elevated low-density lipoprotein cholesterol levels are some of the modifiable risk factors for cardiovascular disease. Alpha-cyclodextrin (a-CD) when given orally has been shown in rats to increase fecal saturated fat excretion and to reduce blood total cholesterol levels in obese hypertriglyceridemic subjects with type 2 diabetes mellitus. In this study, the effects of dietary a-CD on lipid metabolism in low-density lipoprotein receptor knockout mice were investigated. Low-density lipoprotein receptor knockout mice were fed a "Western diet" (21% milk fat) with or without 2.1% of a-CD (10% of dietary fat content) for 14 weeks. At sacrifice, there was no difference in body weight; but significant decreases were observed in plasma cholesterol (15.3%), free cholesterol (20%), cholesterol esters (14%), and phospholipid (17.5%) levels in mice treated with alpha-CD compared with control mice. The decrease in total cholesterol was primarily in the proatherogenic apolipoprotein B-containing lipoprotein fractions, with no significant change in the high-density lipoprotein fraction. Furthermore, alpha-CD improved the blood fatty acid profile, reducing the saturated fatty acids (4.5%) and trans-isomers (11%) while increasing (2.5%) unsaturated fatty acids. In summary, the addition of alpha-CD improved the lipid profile by lowering proatherogenic lipoproteins and trans-fatty acids and by decreasing the ratio of saturated and trans-fatty acids to polyunsaturated fatty acids (-5.8%), thus suggesting that it may be useful as a dietary supplement for reducing cardiovascular disease.

Effects of nurse-managed telemonitoring on blood pressure at 12-month follow-up among urban African Americans.

BACKGROUND: Nearly one in three adults in the United States has hypertension. Hypertension is one of the largest risk factors for cardiovascular diseases, and it is growing in prevalence, especially among African Americans. OBJECTIVES: To test the hypothesis that individuals who participate in usual care (UC) plus blood pressure (BP) telemonitoring (TM) will have a greater reduction in BP from baseline to 12-month follow-up than would individuals who receive UC only. METHODS: A two-group, experimental, longitudinal design with block stratified randomization for antihypertensive medication use was used. African Americans with hypertension were recruited through free BP screenings offered in the community. Data were collected through a structured interview and brief physical exam. Cross tabs, repeated measures analysis of variance, and independent t tests were used to analyze the study's hypothesis. RESULTS: The TM intervention group had a greater reduction in systolic BP (13.0 mm Hg) than the enhanced UC group (7.5 mm Hg; t = -2.09, p = .04) from baseline to the 12-month follow-up. Although the TM intervention group had a greater reduction in diastolic BP (6.3 mm Hg) compared with the enhanced UC group (4.1 mm Hg), the differences were not statistically significant (t = -1.56, p = .12). DISCUSSION: : Telemonitoring of BP resulted in clinically and statistically significant reductions in systolic BP over a 12-month period; if maintained over a longer period of time, the reductions could improve care and outcomes significantly for African Americans with hypertension.

Baseline leptin levels predict change in leptin levels during weight loss in obese breast cancer survivors.

Leptin is an adipocyte-derived hormone involved in regulation of satiety, and it also appears to have a role in breast cancer risk. Leptin therefore might be a useful indicator of the potential preventive effects of weight loss in breast cancer survivors. In this study we examined whether the change in leptin levels could be predicted by weight loss in obese breast cancer survivors. The subjects in this study were participating in a randomized trial of an individualized approach towards weight loss in Detroit, MI. Breast cancer survivors (body mass index of 30-44 kg/m(2)) were enrolled and fasting blood samples were obtained for leptin analysis over 1 year of study. Leptin levels were available from at least two time points for 36 women, and weight change ranged from a gain of 11% to a loss of 25% of baseline weight. Using a repeated-measures regression model, both baseline leptin level and concurrent percent body fat were found to synergistically predict leptin levels. Thus, for women with the same body fat, those with higher baseline leptin levels are predicted to exhibit smaller decreases in leptin with weight loss. Similar results were obtained for body weight and body weight change, but the associations with body fat were stronger. Breast cancer survivors with initially higher leptin levels may differ with regard to regulation of change in leptin during weight loss resulting in relatively smaller changes in leptin with equivalent amounts of weight loss.

Depression, stress, and blood pressure in urban African-American women.

African-American women have disturbingly high rates of hypertension, exceeding those of African-American men and other ethnic groups. Reasons for these disparities are not understood. Depression, more common in women than men, has been linked to endothelial dysfunction, inflammation, metabolic and hematologic abnormalities, and increased sympathetic nervous system activity--all factors associated with cardiovascular disease. A descriptive correlational design was used to test the following hypotheses: 1) African-American women with higher levels of depression will have higher blood pressure (BP) levels, more cardiovascular risk factors, greater stress, and lower social support; and 2) depression will mediate the relationship between stress and BP. A convenience sample of 245 hypertensive African-American women (mean age, 61+/-12.7 years) was recruited through free BP screenings offered in the community. All data were collected during a structured interview and brief physical examination. Pearson r correlation coefficients, analysis of variance, and multiple regression analyses were used to analyze the hypotheses. Women with higher levels of depression had higher diastolic BP and were more likely to smoke, eat fewer fruits and vegetables, and have more stress and less social support. Depression mediated the relationship between stress and diastolic BP. The findings emphasize the importance of assessing both behavioral and psychosocial factors in urban African-American women with hypertension.

Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene.

Fetuin inhibits insulin-induced insulin receptor (IR) autophosphorylation and tyrosine kinase activity in vitro, in intact cells, and in vivo. The fetuin gene (AHSG) is located on human chromosome 3q27, recently identified as a susceptibility locus for type 2 diabetes and the metabolic syndrome. Here, we explore insulin signaling, glucose homeostasis, and the effect of a high-fat diet on weight gain, body fat composition, and glucose disposal in mice carrying two null alleles for the gene encoding fetuin, Ahsg (B6, 129-Ahsg(tm1Mbl)). Fetuin knockout (KO) mice demonstrate increased basal and insulin-stimulated phosphorylation of IR and the downstream signaling molecules mitogen-activated protein kinase (MAPK) and Akt in liver and skeletal muscle. Glucose and insulin tolerance tests in fetuin KO mice indicate significantly enhanced glucose clearance and insulin sensitivity. Fetuin KO mice subjected to euglycemic-hyperinsulinemic clamp show augmented sensitivity to insulin, evidenced by increased glucose infusion rate (P = 0.077) and significantly increased skeletal muscle glycogen content (P < 0.05). When fed a high-fat diet, fetuin KO mice are resistant to weight gain, demonstrate significantly decreased body fat, and remain insulin sensitive. These data suggest that fetuin may play a significant role in regulating postprandial glucose disposal, insulin sensitivity, weight gain, and fat accumulation and may be a novel therapeutic target in the treatment of type 2 diabetes, obesity, and other insulin-resistant conditions.