Head Position in Stroke Trial (HeadPoST)- sitting-up vs lying-flat positioning of patients with acute stroke: study protocol for a cluster randomised controlled trial

Background Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke. Methods/Design We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥30°) head position as a ‘business as usual’ stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period. Discussion HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke. Trial registration ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014

Global and regional brain metabolic scaling and its functional consequences

Background: Information processing in the brain requires large amounts of metabolic energy, the spatial distribution of which is highly heterogeneous reflecting complex activity patterns in the mammalian brain. Results: Here, it is found based on empirical data that, despite this heterogeneity, the volume-specific cerebral glucose metabolic rate of many different brain structures scales with brain volume with almost the same exponent around -0.15. The exception is white matter, the metabolism of which seems to scale with a standard specific exponent -1/4. The scaling exponents for the total oxygen and glucose consumptions in the brain in relation to its volume are identical and equal to $0.86\pm 0.03$, which is significantly larger than the exponents 3/4 and 2/3 suggested for whole body basal metabolism on body mass. Conclusions: These findings show explicitly that in mammals (i) volume-specific scaling exponents of the cerebral energy expenditure in different brain parts are approximately constant (except brain stem structures), and (ii) the total cerebral metabolic exponent against brain volume is greater than the much-cited Kleiber's 3/4 exponent. The neurophysiological factors that might account for the regional uniformity of the exponents and for the excessive scaling of the total brain metabolism are discussed, along with the relationship between brain metabolic scaling and computation.Comment: Brain metabolism scales with its mass well above 3/4 exponen

A distinct adipose tissue gene expression response to caloric restriction predicts 6-mo weight maintenance in obese subjects

BACKGROUND: Weight loss has been shown to reduce risk factors associated with cardiovascular disease and diabetes; however, successful maintenance of weight loss continues to pose a challenge. OBJECTIVE: The present study was designed to assess whether changes in subcutaneous adipose tissue (scAT) gene expression during a low-calorie diet (LCD) could be used to differentiate and predict subjects who experience successful short-term weight maintenance from subjects who experience weight regain. DESIGN: Forty white women followed a dietary protocol consisting of an 8-wk LCD phase followed by a 6-mo weight-maintenance phase. Participants were classified as weight maintainers (WMs; 0-10% weight regain) and weight regainers (WRs; 50-100% weight regain) by considering changes in body weight during the 2 phases. Anthropometric measurements, bioclinical variables, and scAT gene expression were studied in all individuals before and after the LCD. Energy intake was estimated by using 3-d dietary records. RESULTS: No differences in body weight and fasting insulin were observed between WMs and WRs at baseline or after the LCD period. The LCD resulted in significant decreases in body weight and in several plasma variables in both groups. WMs experienced a significant reduction in insulin secretion in response to an oral-glucose-tolerance test after the LCD; in contrast, no changes in insulin secretion were observed in WRs after the LCD. An ANOVA of scAT gene expression showed that genes regulating fatty acid metabolism, citric acid cycle, oxidative phosphorylation, and apoptosis were regulated differently by the LCD in WM and WR subjects. CONCLUSION: This study suggests that LCD-induced changes in insulin secretion and scAT gene expression may have the potential to predict successful short-term weight maintenanc

The dynamics of human body weight change

An imbalance between energy intake and energy expenditure will lead to a change in body weight (mass) and body composition (fat and lean masses). A quantitative understanding of the processes involved, which currently remains lacking, will be useful in determining the etiology and treatment of obesity and other conditions resulting from prolonged energy imbalance. Here, we show that the long-term dynamics of human weight change can be captured by a mathematical model of the macronutrient flux balances and all previous models are special cases of this model. We show that the generic dynamical behavior of body composition for a clamped diet can be divided into two classes. In the first class, the body composition and mass are determined uniquely. In the second class, the body composition can exist at an infinite number of possible states. Surprisingly, perturbations of dietary energy intake or energy expenditure can give identical responses in both model classes and existing data are insufficient to distinguish between these two possibilities. However, this distinction is important for the efficacy of clinical interventions that alter body composition and mass

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Optimization of production, biochemical characterization and In Vitro evaluation of the therapeutic potential of fibrinolytic enzymes from a new Bacillus Amyloliquefaciens

The capacity of fibrinolytic enzymes to degrade blood clots makes them of high relevance in medicine and in the pharmaceutical industry. In this work, forty-three microorganisms of the genus Bacillus were evaluated for their potential to produce fibrinolytic proteases. Thirty bacteria were confirmed as producers of fibrinolytic enzymes, the best results obtained for the strain Bacillus amyloliquefaciens UFPEDA 485. The optimization of the enzyme production conditions was done by a central composite design (CCD) star 23 that allowed to define the optimal conditions for soybean flour and glucose concentrations and agitation rate. The highest fibrinolytic activity (FA) of 813 U mL-1 and a degradation of blood clot in vitro of 62% were obtained in a medium with 2% (w/v) of soybean flour and 1% (w/v) glucose at 200 rpm after 48 h of cultivation, at pH 7.2 and 37 °C. The obtained fibrinolytic enzyme was characterized biochemically. Fibrinolytic activity was inhibited by PMSF (fluoride methylphenylsulfonyl - C7H7FO2S) 91.52% and EDTA (ethylenediaminetetraacetic acid - C10H16N2O8) 89.4%, confirming to be a serine- metallo protease. The optimum pH and temperature were 7.0 and 37 oC, respectively, and the enzyme was stable for 12 h. The fibrinolytic activity at physiological conditions of this enzyme produced by Bacillus amyloliquefaciens UFPEDA 485, as well as its long term stability, demonstrate that it has suitable characteristics for human and veterinary applications, and promises to be a powerful drug for the treatment of vascular diseases.We express our thanks to Coordination for the Improvement of Higher Level Education Personnel (CAPES) - Doctoral Sandwich Program (PDSE) Nº 0259/ 12-8 and National Council for Scientific and Technological Development (CNPq) - Nº 202026/2011-6 for the financial support

Effect of a weight loss intervention on anthropometric measures and metabolic risk factors in pre- versus postmenopausal women

<p>Abstract</p> <p>Background</p> <p>The present study examines changes in body weight, fat mass, metabolic and hormonal parameters in overweight and obese pre- and postmenopausal women who participated in a weight loss intervention.</p> <p>Methods</p> <p>Seventy-two subjects were included in the analysis of this single arm study (premenopausal: 22 women, age 43.7 ± 6.4 years, BMI 31.0 ± 2.4 kg/m²; postmenopausal: 50 women, age 58.2 ± 5.1 years, BMI 32.9 ± 3.7 kg/m²). Weight reduction was achieved by the use of a meal replacement and fat-reduced diet. In addition, from week 6 to 24 participants attended a guided exercise program. Body composition was analyzed with the Bod Pod^®. Blood pressures were taken at every visit and blood was collected at baseline and closeout of the study to evaluate lipids, insulin, cortisol and leptin levels.</p> <p>Results</p> <p>BMI, fat mass, waist circumference, systolic blood pressure, triglycerides, glucose, leptin and cortisol were higher in the postmenopausal women at baseline.</p> <p>Both groups achieved a substantial and comparable weight loss (pre- vs. postmenopausal: 6.7 ± 4.9 vs 6.7 ± 4.4 kg; n.s.). However, in contrast to premenopausal women, weight loss in postmenopausal women was exclusively due to a reduction of fat mass (-5.3 ± 5.1 vs -6.6 ± 4.1 kg; p < 0.01). In premenopausal women 21% of weight loss was attributed to a reduction in lean body mass.</p> <p>Blood pressure, triglycerides, HDL-cholesterol, and glucose improved significantly only in postmenopausal women whereas total cholesterol and LDL-cholesterol were lowered significantly in both groups.</p> <p>Conclusion</p> <p>Both groups showed comparable weight loss and in postmenopausal women weight loss was associated with a pronounced improvement in metabolic risk factors thereby reducing the prevalence of metabolic syndrome.</p

Genetic polymorphisms and weight loss in obesity: A randomised trial of hypo-energetic high-versus low-fat diets

OBJECTIVES: To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet. DESIGN: Randomised, parallel, two-arm, open-label multi-centre trial. SETTING: Eight clinical centres in seven European countries. PARTICIPANTS: 771 obese adult individuals. INTERVENTIONS: 10-wk dietary intervention to hypo-energetic (-600 kcal/d) diets with a targeted fat energy of 20%-25% or 40%-45%, completed in 648 participants. OUTCOME MEASURES: WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants. RESULTS: Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from -0.6 to 0.8 kg, and homozygotes, from -0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to -1.6 kg in heterozygotes, and from 3.8 kg to -2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant. CONCLUSIONS: Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet