Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. METHODS: In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P=0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to -0.05; P=0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P=0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels. CONCLUSIONS: Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02053493.).

Adult energy requirements predicted from doubly labeled water.

BACKGROUND: Estimating energy requirements forms an integral part of developing diet and activity interventions. Current estimates often rely on a product of physical activity level (PAL) and a resting metabolic rate (RMR) prediction. PAL estimates, however, typically depend on subjective self-reported activity or a clinician's best guess. Energy-requirement models that do not depend on an input of PAL may provide an attractive alternative. METHODS: Total daily energy expenditure (TEE) measured by doubly labeled water (DLW) and a metabolic chamber from 119 subjects obtained from a database of pre-intervention measurements measured at Pennington Biomedical Research Center were used to develop a metabolic ward and free-living models that predict energy requirements. Graded models, including different combinations of input variables consisting of age, height, weight, waist circumference, body composition, and the resting metabolic rate were developed. The newly developed models were validated and compared to three independent databases. RESULTS: Sixty-four different linear and nonlinear regression models were developed. The adjusted R2 for models predicting free-living energy requirements ranged from 0.65 with covariates of age, height, and weight to 0.74 in models that included body composition and RMR. Independent validation R2 between actual and predicted TEE varied greatly across studies and between genders with higher coefficients of determination, lower bias, slopes closer to 1, and intercepts closer to zero, associated with inclusion of body composition and RMR covariates. The models were programmed into a user-friendly web-based app available at: http://www.pbrc.edu/research-and-faculty/calculators/energy-requirements/ (Video Demo for Reviewers at: https://www.youtube.com/watch?v=5UKjJeQdODQ ) CONCLUSIONS: Energy-requirement equations that do not require knowledge of activity levels and include all available input variables can provide more accurate baseline estimates. The models are clinically accessible through the web-based application.

Effect of Inorganic Nitrite vs Placebo on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction: The INDIE-HFpEF Randomized Clinical Trial.

Importance: There are few effective treatments for heart failure with preserved ejection fraction (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations has been shown to enhance nitric oxide signaling, which may improve aerobic capacity in HFpEF. Objective: To determine the effect of 4 weeks' administration of inhaled, nebulized inorganic nitrite on exercise capacity in HFpEF. Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled, 2-treatment, crossover trial of 105 patients with HFpEF. Participants were enrolled from July 22, 2016, to September 12, 2017, at 17 US sites, with final date of follow-up of January 2, 2018. Interventions: Inorganic nitrite or placebo administered via micronebulizer device. During each 6-week phase of the crossover study, participants received no study drug for 2 weeks (baseline/washout) followed by study drug (nitrite or placebo) at 46 mg 3 times a day for 1 week followed by 80 mg 3 times a day for 3 weeks. Main Outcomes and Measures: The primary end point was peak oxygen consumption (mL/kg/min). Secondary end points included daily activity levels assessed by accelerometry, health status as assessed by the Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores reflecting better quality of life), functional class, cardiac filling pressures assessed by echocardiography, N-terminal fragment of the prohormone brain natriuretic peptide levels, other exercise indices, adverse events, and tolerability. Outcomes were assessed after treatment for 4 weeks. Results: Among 105 patients who were randomized (median age, 68 years; 56% women), 98 (93%) completed the trial. During the nitrite phase, there was no significant difference in mean peak oxygen consumption as compared with the placebo phase (13.5 vs 13.7 mL/kg/min; difference, -0.20 [95% CI, -0.56 to 0.16]; P = .27). There were no significant between-treatment phase differences in daily activity levels (5497 vs 5503 accelerometry units; difference, -15 [95% CI, -264 to 234]; P = .91), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (62.6 vs 61.9; difference, 1.1 [95% CI, -1.4 to 3.5]; P = .39), functional class (2.5 vs 2.5; difference, 0.1 [95% CI, -0.1 to 0.2]; P = .43), echocardiographic E/e' ratio (16.4 vs 16.6; difference, 0.1 [95% CI, -1.2 to 1.3]; P = .93), or N-terminal fragment of the prohormone brain natriuretic peptide levels (520 vs 533 pg/mL; difference, 11 [95% CI, -53 to 75]; P = .74). Worsening heart failure occurred in 3 participants (2.9%) during the nitrite phase and 8 (7.6%) during the placebo phase. Conclusions and Relevance: Among patients with HFpEF, administration of inhaled inorganic nitrite for 4 weeks, compared with placebo, did not result in significant improvement in exercise capacity. Trial Registration: ClinicalTrials.gov Identifier: NCT02742129.

Lack of Seasonal Differences in Basal Metabolic Rate in Humans: A Cross-Sectional Study.

Some studies indicate that basal metabolic rate is greater in winter than in the summer, suggesting a role for brown fat in human thermogenesis. We examined whether there are clinically meaningful differences in basal metabolic rate under thermoneutral conditions between winter and summer months in inhabitants of Rochester, Minnesota. We collated data from 220 research volunteers studied in the winter (December 1 - February 28) and 214 volunteers studied in the summer (June 1 - August 31), 1995-2012. Basal metabolic rate was measured by indirect calorimetry and body composition by dual-energy X-ray absorptiometry. The effect of season on basal metabolic rate was tested using multivariate regression analysis with basal metabolic rate as the dependent variable and fat-free mass, fat mass, age, sex, and season as the independent variables. The groups were comparable with respect to age, body mass index, fat mass, and fat-free mass. There was no significant difference in basal metabolic rate between winter and summer groups (1 667±322 vs. 1 669±330 kcal/day). Both winter and summer basal metabolic rates were strongly predicted by fat-free mass (Pearson's r=0.75 and r=0.77, respectively, p <0.0001). Using multiple linear regression analysis, basal metabolic rate was significantly, independently predicted by fat-free mass, fat mass, age, and sex, but not season. We conclude that the lack of seasonal variation of thermoneutral basal metabolic rate between winter and summer suggests that modern, Western populations do not engage thermogenically detectable brown fat activity during periods of living in a cold climate.

Supervised, Vigorous Intensity Exercise Intervention for Depressed Female Smokers: A Pilot Study.

INTRODUCTION: Few studies have evaluated exercise interventions for smokers with depression or other psychiatric comorbidities. This pilot study evaluated the potential role of supervised vigorous exercise as a smoking cessation intervention for depressed females. METHODS: Thirty adult women with moderate-severe depressive symptoms were enrolled and randomly assigned to 12 weeks of thrice weekly, in person sessions of vigorous intensity supervised exercise at a YMCA setting (EX; n = 15) or health education (HE; n = 15). All participants received behavioral smoking cessation counseling and nicotine patch therapy. Assessments were done in person at baseline, at the end of 12 weeks of treatment, and at 6 months post-target quit date. Primary end points were exercise adherence (proportion of 36 sessions attended) and biochemically confirmed 7-day point prevalence abstinence at Week 12. Biomarkers of inflammation were explored for differences between treatment groups and between women who smoked and those abstinent at Week 12. RESULTS: Treatment adherence was high for both groups (72% for EX and 66% for HE; p = .55). The Week 12 smoking abstinence rate was higher for EX than HE (11/15 [73%] vs. 5/15 [33%]; p = .028), but no significant differences emerged at 6-month follow-up. Interleukin-6 levels increased more for those smoking than women abstinent at Week 12 (p = .040). CONCLUSIONS: Vigorous intensity supervised exercise is feasible and enhances short-term smoking cessation among depressed female smokers. Innovative and cost-effective strategies to bolster long-term exercise adherence and smoking cessation need evaluation in this population. Inflammatory biomarkers could be examined in future research as mediators of treatment efficacy. IMPLICATIONS: This preliminary study found that vigorous intensity supervised exercise is feasible and enhances short-term smoking cessation among depressed female smokers. This research addressed an important gap in the field. Despite decades of research examining exercise interventions for smoking cessation, few studies were done among depressed smokers or those with comorbid psychiatric disorders. A novel finding was increases in levels of a pro-inflammatory biomarker observed among women who smoked at the end of the intervention compared to those who did not.

Prevention of Child Sexual Abuse by Targeting Pre-Offenders Before First Offense.

The population of potential child abuse offenders has largely been unstudied. In the current study, we examine whether a six-component model used for primary diabetes prevention could be adapted to child sexual abuse pre-offenders, whereby individuals who are prone to sexual abuse but have not yet committed an offense can be prevented from committing a first offense. The six components include: define and track the magnitude of the problem, delineate a well-established risk factor profile so that at-risk persons can be identified, define valid screening tests to correctly rule in those with the disease and rule out those without disease, test effectiveness of interventions-the Dunkelfeld Project is an example, produce and disseminate reliable outcome data so that widespread application can be justified, and establish a system for continuous improvement. By using the diabetes primary prevention model as a model, the number of victims of child sexual abuse might be diminished.

Sick of sitting.

Sitting too much kills. Epidemiological, physiological and molecular data suggest that sedentary lifestyle can explain, in part, how modernity is associated with obesity, more than 30 chronic diseases and conditions and high healthcare costs. Excessive sitting--sitting disease--is not innate to the human condition. People were designed to be bipedal and, before the industrial revolution, people moved substantially more throughout the day than they do presently. It is encouraging that solutions exist to reverse sitting disease. Work environments, schools, communities and cities can be re-imagined and re-invented as walking spaces, and people thereby offered more active, happier, healthier and more productive lives.

Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration.

Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 µg tri-iodothyronine (T3) in 7- and 27-mo-old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones. The increased food intake in the young rats corresponded with a T3-mediated increase in the appetite-regulating proteins agouti-related peptide, neuropeptide Y, and uncoupling protein 2 in the hypothalamus, but no increase occurred in the old rats. Evidence of mitochondrial biogenesis in response to T3 was similar in the soleus muscle and heart of the young and old animals, but less consistent in old plantaris muscle and liver. Despite the comparable increase in EE, T3's effect on mitochondrial function was modulated by age in a tissue-specific manner. We conclude that older rats lack compensatory mechanisms to increase caloric intake in response to a T3-induced increase in EE, demonstrating a detrimental effect of age on energy homeostasis.

Workplace slip, trip and fall injuries and obesity.

The objective of this study was to examine the relationship between slip, trip and fall injuries and obesity in a population of workers at the Idaho National Laboratory (INL) in Idaho Falls, Idaho. INL is an applied engineering facility dedicated to supporting the US Department of Energy's mission. An analysis was performed on injuries reported to the INL Medical Clinic to determine whether obesity was related to an increase in slip, trip and fall injuries. Records were analysed that spanned a 6-year period (2005-2010), and included 8581 employees (mean age, 47 ± 11 years and body mass index [BMI], 29 ± 5 kg/m(2); 34% obesity rate). Of the 189 people who reported slip, trip and fall injuries (mean age, 48 ± 11 years), 51% were obese (P < 0.001 compared with uninjured employees), and their mean BMI was 31 ± 6 kg/m(2) (P < 0.001). Obesity in this population was associated with a greater rate of slip, trip and fall injuries.

The Fidget Factor and the obesity paradox. How small movements have big impact.

The hypothesis is that the Fidget Factor is the innate neurological pulse that propels humans and other species to move to support their health. Fidgets, previously thought to be spontaneous, are neurologically regulated and highly ordered (non-random). Modern societies being chair-based overwhelm Fidget Factor pulses and consequently inflict chair-based living for transportation, labor, and leisure. Despite impulses firing through the nervous system, people sit because environmental design overwhelms the biology. Urbanization and chair-based societies were designed after the industrial revolution to promote productivity; however, the consequence has been opposite. Crushing the natural urge to move-the Fidget Factor-is a public health calamity. Excess sitting is associated with a myriad of detrimental health consequences and impairs productivity. Fidgeting may reduce all-cause mortality associated with excessive sitting. The Fidget Factor offers hope; data demonstrate that workplaces and schools can be designed to promote activity and free people's Fidget Factors. Evidence shows that people are happier, healthier, wealthier, and more successful if their Fidget Factors are freed.

Effects of Experimental Sleep Restriction on Energy Intake, Energy Expenditure, and Visceral Obesity.

BACKGROUND: Although the consequences of sleep deficiency for obesity risk are increasingly apparent, experimental evidence is limited and there are no studies on body fat distribution. OBJECTIVES: The purpose of this study was to investigate the effects of experimentally-induced sleep curtailment in the setting of free access to food on energy intake, energy expenditure, and regional body composition. METHODS: Twelve healthy, nonobese individuals (9 males, age range 19 to 39 years) completed a randomized, controlled, crossover, 21-day inpatient study comprising 4 days of acclimation, 14 days of experimental sleep restriction (4 hour sleep opportunity) or control sleep (9 hour sleep opportunity), and a 3-day recovery segment. Repeated measures of energy intake, energy expenditure, body weight, body composition, fat distribution and circulating biomarkers were acquired. RESULTS: With sleep restriction vs control, participants consumed more calories (P = 0.015), increasing protein (P = 0.050) and fat intake (P = 0.046). Energy expenditure was unchanged (all P > 0.16). Participants gained significantly more weight when exposed to experimental sleep restriction than during control sleep (P = 0.008). While changes in total body fat did not differ between conditions (P = 0.710), total abdominal fat increased only during sleep restriction (P = 0.011), with significant increases evident in both subcutaneous and visceral abdominal fat depots (P = 0.047 and P = 0.042, respectively). CONCLUSIONS: Sleep restriction combined with ad libitum food promotes excess energy intake without varying energy expenditure. Weight gain and particularly central accumulation of fat indicate that sleep loss predisposes to abdominal visceral obesity. (Sleep Restriction and Obesity; NCT01580761).

The energy expenditure of an activity-promoting video game compared to sedentary video games and TV watching.

BACKGROUND: In the present study we investigated the effect of television watching and the use of activity-promoting video games on energy expenditure in obese and lean children. METHODS: Energy expenditure and physical activity were measured while participants were watching television, playing a video game on a traditional sedentary video game console, and while playing the same video game on an activity-promoting video game console. RESULTS: Energy expenditure was significantly greater than television watching and playing video games on a sedentary video game console when children played the video game on the activity-promoting console. When examining movement with accelerometry, children moved significantly more when playing the video game on the Nintendo Wii console. CONCLUSION: Activity-promoting video games have shown to increase movement, and be an important tool to raise energy expenditure by 50% when compared to sedentary activities of daily living.

Effects of a worksite physical activity intervention for hospital nurses who are working mothers.

Hospital nurses who are working mothers are challenged to maintain their personal health and model healthy behaviors for their children. This study aimed to develop and test an innovative 10-week worksite physical activity intervention integrated into the work flow of hospital-based nurses who were mothers. Three volunteer adult medical-surgical nursing units participated as intervention units. Fifty-eight nurses (30 intervention and 28 control) provided baseline and post-intervention repeated measurements of physical activity (steps) and body composition. Intervention participants provided post-intervention focus group feedback. For both groups, daily steps averaged more than 12,400 at baseline and post-intervention. No significant effects were found for physical activity; significant effects were found for fat mass, fat index, and percent fat (p < .03). Focus group findings supported the intervention and other data collected. The worksite holds promise for targeting the health of working mothers. Future research is warranted with a larger sample, longer intervention, and additional measures.

Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity.

Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that high-capacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intra-paraventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT.

Energy intake during activity enhanced video game play.

The purpose of this study was to examine whether the addition of a motor component to video gaming alters energy consumption. To address this problem we used an experimental manipulation design with 9-13 year olds incorporating 'seated video game' and 'activity enhanced video game' conditions, whilst allowing snacks ad libitum. No difference in snacking between the two video gaming conditions was apparent. The children consumed 374 and 383kcalh(-1) during seated and activity enhanced video gaming, respectively. A secondary purpose was to examine consistency of energy intake during free choice video game play. We found no difference in energy intake between four 1h free choice video gaming sessions. Snacking energy intake whilst video gaming was 166% more than the calories required during resting conditions. This study has shown that the addition of a motor component to the video game environment does not alter snack energy intake. However, the high calorific consumption during both seated and activity enhanced video game play highlights the need for an active attempt to restrict snacking whilst playing video games.

Obesity in neurobiology.

Obesity reflects an imbalance between energy uptake and expenditure that is mediated by behavior. Obesity is a growing epidemic and a major risk factor for neurobiological diseases like stroke, dementia, intracranial hypertension and sleep disorders. Conversely, obesity can also be induced by neurobiological disorders and drugs. The etiology of obesity is complex and includes biology, behavior and environment. Physicians are faced with the need to manage obesity while strategies for prevention and sustained weight reduction are limited. Present treatment options comprise lifestyle modification, diet, pharmacotherapy and bariatric surgery. Considerable headway has been made into elucidating the neurobiological underpinnings of obesogenic behavior. There is now a growing understanding of the metabolic, hormonal and behavioral circuitries that contribute to the complex and redundant system for energy balance. Changing the net balance of this system to prevent or reduce obesity requires multimodal and long-term interventions.

Walking Time Is Associated With Hippocampal Volume in Overweight and Obese Office Workers.

Objectives: To investigate the long-term effects on cognition and brain function after installing treadmill workstations in offices for 13 months. Methods: Eighty healthy overweight or obese office workers aged 40-67 years were individually randomized to an intervention group, receiving a treadmill workstation and encouraging emails, or to a control group, continuing to work as usual. Effects on cognitive function, hippocampal volume, prefrontal cortex (PFC) thickness, and circulating brain-derived neurotrophic factor (BDNF) were analyzed. Further, mediation analyses between changes in walking time and light-intensity physical activity (LPA) on changes in BDNF and hippocampal volume between baseline and 13 months, and multivariate analyses of the baseline data with percentage sitting time as the response variable, were performed. Results: No group by time interactions were observed for any of the outcomes. In the mediation analyses, positive associations between changes in walking time and LPA on changes in hippocampal volume were observed, although not mediated by changes in BDNF levels. In the multivariate analyses, a negative association between percentage sitting time and hippocampal volume was observed, however only among those older than 51 years of age. Conclusion: Although no group by time interactions were observed, our analyses suggest that increased walking and LPA may have positive effects on hippocampal volume and that sedentary behavior is associated with brain structures of importance for memory functions. Trial Registration: www.ClinicalTrials.gov as NCT01997970.

Activity-promoting video games and increased energy expenditure.

OBJECTIVES: To test the hypothesis that both children and adults would expend more calories and move more while playing activity-promoting video games compared with sedentary video games. STUDY DESIGN: In this single-group study, 22 healthy children (12 +/- 2 years; 11 male, 11 female) and 20 adults (34 +/- 11 years; 10 male, 10 female) were recruited. Energy expenditure and physical activity were measured while participants were resting, standing, watching television seated, sitting and playing a traditional sedentary video game, and while playing an activity-promoting video game (Nintendo Wii Boxing). Physical activity was measured with accelerometers, and energy expenditure was measured with an indirect calorimeter. RESULTS: Energy expenditure was significantly greater than all other activities when children or adults played Nintendo Wii (mean increase over resting, 189 +/- 63 kcal/hr, P < .001, and 148 +/- 71 kcal/hr, P < .001, respectively). When examining movement with accelerometry, children moved significantly more than adults (55 +/- 5 arbitrary acceleration units and 23 +/- 2 arbitrary acceleration units, respectively, P < .001) while playing Nintendo Wii. CONCLUSION: Activity-promoting video games have the potential to increase movement and energy expenditure in children and adults.