No evidence for metabolic adaptation during exercise-related energy compensation.

The constrained energy model posits that the increased total daily energy expenditure (TDEE) in response to exercise is often less than the energy cost of the exercise prescribed. The mechanisms behind this phenomenon, coined "exercise-related energy compensation" (ExEC), are poorly understood, and it is unknown if ExEC is coupled with metabolic adaptation. Using a randomized controlled 24-week exercise intervention, individuals who demonstrated ExEC were identified. Changes to all components of TDEE and metabolic adaptation were assessed using doubly labeled water over 14 days and room calorimetry over 24-h 48% of individuals exhibited ExEC (-308 ± 158 kcals/day). There were no statistically significant differences in sex, age, or BMI between ExEC and non-ExEC. ExEC was associated with baseline TDEE (r = -0.50, p = 0.006). There were no statistically significant differences in metabolic adaptations for 24 h, sleep, or resting expenditures. These findings reveal that ExEC occurs independent of metabolic adaptation in sedentary components of EE.

Recommendations for the diagnosis and management of vaccine-induced immune thrombotic thrombocytopenia.

There have recently been safety concerns regarding an increased risk of vaccine-induced immune thrombotic thrombocytopenia (VITT) following administration of SARS-CoV-2 adenoviral vector vaccines. The Southern African Society of Thrombosis and Haemostasis reviewed the emerging literature on this idiosyncratic complication. A draft document was produced and revised by consensus agreement by a panel of professionals from various specialties. The recommendations were adjudicated by independent international experts to avoid local bias. We present concise, practical guidelines for the clinical management of VITT.

Periconception weight management in the Women, Infants, and Children program.

INTRODUCTION: Reproductive age women, particularly low-income and minority women, are at risk for obesity. As an integral service provider for these women, the US Department of Agriculture Special Supplemental Nutrition Program for Women, Infants, and Children is uniquely positioned to refine its focus and efforts. METHODS: Strategies for accomplishing this goal include identifying pregnant, inter-partum and post-partum women in need of targeted patient-centred services including education, counselling and support to address weight loss or appropriate gestational weight gain. RESULTS: These services may include calorie-controlled diets, behavioural strategies, alternative methods of education delivery and extending post-partum benefits. Implementation of these strategies is feasible through collaboration with related government subsidized programs and reallocation of funds, staff and other resources. CONCLUSIONS: Given the magnitude of the problem and the adverse outcomes that obesity has on health and quality of life, Women, Infants, and Children can more positively impact the lives of our most vulnerable families, which face an obesogenic environment.

Relationships between misreported energy intake and pregnancy in the pregnancy, infection and nutrition study: new insights from a dynamic energy balance model.

OBJECTIVE: Providing effective dietary counselling so that pregnancy weight gain remains within the 2009 Institute of Medicine (IOM) guidelines requires accurate maternal energy intake measures. Current practice is based on self-reported intake that has been demonstrated unreliable. This study applies an objective calculation of energy intake from a validated mathematical model to identify characteristics of individuals more likely to misreport during pregnancy. METHODS: A validated maternal energy balance equation was used to calculate energy intake from gestational weight gain in 1,368 subjects. The difference between self-reported and model-predicted energy intake was tested for demographics, economic status, education level and maternal health status. RESULTS: A weight gain of 15.2 kg resulted in model-predicted intake during pregnancy of 2,882.97 ± 135.71 kcal day-1, which differed from self-reported intake of 2,180.5 ± 856.0 kcal day-1. The achieved weight gain exceeded the IOM guidelines; however, the model predicted weight gain from self-reported energy intake was below IOM guidelines. Higher income (p = 0.004), education (p = 0.003), birth weight (p = 0.017), gestational diabetes (p = 0.008) and pre-existing diabetes (p < 0.001) were associated with under-reported energy intake. More children living at home (p = 0.001) were associated with more accurate self-reported intake. CONCLUSIONS: When assessing self-reported energy intake in pregnancy studies, birth weight, gestational diabetes status, pre-existing diabetes, higher income and education predict higher under-reporting. Clinicians providing dietary treatment recommendations during pregnancy should be aware that individuals with pre-existing diabetes and gestational diabetes mellitus are more likely to misreport their intake. Additionally, the systems model approach can be applied early in intervention to objectively monitor dietary compliance to treatment recommendations.

Eight weeks of dietary overfeeding increases renal filtration rates in humans: implications for the pathogenesis of diabetic hyperfiltration.

OBJECTIVE: Diabetic nephropathy is characterized at its onset by glomerular hyperfiltration. Prospective studies in humans measuring filtration rates with weight gain are lacking. We investigated renal filtration following weight gain induced by overfeeding. DESIGN: Eight weeks of overfeeding (40% above energy requirements, 44% fat, 15% protein and 41% carbohydrate) as well as a 6-month follow-up after the overfeeding intervention. SUBJECTS: Thirty-five participants (age: 26.7 ±5.3 years; body mass index: 25.5 ± 2.2 kg m(-2) ; 29 m/6f). MEASUREMENTS: Creatinine clearance rate (Ccr) from 24-h urine collection, estimated glomerular filtration rate (eGFR) from the modification of diet in renal disease (MDRD), insulin sensitivity/glucose disposal rate (GDR) by a euglycemic-hyperinsulinemic clamp, components from basic metabolic panels and serum lipid panels. RESULTS: Both eGFR and Ccr increased with overfeeding (P = 0.04) and serum lipids (all P < 0.05), along with a decrease in insulin sensitivity (P = 0.003). Fasting glucose concentration was not affected (P = 0.98), but the per cent change in Ccr correlated positively with the change in GDR with overfeeding (r = 0.39, P = 0.02). Six months following overfeeding, serum glucose was maintained, and no evidence of urinary glucose was observed at any time-point. CONCLUSIONS: These data suggest that renal hyperfiltration may act as a mechanism to preserve insulin sensitivity through maintenance of systemic glucose homoeostasis with caloric excess.

An evolving scientific basis for the prevention and treatment of pediatric obesity.

The 2013 Pennington Biomedical Research Center's Scientific Symposium focused on the treatment and management of pediatric obesity and was designed to (i) review recent scientific advances in the prevention, clinical treatment and management of pediatric obesity, (ii) integrate the latest published and unpublished findings and (iii) explore how these advances can be integrated into clinical and public health approaches. The symposium provided an overview of important new advances in the field, which led to several recommendations for incorporating the scientific evidence into practice. The science presented covered a range of topics related to pediatric obesity, including the role of genetic differences, epigenetic events influenced by in utero development, pre-pregnancy maternal obesity status, maternal nutrition and maternal weight gain on developmental programming of adiposity in offspring. Finally, the relative merits of a range of various behavioral approaches targeted at pediatric obesity were covered, together with the specific roles of pharmacotherapy and bariatric surgery in pediatric populations. In summary, pediatric obesity is a very challenging problem that is unprecedented in evolutionary terms; one which has the capacity to negate many of the health benefits that have contributed to the increased longevity observed in the developed world.

HIV, vascular surgery and cardiovascular outcomes: a South African cohort study.

Risk factors for peri-operative cardiac morbidity are poorly described in HIV-positive patients. This prospective observational study describes cardiovascular risk factors in a cohort of vascular surgical patients of known HIV status. We recruited 225 patients with 73 (32%) being HIV-positive. When compared with HIV-negative patients, the HIV-positive patients were younger (mean (SD) 56.4 (13.3) vs 40.5 (10.4) years, respectively, p < 0.01). They had fewer Revised Cardiac Risk Index cardiovascular risk factors (median (range [IQR]) 1 (0-5 [0-2]) vs 0 (0-2 [0-0]), respectively, p < 0.001), with the exception of congestive cardiac failure (p = 0.23) and renal dysfunction (p = 0.32), and so were of a significantly lower Revised Cardiac Risk Index risk category (p < 0.01). HIV-positive and -negative patients had similar outcomes in: 30-day mortality (p = 0.78); three-day postoperative troponin leak (p = 0.66); and a composite outcome of mortality and troponin release (p = 0.69). We conclude that although HIV-positive patients have fewer cardiovascular risk factors, they have similar peri-operative major adverse cardiac events to HIV-negative patients. Research should focus on why this is the case, and if alternative clinical risk predictors can be developed for HIV patients.

Weight loss composition is one-fourth fat-free mass: a critical review and critique of this widely cited rule.

Maximizing fat loss while preserving lean tissue mass and function is a central goal of modern obesity treatments. A widely cited rule guiding expected loss of lean tissue as fat-free mass (FFM) states that approximately one-fourth of weight loss will be FFM (i.e. ΔFFM/ΔWeight = ∼0.25), with the remaining three-fourths being fat mass. This review examines the dynamic relationships between FFM, fat mass and weight changes that follow induction of negative energy balance with hypocaloric dieting and/or exercise. Historical developments in the field are traced with the 'Quarter FFM Rule' used as a framework to examine evolving concepts on obesity tissue, excess weight and what is often cited as 'Forbes' Rule'. Temporal effects in the fractional contribution of FFM to changes in body weight are examined as are lean tissue moderating effects such as ageing, inactivity and exercise that frequently accompany structured low-calorie diet weight loss protocols. Losses of lean tissue with dieting typically tend to be small, raising questions about study design, power and applied measurement method reliability. Our review elicits important questions related to the fractional loss of lean tissues with dieting and provides a foundation for future research on this topic.

Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE Phase 2) screening and recruitment: methods and results.

The Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE) study is a systematic investigation of sustained 25% calorie restriction (CR) in non-obese humans. CALERIE is a multicenter (3 clinical sites, one coordinating center), parallel group, randomized controlled trial. Participants were recruited, screened, and randomized to the CR or control group with a 2:1 allocation. Inclusion criteria included ages 21-50 years for men and 21-47 years for women, and a body mass index (BMI) of 22.0 ≤ BMI < 28.0 kg/m(2). Exclusion criteria included abnormal laboratory markers, significant medical conditions, psychiatric/behavioral problems, and an inability to adhere to the rigors of the evaluation/intervention schedule. A multi-stage screening process (telephone screen and 3 in-clinic visits) was applied to identify eligible participants. Recruitment was effective and enrollment targets were met on time. 10,856 individuals contacted the clinical sites, of whom 9787 (90%) failed one or more eligibility criteria. Of the 1069 volunteers who started the in-clinic screening, 831 (78%) were either ineligible or dropped. 238 volunteers were enrolled (i.e., initiated the baseline evaluations), 220 were randomized, and 218 started the assigned intervention (2% from the first screening step). This study offered lessons for future multi-center trials engaging non-disease populations. Recruitment strategies must be tailored to specific sites. A multi-disciplinary screening process should be applied to address medical, physical, and psychological/behavioral suitability of participants. Finally, a multi-step screening process with simple criteria first, followed by more elaborate procedures has the potential to reduce the use of study resources.

Why do individuals not lose more weight from an exercise intervention at a defined dose? An energy balance analysis.

Weight loss resulting from an exercise intervention tends to be lower than predicted. Modest weight loss can arise from an increase in energy intake, physiological reductions in resting energy expenditure, an increase in lean tissue or a decrease in non-exercise activity. Lower than expected, weight loss could also arise from weak and invalidated assumptions within predictive models. To investigate these causes, we systematically reviewed studies that monitored compliance to exercise prescriptions and measured exercise-induced change in body composition. Changed body energy stores were calculated to determine the deficit between total daily energy intake and energy expenditures. This information combined with available measurements was used to critically evaluate explanations for low exercise-induced weight loss. We conclude that the small magnitude of weight loss observed from the majority of evaluated exercise interventions is primarily due to low doses of prescribed exercise energy expenditures compounded by a concomitant increase in caloric intake.

Association of ß-2 adrenergic agonist and corticosteroid injection in the treatment of lipomas.

AIM: The aim of this study was to evaluate the efficacy of isoproterenol and prednisolone in the treatment of subcutaneous lipomas. METHODS: The first experiment evaluated in vitro lipolysis induced by isoproterenol 10(-6) M alone and across a range of prednisolone concentrations to determine the optimal dose to maximize lipolysis. The second experiment evaluated lipolysis in a lipoma and subcutaneous fat by in vivo microdialysis in five subjects to isoproterenol 10(-6) M with and without prednisolone 10(-6) M. These five subjects and five additional subjects had a lipoma treated five times a week for 4 weeks in a 4-cm grid with 0.2 ml injections of 10(-6) M isoproterenol and 10(-6) M prednisolone. Lipoma size was followed monthly for 1 year or until surgical removal. RESULTS: Prednisolone increased in vitro lipolysis to isoproterenol and 10(-6) M was the optimal concentration of both drugs. Lipomas responded with less lipolysis to isoproterenol than subcutaneous fat during microdialysis, and prednisolone treatment increased lipolysis in both lipomas and subcutaneous fat. Injection treatment of the lipomas decreased their volume 50%. All but one lipoma grew after treatment. Eight of the 10 subjects elected for surgical treatment, and the histology of the lipomas was normal fat tissue. CONCLUSIONS: Prednisolone and isoproterenol in combination increased lipolysis, and injections of the combination into lipomas decreased their volume 50% over 4 weeks. Eight of the 10 subjects elected for surgical removal.

Lorcaserin for the treatment of obesity.

Obesity is a worldwide epidemic and there is an urgent need for the development of effective pharmacological therapies that target the metabolic and behavioral factors of body weight regulation. Serotonin (5-HT) has been implicated as a critical factor in the short-term (meal-by-meal) regulation of food intake and pharmaceutical companies have invested millions of dollars to discover and develop drug targets for the serotonergic pathway. Lorcaserin is a novel selective agonist of the 5-HT(2C) receptor for weight loss therapy. Preclinical and clinical studies indicate lorcaserin is well tolerated and not associated with cardiac valvulopathy or pulmonary hypertension suggesting that lorcaserin is a selective 5-HT(2C) receptor agonist and has little or no activation of the 5-HT(2B) and 5-HT(2A) receptors, respectively. Lorcaserin acts to alter energy balance through a reduction in energy intake and without an increase in energy expenditure and achieved the U.S. Food and Drug Administration guidelines for weight loss efficacy. It remains to be determined whether or not lorcaserin will be approved for the long-term management of obesity.

Psychosocial and behavioral pre-treatment predictors of weight loss outcomes.

OBJECTIVE: This study tested whether baseline behavioral and psychological variables predict weight and fat loss among overweight, non-obese individuals participating in a six-month calorie restriction trial. Participants (N=48) were randomly assigned to four groups, three of which included a calorie restriction program and one of which served as a healthy diet weight maintenance control. For the purposes of this study, data were analyzed only for participants assigned to the three calorie restriction groups (n=36). Ten psychological and behavioral measures were investigated through principal components factor analysis to examine whether these measures were assessing similar or distinct psychological and behavioral constructs. Based on the obtained six-factor solution, one measure from each domain was selected for inclusion in hierarchical regression analyses, which was used to test the relative importance of psychosocial and behavioral variables in predicting percent weight and fat loss over six months. After controlling for demographic and treatment variables, the behavioral and psychological measures of negative mood states, poor psychosocial functioning, and somatic symptoms were associated with less weight loss (R2=0.68, p<0.001) and fat loss (R2=0.65, p<0.001) over six months. Among overweight individuals, poor psychological adjustment, somatic symptoms, and negative mood states appear to form a psychosocial profile that is predictive of less weight and fat loss in calorie restriction programs.

Methanol half-life during ethanol administration: implications for management of methanol poisoning.

STUDY OBJECTIVE: To determine the half-life of methanol in methanol-poisoned patients who are treated with ethanol but not with hemodialysis. DESIGN: Case series. SETTING: University Hospital, University of Manitoba. PARTICIPANTS: Three methanol-poisoned patients treated with ethanol but not with hemodialysis and three similar patients identified by a literature review. RESULTS: Plots of terminal concentration versus time data were inconsistent with zero-order kinetics and were adequately explained by an apparent first-order process. The median half-life of methanol in these patients was 43.1 hours, with a range of 30.3 to 52.0 hours. CONCLUSION: Because of the significantly increased risk of toxicity and complications during ethanol monotherapy, we suggest that hemodialysis be considered for methanol-poisoned patients who are treated with ethanol infusion.

The uses of theory in health advocacy: policies and programs.

This paper illustrates the utility of theory for health educators who advocate for health promotion policies and programs. It describes how diffusion of innovation and other social science theories were employed by a statewide coalition called the Health Promotion and Education Council of Virginia in its effort to reduce premature and preventable death and disability in the state. To this end the Council sought legislative action to accelerate the diffusion of health promotion throughout the state. Discussing elements of diffusion theory such as working through opinion leaders, creating information-exchange relationships, and tailoring the attributes of the innovation to achieve its objectives, the paper reviews the process through which the Council became an effective advocate, and the strategies it devised to communicate the innovation of health promotion to legislators. The legislation that was generated by the work of the legislative study committee and future uses of theory are also discussed.

Iodination of [Tyr8]-bradykinin-comparison of chloramine-T and lactoperoxidase techniques.

Antigen-antibody kinetics were studied using a hapten which was iodinated by two unique procedures. Using bradykinin, a vasopressor hormone as a model peptide, radioactive iodination (125I) of its 8-tyrosyl analogue was carried out both enzymatically and chemically using modified procedures. Two distinct chemical species were obtained which were characterized on a chromatographic, chemical as well as charge basis as a mono-iodinated form of [Tyr8]-bradykinin using the lactoperoxidase procedure and a di-iodinated entity using chloramine-T technique. The addition of a second iodine atom to the antigen lowers its immunoreactivity for its antibody and thus alters the kinetics of this reaction. Further experiments on the stability (temperature, time of storage, and chemical environment) of these iodinated peptides are described.

An improved ultra-violet halothane meter.

The development of an ultra-violet absorption meter, suitable for the measurement of concentrations of halothane (0-5%) under clinical conditions, is described. The scale is accurate to 0.05% and the zero draft did not exceed 0.25% halothane over 15 h after a 5-min warm-up period. The inherent time of response is about 2 s.