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Sample records for outcome optimal metabolic

  1. Artificial Promoters for Metabolic Optimization

    DEFF Research Database (Denmark)

    Jensen, Peter Ruhdal; Hammer, Karin

    1998-01-01

    In this article, we review some of the expression systems that are available for Metabolic Control Analysis and Metabolic Engineering, and examine their advantages and disadvantages in different contexts. In a recent approach, artificial promoters for modulating gene expression in micro-organisms...

  2. Pareto optimality in organelle energy metabolism analysis.

    Science.gov (United States)

    Angione, Claudio; Carapezza, Giovanni; Costanza, Jole; Lió, Pietro; Nicosia, Giuseppe

    2013-01-01

    In low and high eukaryotes, energy is collected or transformed in compartments, the organelles. The rich variety of size, characteristics, and density of the organelles makes it difficult to build a general picture. In this paper, we make use of the Pareto-front analysis to investigate the optimization of energy metabolism in mitochondria and chloroplasts. Using the Pareto optimality principle, we compare models of organelle metabolism on the basis of single- and multiobjective optimization, approximation techniques (the Bayesian Automatic Relevance Determination), robustness, and pathway sensitivity analysis. Finally, we report the first analysis of the metabolic model for the hydrogenosome of Trichomonas vaginalis, which is found in several protozoan parasites. Our analysis has shown the importance of the Pareto optimality for such comparison and for insights into the evolution of the metabolism from cytoplasmic to organelle bound, involving a model order reduction. We report that Pareto fronts represent an asymptotic analysis useful to describe the metabolism of an organism aimed at maximizing concurrently two or more metabolite concentrations.

  3. An optimization model for metabolic pathways.

    Science.gov (United States)

    Planes, F J; Beasley, J E

    2009-10-15

    Different mathematical methods have emerged in the post-genomic era to determine metabolic pathways. These methods can be divided into stoichiometric methods and path finding methods. In this paper we detail a novel optimization model, based upon integer linear programming, to determine metabolic pathways. Our model links reaction stoichiometry with path finding in a single approach. We test the ability of our model to determine 40 annotated Escherichia coli metabolic pathways. We show that our model is able to determine 36 of these 40 pathways in a computationally effective manner.

  4. Metabolic Syndrome and Outcomes after Renal Intervention

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    Daynene Vykoukal

    2011-01-01

    Full Text Available Metabolic syndrome significantly increases the risk for cardiovascular disease and chronic kidney disease. The increased risk for cardiovascular diseases can partly be caused by a prothrombotic state that exists because of abdominal obesity. Multiple observational studies have consistently shown that increased body mass index as well as insulin resistance and increased fasting insulin levels is associated with chronic kidney disease, even after adjustment for related disorders. Metabolic syndrome appears to be a risk factor for chronic kidney disease, likely due to the combination of dysglycemia and high blood pressure. Metabolic syndrome is associated with markedly reduced renal clinical benefit and increased progression to hemodialysis following endovascular intervention for atherosclerotic renal artery stenosis. Metabolic syndrome is associated with inferior early outcomes for dialysis access procedures.

  5. Genetic Optimization Algorithm for Metabolic Engineering Revisited

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    Tobias B. Alter

    2018-05-01

    Full Text Available To date, several independent methods and algorithms exist for exploiting constraint-based stoichiometric models to find metabolic engineering strategies that optimize microbial production performance. Optimization procedures based on metaheuristics facilitate a straightforward adaption and expansion of engineering objectives, as well as fitness functions, while being particularly suited for solving problems of high complexity. With the increasing interest in multi-scale models and a need for solving advanced engineering problems, we strive to advance genetic algorithms, which stand out due to their intuitive optimization principles and the proven usefulness in this field of research. A drawback of genetic algorithms is that premature convergence to sub-optimal solutions easily occurs if the optimization parameters are not adapted to the specific problem. Here, we conducted comprehensive parameter sensitivity analyses to study their impact on finding optimal strain designs. We further demonstrate the capability of genetic algorithms to simultaneously handle (i multiple, non-linear engineering objectives; (ii the identification of gene target-sets according to logical gene-protein-reaction associations; (iii minimization of the number of network perturbations; and (iv the insertion of non-native reactions, while employing genome-scale metabolic models. This framework adds a level of sophistication in terms of strain design robustness, which is exemplarily tested on succinate overproduction in Escherichia coli.

  6. Optimization of lysine metabolism in Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Rytter, Jakob Vang

    ,000,000 tons. The aim of this project is to optimize the yield of lysine in C. glutamicum using metabolic engineering strategies. According to a genome scale model of C. glutamicum, theoretically there is much room for increasing the lysine yield (Kjeldsen and Nielsen 2009). Lysine synthesis requires NADPH......Commercial pig and poultry production use the essential amino acid lysine as a feed additive with the purpose of optimizing the feed utilization. Lysine is produced by a fermentation process involving either Corynebacterium glutamicum or Escherichia coli. The global annual production is around 1...... the project intends to eliminate. PGI catalyzes the conversion of alpha-D-glucose-6-phosphate to fructose-6-phosphate just downstream of the branch in the glycolysis, but it also catalyzes the reverse reaction. It is unknown whether up- or down-regulation of the pgi is required to increase the flux through...

  7. Optimizing outcomes with polymethylmethacrylate fillers.

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    Gold, Michael H; Sadick, Neil S

    2018-03-30

    The ideal filler should be long-lasting, biocompatible, chemically inert, soft and easy to use, and have a long history of safety. This review focuses on the evolution and development of the PMMA-collagen gel, Bellafill, and the 10 years of postmarketing experience of Bellafill since it received premarket approval (PMA) from the FDA as Artefill in 2006. Artefill was rebranded to Bellafill in 2015. The authors conducted a literature search on PubMed for key articles describing the steps in which Arteplast, a PMMA filler developed in 1989, led to the development of Bellafill, the only PMMA filler approved by the US FDA for the treatment of nasolabial folds and acne scar correction. The factors governing efficacy and safety were also evaluated for the major PMMA fillers available in the world. The process of manufacturing and purifying PMMA has played a major role in minimizing adverse events for Bellafill. Postmarketing surveillance data for the 2007-2016 period show that for more than 530 000 Bellafill syringes distributed worldwide, 11 confirmed granulomas (excluding clinical trial data) (0.002% of syringes sold) have been reported. Data on other PMMA fillers are limited and inconsistent. The authors suggest that adverse events are often attributable to lack of proficiency in treatment technique and other factors. Bellafill has demonstrated an excellent safety and effectiveness profile in multiple clinical studies, customer feedback, and 10 years of postmarketing surveillance experience. Adverse events occur with all fillers for a variety of reasons. In addition to quality of the product, injector skill and technique are critical to ensuring good clinical outcomes. © 2018 Wiley Periodicals, Inc.

  8. Optimizing outcomes with multifocal intraocular lenses

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    Gitansha Shreyas Sachdev

    2017-01-01

    Full Text Available Modern day cataract surgery is evolving from a visual restorative to a refractive procedure. The advent of multifocal intraocular lenses (MFIOLs allows greater spectacle independence and increased quality of life postoperatively. Since the inception in 1980s, MFIOLs have undergone various technical advancements including trifocal and extended depth of vision implants more recently. A thorough preoperative workup including the patients' visual needs and inherent ocular anatomy allows us to achieve superior outcomes. This review offers a comprehensive overview of the various types of MFIOLs and principles of optimizing outcomes through a comprehensive preoperative screening and management of postoperative complications.

  9. Sample preparation optimization in fecal metabolic profiling.

    Science.gov (United States)

    Deda, Olga; Chatziioannou, Anastasia Chrysovalantou; Fasoula, Stella; Palachanis, Dimitris; Raikos, Νicolaos; Theodoridis, Georgios A; Gika, Helen G

    2017-03-15

    Metabolomic analysis of feces can provide useful insight on the metabolic status, the health/disease state of the human/animal and the symbiosis with the gut microbiome. As a result, recently there is increased interest on the application of holistic analysis of feces for biomarker discovery. For metabolomics applications, the sample preparation process used prior to the analysis of fecal samples is of high importance, as it greatly affects the obtained metabolic profile, especially since feces, as matrix are diversifying in their physicochemical characteristics and molecular content. However there is still little information in the literature and lack of a universal approach on sample treatment for fecal metabolic profiling. The scope of the present work was to study the conditions for sample preparation of rat feces with the ultimate goal of the acquisition of comprehensive metabolic profiles either untargeted by NMR spectroscopy and GC-MS or targeted by HILIC-MS/MS. A fecal sample pooled from male and female Wistar rats was extracted under various conditions by modifying the pH value, the nature of the organic solvent and the sample weight to solvent volume ratio. It was found that the 1/2 (w f /v s ) ratio provided the highest number of metabolites under neutral and basic conditions in both untargeted profiling techniques. Concerning LC-MS profiles, neutral acetonitrile and propanol provided higher signals and wide metabolite coverage, though extraction efficiency is metabolite dependent. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Programmed Evolution for Optimization of Orthogonal Metabolic Output in Bacteria

    Science.gov (United States)

    Eckdahl, Todd T.; Campbell, A. Malcolm; Heyer, Laurie J.; Poet, Jeffrey L.; Blauch, David N.; Snyder, Nicole L.; Atchley, Dustin T.; Baker, Erich J.; Brown, Micah; Brunner, Elizabeth C.; Callen, Sean A.; Campbell, Jesse S.; Carr, Caleb J.; Carr, David R.; Chadinha, Spencer A.; Chester, Grace I.; Chester, Josh; Clarkson, Ben R.; Cochran, Kelly E.; Doherty, Shannon E.; Doyle, Catherine; Dwyer, Sarah; Edlin, Linnea M.; Evans, Rebecca A.; Fluharty, Taylor; Frederick, Janna; Galeota-Sprung, Jonah; Gammon, Betsy L.; Grieshaber, Brandon; Gronniger, Jessica; Gutteridge, Katelyn; Henningsen, Joel; Isom, Bradley; Itell, Hannah L.; Keffeler, Erica C.; Lantz, Andrew J.; Lim, Jonathan N.; McGuire, Erin P.; Moore, Alexander K.; Morton, Jerrad; Nakano, Meredith; Pearson, Sara A.; Perkins, Virginia; Parrish, Phoebe; Pierson, Claire E.; Polpityaarachchige, Sachith; Quaney, Michael J.; Slattery, Abagael; Smith, Kathryn E.; Spell, Jackson; Spencer, Morgan; Taye, Telavive; Trueblood, Kamay; Vrana, Caroline J.; Whitesides, E. Tucker

    2015-01-01

    Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields – evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization. Our approach is called Programmed Evolution to capture two concepts. First, a population of cells is programmed with DNA code to enable it to compute solutions to a chosen optimization problem. As analog computers, bacteria process known and unknown inputs and direct the output of their biochemical hardware. Second, the system employs the evolution of bacteria toward an optimal metabolic solution by imposing fitness defined by metabolic output. The current study is a proof-of-concept for Programmed Evolution applied to the optimization of a metabolic pathway for the conversion of caffeine to theophylline in E. coli. Introduced genotype variations included strength of the promoter and ribosome binding site, plasmid copy number, and chaperone proteins. We constructed 24 strains using all combinations of the genetic variables. We used a theophylline riboswitch and a tetracycline resistance gene to link theophylline production to fitness. After subjecting the mixed population to selection, we measured a change in the distribution of genotypes in the population and an increased conversion of caffeine to theophylline among the most fit strains, demonstrating Programmed Evolution. Programmed Evolution inverts the standard paradigm in metabolic engineering by harnessing evolution instead of fighting it. Our modular system enables researchers to program bacteria and use evolution to determine the combination of genetic control elements that optimizes catabolic or anabolic output and to maintain it in a population of cells. Programmed Evolution could be used for applications in energy

  11. Programmed evolution for optimization of orthogonal metabolic output in bacteria.

    Directory of Open Access Journals (Sweden)

    Todd T Eckdahl

    Full Text Available Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields - evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization. Our approach is called Programmed Evolution to capture two concepts. First, a population of cells is programmed with DNA code to enable it to compute solutions to a chosen optimization problem. As analog computers, bacteria process known and unknown inputs and direct the output of their biochemical hardware. Second, the system employs the evolution of bacteria toward an optimal metabolic solution by imposing fitness defined by metabolic output. The current study is a proof-of-concept for Programmed Evolution applied to the optimization of a metabolic pathway for the conversion of caffeine to theophylline in E. coli. Introduced genotype variations included strength of the promoter and ribosome binding site, plasmid copy number, and chaperone proteins. We constructed 24 strains using all combinations of the genetic variables. We used a theophylline riboswitch and a tetracycline resistance gene to link theophylline production to fitness. After subjecting the mixed population to selection, we measured a change in the distribution of genotypes in the population and an increased conversion of caffeine to theophylline among the most fit strains, demonstrating Programmed Evolution. Programmed Evolution inverts the standard paradigm in metabolic engineering by harnessing evolution instead of fighting it. Our modular system enables researchers to program bacteria and use evolution to determine the combination of genetic control elements that optimizes catabolic or anabolic output and to maintain it in a population of cells. Programmed Evolution could be used for applications in

  12. Effects of introducing heterologous pathways on microbial metabolism with respect to metabolic optimality

    DEFF Research Database (Denmark)

    Kim, Hyun Uk; Kim, Byoungjin; Seung, Do Young

    2014-01-01

    reactions are more frequently introduced into various microbial hosts. The genome-scale metabolic simulations of Escherichia coli strains engineered to produce 1,4-butanediol, 1,3-propanediol, and amorphadiene suggest that microbial metabolism shows much different responses to the introduced heterologous...... reactions in a strain-specific manner than typical gene knockouts in terms of the energetic status (e.g., ATP and biomass generation) and chemical production capacity. The 1,4-butanediol and 1,3-propanediol producers showed greater metabolic optimality than the wild-type strains and gene knockout mutants...... for the energetic status, while the amorphadiene producer was metabolically less optimal. For the optimal chemical production capacity, additional gene knockouts were most effective for the strain producing 1,3-propanediol, but not for the one producing 1,4-butanediol. These observations suggest that strains having...

  13. Pregnancy and Infants' Outcome: Nutritional and Metabolic Implications.

    Science.gov (United States)

    Berti, C; Cetin, I; Agostoni, C; Desoye, G; Devlieger, R; Emmett, P M; Ensenauer, R; Hauner, H; Herrera, E; Hoesli, I; Krauss-Etschmann, S; Olsen, S F; Schaefer-Graf, U; Schiessl, B; Symonds, M E; Koletzko, B

    2016-01-01

    Pregnancy is a complex period of human growth, development, and imprinting. Nutrition and metabolism play a crucial role for the health and well-being of both mother and fetus, as well as for the long-term health of the offspring. Nevertheless, several biological and physiological mechanisms related to nutritive requirements together with their transfer and utilization across the placenta are still poorly understood. In February 2009, the Child Health Foundation invited leading experts of this field to a workshop to critically review and discuss current knowledge, with the aim to highlight priorities for future research. This paper summarizes our main conclusions with regards to maternal preconceptional body mass index, gestational weight gain, placental and fetal requirements in relation to adverse pregnancy and long-term outcomes of the fetus (nutritional programming). We conclude that there is an urgent need to develop further human investigations aimed at better understanding of the basis of biochemical mechanisms and pathophysiological events related to maternal-fetal nutrition and offspring health. An improved knowledge would help to optimize nutritional recommendations for pregnancy.

  14. Optimal knockout strategies in genome-scale metabolic networks using particle swarm optimization.

    Science.gov (United States)

    Nair, Govind; Jungreuthmayer, Christian; Zanghellini, Jürgen

    2017-02-01

    Knockout strategies, particularly the concept of constrained minimal cut sets (cMCSs), are an important part of the arsenal of tools used in manipulating metabolic networks. Given a specific design, cMCSs can be calculated even in genome-scale networks. We would however like to find not only the optimal intervention strategy for a given design but the best possible design too. Our solution (PSOMCS) is to use particle swarm optimization (PSO) along with the direct calculation of cMCSs from the stoichiometric matrix to obtain optimal designs satisfying multiple objectives. To illustrate the working of PSOMCS, we apply it to a toy network. Next we show its superiority by comparing its performance against other comparable methods on a medium sized E. coli core metabolic network. PSOMCS not only finds solutions comparable to previously published results but also it is orders of magnitude faster. Finally, we use PSOMCS to predict knockouts satisfying multiple objectives in a genome-scale metabolic model of E. coli and compare it with OptKnock and RobustKnock. PSOMCS finds competitive knockout strategies and designs compared to other current methods and is in some cases significantly faster. It can be used in identifying knockouts which will force optimal desired behaviors in large and genome scale metabolic networks. It will be even more useful as larger metabolic models of industrially relevant organisms become available.

  15. Cancer treatment induced metabolic syndrome: Improving outcome with lifestyle.

    Science.gov (United States)

    Westerink, N L; Nuver, J; Lefrandt, J D; Vrieling, A H; Gietema, J A; Walenkamp, A M E

    2016-12-01

    Increasing numbers of long-term cancer survivors face important treatment related adverse effects. Cancer treatment induced metabolic syndrome (CTIMetS) is an especially prevalent and harmful condition. The aetiology of CTIMetS likely differs from metabolic syndrome in the general population, but effective treatment and prevention methods are probably similar. In this review, we summarize the potential mechanisms leading to the development of CTIMetS after various types of cancer treatment. Furthermore, we propose a safe and accessible method to treat or prevent CTIMetS through lifestyle change. In particular, we suggest that a lifestyle intervention and optimization of energy balance can prevent or mitigate the development of CTIMetS, which may contribute to optimal survivorship care. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Optimizing Aesthetic Outcomes in Delayed Breast Reconstruction

    Directory of Open Access Journals (Sweden)

    Wojciech Dec, MD

    2017-08-01

    Conclusions:. Optimal aesthetic results can be achieved with: (1 restoration of breast skin envelope with tissue expansion when possible, (2 optimal positioning of a small skin paddle to be later incorporated entirely into a nipple areola reconstruction when adequate breast skin surface area is present, (3 limiting the reconstructed breast mound to 2 skin tones when large area skin resurfacing is required, (4 increasing breast volume by deepithelializing, not discarding, the inferior mastectomy flap skin, (5 eccentric division of abdominal flaps when an immediate and delayed bilateral breast reconstructions are performed simultaneously; and (6 performing second-stage breast reconstruction revisions and fat grafting.

  17. Dynamic optimal metabolic control theory: a cybernetic approach for modelling of the central nitrogen metabolism of S. cerevisiae

    NARCIS (Netherlands)

    Riel, van N.A.W.; Giuseppin, M.L.F.; Verrips, C.T.

    2000-01-01

    The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the

  18. FACTORS CONTRIBUTING TO PERINATAL MORTALITY : OPTIMIZING OUTCOME

    Directory of Open Access Journals (Sweden)

    Lakshmi

    2015-03-01

    Full Text Available OBJECTIVE: To evaluate the various causes of perinatal deaths and adopt strategies to improve perinatal outcome at a referral teaching hospital in North Kerala. METHODS: A prospective observational study conducted at Institute of Maternal and Child Health, Government Medical College, Kozhikode. All perinatal deaths during the period January 2013 to December 2014 were analysed and from this factors responsible for perinatal deaths were identified. RESULTS: Out of total 30,042 deliveries , there were 966 perinatal deaths during the study period. 566 were still births and 400 early neonatal deaths. The perinatal mortality rate was 31.1 per 1000 live births. Perinatal asphyxia was the major cause of perinatal mortality. The important factors contributing to perinatal asphyxia were prematurity (39%, abruptio placenta (19% and MSAF ( 12%. Among the antenatal factors, hypertensive disorders of pregnancy leading to iatrogenic elective preterm delivery were the most important. CONCLUSION: Perinatal asphyxia due to prematurity and low birth weight emerged as the most important cause of perinatal mortality in this study and hypertensive disorders of pregnancy were the most important antenatal complication leading to prematurity

  19. Identification of metabolic system parameters using global optimization methods

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    Gatzke Edward P

    2006-01-01

    Full Text Available Abstract Background The problem of estimating the parameters of dynamic models of complex biological systems from time series data is becoming increasingly important. Methods and results Particular consideration is given to metabolic systems that are formulated as Generalized Mass Action (GMA models. The estimation problem is posed as a global optimization task, for which novel techniques can be applied to determine the best set of parameter values given the measured responses of the biological system. The challenge is that this task is nonconvex. Nonetheless, deterministic optimization techniques can be used to find a global solution that best reconciles the model parameters and measurements. Specifically, the paper employs branch-and-bound principles to identify the best set of model parameters from observed time course data and illustrates this method with an existing model of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively simple yet representative system with five dependent states and a total of 19 unknown parameters of which the values are to be determined. Conclusion The efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae example. The method described in this paper is likely to be widely applicable in the dynamic modeling of metabolic networks.

  20. Obesity, metabolic syndrome and Mediterranean diet: Impact on depression outcome.

    Science.gov (United States)

    García-Toro, M; Vicens-Pons, E; Gili, M; Roca, M; Serrano-Ripoll, M J; Vives, M; Leiva, A; Yáñez, A M; Bennasar-Veny, M; Oliván-Blázquez, B

    2016-04-01

    Obesity, metabolic syndrome (MetS) and low adherence to Mediterranean diet are frequent in major depression patients and have been separately related with prognosis. The aim of this study is to analyse their predictive power on major depression outcome, at 6 and 12 months. 273 Major depressive patients completed the Beck Depression Inventory for depressive symptoms and the 14-item Mediterranean diet adherence score. MetS was diagnosed according to the International Diabetes Federation (IDF). At the baseline Mediterranean diet adherence was inversely associated with depressive symptoms (p=0.007). Depression response was more likely in those patients with normal weight (p=0.006) and not MetS (p=0.013) but it was not associated with Mediterranean diet adherence (p=0.625). Those patients with MetS and obesity were less likely to improve symptoms of depression than patients with obesity but not MetS. Obesity and MetS, but not low adherence to the Mediterranean diet at baseline, predicted a poor outcome of depression at 12 months. Our study suggests that MetS is the key factor that impacts negatively in depression prognosis, rather than obesity or diet. If this finding is confirmed, clinicians should be aware about MetS diagnosis and treatment in overweight depressed patients, especially if outcome is not being satisfactory enough. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. In silico strain optimization by adding reactions to metabolic models.

    Science.gov (United States)

    Correia, Sara; Rocha, Miguel

    2012-07-24

    Nowadays, the concerns about the environment and the needs to increase the productivity at low costs, demand for the search of new ways to produce compounds with industrial interest. Based on the increasing knowledge of biological processes, through genome sequencing projects, and high-throughput experimental techniques as well as the available computational tools, the use of microorganisms has been considered as an approach to produce desirable compounds. However, this usually requires to manipulate these organisms by genetic engineering and/ or changing the enviromental conditions to make the production of these compounds possible. In many cases, it is necessary to enrich the genetic material of those microbes with hereologous pathways from other species and consequently adding the potential to produce novel compounds. This paper introduces a new plug-in for the OptFlux Metabolic Engineering platform, aimed at finding suitable sets of reactions to add to the genomes of selected microbes (wild type strain), as well as finding complementary sets of deletions, so that the mutant becomes able to overproduce compounds with industrial interest, while preserving their viability. The necessity of adding reactions to the metabolic model arises from existing gaps in the original model or motivated by the productions of new compounds by the organism. The optimization methods used are metaheuristics such as Evolutionary Algorithms and Simulated Annealing. The usefulness of this plug-in is demonstrated by a case study, regarding the production of vanillin by the bacterium E. coli.

  2. Etiology and outcome of inborn errors of metabolism

    International Nuclear Information System (INIS)

    Choudhry, S.; Khan, M.; Khan, E.A.

    2013-01-01

    Objectives: To study the clinical presentation, diagnostic workup and outcome of children presenting with suspected inborn errors of metabolism. Methods: The cross-sectional study was conducted at the Shifa International Hospital, Islamabad, and included all patients diagnosed with the condition between January 2006 and June 2011. Medical records of the patients were reviewed to collect the relevant data. Results: A total of 10 patients underwent diagnostic work-up. Majority 7 (70%) were males and 6 (60%) presented in the neonatal age group. Seizures and coma were the commonest presentations (n=5; 50% each) followed by breathing difficulty (n=4; 40%) and vomiting (n=2; 20%). The commonest diagnoses were methyl malonic acIdaemia (n=2; 20%), non-ketotic hyperglycinaemia (n=7; 10%), fructose 1,6 diphosphatase deficiency (n=1; 10%), and biotinidase deficiency (n=1; 10%). Mortality was high (n=5; 50%) and half of the survivors had severe neurological impairment. Conclusion: The diagnosis of inborn errors of metabolism requires a high index of suspicion. These disorders have a high mortality and risk of long-term neurological disability. (author)

  3. Optimization of a blueprint for in vitro glycolysis by metabolic real-time analysis

    NARCIS (Netherlands)

    Bujara, Matthias; Schümperli, Michael; Pellaux, René; Heinemann, Matthias; Panke, Sven

    Recruiting complex metabolic reaction networks for chemical synthesis has attracted considerable attention but frequently requires optimization of network composition and dynamics to reach sufficient productivity. As a design framework to predict optimal levels for all enzymes in the network is

  4. Predicting an optimal outcome after radical prostatectomy: the trifecta nomogram.

    Science.gov (United States)

    Eastham, James A; Scardino, Peter T; Kattan, Michael W

    2008-06-01

    The optimal outcome after radical prostatectomy for clinically localized prostate cancer is freedom from biochemical recurrence along with the recovery of continence and erectile function, a so-called trifecta. We evaluated our series of open radical prostatectomy cases to determine the likelihood of this outcome and develop a nomogram predicting the trifecta. We reviewed the records of patients undergoing open radical prostatectomy for clinical stage T1c-T3a prostate cancer at our center during 2000 to 2006. Men were excluded if they received preoperative hormonal therapy, chemotherapy or radiation therapy, if pretreatment prostate specific antigen was more than 50 ng/ml, or if they were impotent or incontinent before radical prostatectomy. A total of 1,577 men were included in the study. Freedom from biochemical recurrence was defined as post-radical prostatectomy prostate specific antigen less than 0.2 ng/ml. Continence was defined as not having to wear any protective pads. Potency was defined as erection adequate for intercourse upon most attempts with or without phosphodiesterase-5 inhibitor. Mean patient age was 58 years and mean pretreatment prostate specific antigen was 6.4 ng/ml. A trifecta outcome (cancer-free status with recovery of continence and potency) was achieved in 62% of patients. In a nomogram developed to predict the likelihood of the trifecta baseline prostate specific antigen was the major predictive factor. Area under the ROC curve for the nomogram was 0.773 and calibration appeared excellent. A trifecta (optimal) outcome can be achieved in most men undergoing radical prostatectomy. The nomogram permits patients to estimate preoperatively their likelihood of an optimal outcome after radical prostatectomy.

  5. Optimality principles in the regulation of metabolic networks.

    Science.gov (United States)

    Berkhout, Jan; Bruggeman, Frank J; Teusink, Bas

    2012-08-29

    One of the challenging tasks in systems biology is to understand how molecular networks give rise to emergent functionality and whether universal design principles apply to molecular networks. To achieve this, the biophysical, evolutionary and physiological constraints that act on those networks need to be identified in addition to the characterisation of the molecular components and interactions. Then, the cellular "task" of the network-its function-should be identified. A network contributes to organismal fitness through its function. The premise is that the same functions are often implemented in different organisms by the same type of network; hence, the concept of design principles. In biology, due to the strong forces of selective pressure and natural selection, network functions can often be understood as the outcome of fitness optimisation. The hypothesis of fitness optimisation to understand the design of a network has proven to be a powerful strategy. Here, we outline the use of several optimisation principles applied to biological networks, with an emphasis on metabolic regulatory networks. We discuss the different objective functions and constraints that are considered and the kind of understanding that they provide.

  6. Optimality Principles in the Regulation of Metabolic Networks

    Directory of Open Access Journals (Sweden)

    Jan Berkhout

    2012-08-01

    Full Text Available One of the challenging tasks in systems biology is to understand how molecular networks give rise to emergent functionality and whether universal design principles apply to molecular networks. To achieve this, the biophysical, evolutionary and physiological constraints that act on those networks need to be identified in addition to the characterisation of the molecular components and interactions. Then, the cellular “task” of the network—its function—should be identified. A network contributes to organismal fitness through its function. The premise is that the same functions are often implemented in different organisms by the same type of network; hence, the concept of design principles. In biology, due to the strong forces of selective pressure and natural selection, network functions can often be understood as the outcome of fitness optimisation. The hypothesis of fitness optimisation to understand the design of a network has proven to be a powerful strategy. Here, we outline the use of several optimisation principles applied to biological networks, with an emphasis on metabolic regulatory networks. We discuss the different objective functions and constraints that are considered and the kind of understanding that they provide.

  7. Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

    Science.gov (United States)

    Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2016-07-01

    The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Cancer treatment induced metabolic syndrome : Improving outcome with lifestyle

    NARCIS (Netherlands)

    Westerink, M. D. N. L.; Nuver, J.; Lefrandt, J. D.; Vrieling, A. H.; Gietema, J. A.; Walenkamp, A. M. E.

    2016-01-01

    Increasing numbers of long-term cancer survivors face important treatment related adverse effects. Cancer treatment induced metabolic syndrome (CTIMetS) is an especially prevalent and harmful condition. The aetiology of CTIMetS likely differs from metabolic syndrome in the general population, but

  9. Simulation Modeling to Compare High-Throughput, Low-Iteration Optimization Strategies for Metabolic Engineering.

    Science.gov (United States)

    Heinsch, Stephen C; Das, Siba R; Smanski, Michael J

    2018-01-01

    Increasing the final titer of a multi-gene metabolic pathway can be viewed as a multivariate optimization problem. While numerous multivariate optimization algorithms exist, few are specifically designed to accommodate the constraints posed by genetic engineering workflows. We present a strategy for optimizing expression levels across an arbitrary number of genes that requires few design-build-test iterations. We compare the performance of several optimization algorithms on a series of simulated expression landscapes. We show that optimal experimental design parameters depend on the degree of landscape ruggedness. This work provides a theoretical framework for designing and executing numerical optimization on multi-gene systems.

  10. DESHARKY: automatic design of metabolic pathways for optimal cell growth.

    Science.gov (United States)

    Rodrigo, Guillermo; Carrera, Javier; Prather, Kristala Jones; Jaramillo, Alfonso

    2008-11-01

    The biological solution for synthesis or remediation of organic compounds using living organisms, particularly bacteria and yeast, has been promoted because of the cost reduction with respect to the non-living chemical approach. In that way, computational frameworks can profit from the previous knowledge stored in large databases of compounds, enzymes and reactions. In addition, the cell behavior can be studied by modeling the cellular context. We have implemented a Monte Carlo algorithm (DESHARKY) that finds a metabolic pathway from a target compound by exploring a database of enzymatic reactions. DESHARKY outputs a biochemical route to the host metabolism together with its impact in the cellular context by using mathematical models of the cell resources and metabolism. Furthermore, we provide the sequence of amino acids for the enzymes involved in the route closest phylogenetically to the considered organism. We provide examples of designed metabolic pathways with their genetic load characterizations. Here, we have used Escherichia coli as host organism. In addition, our bioinformatic tool can be applied for biodegradation or biosynthesis and its performance scales with the database size. Software, a tutorial and examples are freely available and open source at http://soft.synth-bio.org/desharky.html

  11. Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites

    DEFF Research Database (Denmark)

    Kim, Hyun Uk; Charusanti, Pep; Lee, Sang Yup

    2016-01-01

    Metabolic engineering using systems biology tools is increasingly applied to overproduce secondary metabolites for their potential industrial production. In this Highlight, recent relevant metabolic engineering studies are analyzed with emphasis on host selection and engineering approaches...... for the optimal production of various prokaryotic secondary metabolites: native versus heterologous hosts (e.g., Escherichia coli) and rational versus random approaches. This comparative analysis is followed by discussions on systems biology tools deployed in optimizing the production of secondary metabolites....... The potential contributions of additional systems biology tools are also discussed in the context of current challenges encountered during optimization of secondary metabolite production....

  12. Metabolic interrogation as a tool to optimize chemotherapeutic regimens.

    Science.gov (United States)

    Sandulache, Vlad C; Chen, Yunyun; Feng, Lei; William, William N; Skinner, Heath D; Myers, Jeffrey N; Meyn, Raymond E; Li, Jinzhong; Mijiti, Ainiwaer; Bankson, James A; Fuller, Clifton D; Konopleva, Marina Y; Lai, Stephen Y

    2017-03-14

    Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production. Pt compounds induced an acute dose-dependent, transient drop in lactate generation in vitro, which correlated with effects on DNA damage and cell death. Neutralization of free radical stress abrogated these effects. The magnitude of this effect on lactate production correlated with the differential sensitivity of HNSCC cells to Pt compounds (CDDP vs CBP) and p53-driven Pt chemotherapy resistance. Using dual flank xenograft tumors, we demonstrated that Pt-driven effects on lactate levels correlate with effects on tumor growth delay in a dose-dependent manner and that lactate levels can define the temporal profile of Pt chemotherapy-induced metabolic stress. Lactate interrogation also predicted doxorubicin effects on cell death in both solid tumor (HNSCC) and acute myelogenous leukemia (AML) cell lines.Real-time metabolic interrogation of acute changes in cell and tumor lactate levels reflects chemotherapy effects on DNA damage, cell death and tumor growth delay. We have identified a real-time biomarker of chemotherapy effectiveness which can be used to develop adaptive, iterative and personalized treatment regimens against a variety of solid and hematopoietic malignancies.

  13. Early optimal parenteral nutrition and metabolic acidosis in very preterm infants.

    Directory of Open Access Journals (Sweden)

    Francesco Bonsante

    Full Text Available It is currently recognized that an optimized nutritional approach, consisting of an early and substantial supply of protein and energy by parenteral route, may be beneficial for very low birth weight infants and recent guidelines endorse this strategy. However, the impact of the enhanced parenteral nutrition (PN on acid-basic balance has never been investigated. The aim of the present study is to assess the effect of nutrient intake on acid-base homeostasis in a large population of preterm infants on PN.This observational study described the acid-base profile of very preterm infants (≤29 week's gestation receiving PN during the first week of life. For this purpose three different cohorts of infants who received increasing (group 1 to group 3 nutritional intakes were considered. Nutrition data were recorded daily and correlated to acid-base data (pH, base excess, and lactate. The outcome measure to assess metabolic acidosis was the base excess (BE.161 infants were included. 1127 daily nutritional records and 795 blood gas data were analyzed. The three groups were different with regard to nutritional intravenous intakes. Group 3 in particular had a higher mean intake of both amino acids (3.3 ± 0.8 g/kg/d and lipids (2.8 ± 1.4 g/kg/d during the first week of life. Metabolic acidosis was more severe in the group with the highest parenteral intake of amino acids and lipids: mean BE = -8.7 ± 3.4 (group 3; -6.4 ± 3.4 (group 2; -5.1 ± 3.0 (group 1]. At the multivariate analysis the significant risk factors for metabolic acidosis were: gestational age, initial base excess, amino acid and lipid intravenous intakes.Acid-base homeostasis was influenced by the nutritional intake. Earlier and higher intravenous amino acid and lipid intakes particularly increased the risk of metabolic acidosis. The nutritional tolerance was different depending on gestational age, and the smaller infants (24-26 week's gestation displayed greater acidotic disequilibrium

  14. The impact of the metabolic syndrome on the outcome after aortic valve replacement.

    Science.gov (United States)

    Tadic, Marijana; Vukadinovic, Davor; Cvijanovic, Dane; Celic, Vera; Kocica, Mladen; Putnik, Svetozar; Ivanovic, Branislava

    2014-10-01

    The aim of this study was to examine the influence of the metabolic syndrome on the left ventricular geometry as well as on the early and mid-time outcome in patients with aortic stenosis who underwent aortic valve replacement. The study included 182 patients who underwent aortic valve replacement due to aortic stenosis. The metabolic syndrome was defined by the presence of at least three AHA-NHLB (American Heart Association/National Heart, Lung and Blood Institute) criteria. All the patients were followed for at least 2 years after the surgery. The metabolic syndrome did not influence the severity of aortic stenosis (mean gradient and aortic valve area). However, the metabolic syndrome was associated with the reduced prevalence of the normal left ventricular geometry and the increased risk of concentric left ventricular hypertrophy in patients with aortic stenosis. Among the metabolic syndrome criteria, only increased blood pressure was simultaneously associated with the short-term and mid-term outcome, independently of other risk factors. Increased fasting glucose level was an independent predictor of the only 30-day outcome after the valve replacement. The metabolic syndrome and left ventricular hypertrophy were, independently of hypertension and diabetes, associated with the 30-day outcome, as well as incidence of major cerebrovascular and cardiovascular events in the 2-year postoperative period. The metabolic syndrome does not change severity of the aortic stenosis, but significantly impacts the left ventricular remodeling in these patients. The metabolic syndrome and left ventricular hypertrophy, irrespective of hypertension and diabetes, are predictors of the short-term and mid-term outcome of patients with aortic stenosis who underwent aortic valve replacement.

  15. Efficacy and outcome of expanded newborn screening for metabolic diseases - Report of 10 years from South-West Germany *

    Directory of Open Access Journals (Sweden)

    Mengel Eugen

    2011-06-01

    Full Text Available Abstract Background National newborn screening programmes based on tandem-mass spectrometry (MS/MS and other newborn screening (NBS technologies show a substantial variation in number and types of disorders included in the screening panel. Once established, these methods offer the opportunity to extend newborn screening panels without significant investment and cost. However, systematic evaluations of newborn screening programmes are rare, most often only describing parts of the whole process from taking blood samples to long-term evaluation of outcome. Methods In a prospective single screening centre observational study 373 cases with confirmed diagnosis of a metabolic disorder from a total cohort of 1,084,195 neonates screened in one newborn screening laboratory between January 1, 1999, and June 30, 2009 and subsequently treated and monitored in five specialised centres for inborn errors of metabolism were examined. Process times for taking screening samples, obtaining results, initiating diagnostic confirmation and starting treatment as well as the outcome variables metabolic decompensations, clinical status, and intellectual development at a mean age of 3.3 years were evaluated. Results Optimal outcome is achieved especially for the large subgroup of patients with medium-chain acyl-CoA dehydrogenase deficiency. Kaplan-Meier-analysis revealed disorder related patterns of decompensation. Urea cycle disorders, organic acid disorders, and amino acid disorders show an early high and continuous risk, medium-chain acyl-CoA dehydrogenase deficiency a continuous but much lower risk for decompensation, other fatty acid oxidation disorders an intermediate risk increasing towards the end of the first year. Clinical symptoms seem inevitable in a small subgroup of patients with very early disease onset. Later decompensation can not be completely prevented despite pre-symptomatic start of treatment. Metabolic decompensation does not necessarily result in

  16. Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?

    DEFF Research Database (Denmark)

    Cameron, F.J.; Skinner, T.C.; Beaufort, C.E. de

    2008-01-01

    -parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P gender or insulin treatment regimen......Aims To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries. Methods Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate...... a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P 2; d.f. = 3; P diabetes care (r = 0.11; P

  17. Enzyme allocation problems in kinetic metabolic networks: Optimal solutions are elementary flux modes

    Czech Academy of Sciences Publication Activity Database

    Müller, Stefan; Regensburger, G.; Steuer, Ralf

    2014-01-01

    Roč. 347, APR 2014 (2014), s. 182-190 ISSN 0022-5193 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : metabolic optimization * enzyme kinetics * oriented matroid * elementary vector * conformal sum Subject RIV: EI - Biotechnology ; Bionics Impact factor: 2.116, year: 2014

  18. Preoperative cerebral metabolic difference related to the outcome of cochlear implantation in prelingually deaf children

    International Nuclear Information System (INIS)

    Lee, J. H.; Lim, G. C.; Ahn, J. H.; Lee, K. S.; Jeong, J. W.; Kim, J. S.

    2007-01-01

    The outcome of cochlear implantation (CI) has known to be variable. The aim of this study was to evaluate the preoperative regional glucose metabolism difference related to the speech perception outcome after CI in prelingually deaf children. Forty-one prelingually deaf children who underwent CI at age 2∼10 years were included. All patients underwent F-18 FDG brain PET within one month before CI and measured speech perception using the institute version of the CID at 2 years after CI. Patients were classified into younger (2∼6 years) and older (7∼10 years) groups. Each group was also divided into a GOOD (CID scores>80) and a BAD (CID scores<60) subgroup. We assessed regional metabolic difference according to CID scores and age by voxel based analysis (SPM2) comparing normal controls (n =8, 20∼30 years). Speech perception was good in 19 (68%) of 28 younger patients and 5 (38%) of 13 older patients after CI. Regional metabolism of both younger and older GOOD subgroup was significantly decreased in right temporal, left cerebellar and right frontal regions compared to normal controls (uncorrected p<0.001). In younger GOOD subgroup, left frontotemporal and both parietal regions showed decreased metabolism and right frontal, left temporal and anterior cingulate regions showed increased metabolism compared to BAD subgroup (uncorrected p<0.005). In younger group, regional metabolism in left superior frontal, right temporal and right occipital regions showed a significant negative correlation with CID scores (uncorrected p<0.005). In older group, the pattern of regional metabolic difference correlated with CID score was not similar to that of younger group. Preoperative regional cerebral metabolism is decreased in several brain regions related to the language in preligually deaf patients and the neuralplasty of younger patients are different according to the outcome of speech perception after CI

  19. Preoperative cerebral metabolic difference related to the outcome of cochlear implantation in prelingually deaf children

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. H.; Lim, G. C.; Ahn, J. H.; Lee, K. S.; Jeong, J. W.; Kim, J. S. [Asan Medical Center, Seoul (Korea, Republic of)

    2007-07-01

    The outcome of cochlear implantation (CI) has known to be variable. The aim of this study was to evaluate the preoperative regional glucose metabolism difference related to the speech perception outcome after CI in prelingually deaf children. Forty-one prelingually deaf children who underwent CI at age 2{approx}10 years were included. All patients underwent F-18 FDG brain PET within one month before CI and measured speech perception using the institute version of the CID at 2 years after CI. Patients were classified into younger (2{approx}6 years) and older (7{approx}10 years) groups. Each group was also divided into a GOOD (CID scores>80) and a BAD (CID scores<60) subgroup. We assessed regional metabolic difference according to CID scores and age by voxel based analysis (SPM2) comparing normal controls (n =8, 20{approx}30 years). Speech perception was good in 19 (68%) of 28 younger patients and 5 (38%) of 13 older patients after CI. Regional metabolism of both younger and older GOOD subgroup was significantly decreased in right temporal, left cerebellar and right frontal regions compared to normal controls (uncorrected p<0.001). In younger GOOD subgroup, left frontotemporal and both parietal regions showed decreased metabolism and right frontal, left temporal and anterior cingulate regions showed increased metabolism compared to BAD subgroup (uncorrected p<0.005). In younger group, regional metabolism in left superior frontal, right temporal and right occipital regions showed a significant negative correlation with CID scores (uncorrected p<0.005). In older group, the pattern of regional metabolic difference correlated with CID score was not similar to that of younger group. Preoperative regional cerebral metabolism is decreased in several brain regions related to the language in preligually deaf patients and the neuralplasty of younger patients are different according to the outcome of speech perception after CI.

  20. Optimal decoding and information transmission in Hodgkin-Huxley neurons under metabolic cost constraints.

    Science.gov (United States)

    Kostal, Lubomir; Kobayashi, Ryota

    2015-10-01

    Information theory quantifies the ultimate limits on reliable information transfer by means of the channel capacity. However, the channel capacity is known to be an asymptotic quantity, assuming unlimited metabolic cost and computational power. We investigate a single-compartment Hodgkin-Huxley type neuronal model under the spike-rate coding scheme and address how the metabolic cost and the decoding complexity affects the optimal information transmission. We find that the sub-threshold stimulation regime, although attaining the smallest capacity, allows for the most efficient balance between the information transmission and the metabolic cost. Furthermore, we determine post-synaptic firing rate histograms that are optimal from the information-theoretic point of view, which enables the comparison of our results with experimental data. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Design, Optimization and Application of Small Molecule Biosensor in Metabolic Engineering.

    Science.gov (United States)

    Liu, Yang; Liu, Ye; Wang, Meng

    2017-01-01

    The development of synthetic biology and metabolic engineering has painted a great future for the bio-based economy, including fuels, chemicals, and drugs produced from renewable feedstocks. With the rapid advance of genome-scale modeling, pathway assembling and genome engineering/editing, our ability to design and generate microbial cell factories with various phenotype becomes almost limitless. However, our lack of ability to measure and exert precise control over metabolite concentration related phenotypes becomes a bottleneck in metabolic engineering. Genetically encoded small molecule biosensors, which provide the means to couple metabolite concentration to measurable or actionable outputs, are highly promising solutions to the bottleneck. Here we review recent advances in the design, optimization and application of small molecule biosensor in metabolic engineering, with particular focus on optimization strategies for transcription factor (TF) based biosensors.

  2. Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions.

    Directory of Open Access Journals (Sweden)

    Vijayaraghava T S Rao

    Full Text Available Within the microenvironment of multiple sclerosis lesions, oligodendrocytes are subject to metabolic stress reflecting effects of focal ischemia and inflammation. Previous studies have shown that under optimal conditions in vitro, the respiratory activity of human adult brain-derived oligodendrocytes is lower and more predominantly glycolytic compared to oligodendrocytes differentiated in vitro from post natal rat brain oligodendrocyte progenitor cells. In response to sub-lethal metabolic stress, adult human oligodendrocytes reduce overall energy production rate impacting the capacity to maintain myelination. Here, we directly compare the metabolic profiles of oligodendrocytes derived from adult rat brain with oligodendrocytes newly differentiated in vitro from oligodendrocyte progenitor cells obtained from the post natal rat brain, under both optimal culture and metabolic stress (low/no glucose conditions. Oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. Our findings indicate that under optimal conditions, adult rat oligodendrocytes preferentially use glycolysis whereas newly differentiated post natal rat oligodendrocytes, and the oligodendrocyte progenitor cells from which they are derived, mainly utilize oxidative phosphorylation to produce ATP. Metabolic stress increases the rate of ATP production via oxidative phosphorylation and significantly reduces glycolysis in adult oligodendrocytes. The rate of ATP production was relatively unchanged in newly differentiated post natal oligodendrocytes under these stress conditions, while it was significantly reduced in oligodendrocyte progenitor cells. Our study indicates that both age and maturation influence the metabolic profile under optimal and stressed conditions, emphasizing the need to consider these variables for in vitro studies that aim to model adult human disease.

  3. Effects of metabolic syndrome on the functional outcomes of corticosteroid injection for De Quervain tenosynovitis.

    Science.gov (United States)

    Roh, Y H; Noh, J H; Gong, H S; Baek, G H

    2017-06-01

    Metabolic syndrome is a constellation of medical conditions that arise from insulin resistance and abnormal adipose deposition and function. In patients with metabolic syndrome and De Quervain tenosynovitis this might affect the outcome of treatment by local corticosteroid injection. A total of 64 consecutive patients with De Quervain tenosynovitis and metabolic syndrome treated with corticosteroid injection were age- and sex-matched with 64 control patients without metabolic syndrome. The response to treatment, including visual analogue scale score for pain, objective findings consistent with De Quervain tenosynovitis (tenderness at first dorsal compartment, Finkelstein test result), and Disability of the Arm, Shoulder, and Hand score were assessed at 6, 12, and 24 weeks follow-up. Treatment failure was defined as persistence of symptoms or surgical intervention. Prior to treatment, patients with metabolic syndrome had mean initial pain visual analogue scale and Disability of the Arm, Shoulder, and Hand scores similar to those in the control group. The proportion of treatment failure in the metabolic syndrome group (43%) was significantly higher than that in the control group (20%) at 6 months follow-up. The pain visual analogue scale scores in the metabolic syndrome group were higher than the scores in the control group at the 12- and 24-week follow-ups. The Disability of the Arm, Shoulder, and Hand scores of the metabolic syndrome group were higher (more severe symptoms) than those of the control group at the 12- and 24-week follow-ups. Although considerable improvements in symptom severity and hand function will likely occur in patients with metabolic syndrome, corticosteroid injection for De Quervain tenosynovitis is not as effective in these patients compared with age- and sex-matched controls in terms of functional outcomes and treatment failure. III.

  4. Sequential metabolic phases as a means to optimize cellular output in a constant environment.

    Science.gov (United States)

    Palinkas, Aljoscha; Bulik, Sascha; Bockmayr, Alexander; Holzhütter, Hermann-Georg

    2015-01-01

    Temporal changes of gene expression are a well-known regulatory feature of all cells, which is commonly perceived as a strategy to adapt the proteome to varying external conditions. However, temporal (rhythmic and non-rhythmic) changes of gene expression are also observed under virtually constant external conditions. Here we hypothesize that such changes are a means to render the synthesis of the metabolic output more efficient than under conditions of constant gene activities. In order to substantiate this hypothesis, we used a flux-balance model of the cellular metabolism. The total time span spent on the production of a given set of target metabolites was split into a series of shorter time intervals (metabolic phases) during which only selected groups of metabolic genes are active. The related flux distributions were calculated under the constraint that genes can be either active or inactive whereby the amount of protein related to an active gene is only controlled by the number of active genes: the lower the number of active genes the more protein can be allocated to the enzymes carrying non-zero fluxes. This concept of a predominantly protein-limited efficiency of gene expression clearly differs from other concepts resting on the assumption of an optimal gene regulation capable of allocating to all enzymes and transporters just that fraction of protein necessary to prevent rate limitation. Applying this concept to a simplified metabolic network of the central carbon metabolism with glucose or lactate as alternative substrates, we demonstrate that switching between optimally chosen stationary flux modes comprising different sets of active genes allows producing a demanded amount of target metabolites in a significantly shorter time than by a single optimal flux mode at fixed gene activities. Our model-based findings suggest that temporal expression of metabolic genes can be advantageous even under conditions of constant external substrate supply.

  5. Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

    Directory of Open Access Journals (Sweden)

    Monique E. Francois

    2017-10-01

    Full Text Available Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

  6. Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

    Science.gov (United States)

    Francois, Monique E; Gillen, Jenna B; Little, Jonathan P

    2017-01-01

    Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT) have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

  7. Metabolic syndrome: A review of the role of vitamin D in mediating susceptibility and outcome

    Science.gov (United States)

    Strange, Richard C; Shipman, Kate E; Ramachandran, Sudarshan

    2015-01-01

    Despite the well-recognised role of vitamin D in a wide range of physiological processes, hypovitaminosis is common worldwide (prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and insufficient consumption. While generally not at the very low levels associated with rickets, hypovitaminosis D has been implicated in various very different, pathophysiological processes. These include putative effects on the pathogenesis of neoplastic change, inflammatory and demyelinating conditions, cardiovascular disease (CVD) and diabetes. This review focuses on the association between hypovitaminosis D and the metabolic syndrome as well as its component characteristics which are central obesity, glucose homeostasis, insulin resistance, hypertension and atherogenic dyslipidaemia. We also consider the effects of hypovitaminosis D on outcomes associated with the metabolic syndrome such as CVD, diabetes and non-alcoholic fatty liver disease. We structure this review into 3 distinct sections; the metabolic syndrome, vitamin D biochemistry and the putative association between hypovitaminosis D, the metabolic syndrome and cardiovascular risk. PMID:26185598

  8. Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

    DEFF Research Database (Denmark)

    Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

    2008-01-01

    In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome.......In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

  9. Cell wall-bound silicon optimizes ammonium uptake and metabolism in rice cells.

    Science.gov (United States)

    Sheng, Huachun; Ma, Jie; Pu, Junbao; Wang, Lijun

    2018-05-16

    Turgor-driven plant cell growth depends on cell wall structure and mechanics. Strengthening of cell walls on the basis of an association and interaction with silicon (Si) could lead to improved nutrient uptake and optimized growth and metabolism in rice (Oryza sativa). However, the structural basis and physiological mechanisms of nutrient uptake and metabolism optimization under Si assistance remain obscure. Single-cell level biophysical measurements, including in situ non-invasive micro-testing (NMT) of NH4+ ion fluxes, atomic force microscopy (AFM) of cell walls, and electrolyte leakage and membrane potential, as well as whole-cell proteomics using isobaric tags for relative and absolute quantification (iTRAQ), were performed. The altered cell wall structure increases the uptake rate of the main nutrient NH4+ in Si-accumulating cells, whereas the rate is only half in Si-deprived counterparts. Rigid cell walls enhanced by a wall-bound form of Si as the structural basis stabilize cell membranes. This, in turn, optimizes nutrient uptake of the cells in the same growth phase without any requirement for up-regulation of transmembrane ammonium transporters. Optimization of cellular nutrient acquisition strategies can substantially improve performance in terms of growth, metabolism and stress resistance.

  10. Clinical Outcome Metrics for Optimization of Robust Training

    Science.gov (United States)

    Ebert, D.; Byrne, V. E.; McGuire, K. M.; Hurst, V. W., IV; Kerstman, E. L.; Cole, R. W.; Sargsyan, A. E.; Garcia, K. M.; Reyes, D.; Young, M.

    2016-01-01

    Introduction: The emphasis of this research is on the Human Research Program (HRP) Exploration Medical Capability's (ExMC) "Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-Flight Medical Capabilities." Specifically, this project aims to contribute to the closure of gap ExMC 2.02: We do not know how the inclusion of a physician crew medical officer quantitatively impacts clinical outcomes during exploration missions. The experiments are specifically designed to address clinical outcome differences between physician and non-physician cohorts in both near-term and longer-term (mission impacting) outcomes. Methods: Medical simulations will systematically compare success of individual diagnostic and therapeutic procedure simulations performed by physician and non-physician crew medical officer (CMO) analogs using clearly defined short-term (individual procedure) outcome metrics. In the subsequent step of the project, the procedure simulation outcomes will be used as input to a modified version of the NASA Integrated Medical Model (IMM) to analyze the effect of the outcome (degree of success) of individual procedures (including successful, imperfectly performed, and failed procedures) on overall long-term clinical outcomes and the consequent mission impacts. The procedures to be simulated are endotracheal intubation, fundoscopic examination, kidney/urinary ultrasound, ultrasound-guided intravenous catheter insertion, and a differential diagnosis exercise. Multiple assessment techniques will be used, centered on medical procedure simulation studies occurring at 3, 6, and 12 months after initial training (as depicted in the following flow diagram of the experiment design). Discussion: Analysis of procedure outcomes in the physician and non-physician groups and their subsets (tested at different elapsed times post training) will allow the team to 1) define differences between physician and non-physician CMOs in terms of both procedure performance

  11. 13C metabolic flux analysis: optimal design of isotopic labeling experiments.

    Science.gov (United States)

    Antoniewicz, Maciek R

    2013-12-01

    Measuring fluxes by 13C metabolic flux analysis (13C-MFA) has become a key activity in chemical and pharmaceutical biotechnology. Optimal design of isotopic labeling experiments is of central importance to 13C-MFA as it determines the precision with which fluxes can be estimated. Traditional methods for selecting isotopic tracers and labeling measurements did not fully utilize the power of 13C-MFA. Recently, new approaches were developed for optimal design of isotopic labeling experiments based on parallel labeling experiments and algorithms for rational selection of tracers. In addition, advanced isotopic labeling measurements were developed based on tandem mass spectrometry. Combined, these approaches can dramatically improve the quality of 13C-MFA results with important applications in metabolic engineering and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Maternal Obesity: Lifelong Metabolic Outcomes for Offspring from Poor Developmental Trajectories During the Perinatal Period.

    Science.gov (United States)

    Zambrano, Elena; Ibáñez, Carlos; Martínez-Samayoa, Paola M; Lomas-Soria, Consuelo; Durand-Carbajal, Marta; Rodríguez-González, Guadalupe L

    2016-01-01

    The prevalence of obesity in women of reproductive age is increasing in developed and developing countries around the world. Human and animal studies indicate that maternal obesity adversely impacts both maternal health and offspring phenotype, predisposing them to chronic diseases later in life including obesity, dyslipidemia, type 2 diabetes mellitus, and hypertension. Several mechanisms act together to produce these adverse health effects including programming of hypothalamic appetite-regulating centers, increasing maternal, fetal and offspring glucocorticoid production, changes in maternal metabolism and increasing maternal oxidative stress. Effective interventions during human pregnancy are needed to prevent both maternal and offspring metabolic dysfunction due to maternal obesity. This review addresses the relationship between maternal obesity and its negative impact on offspring development and presents some maternal intervention studies that propose strategies to prevent adverse offspring metabolic outcomes. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  13. Optimal conservation outcomes require both restoration and protection.

    Science.gov (United States)

    Possingham, Hugh P; Bode, Michael; Klein, Carissa J

    2015-01-01

    Conservation outcomes are principally achieved through the protection of intact habitat or the restoration of degraded habitat. Restoration is generally considered a lower priority action than protection because protection is thought to provide superior outcomes, at lower costs, without the time delay required for restoration. Yet while it is broadly accepted that protected intact habitat safeguards more biodiversity and generates greater ecosystem services per unit area than restored habitat, conservation lacks a theory that can coherently compare the relative outcomes of the two actions. We use a dynamic landscape model to integrate these two actions into a unified conservation theory of protection and restoration. Using nonlinear benefit functions, we show that both actions are crucial components of a conservation strategy that seeks to optimise either biodiversity conservation or ecosystem services provision. In contrast to conservation orthodoxy, in some circumstances, restoration should be strongly preferred to protection. The relative priority of protection and restoration depends on their costs and also on the different time lags that are inherent to both protection and restoration. We derive a simple and easy-to-interpret heuristic that integrates these factors into a single equation that applies equally to biodiversity conservation and ecosystem service objectives. We use two examples to illustrate the theory: bird conservation in tropical rainforests and coastal defence provided by mangrove forests.

  14. Using predictive analytics and big data to optimize pharmaceutical outcomes.

    Science.gov (United States)

    Hernandez, Inmaculada; Zhang, Yuting

    2017-09-15

    The steps involved, the resources needed, and the challenges associated with applying predictive analytics in healthcare are described, with a review of successful applications of predictive analytics in implementing population health management interventions that target medication-related patient outcomes. In healthcare, the term big data typically refers to large quantities of electronic health record, administrative claims, and clinical trial data as well as data collected from smartphone applications, wearable devices, social media, and personal genomics services; predictive analytics refers to innovative methods of analysis developed to overcome challenges associated with big data, including a variety of statistical techniques ranging from predictive modeling to machine learning to data mining. Predictive analytics using big data have been applied successfully in several areas of medication management, such as in the identification of complex patients or those at highest risk for medication noncompliance or adverse effects. Because predictive analytics can be used in predicting different outcomes, they can provide pharmacists with a better understanding of the risks for specific medication-related problems that each patient faces. This information will enable pharmacists to deliver interventions tailored to patients' needs. In order to take full advantage of these benefits, however, clinicians will have to understand the basics of big data and predictive analytics. Predictive analytics that leverage big data will become an indispensable tool for clinicians in mapping interventions and improving patient outcomes. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  15. Optimal conservation outcomes require both restoration and protection.

    Directory of Open Access Journals (Sweden)

    Hugh P Possingham

    2015-01-01

    Full Text Available Conservation outcomes are principally achieved through the protection of intact habitat or the restoration of degraded habitat. Restoration is generally considered a lower priority action than protection because protection is thought to provide superior outcomes, at lower costs, without the time delay required for restoration. Yet while it is broadly accepted that protected intact habitat safeguards more biodiversity and generates greater ecosystem services per unit area than restored habitat, conservation lacks a theory that can coherently compare the relative outcomes of the two actions. We use a dynamic landscape model to integrate these two actions into a unified conservation theory of protection and restoration. Using nonlinear benefit functions, we show that both actions are crucial components of a conservation strategy that seeks to optimise either biodiversity conservation or ecosystem services provision. In contrast to conservation orthodoxy, in some circumstances, restoration should be strongly preferred to protection. The relative priority of protection and restoration depends on their costs and also on the different time lags that are inherent to both protection and restoration. We derive a simple and easy-to-interpret heuristic that integrates these factors into a single equation that applies equally to biodiversity conservation and ecosystem service objectives. We use two examples to illustrate the theory: bird conservation in tropical rainforests and coastal defence provided by mangrove forests.

  16. Diet-Induced Low-Grade Metabolic Acidosis and Clinical Outcomes: A Review

    Directory of Open Access Journals (Sweden)

    Renata Alves Carnauba

    2017-05-01

    Full Text Available Low-grade metabolic acidosis is a condition characterized by a slight decrease in blood pH, within the range considered normal, and feeding is one of the main factors that may influence the occurrence of such a condition. The excessive consumption of acid precursor foods (sources of phosphorus and proteins, to the detriment of those precursors of bases (sources of potassium, calcium, and magnesium, leads to acid-base balance volubility. If this condition occurs in a prolonged, chronic way, low-grade metabolic acidosis can become significant and predispose to metabolic imbalances such as kidney stone formation, increased bone resorption, reduced bone mineral density, and the loss of muscle mass, as well as the increased risk of chronic diseases such as type 2 diabetes mellitus, hypertension, and non-alcoholic hepatic steatosis. Considering the increase in the number of studies investigating the influence of diet-induced metabolic acidosis on clinical outcomes, this review gathers the available evidence evaluating the association of this disturbance and metabolic imbalances, as well as related mechanisms. It is necessary to look at the western dietary pattern of most countries and the increasing incidence of non-comunicable diseases for the balance between fruit and vegetable intake and the appropriate supply of protein, mainly from animal sources, so that it does not exceed the daily recommendations.

  17. Metabolic alterations and neurodevelopmental outcome of infants with transposition of the great arteries.

    Science.gov (United States)

    Park, I Sook; Yoon, S Young; Min, J Yeon; Kim, Y Hwue; Ko, J Kok; Kim, K Soo; Seo, D Man; Lee, J Hee

    2006-01-01

    Abnormal neurodevelopment has been reported for infants who were born with transposition of the great arteries (TGA) and underwent arterial switch operation (ASO). This study evaluates the cerebral metabolism of TGA infants at birth and before ASO and neurodevelopment 1 year after ASO. Proton magnetic resonance spectroscopy (1H-MRS) was performed on 16 full-term TGA brains before ASO within 3-6 days after birth. The brain metabolite ratios of [NAA/Cr], [Cho/Cr], and [mI/Cr] evaluated measured. Ten infants were evaluated at 1 year using the Bayley Scales of Infants Development II (BSED II). Cerebral metabolism of infants with TGA was altered in parietal white matter (PWM) and occipital gray matter (OGM) at birth before ASO. One year after ASO, [Cho/Cr] in PWM remained altered, but all metabolic ratios in OGM were normal. The results of BSID II at 1 year showed delayed mental and psychomotor development. This delayed neurodevelopmental outcome may reflect consequences of the altered cerebral metabolism in PWM measured by 1H-MRS. It is speculated that the abnormal hemodynamics due to TGA in utero may be responsible for the impaired cerebral metabolism and the subsequent neurodevelopmental deficit.

  18. The effect of exercise training on clinical outcomes in patients with the metabolic syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Ostman, C; Smart, N A; Morcos, D; Duller, A; Ridley, W; Jewiss, D

    2017-08-30

    Purpose: to establish if exercise training improves clinical outcomes in people with metabolic syndrome (MetS). Registered with PROSPERO international prospective register of systematic reviews ( https://www.crd.york.ac.uk/PROSPERO/Identifier:CRD42017055491 ). studies were identified through a MEDLINE search strategy (1985 to Jan 12, 2017), Cochrane controlled trials registry, CINAHL and SPORTDiscus. prospective randomized or controlled trials of exercise training in humans with metabolic syndrome, lasting 12 weeks or more. We included 16 studies with 23 intervention groups; 77,000 patient-hours of exercise training. In analyses of aerobic exercise studies versus control: body mass index was significantly reduced, mean difference (MD) -0.29 (kg m -2 ) (95% CI -0.44, -0.15, p exercise versus control: waist circumference, MD -3.80 cm (95% CI -5.65, -1.95, p exercise interventions. Exercise training improves body composition, cardiovascular, and, metabolic outcomes in people with metabolic syndrome. For some outcome measures, isolated aerobic exercise appears optimal.

  19. The Impact of Host Metabolic Factors on Treatment Outcome in Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Savvidou Savvoula

    2012-01-01

    Full Text Available Background. Recent data suggest that chronic hepatitis C has to be considered a metabolic disease further to a viral infection. The aim of this study was to elaborate on the complex interactions between hepatitis C virus, host metabolic factors, and treatment response. Methods. Demographic, virological, and histological data from 356 consecutive patients were analyzed retrospectively. Hepatic steatosis, obesity, and insulin resistance were examined in relation to their impact on treatment outcome. Comparison between genotype 1 and 3 patients was performed to identify differences in the determinants of hepatic steatosis. Results. Histological evidence of hepatic steatosis was found in 113 patients, distributed in 20.3%, 9.0%, and 2.5% for grades I, II, and III, respectively. Hepatic steatosis was associated with past alcohol abuse (P=0.003 and histological evidence of advanced fibrosis (P<0.001. Older age (OR 2.51, P=0.002, genotype (OR 3.28, P<0.001, cirrhosis (OR 4.23, P=0.005, and hepatic steatosis (OR 2.48, P=0.001 were independent predictors for nonresponse. Correlations of hepatic steatosis with alcohol, insulin resistance, and fibrosis stage were found similar for both genotypes 1 and 3. Conclusions. Host metabolic factors may predict treatment outcome, and this impact remains significant even in genotype 3, where steatosis has been believed to be exclusively virus related.

  20. A mathematical framework for yield (vs. rate) optimization in constraint-based modeling and applications in metabolic engineering.

    Science.gov (United States)

    Klamt, Steffen; Müller, Stefan; Regensburger, Georg; Zanghellini, Jürgen

    2018-02-07

    The optimization of metabolic rates (as linear objective functions) represents the methodical core of flux-balance analysis techniques which have become a standard tool for the study of genome-scale metabolic models. Besides (growth and synthesis) rates, metabolic yields are key parameters for the characterization of biochemical transformation processes, especially in the context of biotechnological applications. However, yields are ratios of rates, and hence the optimization of yields (as nonlinear objective functions) under arbitrary linear constraints is not possible with current flux-balance analysis techniques. Despite the fundamental importance of yields in constraint-based modeling, a comprehensive mathematical framework for yield optimization is still missing. We present a mathematical theory that allows one to systematically compute and analyze yield-optimal solutions of metabolic models under arbitrary linear constraints. In particular, we formulate yield optimization as a linear-fractional program. For practical computations, we transform the linear-fractional yield optimization problem to a (higher-dimensional) linear problem. Its solutions determine the solutions of the original problem and can be used to predict yield-optimal flux distributions in genome-scale metabolic models. For the theoretical analysis, we consider the linear-fractional problem directly. Most importantly, we show that the yield-optimal solution set (like the rate-optimal solution set) is determined by (yield-optimal) elementary flux vectors of the underlying metabolic model. However, yield- and rate-optimal solutions may differ from each other, and hence optimal (biomass or product) yields are not necessarily obtained at solutions with optimal (growth or synthesis) rates. Moreover, we discuss phase planes/production envelopes and yield spaces, in particular, we prove that yield spaces are convex and provide algorithms for their computation. We illustrate our findings by a small

  1. The association of polymorphisms in 5-fluorouracil metabolism genes with outcome in adjuvant treatment of colorectal cancer

    DEFF Research Database (Denmark)

    Shoaib, Afzal; Gusella, Milena; Jensen, Søren Astrup

    2011-01-01

    The purpose of this study was to investigate whether specific combinations of polymorphisms in 5-fluorouracil (5-FU) metabolism-related genes were associated with outcome in 5-FU-based adjuvant treatment of colorectal cancer....

  2. Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

    DEFF Research Database (Denmark)

    Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

    2008-01-01

    In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

  3. Optimization of IVF pregnancy outcomes with donor spermatozoa.

    Science.gov (United States)

    Wang, Jeff G; Douglas, Nataki C; Prosser, Robert; Kort, Daniel; Choi, Janet M; Sauer, Mark V

    2009-03-01

    To identify risk factors for suboptimal IVF outcomes using insemination with donor spermatozoa and to define a lower threshold that may signal a conversion to fertilization by ICSI rather than insemination. Retrospective, age-matched, case-control study of women undergoing non-donor oocyte IVF cycles using either freshly ejaculated (N=138) or cryopreserved donor spermatozoa (N=69). Associations between method of fertilization, semen sample parameters, and pregnancy rates were analyzed. In vitro fertilization of oocytes with donor spermatozoa by insemination results in equivalent fertilization and pregnancy rates compared to those of freshly ejaculated spermatozoa from men with normal semen analyses when the post-processing motility is greater than or equal to 88%. IVF by insemination with donor spermatozoa when the post-processing motility is less than 88% is associated with a 5-fold reduction in pregnancy rates when compared to those of donor spermatozoa above this motility threshold. When the post-processing donor spermatozoa motility is low, fertilization by ICSI is associated with significantly higher pregnancy rates compared to those of insemination. While ICSI does not need to be categorically instituted when using donor spermatozoa in IVF, patients should be counseled that conversion from insemination to ICSI may be recommended based on low post-processing motility.

  4. Optimizing Outcome in the University-Industry Technology Transfer Projects

    Science.gov (United States)

    Alavi, Hamed; Hąbek, Patrycja

    2016-06-01

    Transferring inventions of academic scientists to private enterprises for the purpose of commercialization is long known as University-Industry (firm) Technology Transfer While the importance of this phenomenon is simultaneously raising in public and private sector, only a part of patented academic inventions succeed in passing the process of commercialization. Despite the fact that formal Technology Transfer process and licencing of patented innovations to third party is the main legal tool for safeguarding rights of academic inventors in commercialization of their inventions, it is not sufficient for transmitting tacit knowledge which is necessary in exploitation of transferred technology. Existence of reciprocal and complementary relations between formal and informal technology transfer process has resulted in formation of different models for university-industry organizational collaboration or even integration where licensee firms keep contact with academic inventors after gaining legal right for commercialization of their patented invention. Current paper argues that despite necessity for patents to legally pass the right of commercialization of an invention, they are not sufficient for complete knowledge transmission in the process of technology transfer. Lack of efficiency of formal mechanism to end the Technology Transfer loop makes an opportunity to create innovative interpersonal and organizational connections among patentee and licensee company. With emphasize on need for further elaboration of informal mechanisms as critical and underappreciated aspect of technology transfer process, article will try to answer the questions of how to optimize knowledge transmission process in the framework of University-Industry Technology Transfer Projects? What is the theoretical basis for university-industry technology transfer process? What are organization collaborative models which can enhance overall performance by improving transmission of knowledge in

  5. OPTIMIZING OUTCOME IN THE UNIVERSITY-INDUSTRY TECHNOLOGY TRANSFER PROJECTS

    Directory of Open Access Journals (Sweden)

    Hamed ALAVI

    2016-04-01

    Full Text Available Transferring inventions of academic scientists to private enterprises for the purpose of commercialization is long known as University-Industry (firm Technology Transfer While the importance of this phenomenon is simultaneously raising in public and private sector, only a part of patented academic inventions succeed in passing the process of commercialization. Despite the fact that formal Technology Transfer process and licencing of patented innovations to third party is the main legal tool for safeguarding rights of academic inventors in commercialization of their inventions, it is not sufficient for transmitting tacit knowledge which is necessary in exploitation of transferred technology. Existence of reciprocal and complementary relations between formal and informal technology transfer process has resulted in formation of different models for university-industry organizational collaboration or even integration where licensee firms keep contact with academic inventors after gaining legal right for commercialization of their patented invention. Current paper argues that despite necessity for patents to legally pass the right of commercialization of an invention, they are not sufficient for complete knowledge transmission in the process of technology transfer. Lack of efficiency of formal mechanism to end the Technology Transfer loop makes an opportunity to create innovative interpersonal and organizational connections among patentee and licensee company. With emphasize on need for further elaboration of informal mechanisms as critical and underappreciated aspect of technology transfer process, article will try to answer the questions of how to optimize knowledge transmission process in the framework of University-Industry Technology Transfer Projects? What is the theoretical basis for university-industry technology transfer process? What are organization collaborative models which can enhance overall performance by improving transmission of

  6. Nulliparity is associated with subtle adverse metabolic outcomes in overweight/obese mothers and their offspring.

    Science.gov (United States)

    Seneviratne, Sumudu N; Derraik, José G B; Jiang, Yannan; McCowan, Lesley M E; Gusso, Silmara; Biggs, Janene B; Parry, Graham K; Chiavaroli, Valentina; Cutfield, Wayne S; Hofman, Paul L

    2017-11-01

    We aimed to evaluate metabolic outcomes in overweight/obese nulliparous and multiparous women and their offspring. Seventy-two overweight and obese women who participated in a randomized controlled trial of exercise in pregnancy were included in the study, comparing 18 nulliparous and 54 multiparous women and their singleton offspring. Women were assessed at 19 and 36 weeks of gestation. Fetal growth was measured using standard obstetric ultrasound techniques. Cord blood was collected at birth. Maternal and offspring body composition was assessed using DXA ~2 weeks after delivery. Nulliparous women had higher HbA1c in the third trimester of pregnancy than multiparous women (5.48% vs 5.29%; P=.002) and were more insulin-resistant based on the surrogate marker sex hormone-binding globulin (354 vs 408 nmol/L; P=.047). Nulliparous women also had higher levels of the inflammatory marker tumour necrosis factor-alpha (4.74 vs 3.62 pg/mL; P=.025). At birth, the offspring of nulliparous women were on average 340 g (P=.013) and 0.69 standard deviation scores (P=.026) lighter than those born of multiparous women. Cord blood data showed lower insulin-like growth factor-II (P=.026) and higher IGF binding protein-1 (P=.002) levels in the offspring of nulliparous women. In addition, a less favourable metabolic profile was observed in the offspring of nulliparous women, as indicated by higher triglyceride (P<.001) and interleukin-6 (P=.039) concentrations. Infants born of nulliparous overweight and obese women appear to be exposed to a less favourable metabolic environment in utero, with evidence of subtle adverse metabolic outcomes at birth compared to infants of overweight/obese multiparous women. © 2017 John Wiley & Sons Ltd.

  7. N-Glycosylation optimization of recombinant antibodies in CHO cell through process and metabolic engineering

    DEFF Research Database (Denmark)

    Fan, Yuzhou

    , analysis, control and optimization of N-glycosylation were thoroughly reviewed. In particular, how to control and optimize N-glycosylation in CHO cells was exclusively studied. The main focus of this PhD project is to find effective approaches of modulating N-glycosylation of CHO-derived recombinant...... galactose as feed additives, changing process parameters such as seeding density and cultivation duration are all demonstrated to be effective. The causal explanation of their impact on glycosylation can be various, including product, metabolism, proteome and physiology-associated mechanism. In the middle...... part of the thesis, both literature reviews and experimental applications were provided to demonstrate how to use omics data and implement systems biology to understand biological activities, especially N-glycosylation in CHO cells. In the last part of the thesis, the second strategy that apply genetic...

  8. On the use of metabolic control analysis in the optimization of cyanobacterial biosolar cell factories.

    Science.gov (United States)

    Angermayr, S Andreas; Hellingwerf, Klaas J

    2013-09-26

    Oxygenic photosynthesis will have a key role in a sustainable future. It is therefore significant that this process can be engineered in organisms such as cyanobacteria to construct cell factories that catalyze the (sun)light-driven conversion of CO2 and water into products like ethanol, butanol, or other biofuels or lactic acid, a bioplastic precursor, and oxygen as a byproduct. It is of key importance to optimize such cell factories to maximal efficiency. This holds for their light-harvesting capabilities under, for example, circadian illumination in large-scale photobioreactors. However, this also holds for the "dark" reactions of photosynthesis, that is, the conversion of CO2, NADPH, and ATP into a product. Here, we present an analysis, based on metabolic control theory, to estimate the optimal capacity for product formation with which such cyanobacterial cell factories have to be equipped. Engineered l-lactic acid producing Synechocystis sp. PCC6803 strains are used to identify the relation between production rate and enzymatic capacity. The analysis shows that the engineered cell factories for l-lactic acid are fully limited by the metabolic capacity of the product-forming pathway. We attribute this to the fact that currently available promoter systems in cyanobacteria lack the genetic capacity to a provide sufficient expression in single-gene doses.

  9. Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and Pareto filters.

    Directory of Open Access Journals (Sweden)

    Carlos Pozo

    Full Text Available Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study

  10. Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and Pareto filters.

    Science.gov (United States)

    Pozo, Carlos; Guillén-Gosálbez, Gonzalo; Sorribas, Albert; Jiménez, Laureano

    2012-01-01

    Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the

  11. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  12. Ratings of Broader Autism Phenotype and Personality Traits in Optimal Outcomes from Autism Spectrum Disorder

    Science.gov (United States)

    Suh, Joyce; Orinstein, Alyssa; Barton, Marianne; Chen, Chi-Ming; Eigsti, Inge-Marie; Ramirez-Esparza, Nairan; Fein, Deborah

    2016-01-01

    The study examines whether "optimal outcome" (OO) children, despite no longer meeting diagnostic criteria for Autism Spectrum Disorder (ASD), exhibit personality traits often found in those with ASD. Nine zero acquaintance raters evaluated Broader Autism Phenotype (BAP) and Big Five personality traits of 22 OO individuals, 27 high…

  13. The effect of pre-operative optimization on post-operative outcome in Crohn's disease resections

    DEFF Research Database (Denmark)

    El-Hussuna, Alaa; Iesalnieks, Igors; Horesh, Nir

    2017-01-01

    BACKGROUND: The timing of surgical intervention in Crohn's disease (CD) may depend on pre-operative optimization (PO) which includes different interventions to decrease the risk for unfavourable post-operative outcome. The objective of this study was to investigate the effect of multi-model PO on...

  14. Psychiatric Symptoms in Youth with a History of Autism and Optimal Outcome

    Science.gov (United States)

    Orinstein, Alyssa; Tyson, Katherine E.; Suh, Joyce; Troyb, Eva; Helt, Molly; Rosenthal, Michael; Barton, Marianne L.; Eigsti, Inge-Marie; Kelley, Elizabeth; Naigles, Letitia; Schultz, Robert T.; Stevens, Michael C.; Fein, Deborah A.

    2015-01-01

    Since autism spectrum disorder (ASD) is often comorbid with psychiatric disorders, children who no longer meet criteria for ASD (optimal outcome; OO) may still be at risk for psychiatric disorders. A parent interview for DSM-IV psychiatric disorders (K-SADS-PL) for 33 OO, 42 high-functioning autism (HFA) and 34 typically developing (TD) youth,…

  15. Benefits of SGLT2 Inhibitors beyond glycemic control - A focus on metabolic, cardiovascular, and renal outcomes.

    Science.gov (United States)

    Minze, Molly G; Will, Kayley; Terrell, Brian T; Black, Robin L; Irons, Brian K

    2017-08-16

    Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new pharmacotherapeutic class for the treatment of type 2 diabetes mellitus (T2DM). To evaluate beneficial effects of the SGLT2 inhibitors on metabolic, cardiovascular, and renal outcomes. A Pub-Med search (1966 to July 2017) was performed of published English articles using keywords sodium-glucose co-transporter 2 inhibitors, canagliflozin, dapagliflozin, and empagliflozin. A review of literature citations provided further references. The search identified 17clinical trials and 2 meta-analysis with outcomes of weight loss and blood pressure reduction with dapagliflozin, canagliflozin, or empagliflozin. Three randomized trials focused on either empagliflozin or canagliflozin and reduction of cardiovascular disease and progression of renal disease. SGLT2 inhibitors have a beneficial profile in the treatment of T2DM. They have evidence of reducing weight between 2.9 kilograms when used as monotherapy to 4.7 kilograms when used in combination with metformin, and reduce systolic blood pressure between 3 to 5 mmHg and reduce diastolic blood pressure approximately 2 mmHg. To date, reduction of cardiovascular events was seen specifically with empagliflozin in patients with T2DM and a history of cardiovascular disease. In the same population, empagliflozin was associated with slowing the progression of kidney disease. Moreover, patients with increased risk of cardiovascular disease treated with canagliflozin has decreased risk of death from cardiovascular causes, nonfatal MI, or nonfatal stroke. Data regarding these outcomes with dapagliflozin are underway. SGLT2 inhibitors demonstrate some positive metabolic effects. In addition, empagliflozin specifically has demonstrated reduction in cardiovascular events and delay in the progression of kidney disease in patients with T2DM and a history of cardiovascular disease. Further data is needed to assess if this is a class effect. Copyright© Bentham Science Publishers

  16. Dispositional optimism as predictor of outcome in short- and long-term psychotherapy.

    Science.gov (United States)

    Heinonen, Erkki; Heiskanen, Tiia; Lindfors, Olavi; Härkäpää, Kristiina; Knekt, Paul

    2017-09-01

    Dispositional optimism predicts various beneficial outcomes in somatic health and treatment, but has been little studied in psychotherapy. This study investigated whether an optimistic disposition differentially predicts patients' ability to benefit from short-term versus long-term psychotherapy. A total of 326 adult outpatients with mood and/or anxiety disorder were randomized into short-term (solution-focused or short-term psychodynamic) or long-term psychodynamic therapy and followed up for 3 years. Dispositional optimism was assessed by patients at baseline with the self-rated Life Orientation Test (LOT) questionnaire. Outcome was assessed at baseline and seven times during the follow-up, in terms of depressive (BDI, HDRS), anxiety (SCL-90-ANX, HARS), and general psychiatric symptoms (SCL-90-GSI), all seven follow-up points including patients' self-reports and three including interview-based measures. Lower dispositional optimism predicted faster symptom reduction in short-term than in long-term psychotherapy. Higher optimism predicted equally rapid and eventually greater benefits in long-term, as compared to short-term, psychotherapy. Weaker optimism appeared to predict sustenance of problems early in long-term therapy. Stronger optimism seems to best facilitate engaging in and benefiting from a long-term therapy process. Closer research might clarify the psychological processes responsible for these effects and help fine-tune both briefer and longer interventions to optimize treatment effectiveness for particular patients and their psychological qualities. Weaker dispositional optimism does not appear to inhibit brief therapy from effecting symptomatic recovery. Patients with weaker optimism do not seem to gain added benefits from long-term therapy, but instead may be susceptible to prolonged psychiatric symptoms in the early stages of long-term therapy. © 2016 The British Psychological Society.

  17. Modelling central metabolic fluxes by constraint-based optimization reveals metabolic reprogramming of developing Solanum lycopersicum (tomato) fruit.

    Science.gov (United States)

    Colombié, Sophie; Nazaret, Christine; Bénard, Camille; Biais, Benoît; Mengin, Virginie; Solé, Marion; Fouillen, Laëtitia; Dieuaide-Noubhani, Martine; Mazat, Jean-Pierre; Beauvoit, Bertrand; Gibon, Yves

    2015-01-01

    Modelling of metabolic networks is a powerful tool to analyse the behaviour of developing plant organs, including fruits. Guided by our current understanding of heterotrophic metabolism of plant cells, a medium-scale stoichiometric model, including the balance of co-factors and energy, was constructed in order to describe metabolic shifts that occur through the nine sequential stages of Solanum lycopersicum (tomato) fruit development. The measured concentrations of the main biomass components and the accumulated metabolites in the pericarp, determined at each stage, were fitted in order to calculate, by derivation, the corresponding external fluxes. They were used as constraints to solve the model by minimizing the internal fluxes. The distribution of the calculated fluxes of central metabolism were then analysed and compared with known metabolic behaviours. For instance, the partition of the main metabolic pathways (glycolysis, pentose phosphate pathway, etc.) was relevant throughout fruit development. We also predicted a valid import of carbon and nitrogen by the fruit, as well as a consistent CO2 release. Interestingly, the energetic balance indicates that excess ATP is dissipated just before the onset of ripening, supporting the concept of the climacteric crisis. Finally, the apparent contradiction between calculated fluxes with low values compared with measured enzyme capacities suggest a complex reprogramming of the metabolic machinery during fruit development. With a powerful set of experimental data and an accurate definition of the metabolic system, this work provides important insight into the metabolic and physiological requirements of the developing tomato fruits. © 2014 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

  18. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  19. Language comprehension and brain function in individuals with an optimal outcome from autism

    OpenAIRE

    Eigsti, Inge-Marie; Stevens, Michael C.; Schultz, Robert T.; Barton, Marianne; Kelley, Elizabeth; Naigles, Letitia; Orinstein, Alyssa; Troyb, Eva; Fein, Deborah A.

    2015-01-01

    Although Autism Spectrum Disorder (ASD) is generally a lifelong disability, a minority of individuals with ASD overcome their symptoms to such a degree that they are generally indistinguishable from their typically-developing peers. That is, they have achieved an Optimal Outcome (OO). The question addressed by the current study is whether this normalized behavior reflects normalized brain functioning, or alternatively, the action of compensatory systems. Either possibility is plausible, as mo...

  20. Predicting an Optimal Outcome after Radical Prostatectomy: The “Trifecta” Nomogram

    Science.gov (United States)

    Eastham, James A.; Scardino, Peter T.; Kattan, Michael W.

    2014-01-01

    Purpose The optimal outcome after radical prostatectomy (RP) for clinically localized prostate cancer is freedom from biochemical recurrence (BCR) along with recovery of continence and erectile function, a so-called trifecta. We evaluated our series of open radical prostatectomy patients to determine the likelihood of this outcome and to develop a nomogram predicting the trifecta. Material and Methods We reviewed records of patients undergoing open RP for clinical stage T1c–T3a prostate cancer at our center during 2000–2006. Men were excluded if they received preoperative hormonal therapy, chemotherapy, or radiation therapy; if their pre-treatment PSA was >50 ng/ml; or if they were impotent or incontinent before RP; 1577 men were included in the study. Freedom from BCR was defined as post-RP PSA <0.2 ng/ml. Continence was defined as not having to wear any protective pads. Potency was defined as erections adequate for intercourse on the majority of attempts, with or without a phosphodiesterase-5 inhibitor. Results Mean patient age was 58 years and mean pretreatment PSA was 6.4 ng/ml. A trifecta outcome (cancer-free status with recovery of continence and potency) was achieved in 62% of patients. In a nomogram developed to predict the likelihood of the trifecta, baseline PSA was the major predictive factor. The area under the receiver operating characteristic curve for the nomogram was 0.773, and calibration appeared excellent. Conclusions A trifecta (optimal) outcome can be achieved in the majority of men undergoing RP. The nomogram will permit patients to estimate preoperatively their likelihood of an optimal outcome after RP. PMID:18423693

  1. Treatment of chronic myeloid leukemia: assessing risk, monitoring response, and optimizing outcome.

    Science.gov (United States)

    Shanmuganathan, Naranie; Hiwase, Devendra Keshaorao; Ross, David Morrall

    2017-12-01

    Over the past two decades, tyrosine kinase inhibitors have become the foundation of chronic myeloid leukemia (CML) treatment. The choice between imatinib and newer tyrosine kinase inhibitors (TKIs) needs to be balanced against the known toxicity and efficacy data for each drug, the therapeutic goal being to maximize molecular response assessed by BCR-ABL RQ-PCR assay. There is accumulating evidence that the early achievement of molecular targets is a strong predictor of superior long-term outcomes. Early response assessment provides the opportunity to intervene early with the aim of ensuring an optimal response. Failure to achieve milestones or loss of response can have diverse causes. We describe how clinical and laboratory monitoring can be used to ensure that each patient is achieving an optimal response and, in patients who do not reach optimal response milestones, how the monitoring results can be used to detect resistance and understand its origins.

  2. An exploratory analysis of criteria for the metabolic syndrome and its prediction of long-term cardiovascular outcomes

    NARCIS (Netherlands)

    Girman, C.J.; Dekker, J.M.; Rhodes, T.; Nijpels, M.G.A.A.M.; Stehouwer, C.D.A.; Bouter, L.M.; Heine, R.J.

    2005-01-01

    Studies have shown an increased risk of cardiovascular outcomes with the metabolic syndrome, but information on predictive properties of the National Cholesterol Education Program Adult Treatment Panel 3 (NCEP) criteria is sparse. The authors used data from the Hoorn population-based study in the

  3. Birth weight and long-term metabolic outcomes: does the definition of smallness matter?

    Science.gov (United States)

    Verkauskiene, R; Figueras, F; Deghmoun, S; Chevenne, D; Gardosi, J; Levy-Marchal, M

    2008-01-01

    To establish the role of individual definition of smallness at birth in the association between birth weight and long-term metabolic outcomes. Lipid profile and oral glucose tolerance test were performed in young adults (22 years) born either small (SGA) or appropriate for gestational age (AGA). AGA/SGA were defined by both population-based and customized methods adjusting for individual maternal/pregnancy characteristics. 825 individuals were classified as AGA and 575 as SGA by both methods, 131 were SGA by the population-based method only (SGA(pop)) and 22 were SGA by the customized method only (SGA(cust)). SGA(cust) subjects had higher total cholesterol and triglyceride levels and lower high-density lipoprotein cholesterol concentrations than SGA(pop) and AGA subjects, however, insignificantly when adjusted for age, gender and body mass index. The homeostasis model assessment for insulin resistance (HOMA-IR) index was higher in the SGA(cust) (p = 0.05) and SGA(pop) (p = 0.02) versus the AGA group. Controlling for the HOMA-IR index, the insulinogenic index was significantly lower in the SGA(cust) versus SGA(pop) (p = 0.001) and AGA (p = 0.003) groups. In SGA(cust) individuals, the HOMA-IR index was clearly shifted to higher, while the insulinogenic index to lower tertiles of AGA distribution; SGA(pop) subjects had the HOMA-IR and insulinogenic index predominantly in the highest tertiles. Individualized birth weight standards allow to better identify subjects who failed to reach their genetic potential of intrauterine growth and are at higher risk of metabolic disturbances and impaired insulin secretion later in life. Copyright 2008 S. Karger AG, Basel.

  4. Optimism Moderates the Influence of Pain Catastrophizing on Shoulder Pain Outcome: A Longitudinal Analysis.

    Science.gov (United States)

    Coronado, Rogelio A; Simon, Corey B; Lentz, Trevor A; Gay, Charles W; Mackie, Lauren N; George, Steven Z

    2017-01-01

    Study Design Secondary analysis of prospectively collected data. Background An abundance of evidence has highlighted the influence of pain catastrophizing and fear avoidance on clinical outcomes. Less is known about the interaction of positive psychological resources with these pain-associated distress factors. Objective To assess whether optimism moderates the influence of pain catastrophizing and fear avoidance on 3-month clinical outcomes in patients with shoulder pain. Methods Data from 63 individuals with shoulder pain (mean ± SD age, 38.8 ± 14.9 years; 30 female) were examined. Demographic, psychological, and clinical characteristics were obtained at baseline. Validated measures were used to assess optimism (Life Orientation Test-Revised), pain catastrophizing (Pain Catastrophizing Scale), fear avoidance (Fear-Avoidance Beliefs Questionnaire physical activity subscale), shoulder pain intensity (Brief Pain Inventory), and shoulder function (Pennsylvania Shoulder Score function subscale). Shoulder pain and function were reassessed at 3 months. Regression models assessed the influence of (1) pain catastrophizing and optimism and (2) fear avoidance and optimism. The final multivariable models controlled for factors of age, sex, education, and baseline scores, and included 3-month pain intensity and function as separate dependent variables. Results Shoulder pain (mean difference, -1.6; 95% confidence interval [CI]: -2.1, -1.2) and function (mean difference, 2.4; 95% CI: 0.3, 4.4) improved over 3 months. In multivariable analyses, there was an interaction between pain catastrophizing and optimism (β = 0.19; 95% CI: 0.02, 0.35) for predicting 3-month shoulder function (F = 16.8, R 2 = 0.69, Poptimism lessened the influence of pain catastrophizing on function. There was no evidence of significant moderation of fear-avoidance beliefs for 3-month shoulder pain (P = .090) or function (P = .092). Conclusion Optimism decreased the negative influence of pain

  5. Dynamic optimal control of homeostasis: an integrative system approach for modeling of the central nitrogen metabolism in Saccharomyces cerevisiae.

    Science.gov (United States)

    van Riel, N A; Giuseppin, M L; Verrips, C T

    2000-01-01

    The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the source of the cellular amino acids and proteins, including flavors and potentially valuable biomolecules; therefore, it is also of industrial interest. In the DOMC approach the cell is regarded as an optimally controlled system. Given the metabolic genotype, the cell faces a control problem to maintain an optimal flux distribution in a changing environment. The regulation is based on strategies and balances feedback control of homeostasis and feedforward regulation for adaptation. The DOMC approach is an integrative, holistic approach, not based on mechanistic descriptions and (therefore) not biased by the variation present in biochemical and molecular biological data. It is an effective tool to structure the rapidly increasing amount of data on the function of genes and pathways. The DOMC model is used successfully to predict the responses of pulses of ammonia and glutamine to nitrogen-limited continuous cultures of a wild-type strain and a glutamine synthetase-negative mutant. The simulation results are validated with experimental data.

  6. Is There an Optimal Diet for Weight Management and Metabolic Health?

    Science.gov (United States)

    Thom, George; Lean, Mike

    2017-05-01

    Individuals can lose body weight and improve health status on a wide range of energy (calorie)-restricted dietary interventions. In this paper, we have reviewed the effectiveness of the most commonly utilized diets, including low-fat, low-carbohydrate, and Mediterranean approaches, in addition to commercial slimming programs, meal replacements, and newly popularized intermittent fasting diets. We also consider the role of artificial sweeteners in weight management. Low-fat diets tend to improve low-density lipoprotein cholesterol the most, while lower-carbohydrate diets may preferentially improve triglycerides and high-density lipoprotein cholesterol. However, differences between diets are marginal. Weight loss improves almost all obesity-related co-morbidities and metabolic markers, regardless of the macronutrient composition of the diet, but individuals do vary in preferences and ability to adhere to different diets. Optimizing adherence is the most important factor for weight loss success, and this is enhanced by regular professional contact and supportive behavioral change programs. Maintaining weight losses in the long term remains the biggest challenge, and is undermined by an "obesogenic" environment and biological adaptations that accompany weight loss. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. A review of metabolic and enzymatic engineering strategies for designing and optimizing performance of microbial cell factories

    Directory of Open Access Journals (Sweden)

    Amanda K. Fisher

    2014-08-01

    Full Text Available Microbial cell factories (MCFs are of considerable interest to convert low value renewable substrates to biofuels and high value chemicals. This review highlights the progress of computational models for the rational design of an MCF to produce a target bio-commodity. In particular, the rational design of an MCF involves: (i product selection, (ii de novo biosynthetic pathway identification (i.e., rational, heterologous, or artificial, (iii MCF chassis selection, (iv enzyme engineering of promiscuity to enable the formation of new products, and (v metabolic engineering to ensure optimal use of the pathway by the MCF host. Computational tools such as (i de novo biosynthetic pathway builders, (ii docking, (iii molecular dynamics (MD and steered MD (SMD, and (iv genome-scale metabolic flux modeling all play critical roles in the rational design of an MCF. Genome-scale metabolic flux models are of considerable use to the design process since they can reveal metabolic capabilities of MCF hosts. These can be used for host selection as well as optimizing precursors and cofactors of artificial de novo biosynthetic pathways. In addition, recent advances in genome-scale modeling have enabled the derivation of metabolic engineering strategies, which can be implemented using the genomic tools reviewed here as well.

  8. Etiology, clinical spectrum and outcome of metabolic liver diseases in children

    International Nuclear Information System (INIS)

    Roy, A.; Samanta, T.; Purkait, R.; Mukherji, A.

    2013-01-01

    Objective: To determine the etiology, clinical spectrum and outcome of metabolic liver diseases (MLD) in children admitted in a tertiary care hospital of Eastern India. Study Design: An observational study. Place and Duration of Study: Paediatric Liver Clinic and Paediatrics Inpatient Department of Nilratan Sircar Medical College and Hospital, Kolkata, Eastern India, from April 2009 to March 2011. Methodology: All children aged 0 - 12 years having characteristic clinical features along with diagnostic hallmark of any MLDs were included in this study and data were collected on a pre-designed proforma. After appropriate management and discharge, all patients were followed-up for next 6 months. Results: Fifty one children with mean age 4.34 +- 3.78 years (range 2 days +- 12 years), male: female ratio 1.55:1, were studied. The etiologies were Wilson's disease (33.33%, n = 17); glycogen storage disorder (23.53%, n = 12); galactosemia (19.61%, n = 10); non-alcoholic fatty liver disease (11.76%, n = 6); Gaucher disease (5.88%, n = 3); mucopolysaccharidoses (3.92%, n = 2) and familial hyperlipoproteinemia type-I (1.96%, n = 1). Jaundice (n = 24) and hepatomegaly (n = 47), was the commonest symptom and sign respectively. Of the 17 non-responders, most were Wilson's disease (n = 7) cases. There was statistical difference in outcome with respect to INR > 1.3 at diagnosis (p = 0.026). Conclusion: High index of suspicion, early detection and screening, simple dietary modification and cost effective drugs along with good compliance are sufficient to treat and even prevent evolution of most causes of the MLDs. (author)

  9. Multiple cyber attacks against a target with observation errors and dependent outcomes: Characterization and optimization

    International Nuclear Information System (INIS)

    Hu, Xiaoxiao; Xu, Maochao; Xu, Shouhuai; Zhao, Peng

    2017-01-01

    In this paper we investigate a cybersecurity model: An attacker can launch multiple attacks against a target with a termination strategy that says that the attacker will stop after observing a number of successful attacks or when the attacker is out of attack resources. However, the attacker's observation of the attack outcomes (i.e., random variables indicating whether the target is compromised or not) has an observation error that is specified by both a false-negative and a false-positive probability. The novelty of the model we study is the accommodation of the dependence between the attack outcomes, because the dependence was assumed away in the literature. In this model, we characterize the monotonicity and bounds of the compromise probability (i.e., the probability that the target is compromised). In addition to extensively showing the impact of dependence on quantities such as compromise probability and attack cost, we give methods for finding the optimal strategy that leads to maximum compromise probability or minimum attack cost. This study highlights that the dependence between random variables cannot be assumed away, because the results will be misleading. - Highlights: • A novel cybersecurity model is proposed to accommodate the dependence among attack outcomes. • The monotonicity and bounds of the compromise probability are studied. • The dependence effect on the compromise probability and attack cost is discussed via simulation. • The optimal strategy that leads to maximum compromise probability or minimum attack cost is presented.

  10. Individualized risk assessment in neuroblastoma. Does the tumoral metabolic activity on 123I-MIBG SPECT predict the outcome?

    International Nuclear Information System (INIS)

    Rogasch, Julian M.M.; Furth, Christian; Wedel, Florian; Brenner, Winfried; Amthauer, Holger; Schatka, Imke; Hundsdoerfer, Patrick; Hofheinz, Frank; Krueger, Paul-Christian; Lode, Holger; Eggert, Angelika

    2017-01-01

    Risk-adapted treatment in children with neuroblastoma (NB) is based on clinical and genetic factors. This study evaluated the metabolic tumour volume (MTV) and its asphericity (ASP) in pretherapeutic 123 I-MIBG SPECT for individualized image-based prediction of outcome. This retrospective study included 23 children (11 girls, 12 boys; median age 1.8 years, range 0.3-6.8 years) with newly diagnosed NB consecutively examined with pretherapeutic 123 I-MIBG SPECT. Primary tumour MTV and ASP were defined using semiautomatic thresholds. Cox regression analysis, receiver operating characteristic analysis (cut-off determination) and Kaplan-Meier analysis with the log-rank test for event-free survival (EFS) were performed for ASP, MTV, laboratory parameters (including urinary homovanillic acid-to-creatinine ratio, HVA/C), and clinical (age, stage) and genetic factors. Predictive accuracy of the optimal multifactorial model was determined in terms of Harrell's C and likelihood ratio χ 2 . Median follow-up was 36 months (range 7-107 months; eight patients showed disease progression/relapse, four patients died). The only significant predictors of EFS in the univariate Cox regression analysis were ASP (p = 0.029; hazard ratio, HR, 1.032 for a one unit increase), MTV (p = 0.038; HR 1.012) and MYCN amplification status (p = 0.047; HR 4.67). The mean EFS in patients with high ASP (>32.0%) and low ASP were 21 and 88 months, respectively (p = 0.013), and in those with high MTV (>46.7 ml) and low MTV were 22 and 87 months, respectively (p = 0.023). A combined risk model of either high ASP and high HVA/C or high MTV and high HVA/C best predicted EFS. In this exploratory study, pretherapeutic image-derived and laboratory markers of tumoral metabolic activity in NB (ASP, MTV, urinary HVA/C) allowed the identification of children with a high and low risk of progression/relapse under current therapy. (orig.)

  11. Individualized risk assessment in neuroblastoma. Does the tumoral metabolic activity on {sup 123}I-MIBG SPECT predict the outcome?

    Energy Technology Data Exchange (ETDEWEB)

    Rogasch, Julian M.M.; Furth, Christian; Wedel, Florian; Brenner, Winfried; Amthauer, Holger; Schatka, Imke [Charite - Universitaetsmedizin Berlin, Department of Nuclear Medicine, Berlin (Germany); Hundsdoerfer, Patrick [Charite - Universitaetsmedizin Berlin, Department of Pediatric Oncology/Hematology, Berlin (Germany); Berlin Institute of Health (BIH), Berlin (Germany); Hofheinz, Frank [Helmholtz Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, PET Center, Dresden (Germany); Krueger, Paul-Christian [University Medicine Greifswald, Institute for Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Lode, Holger [University Medicine Greifswald, Department of Pediatric Oncology and Hematology, Greifswald (Germany); Eggert, Angelika [Charite - Universitaetsmedizin Berlin, Department of Pediatric Oncology/Hematology, Berlin (Germany)

    2017-12-15

    Risk-adapted treatment in children with neuroblastoma (NB) is based on clinical and genetic factors. This study evaluated the metabolic tumour volume (MTV) and its asphericity (ASP) in pretherapeutic {sup 123}I-MIBG SPECT for individualized image-based prediction of outcome. This retrospective study included 23 children (11 girls, 12 boys; median age 1.8 years, range 0.3-6.8 years) with newly diagnosed NB consecutively examined with pretherapeutic {sup 123}I-MIBG SPECT. Primary tumour MTV and ASP were defined using semiautomatic thresholds. Cox regression analysis, receiver operating characteristic analysis (cut-off determination) and Kaplan-Meier analysis with the log-rank test for event-free survival (EFS) were performed for ASP, MTV, laboratory parameters (including urinary homovanillic acid-to-creatinine ratio, HVA/C), and clinical (age, stage) and genetic factors. Predictive accuracy of the optimal multifactorial model was determined in terms of Harrell's C and likelihood ratio χ {sup 2}. Median follow-up was 36 months (range 7-107 months; eight patients showed disease progression/relapse, four patients died). The only significant predictors of EFS in the univariate Cox regression analysis were ASP (p = 0.029; hazard ratio, HR, 1.032 for a one unit increase), MTV (p = 0.038; HR 1.012) and MYCN amplification status (p = 0.047; HR 4.67). The mean EFS in patients with high ASP (>32.0%) and low ASP were 21 and 88 months, respectively (p = 0.013), and in those with high MTV (>46.7 ml) and low MTV were 22 and 87 months, respectively (p = 0.023). A combined risk model of either high ASP and high HVA/C or high MTV and high HVA/C best predicted EFS. In this exploratory study, pretherapeutic image-derived and laboratory markers of tumoral metabolic activity in NB (ASP, MTV, urinary HVA/C) allowed the identification of children with a high and low risk of progression/relapse under current therapy. (orig.)

  12. Neonatal screening for inborn errors of metabolism: cost, yield and outcome.

    Science.gov (United States)

    Pollitt, R J; Green, A; McCabe, C J; Booth, A; Cooper, N J; Leonard, J V; Nicholl, J; Nicholson, P; Tunaley, J R; Virdi, N K

    1997-01-01

    OBJECTIVES. To systematically review the literature on inborn errors of metabolism, neonatal screening technology and screening programmes in order to analyse the costs and benefits of introducing screening based on tandem mass-spectrometry (tandem MS) for a wide range of disorders of amino acid and organic acid metabolism in the UK. To evaluate screening for cystic fibrosis, Duchenne muscular dystrophy and other disorders which are tested on an individual basis. HOW THE RESEARCH WAS CONDUCTED. Systematic searches were carried out of the literature on inborn errors of metabolism, neonatal screening programmes, tandem MS-based neonatal screening technology, economic evaluations of neonatal screening programmes and psychological aspects of neonatal screening. Background material on the biology of inherited metabolic disease, the basic philosophy, and the history and current status of the UK screening programme was also collected. Relevant papers in the grey literature and recent publications were identified by hand-searching. Each paper was graded. For each disease an aggregate grade for the state of knowledge in six key areas was awarded. Additional data were prospectively collected on activity and costs in UK neonatal screening laboratories, and expert clinical opinion on current treatment modalities and outcomes. These data were used to construct a decision-analysis model of neonatal screening technologies, comparing tandem MS with the existing phenylketonuria screening methods. This model determined the cost per additional case identified and, for each disease, the additional treatment costs per case, and the cost per life-year saved. All costs and benefits were discounted at 6% per annum. One-way sensitivity analysis was performed showing the effect of varying the discount rate, the incidence rate of each disorder, the number of neonates screened and the cost of tandem MS, on the cost per life-year gained. RESEARCH FINDINGS. The UK screening programmes for

  13. Optimizing time management after perforation by colonoscopy results in better outcome for the patients.

    Science.gov (United States)

    Rumstadt, Bernhard; Schilling, Dieter

    2008-01-01

    Perforation during colonoscopy is a rare but severe complication. The aim of this study was to assess the time management and laparoscopic therapy of this complication and to evaluate patient outcomes. A retrospective analysis was done on 15 patients operated for a perforation from colonoscopy between January 2000 and December 2006. Three perforations occurred during diagnostic and 12 perforations during interventional colonoscopy. Two perforations occurred as transmural thermal injury to the colon wall. Peritonitis was found in 4 cases and significantly correlated with the mean time between perforation and operation. Twelve perforations were oversewn laparoscopically and 3 perforations were oversewn by laparotomy. After laparoscopic treatment, hospital stay was significantly shorter than after laparotomy. One patient had a postoperative wound infection, mortality was 0%. Laparoscopic oversewing is a safe and effective method in the treatment of perforation from colonoscopy. Optimizing the time range between perforation and laparoscopic therapy results in a better outcome for the patients.

  14. Development and optimization of SPECT gated blood pool cluster analysis for the prediction of CRT outcome

    Energy Technology Data Exchange (ETDEWEB)

    Lalonde, Michel, E-mail: mlalonde15@rogers.com; Wassenaar, Richard [Department of Physics, Carleton University, Ottawa, Ontario K1S 5B6 (Canada); Wells, R. Glenn; Birnie, David; Ruddy, Terrence D. [Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7 (Canada)

    2014-07-15

    Purpose: Phase analysis of single photon emission computed tomography (SPECT) radionuclide angiography (RNA) has been investigated for its potential to predict the outcome of cardiac resynchronization therapy (CRT). However, phase analysis may be limited in its potential at predicting CRT outcome as valuable information may be lost by assuming that time-activity curves (TAC) follow a simple sinusoidal shape. A new method, cluster analysis, is proposed which directly evaluates the TACs and may lead to a better understanding of dyssynchrony patterns and CRT outcome. Cluster analysis algorithms were developed and optimized to maximize their ability to predict CRT response. Methods: About 49 patients (N = 27 ischemic etiology) received a SPECT RNA scan as well as positron emission tomography (PET) perfusion and viability scans prior to undergoing CRT. A semiautomated algorithm sampled the left ventricle wall to produce 568 TACs from SPECT RNA data. The TACs were then subjected to two different cluster analysis techniques, K-means, and normal average, where several input metrics were also varied to determine the optimal settings for the prediction of CRT outcome. Each TAC was assigned to a cluster group based on the comparison criteria and global and segmental cluster size and scores were used as measures of dyssynchrony and used to predict response to CRT. A repeated random twofold cross-validation technique was used to train and validate the cluster algorithm. Receiver operating characteristic (ROC) analysis was used to calculate the area under the curve (AUC) and compare results to those obtained for SPECT RNA phase analysis and PET scar size analysis methods. Results: Using the normal average cluster analysis approach, the septal wall produced statistically significant results for predicting CRT results in the ischemic population (ROC AUC = 0.73;p < 0.05 vs. equal chance ROC AUC = 0.50) with an optimal operating point of 71% sensitivity and 60% specificity. Cluster

  15. Development and optimization of SPECT gated blood pool cluster analysis for the prediction of CRT outcome

    International Nuclear Information System (INIS)

    Lalonde, Michel; Wassenaar, Richard; Wells, R. Glenn; Birnie, David; Ruddy, Terrence D.

    2014-01-01

    Purpose: Phase analysis of single photon emission computed tomography (SPECT) radionuclide angiography (RNA) has been investigated for its potential to predict the outcome of cardiac resynchronization therapy (CRT). However, phase analysis may be limited in its potential at predicting CRT outcome as valuable information may be lost by assuming that time-activity curves (TAC) follow a simple sinusoidal shape. A new method, cluster analysis, is proposed which directly evaluates the TACs and may lead to a better understanding of dyssynchrony patterns and CRT outcome. Cluster analysis algorithms were developed and optimized to maximize their ability to predict CRT response. Methods: About 49 patients (N = 27 ischemic etiology) received a SPECT RNA scan as well as positron emission tomography (PET) perfusion and viability scans prior to undergoing CRT. A semiautomated algorithm sampled the left ventricle wall to produce 568 TACs from SPECT RNA data. The TACs were then subjected to two different cluster analysis techniques, K-means, and normal average, where several input metrics were also varied to determine the optimal settings for the prediction of CRT outcome. Each TAC was assigned to a cluster group based on the comparison criteria and global and segmental cluster size and scores were used as measures of dyssynchrony and used to predict response to CRT. A repeated random twofold cross-validation technique was used to train and validate the cluster algorithm. Receiver operating characteristic (ROC) analysis was used to calculate the area under the curve (AUC) and compare results to those obtained for SPECT RNA phase analysis and PET scar size analysis methods. Results: Using the normal average cluster analysis approach, the septal wall produced statistically significant results for predicting CRT results in the ischemic population (ROC AUC = 0.73;p < 0.05 vs. equal chance ROC AUC = 0.50) with an optimal operating point of 71% sensitivity and 60% specificity. Cluster

  16. Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes.

    Science.gov (United States)

    Reinke, Christian; Bevans-Fonti, Shannon; Drager, Luciano F; Shin, Mi-Kyung; Polotsky, Vsevolod Y

    2011-09-01

    Obstructive sleep apnea (OSA) causes intermittent hypoxia (IH) during sleep. Both obesity and OSA are associated with insulin resistance and systemic inflammation, which may be attributable to tissue hypoxia. We hypothesized that a pattern of hypoxic exposure determines both oxygen profiles in peripheral tissues and systemic metabolic outcomes, and that obesity has a modifying effect. Lean and obese C57BL6 mice were exposed to 12 h of intermittent hypoxia 60 times/h (IH60) [inspired O₂ fraction (Fi(O₂)) 21-5%, 60/h], IH 12 times/h (Fi(O₂) 5% for 15 s, 12/h), sustained hypoxia (SH; Fi(O₂) 10%), or normoxia while fasting. Tissue oxygen partial pressure (Pti(O₂)) in liver, skeletal muscle and epididymal fat, plasma leptin, adiponectin, insulin, blood glucose, and adipose tumor necrosis factor-α (TNF-α) were measured. In lean mice, IH60 caused oxygen swings in the liver, whereas fluctuations of Pti(O₂) were attenuated in muscle and abolished in fat. In obese mice, baseline liver Pti(O₂) was lower than in lean mice, whereas muscle and fat Pti(O₂) did not differ. During IH, Pti(O₂) was similar in obese and lean mice. All hypoxic regimens caused insulin resistance. In lean mice, hypoxia significantly increased leptin, especially during SH (44-fold); IH60, but not SH, induced a 2.5- to 3-fold increase in TNF-α secretion by fat. Obesity was associated with striking increases in leptin and TNF-α, which overwhelmed effects of hypoxia. In conclusion, IH60 led to oxygen fluctuations in liver and muscle and steady hypoxia in fat. IH and SH induced insulin resistance, but inflammation was increased only by IH60 in lean mice. Obesity caused severe inflammation, which was not augmented by acute hypoxic regimens.

  17. Reconstruction after complex facial trauma: achieving optimal outcome through multiple contemporary surgeries.

    Science.gov (United States)

    Jaiswal, Rohit; Pu, Lee L Q

    2013-04-01

    Major facial trauma injuries often require complex repair. Traditionally, the reconstruction of such injuries has primarily utilized only free tissue transfer. However, the advent of newer, contemporary procedures may lead to potential reconstructive improvement through the use of complementary procedures after free flap reconstruction. An 18-year-old male patient suffered a major left facial degloving injury resulting in soft-tissue defect with exposed zygoma, and parietal bone. Multiple operations were undertaken in a staged manner for reconstruction. A state-of-the-art free anterolateral thigh (ALT) perforator flap and Medpor implant reconstruction of the midface were initially performed, followed by flap debulking, lateral canthopexy, midface lift with redo canthopexy, scalp tissue expansion for hairline reconstruction, and epidermal skin grafting for optimal skin color matching. Over a follow-up period of 2 years, a good and impressive reconstructive result was achieved through the use of multiple contemporary reconstructive procedures following an excellent free ALT flap reconstruction. Multiple staged reconstructions are essential in producing an optimal outcome in this complex facial injury that would likely not have been produced through a 1-stage traditional free flap reconstruction. Utilizing multiple, sequential contemporary surgeries may substantially improve outcome through the enhancement and refinement of results based on possibly the best initial soft-tissue reconstruction.

  18. Identified metabolic signature for assessing red blood cell unit quality is associated with endothelial damage markers and clinical outcomes

    DEFF Research Database (Denmark)

    Bordbar, Aarash; Johansson, Pär I.; Paglia, Giuseppe

    2016-01-01

    shown no difference of clinical outcome for patients receiving old or fresh RBCs. An overlooked but essential issue in assessing RBC unit quality and ultimately designing the necessary clinical trials is a metric for what constitutes an old or fresh RBC unit. STUDY DESIGN AND METHODS: Twenty RBC units...... years and endothelial damage markers in healthy volunteers undergoing autologous transfusions. CONCLUSION: The state of RBC metabolism may be a better indicator of cellular quality than traditional hematologic variables....

  19. Maternal obesity and metabolic risk to the offspring: why lifestyle interventions may have not achieved the desired outcomes

    OpenAIRE

    Catalano, P; deMouzon, SH

    2015-01-01

    Obesity during pregnancy is associated with an increased risk of short- and long-term metabolic dysfunction in the mother and her offspring. Both higher maternal pregravid body mass index (kg m−2) and excessive gestational weight gain (GWG) have been associated with adverse pregnancy outcomes such as gestational diabetes, preeclampsia and fetal adiposity. Multiple lifestyle intervention trials consisting of weight management using various diets, increased physical activity and behavioral modi...

  20. Optimizing aesthetic outcomes for breast reconstruction in patients with significant macromastia or ptosis

    Directory of Open Access Journals (Sweden)

    Wojciech Dec

    2018-06-01

    Full Text Available Background: Achieving excellent aesthetic outcomes in reconstruction of large or ptotic breasts is especially challenging. Incorporating a Wise pattern into the mastectomy design is effective in reducing the excess breast skin, however it increases the risk of mastectomy skin necrosis. The aim of this study is to describe surgical maneuvers which optimize aesthetic outcomes, anticipate flap volume requirements, and limit mastectomy skin necrosis in autologous reconstruction in patients with macromastia and grade III ptosis. Methods: This is a retrospective review of operative and clinical records of patients who underwent unilateral or bilateral breast reconstruction with autologous tissue between August 2015 and May 2017. Patients were divided into macromastia and ptosis groups. Key surgical maneuvers for safely achieving aesthetically optimal results were identified. Results: A total of 29 breasts were successfully reconstructed in 19 patients with a Wise pattern mastectomy skin reduction. Free flap weights were similar in both groups, mastectomy weights were greater in the macromastia group, p < 0.05. Complications were limited to three cases of wound breakdown and one case of mastectomy skin necrosis. Total number of revision stages was reduced in unilateral reconstructions when a contralateral breast reduction or mastopexy was performed during the first stage. Conclusions: A Wise pattern can safely and effectively be incorporated into a mastectomy incision design in patients who are not candidates for a nipple sparing mastectomy. Optimal aesthetics are achieved with similar volume flaps for both macromastia and ptosis patients. In cases of unilateral breast reconstruction a contralateral breast reduction or mastopexy should be performed at the time of the immediate breast reconstruction. Keywords: Breast reconstruction, Aesthetic breast reconstruction, Macromastia breast reconstruction, Ptosis breast reconstruction

  1. Preoperative Nutritional Optimization for Crohn's Disease Patients Can Improve Surgical Outcome.

    Science.gov (United States)

    Dreznik, Yael; Horesh, Nir; Gutman, Mordechai; Gravetz, Aviad; Amiel, Imri; Jacobi, Harel; Zmora, Oded; Rosin, Danny

    2017-11-01

    Preoperative preparation of patients with Crohn's disease is challenging and there are no specific guidelines regarding nutritional support. The aim of this study was to assess whether preoperative nutritional support influenced the postoperative outcome. A retrospective, cohort study including all Crohn's disease patients who underwent abdominal surgery between 2008 and 2014 was conducted. Patients' characteristics and clinical and surgical data were recorded and analyzed. Eighty-seven patients were included in the study. Thirty-seven patients (42.5%) received preoperative nutritional support (mean albumin level 3.14 vs. 3.5 mg/dL in the non-optimized group; p nutritional status prior to surgery. Preoperative albumin level, after adequate nutritional preparation, was similar between the 2 groups. The 2 groups differ neither in demographic and surgical data, overall post-op complication (p = 0.85), Clavien-Dindo score (p = 0.42), and length of stay (p = 0.1). Readmission rate was higher in the non-optimized group (p = 0.047). Nutritional support can minimize postoperative complications in patients with low albumin levels. Nutritional status should be optimized in order to avoid hazardous complications. © 2017 S. Karger AG, Basel.

  2. A Pilot Study: The importance of inter-individual differences in inorganic arsenic metabolism for birth weight outcome

    Science.gov (United States)

    Gelmann, Elyssa R; Gurzau, Eugen; Gurzau, Anca; Goessler, Walter; Kunrath, Julie

    2013-01-01

    Inorganic arsenic (iAs) exposure is detrimental to birth outcome. We lack information regarding the potential for iAs metabolism to affect fetal growth. Our pilot study evaluated postpartum Romanian women with known birth weight outcome for differences in iAs metabolism. Subjects were chronically exposed to low-to-moderate drinking water iAs. We analyzed well water, arsenic metabolites in urine, and toenail arsenic. Urine iAs and metabolites, toenail iAs, and secondary methylation efficiency increased as an effect of exposure (piAs and metabolites showed a significant interaction effect between exposure and birth weight. Moderately exposed women with low compared to normal birth weight outcome had greater metabolite excretion (piAs >9μg/L (p=0.019). Metabolic partitioning of iAs toward excretion may impair fetal growth. Prospective studies on iAs excretion before and during pregnancy may provide a biomarker for poor fetal growth risk. PMID:24211595

  3. Impact of Targeted Preoperative Optimization on Clinical Outcome in Emergency Abdominal Surgeries: A Prospective Randomized Trial.

    Science.gov (United States)

    Sethi, Ashish; Debbarma, Miltan; Narang, Neeraj; Saxena, Anudeep; Mahobia, Mamta; Tomar, Gaurav Singh

    2018-01-01

    Perforation peritonitis continues to be one of the most common surgical emergencies that need a surgical intervention most of the times. Anesthesiologists are invariably involved in managing such cases efficiently in perioperative period. The assessment and evaluation of Acute Physiology and Chronic Health Evaluation II (APACHE II) score at presentation and 24 h after goal-directed optimization, administration of empirical broad-spectrum antibiotics, and definitive source control postoperatively. Outcome assessment in terms of duration of hospital stay and mortality in with or without optimization was also measured. It is a prospective, randomized, double-blind controlled study in hospital setting. One hundred and one patients aged ≥18 years, of the American Society of Anesthesiologists physical Status I and II (E) with clinical diagnosis of perforation peritonitis posted for surgery were enrolled. Enrolled patients were randomly divided into two groups. Group A is optimized by goal-directed optimization protocol in the preoperative holding room by anesthesiology residents whereas in Group S, managed by surgery residents in the surgical wards without any fixed algorithm. The assessment of APACHE II score was done as a first step on admission and 24 h postoperatively. Duration of hospital stay and mortality in both the groups were also measured and compared. Categorical data are presented as frequency counts (percent) and compared using the Chi-square or Fisher's exact test. The statistical significance for categorical variables was determined by Chi-square analysis. For continuous variables, a two-sample t -test was applied. The mean APACHE II score on admission in case and control groups was comparable. Significant lowering of serial scores in case group was observed as compared to control group ( P = 0.02). There was a significant lowering of mean duration of hospital stay seen in case group (9.8 ± 1.7 days) as compared to control group ( P = 0

  4. [The optimal cutoff value of waist-to-height ratio in Chinese: based on cardiovascular risk and metabolic disease].

    Science.gov (United States)

    Jia, A H; Xu, S Y; Ming, J; Zhou, J; Zhang, W C; Hao, P R; Ji, Q H

    2017-11-01

    Objective: Waist-to-height ratio (WHtR), a measurement of the distribution of body fat, correlated with abdominal obesity indicating that it might be a better predictor of cardiovascular risk and metabolic disease. We, therefore, evaluated optimal WHtR cutoff points according to the risk of framingham risk score (FRS) and metabolic syndrome (MS) in Chinese. Methods: The subjects were from China National Diabetes and Metabolic Disorders Survey during 2007-2008. Receiver operating characteristic analysis was used to examine the optimal cutoff values of WHtR according to the risk of FRS and MS. Results: A total of 27 820 women and 18 419 men were included in the evaluation. The average age was (45.0±13.7) years. The proportions of FRS ≥10% and MS increased with WHtR both in men and women. The cutoff points of WHtR for the risk of FRS ≥10% and MS were 0.51, 0.52 in men, and 0.52, 0.53 in women, respectively. When FRS ≥10% and MS were taken into consideration with a certain weights, the pooled cutoffs of WHtR were 0.51 in men, and 0.53 in women, respectively. By using the similar method, the optimized cutoff points were 0.52, 0.51, 0.50 for men and 0.51, 0.53, 0.54 for women in age group 20-39, 40-59 and ≥60 years, respectively. Conclusions: The optimal cutoffs of WHtR are 0.51 in men, and 0.53 in women for FRS≥10% in combination with MS indicating that this WHtR cutoff points might be used as indexes to evaluate obesity and risk of obesity-related diseases.

  5. Seeing the wood for the trees: a forest of methods for optimization and omic-network integration in metabolic modelling.

    Science.gov (United States)

    Vijayakumar, Supreeta; Conway, Max; Lió, Pietro; Angione, Claudio

    2017-05-30

    Metabolic modelling has entered a mature phase with dozens of methods and software implementations available to the practitioner and the theoretician. It is not easy for a modeller to be able to see the wood (or the forest) for the trees. Driven by this analogy, we here present a 'forest' of principal methods used for constraint-based modelling in systems biology. This provides a tree-based view of methods available to prospective modellers, also available in interactive version at http://modellingmetabolism.net, where it will be kept updated with new methods after the publication of the present manuscript. Our updated classification of existing methods and tools highlights the most promising in the different branches, with the aim to develop a vision of how existing methods could hybridize and become more complex. We then provide the first hands-on tutorial for multi-objective optimization of metabolic models in R. We finally discuss the implementation of multi-view machine learning approaches in poly-omic integration. Throughout this work, we demonstrate the optimization of trade-offs between multiple metabolic objectives, with a focus on omic data integration through machine learning. We anticipate that the combination of a survey, a perspective on multi-view machine learning and a step-by-step R tutorial should be of interest for both the beginner and the advanced user. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Ratings of Broader Autism Phenotype and Personality Traits in Optimal Outcomes from Autism Spectrum Disorder.

    Science.gov (United States)

    Suh, Joyce; Orinstein, Alyssa; Barton, Marianne; Chen, Chi-Ming; Eigsti, Inge-Marie; Ramirez-Esparza, Nairan; Fein, Deborah

    2016-11-01

    The study examines whether "optimal outcome" (OO) children, despite no longer meeting diagnostic criteria for Autism Spectrum Disorder (ASD), exhibit personality traits often found in those with ASD. Nine zero acquaintance raters evaluated Broader Autism Phenotype (BAP) and Big Five personality traits of 22 OO individuals, 27 high functioning individuals with ASD (HFA), and 23 typically developing (TD) peers. HFA children displayed higher ratings than their peers on all BAP traits. OO were indistinguishable from TD, with the exception of greater extraversion (e.g., increased talkativeness), a potential tendency to be less emotionally stable, and pragmatic language deficits such as getting sidetracked in conversation. Overall, OO individuals are not showing BAP characteristics, but may be subject to other mild ADHD-like characteristics.

  7. Maternal obesity and metabolic risk to the offspring: why lifestyle interventions may have not achieved the desired outcomes.

    Science.gov (United States)

    Catalano, P; deMouzon, S H

    2015-04-01

    Obesity during pregnancy is associated with an increased risk of short- and long-term metabolic dysfunction in the mother and her offspring. Both higher maternal pregravid body mass index (kg m(-2)) and excessive gestational weight gain (GWG) have been associated with adverse pregnancy outcomes such as gestational diabetes, preeclampsia and fetal adiposity. Multiple lifestyle intervention trials consisting of weight management using various diets, increased physical activity and behavioral modification techniques have been employed to avoid excessive GWG and improve perinatal outcomes. These randomized controlled trials (RCTs) have achieved modest success in decreasing excessive GWG, although the decrease in GWG was often not within the current Institute of Medicine guidelines. RCTs have generally not had any success with decreasing the risk of maternal gestational diabetes (GDM), preeclampsia or excessive fetal growth often referred to as macrosomia. Although the lack of success for these trials has been attributed to lack of statistical power and poor compliance with study protocols, our own research suggests that maternal pregravid and early pregnancy metabolic condition programs early placenta function and gene expression. These alterations in maternal/placental function occur in the first trimester of pregnancy prior to when most intervention trials are initiated. For example, maternal accrural of adipose tissue relies on prior activation of genes controlling lipogenesis and low-grade inflammation in early pregnancy. These metabolic alterations occur prior to any changes in maternal phenotype. Therefore, trials of lifestyle interventions before pregnancy are needed to demonstrate the safety and efficacy for both the mother and her offspring.

  8. Measuring tele-ICU impact: does it optimize quality outcomes for the critically ill patient?

    Science.gov (United States)

    Goran, Susan F

    2012-04-01

    To determine the relationship between tele-ICU (intensive care unit) implementations and improvement in quality measures and patient outcomes. Tele-ICUs were designed to leverage scarce critical-care experts and promised to improve patient quality. Abstracts and peer-reviewed articles were reviewed to identify the associations between tele-ICU programmes and clinical outcomes, cost savings, and customer satisfaction. Few peer-reviewed studies are available and many variables in each study limit the ability to associate study conclusions to the overall tele-ICU programme. Further research is required to explore the impact of the tele-ICU on patient/family satisfaction. Research findings are highly dependent upon the level of ICU acceptance. The tele-ICU, in collaboration with the ICU team, can be a valuable tool for the enhancement of quality goals although the ability to demonstrate cost savings is extremely complex. Studies clearly indicate that tele-ICU nursing vigilance can enhance patient safety by preventing potential patient harm. Nursing managers and leaders play a vital part in optimizing the quality role of the tele-ICU through supportive modelling and the maximization of ICU integration. © 2012 Blackwell Publishing Ltd.

  9. Concurrently examining unrealistic absolute and comparative optimism: Temporal shifts, individual-difference and event-specific correlates, and behavioural outcomes.

    Science.gov (United States)

    Ruthig, Joelle C; Gamblin, Bradlee W; Jones, Kelly; Vanderzanden, Karen; Kehn, Andre

    2017-02-01

    Researchers have spent considerable effort examining unrealistic absolute optimism and unrealistic comparative optimism, yet there is a lack of research exploring them concurrently. This longitudinal study repeatedly assessed unrealistic absolute and comparative optimism within a performance context over several months to identify the degree to which they shift as a function of proximity to performance and performance feedback, their associations with global individual difference and event-specific factors, and their link to subsequent behavioural outcomes. Results showed similar shifts in unrealistic absolute and comparative optimism based on proximity to performance and performance feedback. Moreover, increases in both types of unrealistic optimism were associated with better subsequent performance beyond the effect of prior performance. However, several differences were found between the two forms of unrealistic optimism in their associations with global individual difference factors and event-specific factors, highlighting the distinctiveness of the two constructs. © 2016 The British Psychological Society.

  10. Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models.

    Science.gov (United States)

    Pozo, Carlos; Marín-Sanguino, Alberto; Alves, Rui; Guillén-Gosálbez, Gonzalo; Jiménez, Laureano; Sorribas, Albert

    2011-08-25

    Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity. Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.

  11. Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

    Directory of Open Access Journals (Sweden)

    Sorribas Albert

    2011-08-01

    Full Text Available Abstract Background Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Results Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC models that extend the power-law formalism to deal with saturation and cooperativity. Conclusions Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.

  12. Context-Specific Metabolic Model Extraction Based on Regularized Least Squares Optimization.

    Directory of Open Access Journals (Sweden)

    Semidán Robaina Estévez

    Full Text Available Genome-scale metabolic models have proven highly valuable in investigating cell physiology. Recent advances include the development of methods to extract context-specific models capable of describing metabolism under more specific scenarios (e.g., cell types. Yet, none of the existing computational approaches allows for a fully automated model extraction and determination of a flux distribution independent of user-defined parameters. Here we present RegrEx, a fully automated approach that relies solely on context-specific data and ℓ1-norm regularization to extract a context-specific model and to provide a flux distribution that maximizes its correlation to data. Moreover, the publically available implementation of RegrEx was used to extract 11 context-specific human models using publicly available RNAseq expression profiles, Recon1 and also Recon2, the most recent human metabolic model. The comparison of the performance of RegrEx and its contending alternatives demonstrates that the proposed method extracts models for which both the structure, i.e., reactions included, and the flux distributions are in concordance with the employed data. These findings are supported by validation and comparison of method performance on additional data not used in context-specific model extraction. Therefore, our study sets the ground for applications of other regularization techniques in large-scale metabolic modeling.

  13. Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease

    DEFF Research Database (Denmark)

    Finan, Brian; Clemmensen, Christoffer; Zhu, Zhimeng

    2016-01-01

    Glucagon and thyroid hormone (T3) exhibit therapeutic potential for metabolic disease but also exhibit undesired effects. We achieved synergistic effects of these two hormones and mitigation of their adverse effects by engineering chemical conjugates enabling delivery of both activities within on...

  14. A hybrid approach identifies metabolic signatures of high-producers for chinese hamster ovary clone selection and process optimization.

    Science.gov (United States)

    Popp, Oliver; Müller, Dirk; Didzus, Katharina; Paul, Wolfgang; Lipsmeier, Florian; Kirchner, Florian; Niklas, Jens; Mauch, Klaus; Beaucamp, Nicola

    2016-09-01

    In-depth characterization of high-producer cell lines and bioprocesses is vital to ensure robust and consistent production of recombinant therapeutic proteins in high quantity and quality for clinical applications. This requires applying appropriate methods during bioprocess development to enable meaningful characterization of CHO clones and processes. Here, we present a novel hybrid approach for supporting comprehensive characterization of metabolic clone performance. The approach combines metabolite profiling with multivariate data analysis and fluxomics to enable a data-driven mechanistic analysis of key metabolic traits associated with desired cell phenotypes. We applied the methodology to quantify and compare metabolic performance in a set of 10 recombinant CHO-K1 producer clones and a host cell line. The comprehensive characterization enabled us to derive an extended set of clone performance criteria that not only captured growth and product formation, but also incorporated information on intracellular clone physiology and on metabolic changes during the process. These criteria served to establish a quantitative clone ranking and allowed us to identify metabolic differences between high-producing CHO-K1 clones yielding comparably high product titers. Through multivariate data analysis of the combined metabolite and flux data we uncovered common metabolic traits characteristic of high-producer clones in the screening setup. This included high intracellular rates of glutamine synthesis, low cysteine uptake, reduced excretion of aspartate and glutamate, and low intracellular degradation rates of branched-chain amino acids and of histidine. Finally, the above approach was integrated into a workflow that enables standardized high-content selection of CHO producer clones in a high-throughput fashion. In conclusion, the combination of quantitative metabolite profiling, multivariate data analysis, and mechanistic network model simulations can identify metabolic

  15. Health Outcomes of Information System Use Lifestyles among Adolescents: Videogame Addiction, Sleep Curtailment and Cardio-Metabolic Deficiencies.

    Science.gov (United States)

    Turel, Ofir; Romashkin, Anna; Morrison, Katherine M

    2016-01-01

    Obesity is a rising problem among adolescents in modern societies; it results in long-term cardio-metabolic problems. Possible overlooked drivers of obesity and its consequent cardio-metabolic deficits include videogame addiction and the resulting curtailed sleep; both are growing problems among adolescents. The objective of this study is to examine possible associations among these concepts in adolescents, as a means to point to plausible interventions. Data were collected from 94 adolescents who play videogames and are enrolled in outpatient clinics, using surveys, wearable sleep monitors (FitBit), physical exams, and blood tests at three points in time. These data were subjected to structural equation modeling (SEM) analyses and bootstrapping-based mediation testing procedures. Videogame addiction among adolescents was negatively associated with sleep duration (β = -0.24). Sleep duration was negatively associated with obesity (β = -0.30), which in turn was associated with elevated blood pressure (β = 0.26), low high-density lipoprotein cholesterol (β = -0.18), high triglycerides (β = 0.61), and high insulin resistance (β = 0.39). The model explained 36.2% of the variation in sleep duration, 32.7% of the variation in obesity, and between 12.8% and 28.1% of the variation in cardio-metabolic indicators. Post-hoc analyses indicated that curtailed sleep is a possible full mediator of the association between videogame addiction, abdominal obesity and the associated cardio-metabolic deficits. The findings point to possible information systems use lifestyle-health links, which behooves researchers and practitioners to pay closer attention to possible adverse health outcomes of technology-related addictions. Interventions that target problematic video-gaming and sleep should be devised as a possible means for improving adolescents' long-term cardio-metabolic health.

  16. The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats.

    Science.gov (United States)

    Maniam, Jayanthi; Antoniadis, Christopher P; Morris, Margaret J

    2015-01-01

    Early-life stress affects metabolic outcomes and choice of diet influences the development of metabolic disease. Here we tested the hypothesis that chronic sugar intake exacerbates metabolic deficits induced by early-life stress. Early-life stress was induced in Sprague-Dawley rats using limited nesting material in early lactation (LN, postnatal days 2-9), and siblings were given chow alone or with additional sucrose post weaning (n = 9-17 per group). Female control and LN siblings had unlimited access to either chow plus water, or chow and water plus 25% sucrose solution (Sucrose), from 3-15 weeks of age. Weekly body weight and food intake were measured. Glucose and insulin tolerance were tested at 13 and 14 weeks of age, respectively. Rats were killed at 15 weeks. Hepatic triglyceride and markers of lipid synthesis - fatty acid synthase, acetyl-CoA carboxylase alpha and oxidation - and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) were examined. Mediators of hepatic glucocorticoid metabolism, specifically 11-beta hydroxysteroid dehydrogenase-1 (11βHSD-1), 5-α reductase, and glucocorticoid and mineralocorticoid receptor mRNAs were also measured. Sucrose increased caloric intake in both groups, but overall energy intake was not altered by LN exposure. LN exposure had no further impact on sucrose-induced glucose intolerance and increased plasma and liver triglycerides. Hepatic markers of fat synthesis and oxidation were concomitantly activated and 11βHSD-1 mRNA expression was increased by 53% in LN-Sucrose versus Con-Sucrose rats. Adiposity was increased by 26% in LN-Sucrose versus Con-Sucrose rats. Thus, LN exposure had minimal adverse metabolic effects despite high-sugar diet postweaning.

  17. Health Outcomes of Information System Use Lifestyles among Adolescents: Videogame Addiction, Sleep Curtailment and Cardio-Metabolic Deficiencies.

    Directory of Open Access Journals (Sweden)

    Ofir Turel

    Full Text Available Obesity is a rising problem among adolescents in modern societies; it results in long-term cardio-metabolic problems. Possible overlooked drivers of obesity and its consequent cardio-metabolic deficits include videogame addiction and the resulting curtailed sleep; both are growing problems among adolescents. The objective of this study is to examine possible associations among these concepts in adolescents, as a means to point to plausible interventions.Data were collected from 94 adolescents who play videogames and are enrolled in outpatient clinics, using surveys, wearable sleep monitors (FitBit, physical exams, and blood tests at three points in time. These data were subjected to structural equation modeling (SEM analyses and bootstrapping-based mediation testing procedures.Videogame addiction among adolescents was negatively associated with sleep duration (β = -0.24. Sleep duration was negatively associated with obesity (β = -0.30, which in turn was associated with elevated blood pressure (β = 0.26, low high-density lipoprotein cholesterol (β = -0.18, high triglycerides (β = 0.61, and high insulin resistance (β = 0.39. The model explained 36.2% of the variation in sleep duration, 32.7% of the variation in obesity, and between 12.8% and 28.1% of the variation in cardio-metabolic indicators. Post-hoc analyses indicated that curtailed sleep is a possible full mediator of the association between videogame addiction, abdominal obesity and the associated cardio-metabolic deficits.The findings point to possible information systems use lifestyle-health links, which behooves researchers and practitioners to pay closer attention to possible adverse health outcomes of technology-related addictions. Interventions that target problematic video-gaming and sleep should be devised as a possible means for improving adolescents' long-term cardio-metabolic health.

  18. The impact of metabolic syndrome on child weight outcomes in pediatric obesity program for Mexican Americans

    Science.gov (United States)

    Adults with metabolic syndrome (MetS) are three to five times more likely to develop type 2 diabetes and cardiovascular disease. Given the long term consequences of MetS, the growing number of children meeting criteria for MetS is concerning. In order to determine the impact of MetS on pediatric wei...

  19. Early Posttransplant Tryptophan Metabolism Predicts Long-term Outcome of Human Kidney Transplantation

    NARCIS (Netherlands)

    Vavrincova-Yaghi, Diana; Seelen, Marc A.; Kema, Ido P.; Deelman, Leo E.; Heuvel, van den Marius; Breukelman, Henk; Van den Eynde, Benoit J.; Henning, Rob H.; van Goor, Harry; Sandovici, Maria

    Background. Chronic transplant dysfunction (CTD) is the leading cause of long-term loss of the renal allograft. So far, no single test is available to reliably predict the risk for CTD. Monitoring of tryptophan (trp) metabolism through indoleamine 2.3-dioxygenase (IDO) has been previously proposed

  20. IsoDesign: a software for optimizing the design of 13C-metabolic flux analysis experiments.

    Science.gov (United States)

    Millard, Pierre; Sokol, Serguei; Letisse, Fabien; Portais, Jean-Charles

    2014-01-01

    The growing demand for (13) C-metabolic flux analysis ((13) C-MFA) in the field of metabolic engineering and systems biology is driving the need to rationalize expensive and time-consuming (13) C-labeling experiments. Experimental design is a key step in improving both the number of fluxes that can be calculated from a set of isotopic data and the precision of flux values. We present IsoDesign, a software that enables these parameters to be maximized by optimizing the isotopic composition of the label input. It can be applied to (13) C-MFA investigations using a broad panel of analytical tools (MS, MS/MS, (1) H NMR, (13) C NMR, etc.) individually or in combination. It includes a visualization module to intuitively select the optimal label input depending on the biological question to be addressed. Applications of IsoDesign are described, with an example of the entire (13) C-MFA workflow from the experimental design to the flux map including important practical considerations. IsoDesign makes the experimental design of (13) C-MFA experiments more accessible to a wider biological community. IsoDesign is distributed under an open source license at http://metasys.insa-toulouse.fr/software/isodes/ © 2013 Wiley Periodicals, Inc.

  1. ReacKnock: identifying reaction deletion strategies for microbial strain optimization based on genome-scale metabolic network.

    Directory of Open Access Journals (Sweden)

    Zixiang Xu

    Full Text Available Gene knockout has been used as a common strategy to improve microbial strains for producing chemicals. Several algorithms are available to predict the target reactions to be deleted. Most of them apply mixed integer bi-level linear programming (MIBLP based on metabolic networks, and use duality theory to transform bi-level optimization problem of large-scale MIBLP to single-level programming. However, the validity of the transformation was not proved. Solution of MIBLP depends on the structure of inner problem. If the inner problem is continuous, Karush-Kuhn-Tucker (KKT method can be used to reformulate the MIBLP to a single-level one. We adopt KKT technique in our algorithm ReacKnock to attack the intractable problem of the solution of MIBLP, demonstrated with the genome-scale metabolic network model of E. coli for producing various chemicals such as succinate, ethanol, threonine and etc. Compared to the previous methods, our algorithm is fast, stable and reliable to find the optimal solutions for all the chemical products tested, and able to provide all the alternative deletion strategies which lead to the same industrial objective.

  2. Incidence, outcomes, and risk factors for retreatment after wavefront-optimized ablations with PRK and LASIK.

    Science.gov (United States)

    Randleman, J Bradley; White, Alfred J; Lynn, Michael J; Hu, Michelle H; Stulting, R Doyle

    2009-03-01

    To analyze and compare retreatment rates after wavefront-optimized photorefractive keratectomy (PRK) and LASIK and determine risk factors for retreatment. A retrospective chart review was performed to identify patients undergoing PRK or LASIK with the wavefront-optimized WaveLight platform from January 2005 through December 2006 targeted for a piano outcome and to determine the rate and risk factors for retreatment surgery in this population. Eight hundred fifty-five eyes were analyzed, including 70 (8.2%) eyes with hyperopic refractions and 785 (91.8%) eyes with myopic refractions. After initial treatment, 72% of eyes were 20/20 or better and 99.5% were 20/40 or better. To improve uncorrected visual acuity, 54 (6.3%) eyes had retreatments performed. No significant differences in retreatment rates were noted based on age (P = .15), sex (P = .8), eye (P = .3), PRK versus LASIK (P = 1.0), room temperature (P = .1) or humidity (P = .9), and no correlation between retreatment rate and month or season of primary surgery (P = .4). There was no correlation between degree of myopia and retreatment rate. Eyes were significantly more likely to undergo retreatment if they were hyperopic (12.8% vs 6.0%, P = .006) or had astigmatism > or = 1.00 diopter (D) (9.1% vs 5.3%, P = .04). Retreatment rate was 6.3% with the WaveLight ALLEGRETTO WAVE excimer laser. This rate was not influenced by age, sex, corneal characteristics, or environmental factors. Eyes with hyperopic refractions or astigmatism > or = 1.00 D were more likely to undergo retreatment.

  3. Treatment outcome of thymic epithelial tumor: prognostic factors and optimal postoperative radiation therapy

    International Nuclear Information System (INIS)

    Oh, Dong Ryul; Ahn, Yong Chan; Kim, Kwan Min; Kim, Jhin Gook; Shim, Young Mog; Han, Jung Ho

    2005-01-01

    This study was conducted to analyze treatment outcome and prognostic significance of World Health Organization (WHO)-defined thymic epithelial tumor (TET) subtype and to assess optimal radiation target volume in patients receiving surgery and adjuvant radiation therapy with TET. The record of 160 patients with TET, who received surgical resection at the Samsung medical Center, from December 1994 to June 2004, were reviewed. 99 patients were treated with postoperative radiation therapy (PORT). PORT was recommended when patients had more than one findings among suspicious incomplete resection or positive resection margin or Masaoka stage II ∼ IV or WHO tumor type B2 ∼ C. PORT performed to primary tumor bed only with a mean dose of 54 Gy. The prognostic factor and pattern of failure were analyzed retrospectively. The overall survival rate at 5 years was 87.3%. Age (more than 60 years 77.8%, less than 60 years 91.1%; ρ = 0.03), Masaoka stage (I 92.2%, II 95.4%, III 82.1%, IV 67.5%; ρ = 0.001), WHO tumor type (A-B1 96.0%, B2-C 82.3%; ρ = 0.001), Extent of resection (R0 resection 92.3%, R1 or 2 resection 72.6%; ρ = 0.001) were the prognostic factors according to univariate analysis. But WHO tumor type was the only significant prognostic factor according to multivariate analysis. Recurrence was observed in 5 patients of 71 Masoka stage I-III patients who received grossly complete tumor removal (R0, R1 resection ) and PORT to primary tumor bed. Mediastinal recurrence was observed in only one patients. There were no recurrence within irradiation field. WHO tumor type was the important prognostic factor to predict survival of patients with TET. This study suggest that PORT to only primary tumor bed was optimal. To avoid pleura-or pericardium-based recurrence, further study of effective chemotherapy should be investigated

  4. The Quadrella: A novel approach to analyzing optimal outcomes after permanent seed prostate brachytherapy

    International Nuclear Information System (INIS)

    Tétreault-Laflamme, Audrey; Zilli, Thomas; Meissner, Aliza; Larrivée, Sandra; Sylvestre, Marie-Pierre; Delouya, Guila

    2014-01-01

    Background and purpose: To study a four-point combined analysis (Quadrella) of optimal outcome among patients treated with exclusive permanent seed prostate brachytherapy (PB), as defined by the likelihood of achieving disease control and preserving normal urinary, gastro-intestinal (GI) and sexual function. Materials and methods: 384 patients with localized prostate cancer underwent PB at our institution with 125 I at a dose level of 144 Gy. Subjects with erectile dysfunction who did not respond to medication were excluded. 281 patients with minimum 3-year follow-up were evaluated. Patients with concurrent biochemical progression-free survival (bPFS), absent urinary and GI toxicities (grade 0 toxicities according to CTCAE v 3.0) and preserved sexual potency (with our without medication) were classified as the Quadrella group. Results: Among the 281 patients analyzed, the Quadrella was achieved in 49.1%, 48.0%, 50.4%, 41.7% and 65.2% in years 3–7, respectively. bPFS rates were 82.6–96.1%, corresponding potency rates were 63.6–82.3%, and normal urinary and GI function rates were 64.8–82.6% and 95–100%, respectively. By multivariate analysis, significant predictors of Quadrella were age (p = 0.015), baseline IPSS (p = 0.03) and time since PB (p = 0.02). Conclusion: Urinary and sexual toxicity remained the most common reasons for excluding patients from a perfect outcome (Quadrella), defined by strict criteria. This analysis can be useful for subsequent comparison between treatment modalities

  5. Identification of parallel and divergent optimization solutions for homologous metabolic enzymes

    Directory of Open Access Journals (Sweden)

    Robert F. Standaert

    2018-06-01

    Full Text Available Metabolic pathway assembly typically involves the expression of enzymes from multiple organisms in a single heterologous host. Ensuring that each enzyme functions effectively can be challenging, since many potential factors can disrupt proper pathway flux. Here, we compared the performance of two enzyme homologs in a pathway engineered to allow Escherichia coli to grow on 4-hydroxybenzoate (4-HB, a byproduct of lignocellulosic biomass deconstruction. Single chromosomal copies of the 4-HB 3-monooxygenase genes pobA and praI, from Pseudomonas putida KT2440 and Paenibacillus sp. JJ-1B, respectively, were introduced into a strain able to metabolize protocatechuate (PCA, the oxidation product of 4-HB. Neither enzyme initially supported consistent growth on 4-HB. Experimental evolution was used to identify mutations that improved pathway activity. For both enzymes, silent mRNA mutations were identified that increased enzyme expression. With pobA, duplication of the genes for PCA metabolism allowed growth on 4-HB. However, with praI, growth required a mutation in the 4-HB/PCA transporter pcaK that increased intracellular concentrations of 4-HB, suggesting that flux through PraI was limiting. These findings demonstrate the value of directed evolution strategies to rapidly identify and overcome diverse factors limiting enzyme activity. Keywords: Lignin, Protocatechuate, Experimental evolution

  6. Identification of parallel and divergent optimization solutions for homologous metabolic enzymes.

    Science.gov (United States)

    Standaert, Robert F; Giannone, Richard J; Michener, Joshua K

    2018-06-01

    Metabolic pathway assembly typically involves the expression of enzymes from multiple organisms in a single heterologous host. Ensuring that each enzyme functions effectively can be challenging, since many potential factors can disrupt proper pathway flux. Here, we compared the performance of two enzyme homologs in a pathway engineered to allow Escherichia coli to grow on 4-hydroxybenzoate (4-HB), a byproduct of lignocellulosic biomass deconstruction. Single chromosomal copies of the 4-HB 3-monooxygenase genes pobA and praI , from Pseudomonas putida KT2440 and Paenibacillus sp. JJ-1B, respectively, were introduced into a strain able to metabolize protocatechuate (PCA), the oxidation product of 4-HB. Neither enzyme initially supported consistent growth on 4-HB. Experimental evolution was used to identify mutations that improved pathway activity. For both enzymes, silent mRNA mutations were identified that increased enzyme expression. With pobA , duplication of the genes for PCA metabolism allowed growth on 4-HB. However, with praI , growth required a mutation in the 4-HB/PCA transporter pcaK that increased intracellular concentrations of 4-HB, suggesting that flux through PraI was limiting. These findings demonstrate the value of directed evolution strategies to rapidly identify and overcome diverse factors limiting enzyme activity.

  7. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Sasanelli, Myriam; Meignan, Michel; Haioun, Corinne; Itti, Emmanuel [Paris-Est University, Nuclear Medicine and Lymphoid Malignancies Unit, Henri Mondor Hospital, Creteil (France); Berriolo-Riedinger, Alina; Casasnovas, Rene-Olivier [Nuclear Medicine and Hematology, Georges-Francois Leclerc Center, Le Bocage Hospital, Dijon (France); Biggi, Alberto; Gallamini, Andrea [Nuclear Medicine and Hematology, Santa Croce e Carle Hospital, Cuneo (Italy); Siegel, Barry A.; Cashen, Amanda F. [Washington University School of Medicine, Nuclear Medicine and Oncology, Siteman Cancer Center, St. Louis, MO (United States); Vera, Pierre; Tilly, Herve [Nuclear Medicine and Hematology, Henri Becquerel Center, Rouen (France); Versari, Annibale [Nuclear Medicine, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia (Italy)

    2014-11-15

    We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL). TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent {sup 18}F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Median follow-up was 39 months. Average pretherapy TMTV was 509 ± 568 cm{sup 3}. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm{sup 3}) and 60 % in the high metabolic burden group (TMTV >550 cm{sup 3}, p = 0.04), and prediction of OS was even better (87 % vs. 60 %, p = 0.0003). Cox regression showed independence of TMTV for OS prediction (p = 0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index. Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL. (orig.)

  8. Therapy optimization in multiple sclerosis: a prospective observational study of therapy compliance and outcomes.

    Science.gov (United States)

    Coyle, Patricia K; Cohen, Bruce A; Leist, Thomas; Markowitz, Clyde; Oleen-Burkey, MerriKay; Schwartz, Marc; Tullman, Mark J; Zwibel, Howard

    2014-03-13

    Data sources for MS research are numerous but rarely provide an objective measure of drug therapy compliance coupled with patient-reported health outcomes. The objective of this paper is to describe the methods and baseline characteristics of the Therapy Optimization in MS (TOP MS) study designed to investigate the relationship between disease-modifying therapy compliance and health outcomes. TOP MS was designed as a prospective, observational, nationwide patient-focused study using an internet portal for data entry. The protocol was reviewed and approved by Sterling IRB. The study was registered with ClinicalTrials.gov. It captured structured survey data monthly from MS patients recruited by specialty pharmacies. Data collection included the clinical characteristics of MS such as MS relapses. Disability, quality of life and work productivity and activity impairment were assessed quarterly with well-validated scales. When events like severe fatigue or new or worsening depression were reported, feedback was provided to treating physicians. The therapy compliance measure was derived from pharmacy drug shipment records uploaded to the study database. The data presented in this paper use descriptive statistics. The TOP MS Study enrolled 2966 participants receiving their disease-modifying therapy (DMT) from specialty pharmacies. The mean age of the sample was 49 years, 80.4% were female, 89.9% were Caucasian and 55.7% were employed full or part time. Mean time since first symptoms was 11.5 years; mean duration since diagnosis was 9.5 years. Patient-reported EDSS was 3.5; 72.2% had a relapsing-remitting disease course. The most commonly reported symptoms at the time of enrollment were fatigue (74.7%), impaired coordination or balance (61.8%) and numbness and tingling (61.2%). Half of the sample was using glatiramer acetate and half was using beta-interferons. Demographic and clinical characteristics of the TOP MS sample at enrollment are consistent with other community

  9. Maternal health issues and cardio-metabolic outcomes in the offspring: a focus on Indigenous populations.

    Science.gov (United States)

    Wicklow, Brandy A; Sellers, Elizabeth A C

    2015-01-01

    Non-communicable diseases (NCDs) including diabetes, obesity and cardiovascular disease are the leading causes of death worldwide. Indigenous populations are disproportionally affected. In an effort to halt the increasing disease burden, the mechanisms underlying the increasing rate of NCDs are an important area of study. Recent evidence has focused on the perinatal period as an influential period impacting the future cardio-metabolic health of the offspring. This concept has been defined as metabolic foetal programming and supports the importance of the developmental origins of health and disease in research and clinical practice, specifically in prevention efforts to protect future generations from NCDs. An understanding of the underlying mechanisms involved is not clear as of yet. However, an understanding of these mechanisms is imperative in order to plan effective intervention strategies. As much of the discussion below is gleaned from large epidemiological studies and animal studies, further research with prospective cohorts is necessary. Copyright © 2014. Published by Elsevier Ltd.

  10. Language and Verbal Memory in Individuals with a History of Autism Spectrum Disorders Who Have Achieved Optimal Outcomes

    Science.gov (United States)

    Tyson, Katherine; Kelley, Elizabeth; Fein, Deborah; Orinstein, Alyssa; Troyb, Eva; Barton, Marianne; Eigsti, Inge-Marie; Naigles, Letitia; Schultz, Robert T.; Stevens, Michael; Helt, Molly; Rosenthal, Michael

    2014-01-01

    Some individuals who lose their autism spectrum disorder diagnosis may continue to display subtle weaknesses in language. We examined language and verbal memory in 44 individuals with high-functioning autism (HFA), 34 individuals with "optimal outcomes" (OO) and 34 individuals with typical development (TD). The OO group scored in the…

  11. Social Function and Communication in Optimal Outcome Children and Adolescents with an Autism History on Structured Test Measures

    Science.gov (United States)

    Orinstein, Alyssa J.; Suh, Joyce; Porter, Kaitlyn; De Yoe, Kaitlin A.; Tyson, Katherine E.; Troyb, Eva; Barton, Marianne L.; Eigsti, Inge-Marie; Stevens, Michael C.; Fein, Deborah A.

    2015-01-01

    Youth who lose their ASD diagnosis may have subtle social and communication difficulties. We examined social and communication functioning in 44 high-functioning autism (HFA), 34 optimal outcome (OO) and 34 typically developing (TD) youth. Results indicated that OO participants had no autism communication symptoms, no pragmatic language deficits,…

  12. DCEO Biotechnology: Tools To Design, Construct, Evaluate, and Optimize the Metabolic Pathway for Biosynthesis of Chemicals

    DEFF Research Database (Denmark)

    Chen, Xiulai; Gao, Cong; Guo, Liang

    2018-01-01

    , and pathway optimization at the systems level, offers a conceptual and technological framework to exploit potential pathways, modify existing pathways and create new pathways for the optimal production of desired chemicals. Here, we summarize recent progress of DCEO biotechnology and examples of its......Chemical synthesis is a well established route for producing many chemicals on a large scale, but some drawbacks still exist in this process, such as unstable intermediates, multistep reactions, complex process control, etc. Biobased production provides an attractive alternative to these challenges......, but how to make cells into efficient factories is challenging. As a key enabling technology to develop efficient cell factories, design-construction-evaluation-optimization (DCEO) biotechnology, which incorporates the concepts and techniques of pathway design, pathway construction, pathway evaluation...

  13. Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder.

    Science.gov (United States)

    Yoon, Sujung; Kim, Jieun E; Hwang, Jaeuk; Kim, Tae-Suk; Kang, Hee Jin; Namgung, Eun; Ban, Soonhyun; Oh, Subin; Yang, Jeongwon; Renshaw, Perry F; Lyoo, In Kyoon

    2016-09-15

    Creatine monohydrate (creatine) augmentation has the potential to accelerate the clinical responses to and enhance the overall efficacy of selective serotonin reuptake inhibitor treatment in women with major depressive disorder (MDD). Although it has been suggested that creatine augmentation may involve the restoration of brain energy metabolism, the mechanisms underlying its antidepressant efficacy are unknown. In a randomized, double-blind, placebo-controlled trial, 52 women with MDD were assigned to receive either creatine augmentation or placebo augmentation of escitalopram; 34 subjects participated in multimodal neuroimaging assessments at baseline and week 8. Age-matched healthy women (n = 39) were also assessed twice at the same intervals. Metabolic and network outcomes were measured for changes in prefrontal N-acetylaspartate and changes in rich club hub connections of the structural brain network using proton magnetic resonance spectroscopy and diffusion tensor imaging, respectively. We found MDD-related metabolic and network dysfunction at baseline. Improvement in depressive symptoms was greater in patients receiving creatine augmentation relative to placebo augmentation. After 8 weeks of treatment, prefrontal N-acetylaspartate levels increased significantly in the creatine augmentation group compared with the placebo augmentation group. Increment in rich club hub connections was also greater in the creatine augmentation group than in the placebo augmentation group. N-acetylaspartate levels and rich club connections increased after creatine augmentation of selective serotonin reuptake inhibitor treatment. Effects of creatine administration on brain energy metabolism and network organization may partly underlie its efficacy in treating women with MDD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Biodegradation of kerosene: Study of growth optimization and metabolic fate of P. janthinellum SDX7

    Directory of Open Access Journals (Sweden)

    Shamiyan R. Khan

    2015-06-01

    Full Text Available Penicillum janthinellum SDX7 was isolated from aged petroleum hydrocarbon-affected soil at the site of Anand, Gujarat, India, and was tested for different pH, temperature, agitation and concentrations for optimal growth of the isolate that was capable of degrading upto 95%, 63% and 58% of 1%, 3% and 5% kerosene, respectively, after a period of 16 days, at optimal growth conditions of pH 6.0, 30 °C and 180 rpm agitation. The GC/MS chromatograms revealed that then-alkane fractions are easily degraded; however, the rate might be lower for branched alkanes, n-alkylaromatics, cyclic alkanes and polynuclear aromatics. The test doses caused a concentration-dependent depletion of carbohydrates of P. janthinellum SDX7 by 3% to 80%, proteins by 4% to 81% and amino acids by 8% to 95% upto 16 days of treatment. The optimal concentration of 3% kerosene resulted in the least reduction of the metabolites of P. janthinellum such as carbohydrates, proteins and amino acids with optimal growth compared to 5% and 1% (v/v kerosene doses on the 12th and 16th day of exposure. Phenols were found to be mounted by 43% to 66% at lower and higher concentrations during the experimental period. Fungal isolate P. janthinellum SDX7 was also tested for growth on various xenobiotic compounds.

  15. Optimal decoding and information transmission in Hodgkin–Huxley neurons under metabolic cost constraints

    Czech Academy of Sciences Publication Activity Database

    Košťál, Lubomír; Kobayashi, R.

    2015-01-01

    Roč. 136, Oct 2015 (2015), s. 3-10 ISSN 0303-2647 R&D Projects: GA ČR(CZ) GA15-08066S Institutional support: RVO:67985823 Keywords : neuronal coding * information transfer * optimal decoding Subject RIV: BD - Theory of Information Impact factor: 1.495, year: 2015

  16. Optimizing Anti-VEGF Treatment Outcomes for Patients with Neovascular Age-Related Macular Degeneration.

    Science.gov (United States)

    Wykoff, Charles C; Clark, W Lloyd; Nielsen, Jared S; Brill, Joel V; Greene, Laurence S; Heggen, Cherilyn L

    2018-02-01

    The introduction of anti-vascular endothelial growth factor (anti-VEGF) drugs to ophthalmology has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). Despite this significant progress, gaps and challenges persist in the diagnosis of nAMD, initiation of treatment, and management of frequent intravitreal injections. Thus, nAMD remains a leading cause of blindness in the United States. To present current knowledge, evidence, and expert perspectives on anti-VEGF therapies in nAMD to support managed care professionals and providers in decision making and collaborative strategies to overcome barriers to optimize anti-VEGF treatment outcomes among nAMD patients. Three anti-VEGF therapies currently form the mainstay of treatment for nAMD, including 2 therapies approved by the FDA for treatment of nAMD (aflibercept and ranibizumab) and 1 therapy approved by the FDA for oncology indications and used off-label for treatment of nAMD (bevacizumab). In clinical trials, each of the 3 agents maintained visual acuity (VA) in approximately 90% or more of nAMD patients over 2 years. However, in long-term and real-world settings, significant gaps and challenges in diagnosis, treatment, and management pose barriers to achieving optimal outcomes for patients with nAMD. Many considerations, including individual patient characteristics, on-label versus off-label treatment, repackaging, and financial considerations, add to the complexity of nAMD decision making and management. Many factors may contribute to additional challenges leading to suboptimal long-term outcomes among nAMD patients, such as delays in diagnosis and/or treatment approval and initiation, individual patient response to different anti-VEGF therapies, lapses in physician regimentation of anti-VEGF injection and monitoring, and inadequate patient adherence to treatment and monitoring. These latter factors highlight the considerable logistical, emotional, and financial burdens of long

  17. Pediatric metabolic outcome comparisons based on a spectrum of obesity and asthmatic symptoms.

    Science.gov (United States)

    Perdue, Ashley D; Cottrell, Lesley A; Lilly, Christa L; Gower, William A; Ely, Brian A; Foringer, Brad; Wright, Melvin L; Neal, William A

    2018-04-20

    Asthma and obesity are two of the most prevalent public health issues for children in the U.S. Trajectories of both have roughly paralleled one another over the past several decades causing many to explore their connection to one another and to other associated health issues such as diabetes and dyslipidemia. Earlier models have commonly designated obesity as the central hub of these associations; however, more recent models have argued connections between pediatric asthma and other obesity-related metabolic conditions regardless of children's obesity risk. To examine the relationships between asthma, obesity, and abnormal metabolic indices. We conducted a cross-sectional study of 179 children ages 7 to 12 years recruited from a rural, Appalachian region. Our model controlled for children's smoke exposure, body mass index percentile, and gender to examine the association between children's asthma (based on pulmonary function tests, medical history, medications, and parent report of severity), lipids (fasting lipid profile), and measures of altered glucose metabolism (glycosylated hemoglobin and homeostatic model assessment 2-insulin resistance). Our findings revealed a statistically significant model for low density lipids, high density lipids, log triglyceride, and homeostatic model assessment 2-insulin resistance; however, a statistically significant main effect for asthma was found for triglycerides. We also found an asthma-obesity interaction effect on children's glycosylated hemoglobin with asthmatic obese children revealing significantly higher glycosylated hemoglobin values than non-asthmatic obese children. Our findings support a connection between asthma and children's glycosylated hemoglobin values; however, this association remains entwined with obesity factors.

  18. Can we reach Pareto optimal outcomes using bottom-up approaches?

    NARCIS (Netherlands)

    V. Sanchez-Anguix (Victor); R. Aydoğan (Reyhan); T. Baarslag (Tim); C.M. Jonker (Catholijn)

    2016-01-01

    textabstractClassically, disciplines like negotiation and decision making have focused on reaching Pareto optimal solutions due to its stability and efficiency properties. Despite the fact that many practical and theoretical algorithms have successfully attempted to provide Pareto optimal solutions,

  19. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    Directory of Open Access Journals (Sweden)

    Hsu Hui-Chi

    2011-04-01

    Full Text Available Abstract Background Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Methods Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. Results We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was

  20. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    International Nuclear Information System (INIS)

    Kao, Kuo-Jang; Chang, Kai-Ming; Hsu, Hui-Chi; Huang, Andrew T

    2011-01-01

    Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was consistent with a unique subset of luminal A intrinsic

  1. Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis.

    Science.gov (United States)

    Bhuiyan, Md Saruar; Ellett, Felix; Murray, Gerald L; Kostoulias, Xenia; Cerqueira, Gustavo M; Schulze, Keith E; Mahamad Maifiah, Mohd Hafidz; Li, Jian; Creek, Darren J; Lieschke, Graham J; Peleg, Anton Y

    2016-08-23

    Innate cellular immune responses are a critical first-line defense against invading bacterial pathogens. Leukocyte migration from the bloodstream to a site of infection is mediated by chemotactic factors that are often host-derived. More recently, there has been a greater appreciation of the importance of bacterial factors driving neutrophil movement during infection. Here, we describe the development of a zebrafish infection model to study Acinetobacter baumannii pathogenesis. By using isogenic A. baumannii mutants lacking expression of virulence effector proteins, we demonstrated that bacterial drivers of disease severity are conserved between zebrafish and mammals. By using transgenic zebrafish with fluorescent phagocytes, we showed that a mutation of an established A. baumannii global virulence regulator led to marked changes in neutrophil behavior involving rapid neutrophil influx to a localized site of infection, followed by prolonged neutrophil dwelling. This neutrophilic response augmented bacterial clearance and was secondary to an impaired A. baumannii phenylacetic acid catabolism pathway, which led to accumulation of phenylacetate. Purified phenylacetate was confirmed to be a neutrophil chemoattractant. These data identify a previously unknown mechanism of bacterial-guided neutrophil chemotaxis in vivo, providing insight into the role of bacterial metabolism in host innate immune evasion. Furthermore, the work provides a potentially new therapeutic paradigm of targeting a bacterial metabolic pathway to augment host innate immune responses and attenuate disease.

  2. Optimization of isopropanol production by engineered cyanobacteria with a synthetic metabolic pathway.

    Science.gov (United States)

    Hirokawa, Yasutaka; Suzuki, Iwane; Hanai, Taizo

    2015-05-01

    Cyanobacterium is an attractive host for the production of various chemicals and alternative fuels using solar energy and carbon dioxide. In previous study, we succeeded to produce isopropanol using engineered Synechococcus elongatus PCC 7942 under dark and anaerobic conditions (0.43 mM, 26.5 mg/l). In the present study, we report the further optimization of this isopropanol producing condition. We then optimized growth conditions for production of isopropanol by the engineered cyanobacteria, including the use of cells in early stationary phase and buffering of the production medium to neutral pH. We observed that shifting of cultures from dark and anaerobic to light and aerobic conditions during the production phase dramatically increased isopropanol production by conversion to isopropanol from acetate, byproduct under dark and anaerobic condition. Under the optimized production conditions, the titer of isopropanol was elevated 6-fold, to 2.42 mM (146 mg/l). Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  3. Effects of simultaneous and optimized sequential cardiac resynchronization therapy on myocardial oxidative metabolism and efficiency.

    Science.gov (United States)

    Christenson, Stuart D; Chareonthaitawee, Panithaya; Burnes, John E; Hill, Michael R S; Kemp, Brad J; Khandheria, Bijoy K; Hayes, David L; Gibbons, Raymond J

    2008-02-01

    Cardiac resynchronization therapy (CRT) can improve left ventricular (LV) hemodynamics and function. Recent data suggest the energy cost of such improvement is favorable. The effects of sequential CRT on myocardial oxidative metabolism (MVO(2)) and efficiency have not been previously assessed. Eight patients with NYHA class III heart failure were studied 196 +/- 180 days after CRT implant. Dynamic [(11)C]acetate positron emission tomography (PET) and echocardiography were performed after 1 hour of: 1) AAI pacing, 2) simultaneous CRT, and 3) sequential CRT. MVO(2) was calculated using the monoexponential clearance rate of [(11)C]acetate (k(mono)). Myocardial efficiency was expressed in terms of the work metabolic index (WMI). P values represent overall significance from repeated measures analysis. Global LV and right ventricular (RV) MVO(2) were not significantly different between pacing modes, but the septal/lateral MVO(2) ratio differed significantly with the change in pacing mode (AAI pacing = 0.696 +/- 0.094 min(-1), simultaneous CRT = 0.975 +/- 0.143 min(-1), and sequential CRT = 0.938 +/- 0.189 min(-1); overall P = 0.001). Stroke volume index (SVI) (AAI pacing = 26.7 +/- 10.4 mL/m(2), simultaneous CRT = 30.6 +/- 11.2 mL/m(2), sequential CRT = 33.5 +/- 12.2 mL/m(2); overall P simultaneous CRT = 4.29 +/- 1.72 mmHg*mL/m(2)*10(6), sequential CRT = 4.79 +/- 1.92 mmHg*mL/m(2)*10(6); overall P = 0.002) also differed between pacing modes. Compared with simultaneous CRT, additional changes in septal/lateral MVO(2), SVI, and WMI with sequential CRT were not statistically significant on post hoc analysis. In this small selected population, CRT increases LV SVI without increasing MVO(2), resulting in improved myocardial efficiency. Additional improvements in LV work, oxidative metabolism, and efficiency from simultaneous to sequential CRT were not significant.

  4. Language comprehension and brain function in individuals with an optimal outcome from autism.

    Science.gov (United States)

    Eigsti, Inge-Marie; Stevens, Michael C; Schultz, Robert T; Barton, Marianne; Kelley, Elizabeth; Naigles, Letitia; Orinstein, Alyssa; Troyb, Eva; Fein, Deborah A

    2016-01-01

    Although Autism Spectrum Disorder (ASD) is generally a lifelong disability, a minority of individuals with ASD overcome their symptoms to such a degree that they are generally indistinguishable from their typically-developing peers. That is, they have achieved an Optimal Outcome (OO). The question addressed by the current study is whether this normalized behavior reflects normalized brain functioning, or alternatively, the action of compensatory systems. Either possibility is plausible, as most participants with OO received years of intensive therapy that could alter brain networks to align with typical function or work around ASD-related neural dysfunction. Individuals ages 8 to 21 years with high-functioning ASD (n = 23), OO (n = 16), or typical development (TD; n = 20) completed a functional MRI scan while performing a sentence comprehension task. Results indicated similar activations in frontal and temporal regions (left middle frontal, left supramarginal, and right superior temporal gyri) and posterior cingulate in OO and ASD groups, where both differed from the TD group. Furthermore, the OO group showed heightened "compensatory" activation in numerous left- and right-lateralized regions (left precentral/postcentral gyri, right precentral gyrus, left inferior parietal lobule, right supramarginal gyrus, left superior temporal/parahippocampal gyrus, left middle occipital gyrus) and cerebellum, relative to both ASD and TD groups. Behaviorally normalized language abilities in OO individuals appear to utilize atypical brain networks, with increased recruitment of language-specific as well as right homologue and other systems. Early intensive learning and experience may normalize behavioral language performance in OO, but some brain regions involved in language processing may continue to display characteristics that are more similar to ASD than typical development, while others show characteristics not like ASD or typical development.

  5. Language comprehension and brain function in individuals with an optimal outcome from autism

    Directory of Open Access Journals (Sweden)

    Inge-Marie Eigsti

    2016-01-01

    Full Text Available Although Autism Spectrum Disorder (ASD is generally a lifelong disability, a minority of individuals with ASD overcome their symptoms to such a degree that they are generally indistinguishable from their typically-developing peers. That is, they have achieved an Optimal Outcome (OO. The question addressed by the current study is whether this normalized behavior reflects normalized brain functioning, or alternatively, the action of compensatory systems. Either possibility is plausible, as most participants with OO received years of intensive therapy that could alter brain networks to align with typical function or work around ASD-related neural dysfunction. Individuals ages 8 to 21 years with high-functioning ASD (n = 23, OO (n = 16, or typical development (TD; n = 20 completed a functional MRI scan while performing a sentence comprehension task. Results indicated similar activations in frontal and temporal regions (left middle frontal, left supramarginal, and right superior temporal gyri and posterior cingulate in OO and ASD groups, where both differed from the TD group. Furthermore, the OO group showed heightened “compensatory” activation in numerous left- and right-lateralized regions (left precentral/postcentral gyri, right precentral gyrus, left inferior parietal lobule, right supramarginal gyrus, left superior temporal/parahippocampal gyrus, left middle occipital gyrus and cerebellum, relative to both ASD and TD groups. Behaviorally normalized language abilities in OO individuals appear to utilize atypical brain networks, with increased recruitment of language-specific as well as right homologue and other systems. Early intensive learning and experience may normalize behavioral language performance in OO, but some brain regions involved in language processing may continue to display characteristics that are more similar to ASD than typical development, while others show characteristics not like ASD or typical development.

  6. Allopurinol Medication Adherence as a Mediator of Optimal Outcomes in Gout Management.

    Science.gov (United States)

    Coburn, Brian W; Bendlin, Kayli A; Sayles, Harlan; Meza, Jane; Russell, Cynthia L; Mikuls, Ted R

    2017-09-01

    Patient and provider factors, including allopurinol medication adherence, affect gout treatment outcomes. The aim of this study was to examine associations of patient and provider factors with optimal gout management. Linking longitudinal health and pharmacy dispensing records to questionnaire data, we assessed patient and provider factors among 612 patients with gout receiving allopurinol during a recent 1-year period. Associations of patient (medication adherence and patient activation) and provider factors (dose escalation, low-dose initiation, and anti-inflammatory prophylaxis) with serum urate (SU) goal achievement of less than 6.0 mg/dL were examined using multivariable logistic regression. Medication adherence was assessed as a mediator of these factors with goal achievement. A majority of patients (63%) were adherent, whereas a minority received dose escalation (31%). Medication adherence was associated with initiation of daily allopurinol doses of 100 mg/d or less (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.20-2.76). In adjusted models, adherence (OR, 2.35; 95% CI, 1.50-3.68) and dose escalation (OR, 2.48; 95% CI, 2.48-4.25) were strongly associated with SU goal attainment. Low starting allopurinol dose was positively associated with SU goal attainment (OR, 1.11; 95% CI, 1.02-1.20) indirectly through early adherence, but also had a negative direct association with SU goal attainment (OR, 0.21; 95% CI, 0.12-0.37). Medication adherence and low starting dose combined with dose escalation represent promising targets for future gout quality improvement efforts. Low starting dose is associated with better SU goal attainment through increased medication adherence, but may be beneficial only in settings where appropriate dose escalation is implemented.

  7. Metabolic engineering of riboflavin production in Ashbya gossypii through pathway optimization.

    Science.gov (United States)

    Ledesma-Amaro, Rodrigo; Serrano-Amatriain, Cristina; Jiménez, Alberto; Revuelta, José Luis

    2015-10-14

    The industrial production of riboflavin mostly relies on the microbial fermentation of flavinogenic microorganisms and Ashbya gossypii is the main industrial producer of the vitamin. Accordingly, bioengineering strategies aimed at increasing riboflavin production in A. gossypii are highly valuable for industry. We analyze the contribution of all the RIB genes to the production of riboflavin in A. gossypii. Two important metabolic rate-limiting steps that limit the overproduction of riboflavin have been found: first, low mRNA levels of the RIB genes hindered the overproduction of riboflavin; second, the competition of the AMP branch for purinogenic precursors also represents a limitation for riboflavin overproduction. Thus, overexpression of the RIB genes resulted in a significant increase in riboflavin yield. Moreover, both the inactivation and the underexpression of the ADE12 gene, which controls the first step of the AMP branch, also proved to have a positive effect on riboflavin production. Accordingly, a strain that combines both the overexpression of the RIB genes and the underexpression of the ADE12 gene was engineered. This strain produced 523 mg/L of riboflavin (5.4-fold higher than the wild-type), which is the highest titer of riboflavin obtained by metabolic engineering in A. gossypii so far. Riboflavin production in A. gossypii is limited by a low transcription activity of the RIB genes. Flux limitation towards AMP provides committed substrate GTP for riboflavin overproduction without detrimental effects on biomass formation. A multiple-engineered Ashbya strain that produces up to 523 mg/L of riboflavin was generated.

  8. Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury.

    Science.gov (United States)

    Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate

    2014-10-01

    Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial

  9. Metabolic tumor burden as marker of outcome in advanced EGFR wild-type NSCLC patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther-Larsen, Anne; Fledelius, Joan; Sorensen, Boe Sandahl

    2016-01-01

    OBJECTIVES: Accurate estimation of the prognosis of advanced non-small cell lung cancer (NSCLC) patients is essential before initiation of palliative treatment; especially in the second and third-line setting. This study was conducted in order to evaluate tumor burden measured on an 2'-deoxy-2...... a prospectively collected cohort. An F-18-FDG-PET/CT scan was conducted prior to erlotinib treatment and tumor burden was measured in terms of metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Median values of MTV and TLG were used for dichotomization of patients. Survival outcome was compared...... between groups.RESULTS: MTV and TLG could be measured in 49 patients. High values of MTV and TLG were significantly correlated with shorter PFS (p

  10. Pasture v. standard dairy cream in high-fat diet-fed mice: improved metabolic outcomes and stronger intestinal barrier.

    Science.gov (United States)

    Benoit, Bérengère; Plaisancié, Pascale; Géloën, Alain; Estienne, Monique; Debard, Cyrille; Meugnier, Emmanuelle; Loizon, Emmanuelle; Daira, Patricia; Bodennec, Jacques; Cousin, Olivier; Vidal, Hubert; Laugerette, Fabienne; Michalski, Marie-Caroline

    2014-08-28

    Dairy products derived from the milk of cows fed in pastures are characterised by higher amounts of conjugated linoleic acid and α-linolenic acid (ALA), and several studies have shown their ability to reduce cardiovascular risk. However, their specific metabolic effects compared with standard dairy in a high-fat diet (HFD) context remain largely unknown; this is what we determined in the present study with a focus on the metabolic and intestinal parameters. The experimental animals were fed for 12 weeks a HFD containing 20 % fat in the form of a pasture dairy cream (PDC) or a standard dairy cream (SDC). Samples of plasma, liver, white adipose tissue, duodenum, jejunum and colon were analysed. The PDC mice, despite a higher food intake, exhibited lower fat mass, plasma and hepatic TAG concentrations, and inflammation in the adipose tissue than the SDC mice. Furthermore, they exhibited a higher expression of hepatic PPARα mRNA and adipose tissue uncoupling protein 2 mRNA, suggesting an enhanced oxidative activity of the tissues. These results might be explained, in part, by the higher amounts of ALA in the PDC diet and in the liver and adipose tissue of the PDC mice. Moreover, the PDC diet was found to increase the proportions of two strategic cell populations involved in the protective function of the intestinal epithelium, namely Paneth and goblet cells in the small intestine and colon, compared with the SDC diet. In conclusion, a PDC HFD leads to improved metabolic outcomes and to a stronger gut barrier compared with a SDC HFD. This may be due, at least in part, to the protective mechanisms induced by specific lipids.

  11. Optimism, social support, and mental health outcomes in patients with advanced cancer.

    Science.gov (United States)

    Applebaum, Allison J; Stein, Emma M; Lord-Bessen, Jennifer; Pessin, Hayley; Rosenfeld, Barry; Breitbart, William

    2014-03-01

    Optimism and social support serve as protective factors against distress in medically ill patients. Very few studies have specifically explored the ways in which these variables interact to impact quality of life (QOL), particularly among patients with advanced cancer. The present study examined the role of optimism as a moderator of the relationship between social support and anxiety, depression, hopelessness, and QOL among patients with advanced cancer. Participants (N = 168) completed self-report assessments of psychosocial, spiritual, and physical well-being, including social support, optimism, hopelessness, depressive and anxious symptoms, and QOL. Hierarchical multiple regression analyses were conducted to determine the extent to which social support and optimism were associated with depressive and anxious symptomatology, hopelessness and QOL, and the potential role of optimism as a moderator of the relationship between social support and these variables. Higher levels of optimism were significantly associated with fewer anxious and depressive symptoms, less hopelessness, and better QOL. Higher levels of perceived social support were also significantly associated with better QOL. Additionally, optimism moderated the relationship between social support and anxiety, such that there was a strong negative association between social support and anxiety for participants with low optimism. This study highlights the importance of optimism and social support in the QOL of patients with advanced cancer. As such, interventions that attend to patients' expectations for positive experiences and the expansion of social support should be the focus of future clinical and research endeavors. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Optimization of 64Cu production for Radio-metabolic therapy and for PET

    International Nuclear Information System (INIS)

    Groppi, F.; Bonardi, M.; Birattari, C.; Gini, L.; Guariglia, S.; Mainardi, C.; Menapace, E.

    2002-01-01

    The 6 4C u is a very interesting radioisotope for nuclear biomedical applications, due to its physical characteristics: a) it decay β+ and β- with maximum energy equal to 653 keV and 578 keV respectively, that correspond to maximum range of β+ in soft tissue ∼ 2.7 mm and average range ∼ 1 mm. In this way it is possible to give a local dose in the region of interest and to have a high resolution in the PET images; b) it has an half life of 12.7 h, that is suitable for medical applications, reducing the exposure of personnel and of the patients and the problem of waste discharge; c) besides the gamma of annihilation (36%), it has only one γ emission at 1345.84 keV (0.473%) with low intensity: this reduces the dose to healthy tissue and to medical personnel. For these reasons 6 4C u can be considered a dual purpose radionuclide: it can be used both to localise and measure the tumour mass through the PET tomography and for the metabolic therapy of the tumour itself. Cu(2.) forms a class of stable classical complexes and chelates with ditio carbamates (DTC), like ethylmethyl-DTC and tiosemicarbazonates, like pyruvaldehyde-bis-(N 4 -methyl semicarbazone (PTSM) and acetyl-bis-(N 4 -methyl semicarbazone) (ATSM), and finally with aza macrocyclic chelants (cyclens, cyclams, sarcofands), like DOTA, DOTP and SarAr). The behaviour of some of them has been already investigated in both cell cultures, rats and humans since the end of the 90-ties

  13. Effect of Metabolic Syndrome on the Functional Outcome of Corticosteroid Injection for Lateral Epicondylitis: Retrospective Matched Case-Control Study.

    Science.gov (United States)

    Roh, Young Hak; Oh, Minjoon; Noh, Jung Ho; Gong, Hyun Sik; Baek, Goo Hyun

    2017-09-07

    Both obesity and diabetes mellitus are well-known risk factors for tendinopathies. We retrospectively compared the efficacy of single corticosteroid injections in treating lateral epicondylitis in patients with and without metabolic syndrome (MetS). Fifty-one patients with lateral epicondylitis and MetS were age- and sex-matched with 51 controls without MetS. Pain severity, Disability of the Arm, Shoulder, and Hand score, and grip strength were assessed at base line and at 6, 12 and 24 weeks post-injection. The pain scores in the MetS group were greater than those in the control group at 6 and 12 weeks. The disability scores and grip strength in the MetS group were significantly worse than those of the control group at 6 weeks. However, there were no significant differences at 24 weeks between the groups in terms of pain, disability scores and grip strengths. After 24 weeks, three patients (6%) in the control group and five patients (10%) in the MetS group had surgical decompression (p = 0.46). Patients with MetS are at risk for poor functional outcome after corticosteroid injection for lateral epicondylitis in the short term, but in the long term there was no difference in outcomes of steroid injection in patients with and without MetS.

  14. Regular consumption from fast food establishments relative to other restaurants is differentially associated with metabolic outcomes in young adults.

    Science.gov (United States)

    Duffey, Kiyah J; Gordon-Larsen, Penny; Steffen, Lyn M; Jacobs, David R; Popkin, Barry M

    2009-11-01

    Although away-from-home eating is adversely associated with weight, other comorbidities have not been examined; therefore, we sought to determine the associations of fast food (e.g. Wendy's, McDonalds) and restaurant (sit-down style) consumption (times per week) with weight and multiple metabolic outcomes, including homeostatic model assessment insulin resistance (HOMA-IR), waist circumference, and plasma triglycerides (TG), LDL cholesterol, and HDL cholesterol (HDL-C). We used 3 waves of data (exam y 7, 10, and 20) from the Coronary Artery Risk Development in Young Adults Study, a prospective cohort study of black and white young adults [aged 25-42 y in 1992-93, n = 3643 (men, 1659; women, 1984)]. Individuals in the highest (vs. lowest) quartile of baseline (defined as the mean of y 7 and 10) fast food consumption had higher y 20 weight [adjusted mean (95% CI): 5.6 kg (CI, 2.1, 9.2); P = 0.002], HOMA-IR [0.9 (CI, 0.4, 1.3); P < 0.001], waist circumference [5.3 cm (CI, 2.8, 7.9); P < 0.000], TG concentrations [0.25 mmol/L (CI, 0.10, 0.40), 22.7 mg/dL (CI, 9.1, 36.3); P = 0.001], and lower HDL-C concentrations [-0.014 mmol/L (CI, -0.215, -0.067), 5.4 mg/dL (CI, -8.3, -2.6); P < 0.000]. Baseline restaurant consumption was unrelated to y 20 outcomes. Adjusted change in weekly restaurant (P < 0.05) and fast food intake (P < 0.001) was associated with 13-y changes in body weight [0.09 kg (CI, 0.02, 0.17) and 0.15 kg (CI, 0.06, 0.24), respectively] and waist circumference [0.08 cm (CI, 0.02, 0.14) and 0.12 cm (CI, 0.04, 0.20), respectively]. Fast food consumption may be an important target for the prevention of adverse metabolic health outcomes.

  15. Outcomes of Optimized over Standard Protocol of Rabbit Antithymocyte Globulin for Severe Aplastic Anemia: A Single-Center Experience

    Science.gov (United States)

    Ge, Meili; Shao, Yingqi; Huang, Jinbo; Huang, Zhendong; Zhang, Jing; Nie, Neng; Zheng, Yizhou

    2013-01-01

    Background Previous reports showed that outcome of rabbit antithymocyte globulin (rATG) was not satisfactory as the first-line therapy for severe aplastic anemia (SAA). We explored a modifying schedule of administration of rATG. Design and Methods Outcomes of a cohort of 175 SAA patients, including 51 patients administered with standard protocol (3.55 mg/kg/d for 5 days) and 124 cases with optimized protocol (1.97 mg/kg/d for 9 days) of rATG plus cyclosporine (CSA), were analyzed retrospectively. Results Of all 175 patients, response rates at 3 and 6 months were 36.6% and 56.0%, respectively. 51 cases received standard protocol had poor responses at 3 (25.5%) and 6 months (41.2%). However, 124 patients received optimized protocol had better responses at 3 (41.1%, P = 0.14) and 6 (62.1%, P = 0.01). Higher incidences of infection (57.1% versus 37.9%, P = 0.02) and early mortality (17.9% versus 0.8%, P<0.001) occurred in patients received standard protocol compared with optimized protocol. The 5-year overall survival in favor of the optimized over standard rATG protocol (76.0% versus. 50.3%, P<0.001) was observed. By multivariate analysis, optimized protocol (RR = 2.21, P = 0.04), response at 3 months (RR = 10.31, P = 0.03) and shorter interval (<23 days) between diagnosis and initial dose of rATG (RR = 5.35, P = 0.002) were independent favorable predictors of overall survival. Conclusions Optimized instead of standard rATG protocol in combination with CSA remained efficacious as a first-line immunosuppressive regimen for SAA. PMID:23554855

  16. SU-E-T-368: Evaluating Dosimetric Outcome of Modulated Photon Radiotherapy (XMRT) Optimization for Head and Neck Patients

    Energy Technology Data Exchange (ETDEWEB)

    McGeachy, P; Villarreal-Barajas, JE; Khan, R [University of Calgary, Calgary, AB (Canada); Tom Baker Cancer Centre, Calgary, AB (Canada); Zinchenko, Y [University of Calgary, Calgary, AB (Canada)

    2015-06-15

    Purpose: The dosimetric outcome of optimized treatment plans obtained by modulating the photon beamlet energy and fluence on a small cohort of four Head and Neck (H and N) patients was investigated. This novel optimization technique is denoted XMRT for modulated photon radiotherapy. The dosimetric plans from XMRT for H and N treatment were compared to conventional, 6 MV intensity modulated radiotherapy (IMRT) optimization plans. Methods: An arrangement of two non-coplanar and five coplanar beams was used for all four H and N patients. Both XMRT and IMRT were subject to the same optimization algorithm, with XMRT optimization allowing both 6 and 18 MV beamlets while IMRT was restricted to 6 MV only. The optimization algorithm was based on a linear programming approach with partial-volume constraints implemented via the conditional value-at-risk method. H and N constraints were based off of those mentioned in the Radiation Therapy Oncology Group 1016 protocol. XMRT and IMRT solutions were assessed using metrics suggested by International Commission on Radiation Units and Measurements report 83. The Gurobi solver was used in conjunction with the CVX package to solve each optimization problem. Dose calculations and analysis were done in CERR using Monte Carlo dose calculation with VMC{sub ++}. Results: Both XMRT and IMRT solutions met all clinical criteria. Trade-offs were observed between improved dose uniformity to the primary target volume (PTV1) and increased dose to some of the surrounding healthy organs for XMRT compared to IMRT. On average, IMRT improved dose to the contralateral parotid gland and spinal cord while XMRT improved dose to the brainstem and mandible. Conclusion: Bi-energy XMRT optimization for H and N patients provides benefits in terms of improved dose uniformity to the primary target and reduced dose to some healthy structures, at the expense of increased dose to other healthy structures when compared with IMRT.

  17. Optimal timing of periodontal disease treatment for prevention of adverse pregnancy outcomes: before or during pregnancy?

    Science.gov (United States)

    Xiong, Xu; Buekens, Pierre; Goldenberg, Robert L; Offenbacher, Steven; Qian, Xu

    2011-08-01

    Several large randomized controlled clinical trials failed to find that standard periodontal therapy during pregnancy reduces the incidence of adverse pregnancy outcomes (eg, preterm birth and low birthweight). However, treating periodontal disease during pregnancy may be too late to reduce the inflammation that is related to the adverse pregnancy outcomes. Moreover, periodontal treatment during pregnancy can cause bacteremia, which itself may initiate the pathway leading to the adverse pregnancy outcomes. Finally, the periodontal treatments provided during pregnancy are not always effective in preventing the progression of periodontal disease during pregnancy. Pregnancy may not be an appropriate period for periodontal intervention(s). We hypothesize that periodontal treatment before pregnancy may reduce the rates of adverse pregnancy outcomes. Future randomized controlled trials are needed to test if treating periodontal disease in the prepregnancy period reduces the rate of adverse pregnancy outcomes. Copyright © 2011 Mosby, Inc. All rights reserved.

  18. Effect of simple, targeted diet in pregnant women with metabolic risk factors on maternal and fetal outcomes (ESTEEM): study protocol for a pragmatic multicentre randomised trial

    NARCIS (Netherlands)

    Al Wattar, Bassel H.; Dodds, Julie; Placzek, Anna; Spyreli, Eleni; Moore, Amanda; Hooper, Richard; Beresford, Lee; Roseboom, Tessa J.; Bes-Rastrollo, Maira; Hitman, Graham; Khan, Khalid S.; Thangaratinam, Shakila

    2016-01-01

    Women with metabolic risk factors are at higher risk of adverse pregnancy outcomes. Mediterranean-based dietary interventions have the potential to minimise these risks. We aim to evaluate the effectiveness of a simple, targeted intervention modelled on Mediterranean diet in preventing maternal and

  19. Increased vaspin levels are associated with beneficial metabolic outcome pre- and post-bariatric surgery.

    Directory of Open Access Journals (Sweden)

    HuiLing Lu

    Full Text Available Vaspin (visceral-adipose-tissue-derived-serine-protease-inhibitor is a recently identified adipokine with putative insulin-sensitizing properties. Plasma vaspin responses to surgery-induced weight loss are sparse and contradictory.We evaluated changes in vaspin levels and relationship to post-operative outcomes in men (n = 22 and women (n = 55 undergoing biliopancreatic-diversion/duodenal-switch bariatric surgery. Body composition and plasma parameters were measured at baseline, acutely (1 and 5 days and medium-term (6 and 12 months post-surgery.Fasting preoperative vaspin concentrations were comparable in men vs women. The distribution was biphasic (both men and women with a nadir of 2.5 ng/ml. Subjects were divided into high (≥2.5 ng/mL, HI-group and low (<2.5 ng/mL, LO-group vaspin level. Both groups had comparable sex distribution, age and BMI, but the HI-vaspin group had lower insulin, HOMA, and triglyceride and higher HDL-cholesterol, acylation stimulating protein (ASP and IL-6 levels (all p<0.05. Post-operatively, both groups decreased BMI comparably over 12 months; the HI-vaspin group maintained high vaspin levels, while the LO-vaspin group gradually increased their levels with weight loss over 12 months. The HI-vaspin group maintained a better glucose, insulin, HOMA, fructosamine, HDL-cholesterol, and triglyceride profile throughout. The HI-vaspin group also had higher gamma-glutamyltransferase and ASP profiles. Finally, baseline vaspin level inversely correlated significantly with baseline and 12-month insulin, HOMA, triglyceride and positively correlated with HDL and ASP. Twelve-month vaspin also correlated similarly, including an inverse correlation with BMI.Globally, this study supports the concept of vaspin as a beneficial adipokine in obesity, which may potentially lead to possible therapeutic targets.

  20. Effects of a Weight Loss Program on Metabolic Syndrome, Eating Disorders and Psychological Outcomes: Mediation by Endocannabinoids.

    Science.gov (United States)

    Pataky, Zoltan; Carrard, Isabelle; Gay, Valerie; Thomas, Aurélien; Carpentier, Anne; Bobbioni-Harsch, Elisabetta; Golay, Alain

    2018-04-10

    To evaluate the effects of weight loss on endocannabinoids, cardiometabolic and psychological parameters, eating disorders (ED) as well as quality of life (QoL) and to elucidate the role of endocannabinoids in metabolic syndrome (MS). In total, 114 patients with obesity were prospectively included in a 12-month weight loss program. Plasma endocannabinoids were measured by mass spectrometry; ED, psychological and QoL-related parameters were evaluated by self-reported questionnaires; physical activity was measured by accelerometer. Nutritional assessment was done by a 3-day food diary. Among completers (n = 87), body weight decreased in 35 patients (-9.1 ± 8.6 kg), remained stable in 39 patients, and increased in 13 patients (+5.8 ± 3.4 kg). 75% of patients with MS at baseline were free of MS at follow-up, and their baseline plasma N-palmitoylethanolamide (PEA) values were significantly lower when compared to patients with persisting MS. At baseline, there was a positive relationship between PEA and waist circumference (p = 0.005, R2 = 0.08), fasting glucose (p < 0.0001, R2 = 0.12), total cholesterol (p = 0.001, R2 = 0.11), triglycerides (p = 0.001, R2 = 0.11), LDL-cholesterol (p = 0.03, R2 = 0.05) as well as depression score (p = 0.002, R2 = 0.29). Plasma PEA might play a role in metabolic improvement after weight loss. Even in subjects without weight loss, a multidisciplinary intervention improves psychological outcomes, ED, and QoL. © 2018 The Author(s) Published by S. Karger GmbH, Freiburg.

  1. Effects of a Weight Loss Program on Metabolic Syndrome, Eating Disorders and Psychological Outcomes: Mediation by Endocannabinoids?

    Directory of Open Access Journals (Sweden)

    Zoltan Pataky

    2018-04-01

    Full Text Available Objective: To evaluate the effects of weight loss on endocannabinoids, cardiometabolic and psychological parameters, eating disorders (ED as well as quality of life (QoL and to elucidate the role of endocannabinoids in metabolic syndrome (MS. Methods: In total, 114 patients with obesity were prospectively included in a 12-month weight loss program. Plasma endocannabinoids were measured by mass spectrometry; ED, psychological and QoL-related parameters were evaluated by self-reported questionnaires; physical activity was measured by accelerometer. Nutritional assessment was done by a 3-day food diary. Results: Among completers (n = 87, body weight decreased in 35 patients (-9.1 ± 8.6 kg, remained stable in 39 patients, and increased in 13 patients (+5.8 ± 3.4 kg. 75% of patients with MS at baseline were free of MS at follow-up, and their baseline plasma N-palmitoylethanolamide (PEA values were significantly lower when compared to patients with persisting MS. At baseline, there was a positive relationship between PEA and waist circumference (p = 0.005, R2 = 0.08, fasting glucose (p 2 = 0.12, total cholesterol (p = 0.001, R2 = 0.11, triglycerides (p = 0.001, R2 = 0.11, LDL-cholesterol (p = 0.03, R2 = 0.05 as well as depression score (p = 0.002, R2 = 0.29. Conclusion: Plasma PEA might play a role in metabolic improvement after weight loss. Even in subjects without weight loss, a multidisciplinary intervention improves psychological outcomes, ED, and QoL.

  2. Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring.

    Science.gov (United States)

    Bolton, Jessica L; Auten, Richard L; Bilbo, Staci D

    2014-03-01

    Environmental chemical exposures during critical windows of development may contribute to the escalating prevalence of obesity. We tested the hypothesis that prenatal exposure to diesel exhaust particles (DEP), a primary component of air pollution, would prime microglia long-term, resulting in exacerbated metabolic and affective outcomes following exposure to a high-fat diet in adulthood. Time-mated mouse dams were intermittently exposed to respiratory instillations of either vehicle (VEH) or DEP throughout gestation. Adult male and female offspring were then fed either a low-fat diet (LFD) or high-fat diet (HFD) for 9 weeks. The male offspring of DEP-exposed dams exhibited exaggerated weight gain, insulin resistance, and anxiety-like behavior on HFD compared to the male offspring of VEH-exposed dams, whereas female offspring did not differ according to prenatal treatment. Furthermore, HFD induced evidence of macrophage infiltration of both adipose tissue and the brain in both sexes, but these cells were more activated specifically in DEP/HFD males. DEP/HFD males also expressed markedly higher levels of microglial/macrophage, but not astrocyte, activation markers in the hippocampus, whereas females exhibited only a suppression of astrocyte activation markers due to HFD. In a second experiment, DEP male offspring mounted an exaggerated peripheral IL-1β response to an LPS challenge at postnatal day (P)30, whereas their central IL-1β response did not differ from VEH male offspring, which is suggestive of macrophage priming due to prenatal DEP exposure. In sum, prenatal air pollution exposure "programs" offspring for increased susceptibility to diet-induced metabolic, behavioral, and neuroinflammatory changes in adulthood in a sexually dimorphic manner. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Exposure to Perfluoroalkyl Substances and Metabolic Outcomes in Pregnant Women: Evidence from the Spanish INMA Birth Cohorts.

    Science.gov (United States)

    Matilla-Santander, Nuria; Valvi, Damaskini; Lopez-Espinosa, Maria-Jose; Manzano-Salgado, Cyntia B; Ballester, Ferran; Ibarluzea, Jesús; Santa-Marina, Loreto; Schettgen, Thomas; Guxens, Mònica; Sunyer, Jordi; Vrijheid, Martine

    2017-11-13

    Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS exposure susceptibility. We evaluated the associations between PFAS exposures and metabolic outcomes in pregnant women. We analyzed 1,240 pregnant women from the Spanish INMA [Environment and Childhood Project (INfancia y Medio Ambiente)] birth cohort study (recruitment period: 2003-2008) with measured first pregnancy trimester plasma concentrations of four PFASs (in nanograms/milliliter). We used logistic regression models to estimate associations of PFASs (log 10 -transformed and categorized into quartiles) with impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM), and we used linear regression models to estimate associations with first-trimester serum levels of triglycerides, total cholesterol, and C-reactive protein (CRP). Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were positively associated with IGT (137 cases) [OR per log 10 -unit increase=1.99 (95% CI: 1.06, 3.78) and OR=1.65 ( 95% CI: 0.99, 2.76), respectively]. PFOS and PFHxS associations with GDM (53 cases) were in a similar direction, but less precise. PFOS and perfluorononanoate (PFNA) were negatively associated with triglyceride levels [percent median change per log 10 -unit increase=-5.86% (95% CI: -9.91%, -1.63%) and percent median change per log 10 -unit increase=-4.75% (95% CI: -8.16%, -0.61%, respectively], whereas perfluorooctanoate (PFOA) was positively associated with total cholesterol [percent median change per log 10 -unit increase=1.26% (95% CI: 0.01%, 2.54%)]. PFASs were not associated with CRP in the subset of the population with available data ( n =640). Although further confirmation is required, the findings from this study suggest that PFAS exposures during pregnancy may

  4. Metabolic and cardiovascular outcomes of fatherhood: results from a cohort of study in subjects with sexual dysfunction.

    Science.gov (United States)

    Fisher, Alessandra D; Rastrelli, Giulia; Bandini, Elisa; Corona, Giovanni; Balzi, Daniela; Melani, Cecilia; Monami, Matteo; Matta, Vanessa; Mannucci, Edoardo; Maggi, Mario

    2012-11-01

    Previous cross-sectional and longitudinal studies reported a negative correlation between fatherhood and testosterone (T) levels, likely due to a centrally mediated downregulation of the hypothalamic-pituitary-gonadal axis. Moreover, epidemiological data indicate that fatherhood might affect metabolic and cardiovascular outcomes, although different results have been reported. Up to now, no studies have evaluated these associations in a population of men seeking treatment for sexual dysfunction (SD). To explore biological and clinical correlates of number of children (NoC) and its possible associations with forthcoming major cardiovascular events (MACE) in a sample of men with SD. A consecutive series of 4,045 subjects (mean age 52 ± 13.1 years old) attending the Outpatient Clinic for SD was retrospectively studied. A subset of the previous sample (N = 1,687) was enrolled in a longitudinal study. Information on MACE was obtained through the City of Florence Registry Office. Among patients studied, 31.6% had no children, while 26.3% reported having one child, 33.4% two, and 8.8% three or more children. Although fatherhood was negatively related with follicle-stimulating hormone levels and positively with testis volume, we found a NoC-dependent, stepwise decrease in T plasma levels, not compensated by a concomitant increase in luteinizing hormone. NoC was associated with a worse metabolic and cardiovascular profile, as well as worse penile blood flows and a higher prevalence of metabolic syndrome (MetS). In the longitudinal study, after adjusting for confounders, NoC was independently associated with a higher incidence of MACE. However, when the presence of MetS was introduced as a further covariate, the association was no longer significant. This study supports the hypothesis that bond maintenance contexts and fatherhood are associated with an adaptive downregulation of the gonadotropin-gonadal axis, even in a sample of men with SD. Moreover, our data suggest that

  5. Exposure to Perfluoroalkyl Substances and Metabolic Outcomes in Pregnant Women: Evidence from the Spanish INMA Birth Cohorts

    Science.gov (United States)

    Matilla-Santander, Nuria; Valvi, Damaskini; Lopez-Espinosa, Maria-Jose; Manzano-Salgado, Cyntia B.; Ballester, Ferran; Ibarluzea, Jesús; Santa-Marina, Loreto; Schettgen, Thomas; Guxens, Mònica; Sunyer, Jordi

    2017-01-01

    Background: Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS exposure susceptibility. Objective: We evaluated the associations between PFAS exposures and metabolic outcomes in pregnant women. Methods: We analyzed 1,240 pregnant women from the Spanish INMA [Environment and Childhood Project (INfancia y Medio Ambiente)] birth cohort study (recruitment period: 2003–2008) with measured first pregnancy trimester plasma concentrations of four PFASs (in nanograms/milliliter). We used logistic regression models to estimate associations of PFASs (log10-transformed and categorized into quartiles) with impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM), and we used linear regression models to estimate associations with first-trimester serum levels of triglycerides, total cholesterol, and C-reactive protein (CRP). Results: Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were positively associated with IGT (137 cases) [OR per log10-unit increase=1.99 (95% CI: 1.06, 3.78) and OR=1.65 ( 95% CI: 0.99, 2.76), respectively]. PFOS and PFHxS associations with GDM (53 cases) were in a similar direction, but less precise. PFOS and perfluorononanoate (PFNA) were negatively associated with triglyceride levels [percent median change per log10-unit increase=−5.86% (95% CI: −9.91%, −1.63%) and percent median change per log10-unit increase=−4.75% (95% CI: −8.16%, −0.61%, respectively], whereas perfluorooctanoate (PFOA) was positively associated with total cholesterol [percent median change per log10-unit increase=1.26% (95% CI: 0.01%, 2.54%)]. PFASs were not associated with CRP in the subset of the population with available data (n=640). Conclusions: Although further confirmation is required, the findings from this

  6. Metabolic syndrome and fatal outcomes in the post-stroke event: a 5-year cohort study in Cameroon.

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    Eric Vounsia Balti

    Full Text Available BACKGROUND AND PURPOSE: Determinants of post-acute stroke outcomes in Africa have been less investigated. We assessed the association of metabolic syndrome (MetS and insulin resistance with post-stroke mortality in patients with first-ever-in-lifetime stroke in the capital city of Cameroon (sub-Saharan Africa. METHODS: Patients with an acute first-stroke event (n = 57 were recruited between May and October 2006, and followed for 5 years for mortality outcome. MetS definition was based on the Joint Interim Statement 2009, insulin sensitivity/resistance assessed via glucose-to-insulin ratio, quantitative insulin sensitivity check index and homeostatic model assessment. RESULTS: Overall, 24 (42% patients deceased during follow-up. The prevalence of MetS was higher in patients who died after 28 days, 1 year and 5 years from any cause or cardiovascular-related causes (all p≤0.040. MetS was associated with an increased overall mortality both after 1 year (39% vs. 9% and 5 years of follow-up (55% vs. 26%, p = 0.022. Similarly, fatal events due to cardiovascular-related conditions were more frequent in the presence of MetS both 1 year (37% vs. 9% and 5 years after the first-ever-in-lifetime stroke (43% vs. 13%, p = 0.017. Unlike biochemical measures of insulin sensitivity and resistance (non-significant, in age- and sex-adjusted Cox models, MetS was associated with hazard ratio (95% CI of 2.63 (1.03-6.73 and 3.54 (1.00-12.56 respectively for all-cause and cardiovascular mortality 5 years after stroke onset. CONCLUSION: The Joint Interim Statement 2009 definition of MetS may aid the identification of a subgroup of black African stroke patients who may benefit from intensification of risk factor management.

  7. Refractive outcomes of an advanced aspherically optimized profile for myopia corrections by LASIK: a retrospective comparison with the standard aspherically optimized profile

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    Meyer B

    2015-02-01

    Full Text Available Bertram Meyer,1 Georg Sluyterman van Langeweyde,2 Matthias Wottke2 1Augencentrum Köln, Cologne, Germany; 2Carl Zeiss Meditec AG, Jena, Germany Purpose: A retrospective comparison of refractive outcomes of a new, aspherically optimized profile with an enhanced energy correction feature (Triple-A and the conventionally used aspherically optimized profile (ASA, or aberration smart ablation for correction of low-to-high myopia.Setting: Augen-OP-Centrum, Cologne, GermanyDesign: Retrospective nonrandomized comparative studyMethods: A central database at the Augen-OP-Centrum was used to gather retrospective data for low-to-high myopia (up to -10 D. One hundred and seven eyes (56 patients were treated with the ASA profile, and 79 eyes (46 patients were treated with the Triple-A profile. Postoperative outcomes were evaluated at 1 month, 3 months, 6 months, and 1 year follow-up time points.Results: The Triple-A profile showed better predictability indicated by a significantly lower standard deviation of residuals (0.32–0.34 vs 0.36–0.44, Triple-A vs ASA in the 6-month to 1-year period. The Triple-A group had better stability across all time intervals and achieved better postoperative astigmatism improvements with significantly lower scatter. This group achieved better safety at 1 year, with 100% of eyes showing no change or gain in Snellen lines, compared with 97% in the ASA group. A better safety index was observed for the Triple-A group at later time points. The Triple-A group had a better efficacy index and a higher percentage of eyes with an uncorrected Snellen visual acuity of 20/20 or greater at all investigated follow-up time points.Conclusion: The new aspherically optimized Triple-A profile can safely and effectively correct low-to-high myopia. It has demonstrated superiority over the ASA profile in most refractive outcomes. Keywords: Triple-A, wavefront measurements, corneal aberrations, corneal asphericity, ablation profile

  8. Clinical predictors and outcome of metabolic acidosis in under-five children admitted to an urban hospital in Bangladesh with diarrhea and pneumonia.

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    Chisti, Mohammod J; Ahmed, Tahmeed; Ashraf, Hasan; Faruque, A S G; Bardhan, Pradip K; Dey, Sanjoy Kumer; Huq, Sayeeda; Das, Sumon Kumar; Salam, Mohammed A

    2012-01-01

    Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. We prospectively enrolled all under-five children (n = 164) admitted to the Special Care Ward (SCW) of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98) and without metabolic acidosis (n = 66). Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039) compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62-7.89, p = 0.002), and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01-1.04, p = 0.005). Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05) among the groups. Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children. However, metabolic acidosis in young diarrheal children had no impact on the

  9. Clinical predictors and outcome of metabolic acidosis in under-five children admitted to an urban hospital in Bangladesh with diarrhea and pneumonia.

    Directory of Open Access Journals (Sweden)

    Mohammod J Chisti

    Full Text Available BACKGROUND: Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. METHODS: We prospectively enrolled all under-five children (n = 164 admitted to the Special Care Ward (SCW of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98 and without metabolic acidosis (n = 66. RESULTS: Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039 compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62-7.89, p = 0.002, and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01-1.04, p = 0.005. Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05 among the groups. CONCLUSION AND SIGNIFICANCE: Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children

  10. Health Care Transition for Young Adults With Type 1 Diabetes: Stakeholder Engagement for Defining Optimal Outcomes.

    Science.gov (United States)

    Pierce, Jessica S; Aroian, Karen; Schifano, Elizabeth; Milkes, Amy; Schwindt, Tiani; Gannon, Anthony; Wysocki, Tim

    2017-10-01

    Research on the transition to adult care for young adults with type 1 diabetes (T1D) emphasizes transition readiness, with less emphasis on transition outcomes. The relatively few studies that focus on outcomes use a wide variety of measures with little reliance on stakeholder engagement for measure selection. This study engaged multiple stakeholders (i.e., young adults with T1D, parents, pediatric and adult health care providers, and experts) in qualitative interviews to identify the content domain for developing a multidimensional measure of health care transition (HCT) outcomes. The following constructs were identified for a planned measure of HCT outcomes: biomedical markers of T1D control; T1D knowledge/skills; navigation of a new health care system; integration of T1D into emerging adult roles; balance of parental involvement with autonomy; and "ownership" of T1D self-management. The results can guide creation of an initial item pool for a multidimensional profile of HCT outcomes. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  11. The Effect of Dispositional Optimism on Health Outcomes in Patient with Heart Failure

    Science.gov (United States)

    2013-03-08

    pressure, waist circumference, fasting glucose , triglycerides , smoking status, physical activity, alcohol consumption, lipid-lowering and hypertension...abnormal glucose 50 tolerance, cholesterol levels, statin use, alcohol intake, smoking status, and age, Optimism was only associated with lower...levels was also assessed (Bolger et al., 2002). Measures of Heart Failure Severity A standard clinical severity index of HF symptom

  12. Refractive Outcomes, Contrast Sensitivity, HOAs, and Patient Satisfaction in Moderate Myopia: Wavefront-Optimized Versus Tissue-Saving PRK.

    Science.gov (United States)

    Nassiri, Nader; Sheibani, Kourosh; Azimi, Abbas; Khosravi, Farinaz Mahmoodi; Heravian, Javad; Yekta, Abasali; Moghaddam, Hadi Ostadi; Nassiri, Saman; Yasseri, Mehdi; Nassiri, Nariman

    2015-10-01

    To compare refractive outcomes, contrast sensitivity, higher-order aberrations (HOAs), and patient satisfaction after photorefractive keratectomy for correction of moderate myopia with two methods: tissue saving versus wavefront optimized. In this prospective, comparative study, 152 eyes (80 patients) with moderate myopia with and without astigmatism were randomly divided into two groups: the tissue-saving group (Technolas 217z Zyoptix laser; Bausch & Lomb, Rochester, NY) (76 eyes of 39 patients) or the wavefront-optimized group (WaveLight Allegretto Wave Eye-Q laser; Alcon Laboratories, Inc., Fort Worth, TX) (76 eyes of 41 patients). Preoperative and 3-month postoperative refractive outcomes, contrast sensitivity, HOAs, and patient satisfaction were compared between the two groups. The mean spherical equivalent was -4.50 ± 1.02 diopters. No statistically significant differences were detected between the groups in terms of uncorrected and corrected distance visual acuity and spherical equivalent preoperatively and 3 months postoperatively. No statistically significant differences were seen in the amount of preoperative to postoperative contrast sensitivity changes between the two groups in photopic and mesopic conditions. HOAs and Q factor increased in both groups postoperatively (P = .001), with the tissue-saving method causing more increases in HOAs (P = .007) and Q factor (P = .039). Patient satisfaction was comparable between both groups. Both platforms were effective in correcting moderate myopia with or without astigmatism. No difference in refractive outcome, contrast sensitivity changes, and patient satisfaction between the groups was observed. Postoperatively, the tissue-saving method caused a higher increase in HOAs and Q factor compared to the wavefront-optimized method, which could be due to larger optical zone sizes in the tissue-saving group. Copyright 2015, SLACK Incorporated.

  13. Family-based risk reduction of obesity and metabolic syndrome: an overview and outcomes of the Idaho Partnership for Hispanic Health.

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    Schwartz, Rachel; Powell, Linda; Keifer, Matthew

    2013-01-01

    Mexican American women have the highest incidence of metabolic syndrome among all U.S. demographic groups. This paper details an innovative approach to reducing the risks for metabolic syndrome among Hispanic families in rural Idaho. Compañeros en Salud (CeS) is a promotora-led wellness program and community-based participatory research project from the Idaho Partnership for Hispanic Health. As behavior change is the first line of prevention and treatment of obesity and metabolic syndrome, the program aimed to improve nutrition and physical activity behaviors as well as increase community support and infrastructure for healthy living. CeS has demonstrated substantial improvement in health outcomes, with statistically significant reductions in weight, BMI, metabolic syndrome risk, A1c, glucose, blood pressure, and cholesterol, from pre-intervention to post-intervention and/or pre-intervention to one-year follow-up. These outcomes suggest the CeS model as a promising best practice for effecting individual and family-level physiologic and behavioral outcomes for obesity prevention.

  14. Predicting Optimal Outcomes in Cognitive Therapy or Interpersonal Psychotherapy for Depressed Individuals Using the Personalized Advantage Index Approach.

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    Marcus J H Huibers

    Full Text Available Although psychotherapies for depression produce equivalent outcomes, individual patients respond differently to different therapies. Predictors of outcome have been identified in the context of randomized trials, but this information has not been used to predict which treatment works best for the depressed individual. In this paper, we aim to replicate a recently developed treatment selection method, using data from an RCT comparing the effects of cognitive therapy (CT and interpersonal psychotherapy (IPT.134 depressed patients completed the pre- and post-treatment BDI-II assessment. First, we identified baseline predictors and moderators. Second, individual treatment recommendations were generated by combining the identified predictors and moderators in an algorithm that produces the Personalized Advantage Index (PAI, a measure of the predicted advantage in one therapy compared to the other, using standard regression analyses and the leave-one-out cross-validation approach.We found five predictors (gender, employment status, anxiety, personality disorder and quality of life and six moderators (somatic complaints, cognitive problems, paranoid symptoms, interpersonal self-sacrificing, attributional style and number of life events of treatment outcome. The mean average PAI value was 8.9 BDI points, and 63% of the sample was predicted to have a clinically meaningful advantage in one of the therapies. Those who were randomized to their predicted optimal treatment (either CT or IPT had an observed mean end-BDI of 11.8, while those who received their predicted non-optimal treatment had an end-BDI of 17.8 (effect size for the difference = 0.51.Depressed patients who were randomized to their predicted optimal treatment fared much better than those randomized to their predicted non-optimal treatment. The PAI provides a great opportunity for formal decision-making to improve individual patient outcomes in depression. Although the utility of the PAI

  15. Achieving optimal delivery of follow-up care for prostate cancer survivors: improving patient outcomes

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    Hudson SV

    2015-03-01

    Full Text Available Shawna V Hudson,1 Denalee M O’Malley,2 Suzanne M Miller3 1Department of Family Medicine and Community Health, Rutgers Robert Wood Johnson Medical School, Somerset, 2Rutgers School of Social Work, New Brunswick, NJ, 3Cancer Prevention and Control Program, Fox Chase Cancer Center/Temple University Health System, Philadelphia, PA, USA Background: Prostate cancer is the most commonly diagnosed cancer in men in the US, and the second most prevalent cancer in men worldwide. High incidence and survival rates for prostate cancer have resulted in a large and growing population of long-term prostate cancer survivors. Long-term follow-up guidelines have only recently been developed to inform approaches to this phase of care for the prostate cancer population. Methods: A PubMed search of English literature through August 2014 was performed. Articles were retrieved and reviewed to confirm their relevance. Patient-reported measures that were used in studies of long-term prostate cancer survivors (ie, at least 2 years posttreatment were reviewed and included in the review. Results: A total of 343 abstracts were initially identified from the database search. After abstract review, 105 full-text articles were reviewed of which seven met inclusion criteria. An additional 22 articles were identified from the references of the included articles, and 29 were retained. From the 29 articles, 68 patient-reported outcome measures were identified. The majority (75% were multi-item scales that had been previously validated in existing literature. We identified four main areas of assessment: 1 physical health; 2 quality of life – general, physical, and psychosocial; 3 health promotion – physical activity, diet, and tobacco cessation; and 4 care quality outcomes. Conclusion: There are a number of well-validated measures that assess patient-reported outcomes that document key aspects of long-term follow-up with respect to patient symptoms and quality of life. However

  16. Subjective Happiness Optimizes Educational Outcomes: Evidence from Filipino High School Students.

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    Datu, Jesus Alfonso D; Valdez, Jana Patricia; Cabrera, Ian Kenneth; Salanga, Maria Guadalupe

    2017-10-30

    Subjective happiness has been found to be associated with key psychological outcomes. However, there is paucity of research that assessed how subjective happiness is related to a number of positive student outcomes in the educational setting. The objective of the study was to assess the associations of subjective happiness with academic engagement, flourishing, and school resilience among 606 Filipino high school students (m age = 13.87; n boys = 300, n girls = 305, n missing = 1) in the Philippine context. Results of path analysis demonstrated that subjective happiness positively predicted behavioral engagement (β = .08, p < .01), emotional engagement (β = .08, p < .01), flourishing (β = .17, p < .01), and school resilience (β = .18, p < .01) even after controlling for gender. The theoretical and practical implications of the findings are discussed.

  17. Effects of High Intensity Interval Training and Strength Training on Metabolic, Cardiovascular and Hormonal Outcomes in Women with Polycystic Ovary Syndrome: A Pilot Study.

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    Ida Almenning

    Full Text Available Polycystic ovary syndrome is a common endocrinopathy in reproductive-age women, and associates with insulin resistance. Exercise is advocated in this disorder, but little knowledge exists on the optimal exercise regimes. We assessed the effects of high intensity interval training and strength training on metabolic, cardiovascular, and hormonal outcomes in women with polycystic ovary syndrome.Three-arm parallel randomized controlled trial. Thirty-one women with polycystic ovary syndrome (age 27.2 ± 5.5 years; body mass index 26.7 ± 6.0 kg/m2 were randomly assigned to high intensity interval training, strength training, or a control group. The exercise groups exercised three times weekly for 10 weeks.The main outcome measure was change in homeostatic assessment of insulin resistance (HOMA-IR. HOMA-IR improved significantly only after high intensity interval training, by -0.83 (95% confidence interval [CI], -1.45, -0.20, equal to 17%, with between-group difference (p = 0.014. After high intensity interval training, high-density lipoprotein cholesterol increased by 0.2 (95% CI, 0.02, 0.5 mmol/L, with between group difference (p = 0.04. Endothelial function, measured as flow-mediated dilatation of the brachial artery, increased significantly after high intensity interval training, by 2.0 (95% CI, 0.1, 4.0 %, between-group difference (p = 0.08. Fat percentage decreased significantly after both exercise regimes, without changes in body weight. After strength training, anti-Müllarian hormone was significantly reduced, by -14.8 (95% CI, -21.2, -8.4 pmol/L, between-group difference (p = 0.04. There were no significant changes in high-sensitivity C-reactive protein, adiponectin or leptin in any group.High intensity interval training for ten weeks improved insulin resistance, without weight loss, in women with polycystic ovary syndrome. Body composition improved significantly after both strength training and high intensity interval training. This pilot

  18. Effects of High Intensity Interval Training and Strength Training on Metabolic, Cardiovascular and Hormonal Outcomes in Women with Polycystic Ovary Syndrome: A Pilot Study.

    Science.gov (United States)

    Almenning, Ida; Rieber-Mohn, Astrid; Lundgren, Kari Margrethe; Shetelig Løvvik, Tone; Garnæs, Kirsti Krohn; Moholdt, Trine

    2015-01-01

    Polycystic ovary syndrome is a common endocrinopathy in reproductive-age women, and associates with insulin resistance. Exercise is advocated in this disorder, but little knowledge exists on the optimal exercise regimes. We assessed the effects of high intensity interval training and strength training on metabolic, cardiovascular, and hormonal outcomes in women with polycystic ovary syndrome. Three-arm parallel randomized controlled trial. Thirty-one women with polycystic ovary syndrome (age 27.2 ± 5.5 years; body mass index 26.7 ± 6.0 kg/m2) were randomly assigned to high intensity interval training, strength training, or a control group. The exercise groups exercised three times weekly for 10 weeks. The main outcome measure was change in homeostatic assessment of insulin resistance (HOMA-IR). HOMA-IR improved significantly only after high intensity interval training, by -0.83 (95% confidence interval [CI], -1.45, -0.20), equal to 17%, with between-group difference (p = 0.014). After high intensity interval training, high-density lipoprotein cholesterol increased by 0.2 (95% CI, 0.02, 0.5) mmol/L, with between group difference (p = 0.04). Endothelial function, measured as flow-mediated dilatation of the brachial artery, increased significantly after high intensity interval training, by 2.0 (95% CI, 0.1, 4.0) %, between-group difference (p = 0.08). Fat percentage decreased significantly after both exercise regimes, without changes in body weight. After strength training, anti-Müllarian hormone was significantly reduced, by -14.8 (95% CI, -21.2, -8.4) pmol/L, between-group difference (p = 0.04). There were no significant changes in high-sensitivity C-reactive protein, adiponectin or leptin in any group. High intensity interval training for ten weeks improved insulin resistance, without weight loss, in women with polycystic ovary syndrome. Body composition improved significantly after both strength training and high intensity interval training. This pilot study

  19. Knowledge Translation to Optimize Adult Inpatient Glycemic Management with Basal Bolus Insulin Therapy and Improve Patient Outcomes.

    Science.gov (United States)

    Helmle, Karmon E; Chacko, Sunita; Chan, Trevor; Drake, Alison; Edwards, Alun L; Moore, Glenda E; Philp, Leta C; Popeski, Naomi; Roedler, Rhonda L; Rogers, Edwin J R; Zimmermann, Gabrielle L; McKeen, Julie

    2017-12-27

    To develop and evaluate a Basal Bolus Insulin Therapy (BBIT) Knowledge Translation toolkit to address barriers to adoption of established best practice with BBIT in the care of adult inpatients. This study was conducted in 2 phases and focused on the hospitalist provider group across 4 acute care facilities in Calgary. Phase 1 involved a qualitative evaluation of provider and site specific barriers and facilitators, which were mapped to validated interventions using behaviour change theory. This informed the co-development and optimization of the BBIT Knowledge Translation toolkit, with each tool targeting a specific barrier to improved diabetes care practice, including BBIT ordering. In Phase 2, the BBIT Knowledge Translation toolkit was implemented and evaluated, focusing on BBIT ordering frequency, as well as secondary outcomes of hyperglycemia (patient-days with BG >14.0 mmol/L), hypoglycemia (patient-days with BG Knowledge Translation toolkit resulted in a significant 13% absolute increase in BBIT ordering. Hyperglycemic patient-days were significantly reduced, with no increase in hypoglycemia. There was a significant, absolute 14% reduction in length of stay. The implementation of an evidence-informed, multifaceted BBIT Knowledge Translation toolkit effectively reduced a deeply entrenched in-patient diabetes care gap. The resulting sustained practice change improved patient clinical and system resource utilization outcomes. This systemic approach to implementation will guide further scale and spread of glycemic optimization initiatives. Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  20. A Brief Recap of Tips and Surgical Manoeuvres to Enhance Optimal Outcome of Surgically Placed Peritoneal Dialysis Catheters

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    Jodie H. Frost

    2012-01-01

    Full Text Available Background. Peritoneal dialysis (PD is an effective option of renal replacement therapy for ESRF, offering advantages over haemodialysis. Peritoneal dialysis catheter (PDC placement is thought to be the key to successful PD and the economic advantages are lost if a patient switches to HD in the 1st year. This paper is a brief document elaborating a recap of published literature, looking at various surgical tips and manoeuvres to enhance optimal outcome of PDC placement. Methods. A search strategy assessing for access team, preoperative antibiotic prophylaxis, type of catheter, catheter exit site, intraoperative catheter trial, optimal time to commence PD, hernia repairs, number of cuffs, catheter-embedding procedures, rectus sheath tunnelling, laparoscopic fixing, omentopexy, omentectomy, the “Y”-Tec system, resection of epiploic appendages, adhesiolysis, a trained surgeon, and perioperative catheter care protocol was used looking at various databases. Findings. The complications of catheterrelated dysfunction can be reduced with advanced planning of access placement, immaculate surgery, and attention to catheter insertion techniques. Conclusion. The success of a peritoneal dialysis programme depends upon functional and durable long term access to the peritoneal cavity; this depends on placement techniques and competent surgeons and psychosocial support to the patient. The various technical tips and manoeuvres elaborated here should be considered options carried out to improve outcome and reduce catheter dysfunction.

  1. Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

    Science.gov (United States)

    Adams, Hugo Ja; de Klerk, John Mh; Fijnheer, Rob; Heggelman, Ben Gf; Dubois, Stefan V; Nievelstein, Rutger Aj; Kwee, Thomas C

    2016-06-01

    There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.

  2. Waist-to-Height Ratio and Triglycerides/High-Density Lipoprotein Cholesterol Were the Optimal Predictors of Metabolic Syndrome in Uighur Men and Women in Xinjiang, China.

    Science.gov (United States)

    Chen, Bang-Dang; Yang, Yi-Ning; Ma, Yi-Tong; Pan, Shuo; He, Chun-Hui; Liu, Fen; Ma, Xiang; Fu, Zhen-Yan; Li, Xiao-Mei; Xie, Xiang; Zheng, Ying-Ying

    2015-06-01

    This study aimed to identify the best single predictor of metabolic syndrome by comparing the predictive ability of various anthropometric and atherogenic parameters among a Uighur population in Xinjiang, northwest China. A total of 4767 Uighur participants were selected from the Cardiovascular Risk Survey (CRS), which was carried out from October, 2007, to March, 2010. Anthropometric data, blood pressure, serum concentration of serum total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and fasting glucose were documented. Prevalence of metabolic syndrome and its individual components were confirmed according to International Diabetes Federation (IDF) criteria. Area under the receiver operating characteristic curve (AUC) of each variable for the presence of metabolic syndrome was compared. The sensitivity (Sen), specificity (Spe), distance in the receiver operating characteristic (ROC) curve, and cutoffs of each variable for the presence of metabolic syndrome were calculated. In all, 23.7% of men had the metabolic syndrome, whereas 40.1% of women had the metabolic syndrome in a Uighur population in Xinjiang; the prevalence of metabolic syndrome in women was significantly higher than that in men (PAUC value (AUC=0.838); it was followed by TGs/HDL-C (AUC=0.826), body mass index (BMI) (AUC=0.812), waist-to-hip ratio (WHR) (AUC=0.781), and body adiposity index (BAI) (AUC=0.709). In women, the TGs/HDL-C had the highest AUC value (AUC=0.815); it was followed by WHtR (AUC=0.780), WHR (AUC=0.730), BMI (AUC=0.719), and BAI (AUC=0.699). Similarly, among all five anthropometric and atherogenic parameters, the WHtR had the shortest ROC distance of 0.32 (Sen=85.40%, Spe=71.6%), and the optimal cutoff for WHtR was 0.55 in men. In women, TGs/HDL-C had the shortest ROC distance of 0.35 (Sen=75.29%, Spe=75.18%), and the optimal cutoff of TGs/HDL-C was 1.22. WHtR was the best predictor of metabolic

  3. Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Elaine Holmes

    2006-08-01

    Full Text Available The identification of schizophrenia biomarkers is a crucial step towards improving current diagnosis, developing new presymptomatic treatments, identifying high-risk individuals and disease subgroups, and assessing the efficacy of preventative interventions at a rate that is not currently possible.(1H nuclear magnetic resonance spectroscopy in conjunction with computerized pattern recognition analysis were employed to investigate metabolic profiles of a total of 152 cerebrospinal fluid (CSF samples from drug-naïve or minimally treated patients with first-onset paranoid schizophrenia (referred to as "schizophrenia" in the following text and healthy controls. Partial least square discriminant analysis showed a highly significant separation of patients with first-onset schizophrenia away from healthy controls. Short-term treatment with antipsychotic medication resulted in a normalization of the disease signature in over half the patients, well before overt clinical improvement. No normalization was observed in patients in which treatment had not been initiated at first presentation, providing the first molecular evidence for the importance of early intervention for psychotic disorders. Furthermore, the alterations identified in drug-naïve patients could be validated in a test sample set achieving a sensitivity and specificity of 82% and 85%, respectively.Our findings suggest brain-specific alterations in glucoregulatory processes in the CSF of drug-naïve patients with first-onset schizophrenia, implying that these abnormalities are intrinsic to the disease, rather than a side effect of antipsychotic medication. Short-term treatment with atypical antipsychotic medication resulted in a normalization of the CSF disease signature in half the patients well before a clinical improvement would be expected. Furthermore, our results suggest that the initiation of antipsychotic treatment during a first psychotic episode may influence treatment response

  4. Dose escalation with 3D conformal treatment: five year outcomes, treatment optimization, and future directions

    International Nuclear Information System (INIS)

    Hanks, Gerald E.; Hanlon, Alexandra L. M.S.; Schultheiss, Timothy E.; Pinover, Wayne H.; Movsas, Benjamin; Epstein, Barry E.; Hunt, Margie

    1998-01-01

    Purpose: To report the 5-year outcomes of dose escalation with 3D conformal treatment (3DCRT) of prostate cancer. Methods and Materials: Two hundred thirty-two consecutive patients were treated with 3DCRT alone between 6/89 and 10/92 with ICRU reporting point dose that increased from 63 to 79 Gy. The median follow-up was 60 months, and any patient free of clinical or biochemical evidence of disease was termed bNED. Biochemical failure was defined as prostate-specific antigen (PSA) rising on two consecutive recordings and exceeding 1.5 ng/ml. Morbidity was reported by the Radiation Therapy Oncology Group (RTOG) scale, the Late Effects Normal Tissue (LENT) scale, and a Fox Chase modification of the latter (FC-LENT). All patients were treated with a four-field technique with a 1 cm clinical target volume (CTV) to planning target volume (PTV) margin to the prostate or prostate boost; the CTV and gross tumor volume (GTV) were the same. Actuarial rates of outcome were calculated by Kaplan-Meier and cumulative incidence methods and compared using the log rank and Gray's test statistic, respectively. Cox regression models were used to establish prognostic factors predictive of the various measures of outcome. Five-year Kaplan-Meier bNED rates were utilized by dose group to estimate logit response models for bNED and late morbidity. Results: PSA 10 ng/ml based on 5-year bNED results. No dose response was observed for patients with pretreatment PSA 10 ng/ml strongly suggests that clinical trials employing radiation should investigate the use of 3DCRT and prostate doses of 76-80 Gy

  5. Optimizing the Risk Assessment in Upper Gastrointestinal Bleeding: Comparison of 5 Scores Predicting 7 Outcomes

    Directory of Open Access Journals (Sweden)

    Tiago Cúrdia Gonçalves

    2018-05-01

    Full Text Available Introduction: Although different scores have been suggested to predict outcomes in the setting of upper gastrointestinal bleeding (UGIB, few comparative studies between simplified versions of older scores and recent scores have been published. We aimed to evaluate the accuracy of pre- (PreRS and postendoscopic Rockall scores (PostRS, the Glasgow-Blatchford score (GBS and its simplified version (sGBS, as well as the AIMS65 score in predicting different clinical outcomes. Methods: In this retrospective study, PreRS, PostRS, GBS, sGBS, and AIMS65 score were calculated, and then, areas under the receiver operating characteristic curve were used to evaluate the performance of each score to predict blood transfusion, endoscopic therapy, surgery, admission to intensive/intermediate care unit, length of hospital stay, as well as 30-day rebleeding or mortality. Results: PreRS, PostRS, GBS, and sGBS were calculated for all the 433 included patients, but AIMS65 calculation was only possible for 315 patients. Only the PreRS and PostRS were able to fairly predict 30-day mortality. The GBS and sGBS were good in predicting blood transfusion and reasonable in predicting surgery. None of the studied scores were good in predicting the need for endoscopic therapy, admission to intensive/intermediate care unit, length of hospital stay, and 30-day rebleeding. Conclusions: Owing to the identified limitations, none of the 5 studied scores could be singly used to predict all the clinically relevant outcomes in the setting of UGIB. The sGBS was as precise as the GBS in predicting blood transfusion and surgery. The PreRS and PostRS were the only scores that could predict 30-day mortality. An algorithm using the PreRS and the sGBS as an initial approach to patients with UGIB is presented and suggested.

  6. Quality Improvement in Anesthesiology - Leveraging Data and Analytics to Optimize Outcomes.

    Science.gov (United States)

    Valentine, Elizabeth A; Falk, Scott A

    2018-03-01

    Quality improvement is at the heart of practice of anesthesiology. Objective data are critical for any quality improvement initiative; when possible, a combination of process, outcome, and balancing metrics should be evaluated to gauge the value of an intervention. Quality improvement is an ongoing process; iterative reevaluation of data is required to maintain interventions, ensure continued effectiveness, and continually improve. Dashboards can facilitate rapid analysis of data and drive decision making. Large data sets can be useful to establish benchmarks and compare performance against other providers, practices, or institutions. Audit and feedback strategies are effective in facilitating positive change. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Optimizing survival outcomes for adult patients with nontraumatic cardiac arrest [digest].

    Science.gov (United States)

    Jung, Julianna; Zaurova, Milana

    2016-10-22

    Patient survival after cardiac arrest can be improved significantly with prompt and effective resuscitative care. This systematic review analyzes the basic life support factors that improve survival outcome, including chest compression technique and rapid defibrillation of shockable rhythms. For patients who are successfully resuscitated, comprehensive postresuscitation care is essential. Targeted temperature management is recommended for all patients who remain comatose, in addition to careful monitoring of oxygenation, hemodynamics, and cardiac rhythm. Management of cardiac arrest in circumstances such as pregnancy, pulmonary embolism, opioid overdose and other toxicologic causes, hypothermia, and coronary ischemia are also reviewed. [Points & Pearls is a digest of Emergency Medicine Practice].

  8. Defining Optimal Aerobic Exercise Parameters to Affect Complex Motor and Cognitive Outcomes after Stroke: A Systematic Review and Synthesis

    Directory of Open Access Journals (Sweden)

    S. M. Mahmudul Hasan

    2016-01-01

    Full Text Available Although poststroke aerobic exercise (AE increases markers of neuroplasticity and protects perilesional tissue, the degree to which it enhances complex motor or cognitive outcomes is unknown. Previous research suggests that timing and dosage of exercise may be important. We synthesized data from clinical and animal studies in order to determine optimal AE training parameters and recovery outcomes for future research. Using predefined criteria, we included clinical trials of stroke of any type or duration and animal studies employing any established models of stroke. Of the 5,259 titles returned, 52 articles met our criteria, measuring the effects of AE on balance, lower extremity coordination, upper limb motor skills, learning, processing speed, memory, and executive function. We found that early-initiated low-to-moderate intensity AE improved locomotor coordination in rodents. In clinical trials, AE improved balance and lower limb coordination irrespective of intervention modality or parameter. In contrast, fine upper limb recovery was relatively resistant to AE. In terms of cognitive outcomes, poststroke AE in animals improved memory and learning, except when training was too intense. However, in clinical trials, combined training protocols more consistently improved cognition. We noted a paucity of studies examining the benefits of AE on recovery beyond cessation of the intervention.

  9. Treatment of edentulism: optimizing outcomes with tissue management and impression techniques.

    Science.gov (United States)

    Salinas, Thomas J

    2009-02-01

    Significant numbers of patients throughout the world seek treatment for edentulism. The trend toward tissue-integrated prostheses has been a monumental step in restoring edentulous patients to function; however, this treatment can be out of reach for those who fail to qualify or those who do not have sufficient resources to afford it. In these cases, conventional dentures remain an important primary course of treatment. Attention to detail when diagnosing, treatment planning, and performing treatment for these patients is still a prime consideration for the best possible outcome. In particular, many experienced denture wearers are afflicted with chronically inflamed denture-bearing mucosa. Clinicians must recognize the need for tissue conditioning, choices of impression materials, and accepted fabrication techniques that can have favorable outcomes when matched with patients who are philosophical and realistic in their expectations. The purpose of this article is to review impression philosophies, associated materials, and methods of tissue conditioning. Retention and stability of the denture bases can be augmented by the routine use of denture adhesive, and indications for use of denture adhesive will be discussed.

  10. Optimization of prosthetic foot stiffness to reduce metabolic cost and intact knee loading during below-knee amputee walking: a theoretical study.

    Science.gov (United States)

    Fey, Nicholas P; Klute, Glenn K; Neptune, Richard R

    2012-11-01

    Unilateral below-knee amputees develop abnormal gait characteristics that include bilateral asymmetries and an elevated metabolic cost relative to non-amputees. In addition, long-term prosthesis use has been linked to an increased prevalence of joint pain and osteoarthritis in the intact leg knee. To improve amputee mobility, prosthetic feet that utilize elastic energy storage and return (ESAR) have been designed, which perform important biomechanical functions such as providing body support and forward propulsion. However, the prescription of appropriate design characteristics (e.g., stiffness) is not well-defined since its influence on foot function and important in vivo biomechanical quantities such as metabolic cost and joint loading remain unclear. The design of feet that improve these quantities could provide considerable advancements in amputee care. Therefore, the purpose of this study was to couple design optimization with dynamic simulations of amputee walking to identify the optimal foot stiffness that minimizes metabolic cost and intact knee joint loading. A musculoskeletal model and distributed stiffness ESAR prosthetic foot model were developed to generate muscle-actuated forward dynamics simulations of amputee walking. Dynamic optimization was used to solve for the optimal muscle excitation patterns and foot stiffness profile that produced simulations that tracked experimental amputee walking data while minimizing metabolic cost and intact leg internal knee contact forces. Muscle and foot function were evaluated by calculating their contributions to the important walking subtasks of body support, forward propulsion and leg swing. The analyses showed that altering a nominal prosthetic foot stiffness distribution by stiffening the toe and mid-foot while making the ankle and heel less stiff improved ESAR foot performance by offloading the intact knee during early to mid-stance of the intact leg and reducing metabolic cost. The optimal design also

  11. Fasting, Diabetes, and Optimizing Health Outcomes for Ramadan Observers: A Literature Review.

    Science.gov (United States)

    Almansour, Hadi A; Chaar, Betty; Saini, Bandana

    2017-04-01

    Globally, and in Australia, diabetes has become a common chronic health condition. Diabetes is also quite prevalent in culturally and linguistically diverse pockets of the Australian population, including Muslims. There are over 90 million Muslims with diabetes worldwide. Diabetes management and medication use can be affected by religious practices such as fasting during Ramadan. During Ramadan, Muslims refrain from oral or intravenous substances from sunrise to sunset. This may lead to many potential health or medication-related risks for patients with diabetes who observe this religious practice. This literature review aimed to explore (1) health care-related interventions and (2) intentions, perspectives, or needs of health care professionals (HCPs) to provide clinical services to patients with diabetes while fasting during Ramadan with a view to improve health outcomes for those patients. Using a scoping review approach, a comprehensive search was conducted. Databases searched systematically included PubMed, Medline, Embase, and International Pharmaceutical Abstracts. Studies published in English that described interventions or intentions to provide interventions regarding diabetes and Ramadan fasting were included. Fourteen published articles that met the inclusion criteria were retrieved and content analyzed. Of those, nine intervention studies regarded diabetes management education. Five studies described professional service intention, four of which were related to the role of pharmacists in diabetes management in Qatar, Australia, and Egypt, and one French study examined the general practitioners' (GPs) experiences in diabetes management for Ramadan observers. The intervention studies had promising outcomes for diabetes management during Ramadan. Effect sizes for improvement in HbA1c post intervention ranged widely from -1.14 to 1.7. Pharmacists appeared to be willing to participate in programs to help fasting patients with diabetes achieve a safe

  12. New developments in understanding development defects of enamel: optimizing clinical outcomes.

    Science.gov (United States)

    Kilpatrick, Nicky

    2009-12-01

    Developmental defects of enamel appear to be presenting with increasing frequency and with this comes significant clinical challenges. Affected teeth, in particular first permanent molars, are susceptible to dental caries as they are not only more porous but also very sensitive making effective oral hygiene difficult. Affected children require more dental treatment than their unaffected peers while also suffering greater pain and anxiety. Current clinical approaches focus on the placement of contemporary adhesive restorative materials onto the compromised tooth which in turn, fail, leading to premature loss of permanent molars with associated repercussions. Incomplete understanding of the structure, composition and behaviour of affected enamel means that clinical protocols are, as yet, empiric rather than evidence based. This review summarises contemporary evidence regarding this condition and identifies potential areas for future research which would assist in improving clinical outcomes.

  13. Optimizing Outcomes in Pharyngoesophageal Reconstruction and Neck Resurfacing: 10-Year Experience of 294 Cases.

    Science.gov (United States)

    Sharaf, Basel; Xue, Amy; Solari, Mario G; Boa, Olivier; Liu, Jun; Hanasono, Matthew M; Skoracki, Roman; Yu, Peirong; Selber, Jesse C

    2017-01-01

    Pharyngoesophageal reconstruction is a complex endeavor that poses many challenges. This 10-year series examines factors impacting the need for neck skin resurfacing and evaluates the impact of reconstructive modalities on outcomes. A review identified 294 patients who underwent pharyngoesophageal reconstruction from 2002 to 2012. Patients were divided based on neck skin resurfacing requirements. Patients undergoing neck resurfacing were further subdivided into reconstructive technique, including a second skin paddle or muscle component from the same free flap pedicle, a local flap, or a second free flap. All groups were compared by comorbidities, complications, and functional outcomes. Of 294 patients, 179 (60.9 percent) required neck skin resurfacing. In the resurfaced group, there were 90 circumferential defects (50.3 percent) and 89 partial defects (49.7 percent). In the resurfaced group, 110 (61.4 percent) underwent reconstruction with a second skin paddle from the same free flap pedicle, 21 (11.7 percent) underwent reconstruction with a muscle component from the same pedicle, and 25 (13.9 percent) received a pectoralis major flap. There were five external paddle flap losses in the resurfaced group (2.8 percent) and no internal flap losses. Overall complications were similar among groups. The resurfaced group had a lower pharyngocutaneous fistula rate (4.5 percent) compared with the primary closure group (11.3 percent) (p = 0.026). Prior neck surgery and radiation therapy were strong predictors of neck skin resurfacing (p resurfacing is often required in salvage pharyngoesophageal reconstruction. Providing additional vascularized tissue over the neoconduit is predictive of lower pharyngocutaneous fistula rates. An algorithmic approach to neck resurfacing is presented.

  14. Sub-Optimal Management of Type 2 Diabetes Mellitus – A Local Audit

    African Journals Online (AJOL)

    Original Research: Sub-Optimal Management of Type 2 Diabetes Mellitus – A Local Audit ... despite clinical trial data documenting improved outcomes associated not ... were used to define the Metabolic Syndrome.9 Central obesity was.

  15. MiYA, an efficient machine-learning workflow in conjunction with the YeastFab assembly strategy for combinatorial optimization of heterologous metabolic pathways in Saccharomyces cerevisiae.

    Science.gov (United States)

    Zhou, Yikang; Li, Gang; Dong, Junkai; Xing, Xin-Hui; Dai, Junbiao; Zhang, Chong

    2018-05-01

    Facing boosting ability to construct combinatorial metabolic pathways, how to search the metabolic sweet spot has become the rate-limiting step. We here reported an efficient Machine-learning workflow in conjunction with YeastFab Assembly strategy (MiYA) for combinatorial optimizing the large biosynthetic genotypic space of heterologous metabolic pathways in Saccharomyces cerevisiae. Using β-carotene biosynthetic pathway as example, we first demonstrated that MiYA has the power to search only a small fraction (2-5%) of combinatorial space to precisely tune the expression level of each gene with a machine-learning algorithm of an artificial neural network (ANN) ensemble to avoid over-fitting problem when dealing with a small number of training samples. We then applied MiYA to improve the biosynthesis of violacein. Feed with initial data from a colorimetric plate-based, pre-screened pool of 24 strains producing violacein, MiYA successfully predicted, and verified experimentally, the existence of a strain that showed a 2.42-fold titer improvement in violacein production among 3125 possible designs. Furthermore, MiYA was able to largely avoid the branch pathway of violacein biosynthesis that makes deoxyviolacein, and produces very pure violacein. Together, MiYA combines the advantages of standardized building blocks and machine learning to accelerate the Design-Build-Test-Learn (DBTL) cycle for combinatorial optimization of metabolic pathways, which could significantly accelerate the development of microbial cell factories. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  16. Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate.

    Science.gov (United States)

    Mayer, Lori; Fink, Mary Kay; Sammarco, Carrie; Laing, Lisa

    2018-04-01

    Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing-remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

  17. Outcomes In Two Massachusetts Hospital Systems Give Reason For Optimism About Communication-And-Resolution Programs.

    Science.gov (United States)

    Mello, Michelle M; Kachalia, Allen; Roche, Stephanie; Niel, Melinda Van; Buchsbaum, Lisa; Dodson, Suzanne; Folcarelli, Patricia; Benjamin, Evan M; Sands, Kenneth E

    2017-10-01

    Through communication-and-resolution programs, hospitals and liability insurers communicate with patients when adverse events occur; investigate and explain what happened; and, where appropriate, apologize and proactively offer compensation. Using data recorded by program staff members and from surveys of involved clinicians, we examined case outcomes of a program used by two academic medical centers and two of their community hospitals in Massachusetts in the period 2013-15. The hospitals demonstrated good adherence to the program protocol. Ninety-one percent of the program events did not meet compensation eligibility criteria, and those events that did were not costly to resolve (the median payment was $75,000). Only 5 percent of events led to malpractice claims or lawsuits. Clinicians were supportive of the program but desired better communication about it from staff members. Our findings suggest that communication-and-resolution programs will not lead to higher liability costs when hospitals adhere to their commitment to offer compensation proactively. Project HOPE—The People-to-People Health Foundation, Inc.

  18. The Effect of Anxiety, Depression, and Optimism on Postoperative Satisfaction and Clinical Outcomes in Lumbar Spinal Stenosis and Degenerative Spondylolisthesis Patients: Cohort Study.

    Science.gov (United States)

    Lee, Jaewon; Kim, Hong-Sik; Shim, Kyu-Dong; Park, Ye-Soo

    2017-06-01

    The aim of this study is to evaluate the effect of depression, anxiety, and optimism on postoperative satisfaction and clinical outcomes in patients who underwent less than two-level posterior instrumented fusions for lumbar spinal stenosis and degenerative spondylolisthesis. Preoperative psychological status of subjects, such as depression, anxiety, and optimism, was evaluated using the Hospital Anxiety and Depression Scale (HADS) and the Revised Life Orientation Test (LOT-R). Clinical evaluation was determined by measuring changes in a visual analogue scale (VAS) and the Oswestry Disability Index (ODI) before and after surgery. Postoperative satisfaction of subjects assessed using the North American Spine Society lumbar spine questionnaire was comparatively analyzed against the preoperative psychological status. The correlation between patient's preoperative psychological status (depression, anxiety, and optimism) and clinical outcomes (VAS and ODI) was evaluated. VAS and ODI scores significantly decreased after surgery ( p optimism) was not related to the degree of improvement in clinical outcomes (VAS and ODI) after surgery. However, postoperative satisfaction was moderately correlated with optimism. Anxiety and optimism were more correlated with patient satisfaction than clinical outcomes. Accordingly, the surgeon can predict postoperative satisfaction of patients based on careful evaluation of psychological status before surgery.

  19. Metabolic and Physiological Responses of Shiraz and Cabernet Sauvignon (Vitis vinifera L. to Near Optimal Temperatures of 25 and 35 °C

    Directory of Open Access Journals (Sweden)

    Uri Hochberg

    2015-10-01

    Full Text Available Shiraz and Cabernet Sauvignon (Cs grapevines were grown at near optimal temperatures (25 or 35 °C. Gas exchange, fluorescence, metabolic profiling and correlation based network analysis were used to characterize leaf physiology. When grown at 25 °C, the growth rate and photosynthesis of both cultivars were similar. At 35 °C Shiraz showed increased respiration, non-photochemical quenching and reductions of photosynthesis and growth. In contrast, Cs maintained relatively stable photosynthetic activity and growth regardless of the condition. In both cultivars, growth at 35 °C resulted in accumulations of secondary sugars (raffinose, fucose and ribulose and reduction of primary sugars concentration (glucose, fructose and sucrose, more noticeably in Shiraz than Cs. In spite of similar patterns of metabolic changes in response to growth at 35 °C, significant differences in important leaf antioxidants and antioxidant precursors (DHA/ascorbate, quinates, cathechins characterized the cultivar response. Correlation analysis reinforced Shiraz sensitivity to the 35 °C, showing higher number of newly formed edges at 35 °C and higher modularity in Shiraz as compared to Cs. The results suggest that the optimal growth temperatures of grapevines are cultivar dependent, and allow a first insight into the variability of the metabolic responses of grapevines under varied temperatures.

  20. Metabolic and Physiological Responses of Shiraz and Cabernet Sauvignon (Vitis vinifera L.) to Near Optimal Temperatures of 25 and 35 °C.

    Science.gov (United States)

    Hochberg, Uri; Batushansky, Albert; Degu, Asfaw; Rachmilevitch, Shimon; Fait, Aaron

    2015-10-14

    Shiraz and Cabernet Sauvignon (Cs) grapevines were grown at near optimal temperatures (25 or 35 °C). Gas exchange, fluorescence, metabolic profiling and correlation based network analysis were used to characterize leaf physiology. When grown at 25 °C, the growth rate and photosynthesis of both cultivars were similar. At 35 °C Shiraz showed increased respiration, non-photochemical quenching and reductions of photosynthesis and growth. In contrast, Cs maintained relatively stable photosynthetic activity and growth regardless of the condition. In both cultivars, growth at 35 °C resulted in accumulations of secondary sugars (raffinose, fucose and ribulose) and reduction of primary sugars concentration (glucose, fructose and sucrose), more noticeably in Shiraz than Cs. In spite of similar patterns of metabolic changes in response to growth at 35 °C, significant differences in important leaf antioxidants and antioxidant precursors (DHA/ascorbate, quinates, cathechins) characterized the cultivar response. Correlation analysis reinforced Shiraz sensitivity to the 35 °C, showing higher number of newly formed edges at 35 °C and higher modularity in Shiraz as compared to Cs. The results suggest that the optimal growth temperatures of grapevines are cultivar dependent, and allow a first insight into the variability of the metabolic responses of grapevines under varied temperatures.

  1. The main factors influencing canine demodicosis treatment outcome and determination of optimal therapy.

    Science.gov (United States)

    Arsenović, Milica; Pezo, Lato; Vasić, Nebojša; Ćirić, Rodoljub; Stefanović, Milan

    2015-07-01

    The main idea of this research was to evaluate the efficacy of canine demodicosis conventional treatments using mathematical analyses. All available papers published between 1980 and 2014 were used in this study. One hundred six clinical trials enrolling 3414 cases of generalized demodicosis in dogs are studied. Dogs entered in the analysis were only the ones in which the disease occurred naturally, excluding the studies in which transplantation of Demodex canis mites was done from other animals. In conventional acaricide treatments, sorted according to active substances (moxidectin, amitraz, doramectin, ivermectin, and milbemycin oxime), the way of application (spot-on, dips, orally, or subcutaneous), concentration, and interval of application were used as input parameters in mathematical modeling. Data of interest were the treatment outcome, the number of dogs that went into remission, the number of animals not responding to treatment microscopically, the average duration of therapy, the follow-up period, the number of patients with disease recurrence, the number of adverse effects, and the number of animals with side effects. Dogs lost to follow-up or when the treatment was discontinued, due to various reasons not in connection with the therapy protocol, were not considered. Statistical and mathematical analyses were applied for prediction of the drugs' effectiveness. Developed mathematical models showed satisfactorily r (2), higher than 0.87. Good evidence for recommending the use of milbemycin oxime PO (0.5 mg/kg, daily) and moxidectin spot-on (Advocate®, Bayer) weekly is found. A bit less effective therapies were based on ivermectin PO (0.5 mg/kg, daily), moxidectin PO (0.35 mg/kg, daily), and amitraz dips (0.05 % solution, weekly), respectively. It is important to keep in mind that Advocate® is recommended by the manufacturer for use in milder cases.

  2. Health Outcomes of Information System Use Lifestyles among Adolescents: Videogame Addiction, Sleep Curtailment and Cardio-Metabolic Deficiencies

    OpenAIRE

    Turel, Ofir; Romashkin, Anna; Morrison, Katherine M.

    2016-01-01

    Background and Objective Obesity is a rising problem among adolescents in modern societies; it results in long-term cardio-metabolic problems. Possible overlooked drivers of obesity and its consequent cardio-metabolic deficits include videogame addiction and the resulting curtailed sleep; both are growing problems among adolescents. The objective of this study is to examine possible associations among these concepts in adolescents, as a means to point to plausible interventions. Methods Data ...

  3. Maternal Diabetes in Pregnancy: Early and Long-Term Outcomes on the Offspring and the Concept of “Metabolic Memory”

    Directory of Open Access Journals (Sweden)

    Akadiri Yessoufou

    2011-01-01

    Full Text Available The adverse outcomes on the offspring from maternal diabetes in pregnancy are substantially documented. In this paper, we report main knowledge on impacts of maternal diabetes on early and long-term health of the offspring, with specific comments on maternal obesity. The main adverse outcome on progenies from pregnancy complicated with maternal diabetes appears to be macrosomia, as it is commonly known that intrauterine exposure to hyperglycemia increases the risk and programs the offspring to develop diabetes and/or obesity at adulthood. This “fetal programming”, due to intrauterine diabetic milieu, is termed as “metabolic memory”. In gestational diabetes as well as in macrosomia, the complications include metabolic abnormalities, degraded antioxidant status, disrupted immune system and potential metabolic syndrome in adult offspring. Furthermore, there is evidence that maternal obesity may also increase the risk of obesity and diabetes in offspring. However, women with GDM possibly exhibit greater macrosomia than obese women. Obesity and diabetes in pregnancy have independent and additive effects on obstetric complications, and both require proper management. Management of gestational diabetes mellitus and maternal obesity is essential for maternal and offspring's good health. Increasing physical activity, preventing gestational weight gain, and having some qualitative nutritional habits may be beneficial during both the pregnancy and offspring's future life.

  4. Outcomes of On-pump Coronary Artery Bypass Grafting in Patients with Metabolic Syndrome in Mashhad, Iran

    Directory of Open Access Journals (Sweden)

    Aliasghar Moeinipour

    2017-09-01

    Full Text Available Introduction: Metabolic syndrome (MS is considered as an important risk factor for advanced coronary artery disease. This condition can increase the mortality and morbidity in the patients undergoing coronary artery bypass graft (CABG surgery. The aim of the study was compared mortality and morbidity after off Pump- CABG surgery between patients with and without the Metabolic syndrome. Materials & Methods: This prospective cross-sectional study was conducted on 120 patients, who underwent off-pump CABG surgery between October 2014-October 2016. The participants were equally divided into two groups including the patients with and without MS (MS and non-MS, respectively. Results: According to the results, 68 (56.6% patients were male. Furthermore, out of the 60 participants with MS, 36 (60% cases were male. The mean ages of the MS and non-MS groups were 64.96±9.6 and 65.62±10.6 P=0.6 years, respectively. No statistically significant difference was observed between the two groups in terms of the mortality and morbidity (e.g., surgical wound infection, length of Intensive Care Unit and hospital stay, atrial fibrillation rhythm, and bleeding in the first 24 h. The intubation time in patients with Metabolic Syndrome was significantly higher than patients without Metabolic Syndrome (6.66 ± 1.97 vs 5.83 ± 1.93 respectively; P=0.007 Conclusion: Metabolic syndrome was not associated with higher mortality and morbidity after CABG surgery compare to patients without Metabolic syndrome, although patients with Metabolic syndrome had higher risk for long intubation time.

  5. Systematic optimization of fed-batch simultaneous saccharification and fermentation at high-solid loading based on enzymatic hydrolysis and dynamic metabolic modeling of Saccharomyces cerevisiae.

    Science.gov (United States)

    Unrean, Pornkamol; Khajeeram, Sutamat; Laoteng, Kobkul

    2016-03-01

    An integrative simultaneous saccharification and fermentation (SSF) modeling is a useful guiding tool for rapid process optimization to meet the techno-economic requirement of industrial-scale lignocellulosic ethanol production. In this work, we have developed the SSF model composing of a metabolic network of a Saccharomyces cerevisiae cell associated with fermentation kinetics and enzyme hydrolysis model to quantitatively capture dynamic responses of yeast cell growth and fermentation during SSF. By using model-based design of feeding profiles for substrate and yeast cell in the fed-batch SSF process, an efficient ethanol production with high titer of up to 65 g/L and high yield of 85 % of theoretical yield was accomplished. The ethanol titer and productivity was increased by 47 and 41 %, correspondingly, in optimized fed-batch SSF as compared to batch process. The developed integrative SSF model is, therefore, considered as a promising approach for systematic design of economical and sustainable SSF bioprocessing of lignocellulose.

  6. mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.

    Science.gov (United States)

    Sinclair, Charles; Bommakanti, Gayathri; Gardinassi, Luiz; Loebbermann, Jens; Johnson, Matthew Joseph; Hakimpour, Paul; Hagan, Thomas; Benitez, Lydia; Todor, Andrei; Machiah, Deepa; Oriss, Timothy; Ray, Anuradha; Bosinger, Steven; Ravindran, Rajesh; Li, Shuzhao; Pulendran, Bali

    2017-09-08

    Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103 + DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b + DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (T H 2) to neutrophilic T H 17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  7. Exposure to Perfluoroalkyl Substances and Metabolic Outcomes in Pregnant Women: Evidence from the Spanish INMA Birth Cohorts

    NARCIS (Netherlands)

    Matilla-Santander, N. (Nuria); D. Valvi (Damaskini); M.-J. Lopez-Espinosa (Maria-Jose); Manzano-Salgado, C.B. (Cyntia B.); F. Ballester (Ferran); J. Ibarluzea (Jesús); L. Santa-Marina (Loreto); T. Schettgen (Thomas); M. Guxens Junyent (Mònica); J. Sunyer (Jordi); M. Vrijheid (Martine)

    2017-01-01

    textabstractBACKGROUND: Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS

  8. Optimizing Functional Outcomes in Mandibular Condyle Reconstruction With the Free Fibula Flap Using Computer-Aided Design and Manufacturing Technology.

    Science.gov (United States)

    Lee, Z-Hye; Avraham, Tomer; Monaco, Casian; Patel, Ashish A; Hirsch, David L; Levine, Jamie P

    2018-05-01

    planning and intraoperative manipulation with optimal functional outcomes. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Metabolic Compensation of Fitness Costs Is a General Outcome for Antibiotic-Resistant Pseudomonas aeruginosa Mutants Overexpressing Efflux Pumps.

    Science.gov (United States)

    Olivares Pacheco, Jorge; Alvarez-Ortega, Carolina; Alcalde Rico, Manuel; Martínez, José Luis

    2017-07-25

    It is generally assumed that the acquisition of antibiotic resistance is associated with a fitness cost. We have shown that overexpression of the MexEF-OprN efflux pump does not decrease the fitness of a resistant Pseudomonas aeruginosa strain compared to its wild-type counterpart. This lack of fitness cost was associated with a metabolic rewiring that includes increased expression of the anaerobic nitrate respiratory chain when cells are growing under fully aerobic conditions. It was not clear whether this metabolic compensation was exclusive to strains overexpressing MexEF-OprN or if it extended to other resistant strains that overexpress similar systems. To answer this question, we studied a set of P. aeruginosa mutants that independently overexpress the MexAB-OprM, MexCD-OprJ, or MexXY efflux pumps. We observed increased expression of the anaerobic nitrate respiratory chain in all cases, with a concomitant increase in NO 3 consumption and NO production. These efflux pumps are proton/substrate antiporters, and their overexpression may lead to intracellular H + accumulation, which may in turn offset the pH homeostasis. Indeed, all studied mutants showed a decrease in intracellular pH under anaerobic conditions. The fastest way to eliminate the excess of protons is by increasing oxygen consumption, a feature also displayed by all analyzed mutants. Taken together, our results support metabolic rewiring as a general mechanism to avoid the fitness costs derived from overexpression of P. aeruginosa multidrug efflux pumps. The development of drugs that block this metabolic "reaccommodation" might help in reducing the persistence and spread of antibiotic resistance elements among bacterial populations. IMPORTANCE It is widely accepted that the acquisition of resistance confers a fitness cost in such a way that in the absence of antibiotics, resistant populations will be outcompeted by susceptible ones. Based on this assumption, antibiotic cycling regimes have been

  10. Optimal cutoff points for HOMA-IR and QUICKI in the diagnosis of metabolic syndrome and non-alcoholic fatty liver disease: A population based study.

    Science.gov (United States)

    Motamed, Nima; Miresmail, Seyed Javad Haji; Rabiee, Behnam; Keyvani, Hossein; Farahani, Behzad; Maadi, Mansooreh; Zamani, Farhad

    2016-03-01

    The present study was carried out to determine the optimal cutoff points for homeostatic model assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) in the diagnosis of metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). The baseline data of 5511 subjects aged ≥18years of a cohort study in northern Iran were utilized to analyze. Receiver operating characteristic (ROC) analysis was conducted to determine the discriminatory capability of HOMA-IR and QUICKI in the diagnosis of MetS and NAFLD. Youden index was utilized to determine the optimal cutoff points of HOMA-IR and QUICKI in the diagnosis of MetS and NAFLD. The optimal cutoff points for HOMA-IR in the diagnosis of MetS and NAFLD were 2.0 [sensitivity=64.4%, specificity=66.8%] and 1.79 [sensitivity=66.2%, specificity=62.2%] in men and were 2.5 [sensitivity=57.6%, specificity=67.9%] and 1.95 [sensitivity=65.1%, specificity=54.7%] in women respectively. Furthermore, the optimal cutoff points for QUICKI in the diagnosis of MetS and NAFLD were 0.343 [sensitivity=63.7%, specificity=67.8%] and 0.347 [sensitivity=62.9%, specificity=65.0%] in men and were 0.331 [sensitivity=55.7%, specificity=70.7%] and 0.333 [sensitivity=53.2%, specificity=67.7%] in women respectively. Not only the optimal cutoff points of HOMA-IR and QUICKI were different for MetS and NAFLD, but also different cutoff points were obtained for men and women for each of these two conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Metabolic tumour burden assessed by {sup 18}F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Hua-Xiang; Chen, Tao; Wang, Wen-Quan; Wu, Chun-Tao; Liu, Chen; Long, Jiang; Xu, Jin; Liu, Liang; Yu, Xian-Jun [Fudan University, Shanghai Cancer Center, Pancreatic Cancer Institute and Department of Pancreatic and Hepatobiliary Surgery, Shanghai (China); Fudan University, Department of Oncology, Shanghai Medical College, Shanghai (China); Zhang, Ying-Jian [Fudan University, Shanghai Cancer Center, Department of Nuclear Medicine, Shanghai (China); Fudan University, Department of Oncology, Shanghai Medical College, Shanghai (China); Chen, Run-Hao [Fudan University, Department of General Surgery, Jinshan Hospital, Shanghai (China)

    2014-06-15

    Tumour burden is one of the most important prognosticators for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the predictive significance of metabolic tumour burden measured by {sup 18}F-FDG PET/CT in patients with resectable PDAC. Included in the study were 122 PDAC patients who received preoperative {sup 18}F-FDG PET/CT examination and radical pancreatectomy. Metabolic tumour burden in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), pathological tumour burden (tumour size), serum tumour burden (baseline serum CA19-9 level), and metabolic activity (maximum standard uptake value, SUVmax) were determined, and compared for their performance in predicting overall survival (OS) and recurrence-free survival (RFS). MTV and TLG were significantly associated with baseline serum CA19-9 level (P = 0.001 for MTV, P < 0.001 for TLG) and tumour size (P < 0.001 for MTV, P = 0.001 for TLG). Multivariate analysis showed that MTV, TLG and baseline serum CA19-9 level as either categorical or continuous variables, but not tumour size or SUVmax, were independent risk predictors for both OS and RFS. Time-dependent receiving operating characteristics analysis further indicated that better predictive performances for OS and RFS were achieved by MTV and TLG compared to baseline serum CA19-9 level, SUVmax and tumour size (P < 0.001 for all). MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC. (orig.)

  12. Metabolic tumour burden assessed by 18F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection

    International Nuclear Information System (INIS)

    Xu, Hua-Xiang; Chen, Tao; Wang, Wen-Quan; Wu, Chun-Tao; Liu, Chen; Long, Jiang; Xu, Jin; Liu, Liang; Yu, Xian-Jun; Zhang, Ying-Jian; Chen, Run-Hao

    2014-01-01

    Tumour burden is one of the most important prognosticators for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the predictive significance of metabolic tumour burden measured by 18 F-FDG PET/CT in patients with resectable PDAC. Included in the study were 122 PDAC patients who received preoperative 18 F-FDG PET/CT examination and radical pancreatectomy. Metabolic tumour burden in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), pathological tumour burden (tumour size), serum tumour burden (baseline serum CA19-9 level), and metabolic activity (maximum standard uptake value, SUVmax) were determined, and compared for their performance in predicting overall survival (OS) and recurrence-free survival (RFS). MTV and TLG were significantly associated with baseline serum CA19-9 level (P = 0.001 for MTV, P < 0.001 for TLG) and tumour size (P < 0.001 for MTV, P = 0.001 for TLG). Multivariate analysis showed that MTV, TLG and baseline serum CA19-9 level as either categorical or continuous variables, but not tumour size or SUVmax, were independent risk predictors for both OS and RFS. Time-dependent receiving operating characteristics analysis further indicated that better predictive performances for OS and RFS were achieved by MTV and TLG compared to baseline serum CA19-9 level, SUVmax and tumour size (P < 0.001 for all). MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC. (orig.)

  13. A trial of reduced carbohydrate diet to improve metabolic outcomes and decrease adiposity in obese peripubertal African American girls: does macronutrient profile matter?

    Science.gov (United States)

    Casazza, Krista; Cardel, Michelle; Dulin-Keita, Akilah; Hanks, Lynae J.; Gower, Barbara A.; Newton, Anna L.; Wallace, Stephenie

    2011-01-01

    Objectives Obesity prevalence among African American (AA) girls is higher than that of other groups. As typical calorie-restriction obesity treatment strategies have had limited success, alterations in macronutrient composition might effectively improve metabolic outcomes in this population and impact future body composition trajectories. The objective was to evaluate the efficacy of a moderately restricted carbohydrate (CHO) versus a standard CHO diet on weight/fat loss and metabolic parameters in overweight/obese AA girls aged 9–14 years. Methods A total of 26 AA girls (ranging from 92nd BMI percentile and above) were assigned to either a reduced- (SPEC: 42% calories from CHO, n=12) or a standard- (STAN: 55% of calories from CHO, n=14) CHO diet (protein held constant) for 16-weeks. All meals were provided and clinically tailored to meet the estimated energy requirements (REE × 1.2 in eucaloric phase and REE × 1.2 – 1000kcal in energy deficit phase). The first five-weeks encompassed a eucaloric phase evaluating metabolic changes in the absence of weight change. The subsequent 11-weeks were hypocaloric (1000kcal/d deficit) in effort to promote weight/fat loss. Meal tests were performed during the eucaloric phase for metabolic analyses. Dual-energy x-ray absorptiometry (DXA) was used to evaluate body composition. Results Both groups had reductions in weight/adiposity but the difference did not reach significance. The solid meal test indicated improved glucose/insulin homeostasis on the SPEC diet up to three hours post-ingestion. In addition, significantly lower triglycerides (pdiet. Conclusions Dietary CHO reduction favorably influences metabolic parameters but did not result in greater weight/fat loss relative to a standard diet in obese AA girls. Future research is needed to determine long-term effectiveness of a reduced CHO diet on glucose and insulin homeostasis and how it may apply to weight maintenance/fat loss during development alone and/or in

  14. Treatment of metabolic syndrome by combination of physical activity and diet needs an optimal protein intake: a randomized controlled trial.

    Science.gov (United States)

    Dutheil, Frédéric; Lac, Gérard; Courteix, Daniel; Doré, Eric; Chapier, Robert; Roszyk, Laurence; Sapin, Vincent; Lesourd, Bruno

    2012-09-17

    The recommended dietary allowance (RDA) for protein intake has been set at 1.0-1.3 g/kg/day for senior. To date, no consensus exists on the lower threshold intake (LTI = RDA/1.3) for the protein intake (PI) needed in senior patients ongoing both combined caloric restriction and physical activity treatment for metabolic syndrome. Considering that age, caloric restriction and exercise are three increasing factors of protein need, this study was dedicated to determine the minimal PI in this situation, through the determination of albuminemia that is the blood marker of protein homeostasis. Twenty eight subjects (19 M, 9 F, 61.8 ± 6.5 years, BMI 33.4 ± 4.1 kg/m²) with metabolic syndrome completed a three-week residential programme (Day 0 to Day 21) controlled for nutrition (energy balance of -500 kcal/day) and physical activity (3.5 hours/day). Patients were randomly assigned in two groups: Normal-PI (NPI: 1.0 g/kg/day) and High-PI (HPI: 1.2 g/kg/day). Then, patients returned home and were followed for six months. Albuminemia was measured at D0, D21, D90 and D180. At baseline, PI was spontaneously 1.0 g/kg/day for both groups. Albuminemia was 40.6 g/l for NPI and 40.8 g/l for HPI. A marginal protein under-nutrition appeared in NPI with a decreased albuminemia at D90 below 35 g/l (34.3 versus 41.5 g/l for HPI, p treatment based on restricted diet and exercise in senior people with metabolic syndrome, the lower threshold intake for protein must be set at 1.2 g/kg/day to maintain blood protein homeostasis.

  15. Improved body weight and metabolic outcomes in overweight or obese psychiatric patients switched to amisulpride from other atypical antipsychotics.

    Science.gov (United States)

    Lin, Chao-Cheng; Bai, Ya-Mei; Wang, Ying-Chieh; Chen, Tzu-Ting; Lai, I-Ching; Chen, Jen-Yeu; Chen, Shiow-Yi; Gau, Susan S F; Liou, Ying-Jay

    2009-12-01

    Switching to a different second-generation antipsychotic (SGA) with a lower risk of weight gain is recommended for overweight or obese psychiatric patients undergoing SGA treatment. However, there have been no complete reports regarding the long-term metabolic effects of switching to amisulpride. In this open-label 1-year study, we investigated the effects on body weight and other metabolic profiles when psychiatric patients treated with another SGA were switched to amisulpride treatment. Forty-six schizophrenia or schizoaffective inpatients with a body mass index greater than 27 kg/m were enrolled in the switch group. These patients were cross-titrated to amisulpride treatment and followed up for 1 year prospectively. Another 46 inpatients matched with the baseline body mass index of those in the switch group were enrolled as the control group retrospectively. The results showed that the switch group had greater weight loss than the control group (7.80 +/- 6.67 vs 2.60 +/- 6.23 kg, respectively; repeated-measure analysis of variance, P < 0.0005). During the treatment course, the amisulpride-treated patients showed significantly decreased fasting triglyceride, total cholesterol, glucose, and insulin resistance levels; decreased diastolic blood pressure and pulse rate; and a significant increase in high-density lipoprotein cholesterol levels after switching to amisulpride (all with a P < 0.05). The prevalence of metabolic syndrome in amisulpride-treated patients also decreased significantly from 65.2% to 30.4% (McNemar test, P < 0.0005). These findings suggest that switching to amisulpride could be an effective treatment of overweight or obese psychiatric patients treated previously with other SGAs.

  16. The efficiency of telemedicine to optimize metabolic control in patients with type 1 diabetes mellitus: Telemed study.

    Science.gov (United States)

    Esmatjes, Enric; Jansà, Margarida; Roca, Daria; Pérez-Ferre, Natalia; del Valle, Laura; Martínez-Hervás, Sergio; Ruiz de Adana, Marisol; Linares, Francisca; Batanero, Ricardo; Vázquez, Federico; Gomis, Ramon; de Solà-Morales, Oriol

    2014-07-01

    This study evaluated the impact of an Internet-based telematic system on the economic and clinical management of patients with type 1 diabetes mellitus. This 6-month prospective, randomized, comparative, open, multicenter study included patients with type 1 diabetes >18 years old treated with multiple insulin doses and with a glycated hemoglobin (HbA1c) level of >8%. We compared an intervention group (IG) (two face-to-face and five telematic appointments) with a control group (CG) (seven face-to-face appointments). The variables studied were (1) patient and healthcare team costs, (2) metabolic control, (3) knowledge of diabetes, (4) quality of life, and (5) self-care treatment adherence. Of the 154 patients included, 118 (76.6%) completed the study (IG, 54; CG, 64). The time used by the CG to follow the program was 823±645 min versus 353±222 min in the IG (Pknowledge and self-care treatment adherence. The use of interactive telematic appointments in subjects with type 1 diabetes and inadequate metabolic control is an efficient strategy, providing results comparable to those of face-to-face appointments in relation to improvement in glycemic control, knowledge acquisition, and self-care treatment adherence, with a significant reduction in the time used, especially by patients.

  17. Predicting optimal outcomes in cognitive therapy or interpersonal psychotherapy for depressed individuals using the personalized advantage index approach

    NARCIS (Netherlands)

    Huibers, M.J.H.; Cohen, Z.D.; Lemmens, L.H.J.M.; Arntz, A.; Peeters, F.P.M.L.; Cuijpers, P.; DeRubeis, R.J.

    2015-01-01

    Introduction: Although psychotherapies for depression produce equivalent outcomes, individual patients respond differently to different therapies. Predictors of outcome have been identified in the context of randomized trials, but this information has not been used to predict which treatment works

  18. Predicting optimal outcomes in cognitive therapy or interpersonal psychotherapy for depressed individuals using the personalized advantage index approach

    NARCIS (Netherlands)

    Huibers, M.J.H.; Cohen, Z.D.; Lemmens, L.H.J.M.; Arntz, A.; Peeters, F.P.M.L.; Cuijpers, P.; DeRubeis, R.J.

    2015-01-01

    Introduction Although psychotherapies for depression produce equivalent outcomes, individual patients respond differently to different therapies. Predictors of outcome have been identified in the context of randomized trials, but this information has not been used to predict which treatment works

  19. Hypoxia determines survival outcomes of bacterial infection through HIF-1α-dependent reprogramming of leukocyte metabolism

    OpenAIRE

    Thompson, A.A.R.; Dickinson, R.S.; Murphy, F.; Thomson, J.P.; Marriott, H.M.; Tavares, A.; Willson, J.; Williams, L.; Lewis, A.; Mirchandani, A.; Coelho, P.D.S.; Doherty, C.; Ryan, E.; Watts, E.; Morton, N.M.

    2017-01-01

    Hypoxia and bacterial infection frequently coexist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both Staphylococcus aureus and Streptococcus pneumoniae infections rapidly induced progressive neutrophil-mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning ...

  20. [Metabolic acidosis].

    Science.gov (United States)

    Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

    2016-01-01

    Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

  1. Exposure of clinical MRSA heterogeneous strains to β-lactams redirects metabolism to optimize energy production through the TCA cycle.

    Directory of Open Access Journals (Sweden)

    Mignon A Keaton

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA has emerged as one of the most important pathogens both in health care and community-onset infections. The prerequisite for methicillin resistance is mecA, which encodes a β-lactam-insensitive penicillin binding protein PBP2a. A characteristic of MRSA strains from hospital and community associated infections is their heterogeneous expression of resistance to β-lactam (HeR in which only a small portion (≤ 0.1% of the population expresses resistance to oxacillin (OXA ≥ 10 µg/ml, while in other isolates, most of the population expresses resistance to a high level (homotypic resistance, HoR. The mechanism associated with heterogeneous expression requires both increase expression of mecA and a mutational event that involved the triggering of a β-lactam-mediated SOS response and related lexA and recA genes. In the present study we investigated the cellular physiology of HeR-MRSA strains during the process of β-lactam-mediated HeR/HoR selection at sub-inhibitory concentrations by using a combinatorial approach of microarray analyses and global biochemical profiling employing gas chromatography/mass spectrometry (GC/MS and liquid chromatography/mass spectrometry (LC/MS to investigate changes in metabolic pathways and the metabolome associated with β-lactam-mediated HeR/HoR selection in clinically relevant heterogeneous MRSA. We found unique features present in the oxacillin-selected SA13011-HoR derivative when compared to the corresponding SA13011-HeR parental strain that included significant increases in tricarboxyl citric acid (TCA cycle intermediates and a concomitant decrease in fermentative pathways. Inactivation of the TCA cycle enzyme cis-aconitase gene in the SA13011-HeR strain abolished β-lactam-mediated HeR/HoR selection demonstrating the significance of altered TCA cycle activity during the HeR/HoR selection. These results provide evidence of both the metabolic cost and the

  2. Exposure of clinical MRSA heterogeneous strains to β-lactams redirects metabolism to optimize energy production through the TCA cycle.

    Science.gov (United States)

    Keaton, Mignon A; Rosato, Roberto R; Plata, Konrad B; Singh, Christopher R; Rosato, Adriana E

    2013-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the most important pathogens both in health care and community-onset infections. The prerequisite for methicillin resistance is mecA, which encodes a β-lactam-insensitive penicillin binding protein PBP2a. A characteristic of MRSA strains from hospital and community associated infections is their heterogeneous expression of resistance to β-lactam (HeR) in which only a small portion (≤ 0.1%) of the population expresses resistance to oxacillin (OXA) ≥ 10 µg/ml, while in other isolates, most of the population expresses resistance to a high level (homotypic resistance, HoR). The mechanism associated with heterogeneous expression requires both increase expression of mecA and a mutational event that involved the triggering of a β-lactam-mediated SOS response and related lexA and recA genes. In the present study we investigated the cellular physiology of HeR-MRSA strains during the process of β-lactam-mediated HeR/HoR selection at sub-inhibitory concentrations by using a combinatorial approach of microarray analyses and global biochemical profiling employing gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) to investigate changes in metabolic pathways and the metabolome associated with β-lactam-mediated HeR/HoR selection in clinically relevant heterogeneous MRSA. We found unique features present in the oxacillin-selected SA13011-HoR derivative when compared to the corresponding SA13011-HeR parental strain that included significant increases in tricarboxyl citric acid (TCA) cycle intermediates and a concomitant decrease in fermentative pathways. Inactivation of the TCA cycle enzyme cis-aconitase gene in the SA13011-HeR strain abolished β-lactam-mediated HeR/HoR selection demonstrating the significance of altered TCA cycle activity during the HeR/HoR selection. These results provide evidence of both the metabolic cost and the adaptation that He

  3. An optimized histochemical method to assess skeletal muscle glycogen and lipid stores reveals two metabolically distinct populations of type I muscle fibers

    DEFF Research Database (Denmark)

    Prats Gavalda, Clara; Gomez-Cabello, Alba; Nordby, Pernille

    2013-01-01

    Skeletal muscle energy metabolism has been a research focus of physiologists for more than a century. Yet, how the use of intramuscular carbohydrate and lipid energy stores are coordinated during different types of exercise remains a subject of debate. Controversy arises from contradicting data...... preservation of muscle energy stores, air drying cryosections or cycles of freezing-thawing need to be avoided. Furthermore, optimization of the imaging settings in order to specifically image intracellular lipid droplets stained with oil red O or Bodipy-493/503 is shown. When co-staining lipid droplets...... distinct myosin heavy chain I expressing fibers: I-1 fibers have a smaller crossectional area, a higher density of lipid droplets, and a tendency to lower glycogen content compared to I-2 fibers. Type I-2 fibers have similar lipid content than IIA. Exhaustive exercise lead to glycogen depletion in type IIA...

  4. Modeling metabolic networks in C. glutamicum: a comparison of rate laws in combination with various parameter optimization strategies

    Directory of Open Access Journals (Sweden)

    Oldiges Marco

    2009-01-01

    Full Text Available Abstract Background To understand the dynamic behavior of cellular systems, mathematical modeling is often necessary and comprises three steps: (1 experimental measurement of participating molecules, (2 assignment of rate laws to each reaction, and (3 parameter calibration with respect to the measurements. In each of these steps the modeler is confronted with a plethora of alternative approaches, e. g., the selection of approximative rate laws in step two as specific equations are often unknown, or the choice of an estimation procedure with its specific settings in step three. This overall process with its numerous choices and the mutual influence between them makes it hard to single out the best modeling approach for a given problem. Results We investigate the modeling process using multiple kinetic equations together with various parameter optimization methods for a well-characterized example network, the biosynthesis of valine and leucine in C. glutamicum. For this purpose, we derive seven dynamic models based on generalized mass action, Michaelis-Menten and convenience kinetics as well as the stochastic Langevin equation. In addition, we introduce two modeling approaches for feedback inhibition to the mass action kinetics. The parameters of each model are estimated using eight optimization strategies. To determine the most promising modeling approaches together with the best optimization algorithms, we carry out a two-step benchmark: (1 coarse-grained comparison of the algorithms on all models and (2 fine-grained tuning of the best optimization algorithms and models. To analyze the space of the best parameters found for each model, we apply clustering, variance, and correlation analysis. Conclusion A mixed model based on the convenience rate law and the Michaelis-Menten equation, in which all reactions are assumed to be reversible, is the most suitable deterministic modeling approach followed by a reversible generalized mass action kinetics

  5. Metabolic engineering of E. coli top 10 for production of vanillin through FA catabolic pathway and bioprocess optimization using RSM.

    Science.gov (United States)

    Chakraborty, Debkumar; Gupta, Gaganjot; Kaur, Baljinder

    2016-12-01

    Metabolic engineering and construction of recombinant Escherichia coli strains carrying feruloyl-CoA synthetase and enoyl-CoA hydratase genes for the bioconversion of ferulic acid to vanillin offers an alternative way to produce vanillin. Isolation and designing of fcs and ech genes was carried out using computer assisted protocol and the designed vanillin biosynthetic gene cassette was cloned in pCCIBAC expression vector for introduction in E. coli top 10. Recombinant strain was implemented for the statistical optimization of process parameters influencing F A to vanillin biotransformation. CCD matrix constituted of process variables like FA concentration, time, temperature and biomass with intracellular, extracellular and total vanillin productions as responses. Production was scaled up and 68 mg/L of vanillin was recovered from 10 mg/L of FA using cell extracts from 1 mg biomass within 30 min. Kinetic activity of enzymes were characterized. From LCMS-ESI analysis a metabolic pathway of FA degradation and vanillin production was predicted. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Metabolic engineering of Pediococcus acidilactici BD16 for production of vanillin through ferulic acid catabolic pathway and process optimization using response surface methodology.

    Science.gov (United States)

    Kaur, Baljinder; Chakraborty, Debkumar; Kumar, Balvir

    2014-10-01

    Occurrence of feruloyl-CoA synthetase (fcs) and enoyl-CoA hydratase (ech) genes responsible for the bioconversion of ferulic acid to vanillin have been reported and characterized from Amycolatopsis sp., Streptomyces sp., and Pseudomonas sp. Attempts have been made to express these genes in Escherichia coli DH5α, E. coli JM109, and Pseudomonas fluorescens. However, none of the lactic acid bacteria strain having GRAS status was previously proposed for heterologous expression of fcs and ech genes for production of vanillin through biotechnological process. Present study reports heterologous expression of vanillin synthetic gene cassette bearing fcs and ech genes in a dairy isolate Pediococcus acidilactici BD16. After metabolic engineering, statistical optimization of process parameters that influence ferulic acid to vanillin biotransformation in the recombinant strain was carried out using central composite design of response surface methodology. After scale-up of the process, 3.14 mM vanillin was recovered from 1.08 mM ferulic acid per milligram of recombinant cell biomass within 20 min of biotransformation. From LCMS-ESI spectral analysis, a metabolic pathway of phenolic biotransformations was predicted in the recombinant P. acidilactici BD16 (fcs (+)/ech (+)).

  7. Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism *

    OpenAIRE

    Thompson, A.A.R.; Dickinson, R.S.; Murphy, F.; Thomson, J. P.; Marriott, H.M.; Tavares, A.; Willson, J.; Williams, L.; Lewis, A.; Mirchandani, A.; Dos Santos Coelho, P.; Doherty, C.; Ryan, E.; Watts, E.; Morton, N. M.

    2017-01-01

    Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer...

  8. Determination of the optimal minimum radioiodine dose in patients with Graves' disease: a clinical outcome study

    Energy Technology Data Exchange (ETDEWEB)

    Howarth, D.; Tan, P.; Booker, J. [Pacific Medical Imaging, Newcastle, NSW (Australia); Epstein, M. [Dept. of Endocrinology, John Hunter Hospital, Newcastle, NSW (Australia); Lan, L. [High-Dependency Unit, St. George Hospital, Sydney, NSW (Australia)

    2001-10-01

    The study was performed under the auspices of the International Atomic Energy Commission, Vienna, Austria, with the aim of determining the optimal minimum therapeutic dose of iodine-131 for Graves' disease. The study was designed as a single-blinded randomised prospective outcome trial. Fifty-eight patients were enrolled, consisting of 50 females and 8 males aged from 17 to 75 years. Each patient was investigated by clinical assessment, biochemical and immunological assessment, thyroid ultrasound, technetium-99m thyroid scintigraphy and 24-h thyroid {sup 131}I uptake. Patients were then randomised into two treatment groups, one receiving 60 Gy and the other receiving 90 Gy thyroid tissue absorbed dose of radioiodine. The end-point markers were clinical and biochemical response to treatment. The median follow-up period was 37.5 months (range, 24-48 months). Among the 57 patients who completed final follow-up, a euthyroid state was achieved in 26 patients (46%), 27 patients (47%) were rendered hypothyroid and four patients (7%) remained hyperthyroid. Thirty-four patients (60%) remained hyperthyroid at 6 months after the initial radioiodine dose (median dose 126 MBq), and a total of 21 patients required additional radioiodine therapy (median total dose 640 MBq; range 370-1,485 MBq). At 6-month follow-up, of the 29 patients who received a thyroid tissue dose of 90 Gy, 17 (59%) remained hyperthyroid. By comparison, of the 28 patients who received a thyroid tissue dose of 60 Gy, 17 (61%) remained hyperthyroid. No significant difference in treatment response was found (P=0.881). At 6 months, five patients in the 90-Gy group were hypothyroid, compared to two patients in the 60-Gy group (P=0.246). Overall at 6 months, non-responders to low-dose therapy had a significantly larger thyroid gland mass (respective means: 35.9 ml vs 21.9 ml) and significantly higher levels of serum thyroglobulin (respective means: 597.6 {mu}g/l vs 96.9 {mu}g/l). Where low-dose radioiodine

  9. Outcomes of pulmonary valve replacement in 170 patients with chronic pulmonary regurgitation after relief of right ventricular outflow tract obstruction: implications for optimal timing of pulmonary valve replacement.

    Science.gov (United States)

    Lee, Cheul; Kim, Yang Min; Lee, Chang-Ha; Kwak, Jae Gun; Park, Chun Soo; Song, Jin Young; Shim, Woo-Sup; Choi, Eun Young; Lee, Sang Yun; Baek, Jae Suk

    2012-09-11

    The objectives of this study were to evaluate outcomes of pulmonary valve replacement (PVR) in patients with chronic pulmonary regurgitation (PR) and to better define the optimal timing of PVR. Although PVR is effective in reducing right ventricular (RV) volume overload in patients with chronic PR, the optimal timing of PVR is not well defined. A total of 170 patients who underwent PVR between January 1998 and March 2011 for chronic PR were retrospectively analyzed. To define the optimal timing of PVR, pre-operative and post-operative cardiac magnetic resonance imaging (MRI) data (n = 67) were analyzed. The median age at the time of PVR was 16.7 years. Follow-up completeness was 95%, and the median follow-up duration was 5.9 years. Overall and event-free survival at 10 years was 98% and 70%, respectively. Post-operative MRI showed significant reduction in RV volumes and significant improvement in biventricular function. Receiver-operating characteristic curve analysis revealed a cutoff value of 168 ml/m(2) for non-normalization of RV end-diastolic volume index (EDVI) and 80 ml/m(2) for RV end-systolic volume index (ESVI). Cutoff values for optimal outcome (normalized RV volumes and function) were 163 ml/m(2) for RV EDVI and 80 ml/m(2) for RV ESVI. Higher pre-operative RV ESVI was identified as a sole independent risk factor for suboptimal outcome. Midterm outcomes of PVR in patients with chronic PR were acceptable. PVR should be considered before RV EDVI exceeds 163 ml/m(2) or RV ESVI exceeds 80 ml/m(2), with more attention to RV ESVI. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Induced bioelectrochemical metabolism for bioremediation of petroleum refinery wastewater: Optimization of applied potential and flow of wastewater.

    Science.gov (United States)

    Mohanakrishna, Gunda; Al-Raoush, Riyadh I; Abu-Reesh, Ibrahim M

    2018-07-01

    Hybrid based bioelectrochemical system (BES) configured with embedded anode and cathode electrodes in soil was tested for the bioelectrochemical degradation of petroleum refinery wastewater (PRW). Four applied potentials were studied to optimize under batch mode operation, among which 2 V resulted in higher COD degradation (69.2%) and power density (725 mW/m 2 ) during 7 days of operation. Further studies with continuous mode of operation at optimized potential (2 V) showed that hydraulic retention time (HRT) of 19 h achieved the highest COD removal (37%) and highest power density (561 mW/m 2 ). BES function with respect to treatment efficiencies of other pollutants of PRW was also identified with respect to oil and grease (batch mode, 91%; continuous mode, 34%), total dissolved salts (batch mode, 53%; continuous mode, 24%) and sulfates (batch mode, 59%; continuous mode, 42%). Soil microenvironment in association with BES forms complex processes, providing suitable conditions for efficient treatment of PRW. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7–9 years of age

    Science.gov (United States)

    Rush, Elaine C; Plank, Lindsay D; Lu, Jun; Obolonkin, Victor; Coat, Suzette

    2018-01-01

    Objective To compare body composition and metabolic outcomes at 7–9 years in offspring of women with gestational diabetes (GDM) randomized to metformin (±insulin) or insulin treatment during pregnancy. Research design and methods Children were assessed at 7 years in Adelaide (n=109/181) and 9 years in Auckland (n=99/396) by anthropometry, bioimpedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI) (n=92/99) and fasting bloods (n=82/99). Results In the Adelaide subgroup, mothers were similar at enrollment. Women randomized to metformin versus insulin had higher treatment glycemia (p=0.002) and more infants with birth weight >90th percentile (20.7% vs 5.9%; p=0.029). At 7 years, there were no differences in offspring measures. In Auckland, at enrollment, women randomized to metformin had a higher body mass index (BMI) (p=0.08) but gained less weight during treatment (p=0.07). Offspring birth measures were similar. At 9 years, metformin offspring were larger by measures of weight, arm and waist circumferences, waist:height (p<0.05); BMI, triceps skinfold (p=0.05); DXA fat mass and lean mass (p=0.07); MRI abdominal fat volume (p=0.051). Body fat percent was similar between treatment groups by DXA and BIA. Abdominal fat percentages (visceral adipose tissue, subcutaneous adipose tissue and liver) were similar by MRI. Fasting glucose, triglyceride, insulin, insulin resistance, glycosylated hemoglobin (HbA1c), cholesterol, liver transaminases, leptin and adiponectin were similar. Conclusions Metformin or insulin for GDM was associated with similar offspring total and abdominal body fat percent and metabolic measures at 7–9 years. Metformin-exposed children were larger at 9 years. Metformin may interact with fetal environmental factors to influence offspring outcomes. PMID:29682291

  12. Optimal cutoff points for the detection of undiagnosed type 2 diabetes, hypertension and metabolic syndrome in Mexican adults.

    Science.gov (United States)

    Rojas-Martínez, Rosalba; Aguilar-Salinas, Carlos A; Jiménez-Corona, Aída

    2012-01-01

    To compare the waist circumference cutoff points established by the American Heart Association and the National Heart, Lung and Blood Institute (AHA/NHLBI) with those of the International Diabetes Federation (IDF) for the screening of diabetes, hypertension, and metabolic syndrome in Mexican adults. This study comprised a subsample of the ENSANUT 2006. Subjects without diabetes and hypertension and non-pregnant women were included. Sensitivity, specificity, and predictive values were compared using AUC and the positive likelihood ratio test [LR(+)]. In subjects aged ≥40 years, sensitivity for detection of diabetes and hypertension was higher for the IDF thresholds (85.34 and 86.87%, respectively) compared with those of the AHA/NHLBI (59.49 and 52.41%, respectively). LR(+) were higher for IDF thresholds compared with AHA/NHLBI. Similar results in subjects aged ≥65 years were observed. The measurement of abdominal obesity defined by the IDF was a better screening tool for diabetes and hypertension, considering that initially a high sensitivity and low cost tool at population level is required.

  13. Engineering metabolic pathways in Amycolatopsis japonicum for the optimization of the precursor supply for heterologous brasilicardin congeners production

    Directory of Open Access Journals (Sweden)

    Paul N. Schwarz

    2018-03-01

    Full Text Available The isoprenoid brasilicardin A is a promising immunosuppressant compound with a unique mode of action, high potency and reduced toxicity compared to today's standard drugs. However, production of brasilicardin has been hampered since the producer strain Nocardia terpenica IFM0406 synthesizes brasilicardin in only low amounts and is a biosafety level 2 organism. Previously, we were able to heterologously express the brasilicardin gene cluster in the nocardioform actinomycete Amycolatopsis japonicum. Four brasilicardin congeners, intermediates of the BraA biosynthesis, were produced. Since chemical synthesis of the brasilicardin core structure has remained elusive we intended to produce high amounts of the brasilicardin backbone for semi synthesis and derivatization. Therefore, we used a metabolic engineering approach to increase heterologous production of brasilicardin in A. japonicum. Simultaneous heterologous expression of genes encoding the MVA pathway and expression of diterpenoid specific prenyltransferases were used to increase the provision of the isoprenoid precursor isopentenyl diphosphate (IPP and to channel the precursor into the direction of diterpenoid biosynthesis. Both approaches contributed to an elevated heterologous production of the brasilicardin backbone, which can now be used as a starting point for semi synthesis of new brasilicardin congeners with better properties.

  14. Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride in optimal heart metabolism and function.

    Science.gov (United States)

    Khan, Raffay S; Lin, Yan; Hu, Yunying; Son, Ni-Huiping; Bharadwaj, Kalyani G; Palacios, Carla; Chokshi, Aalap; Ji, Ruiping; Yu, Shuiqing; Homma, Sunichi; Schulze, P Christian; Tian, Rong; Goldberg, Ira J

    2013-12-01

    Hearts utilize fatty acids as a primary source of energy. The sources of those lipids include free fatty acids and lipoprotein triglycerides. Deletion of the primary triglyceride-hydrolyzing enzyme lipoprotein lipase (LPL) leads to cardiac dysfunction. Whether heart LPL-knockout (hLPL0) mice are compromised due a deficiency in energetic substrates is unknown. To test whether alternative sources of energy will prevent cardiac dysfunction in hLPL0 mice, two different models were used to supply nonlipid energy. 1) hLPL0 mice were crossed with mice transgenically expressing GLUT1 in cardiomyocytes to increase glucose uptake into the heart; this cross-corrected cardiac dysfunction, reduced cardiac hypertrophy, and increased myocardial ATP. 2) Mice were randomly assigned to a sedentary or training group (swimming) at 3 mo of age, which leads to increased skeletal muscle production of lactate. hLPL0 mice had greater expression of the lactate transporter monocarboxylate transporter-1 (MCT-1) and increased cardiac lactate uptake. Compared with hearts from sedentary hLPL0 mice, hearts from trained hLPL0 mice had adaptive hypertrophy and improved cardiac function. We conclude that defective energy intake and not the reduced uptake of fat-soluble vitamins or cholesterol is responsible for cardiac dysfunction in hLPL0 mice. In addition, our studies suggest that adaptations in cardiac metabolism contribute to the beneficial effects of exercise on the myocardium of patients with heart failure.

  15. The metabolic syndrome: prevalence, CHD risk, and treatment.

    Science.gov (United States)

    Sarti, Cinzia; Gallagher, John

    2006-01-01

    An increased risk of coronary heart disease (CHD) morbidity and mortality is associated with the metabolic syndrome, a condition characterized by the concomitant presence of several abnormalities, including abdominal obesity, dyslipidemia, hypertension, insulin resistance (with or without glucose intolerance or diabetes), microalbuminuria, prothrombotic, and proinflammatory states. Estimates of the prevalence of the metabolic syndrome indicate that this condition is now common and likely to increase dramatically over the coming decades, in parallel with greater rates of obesity and Type 2 diabetes. Risk factors for the metabolic syndrome are already present in obese children and adolescents. Thus, identifying and treating all affected individuals promptly and optimally are critical to ensure that this potentially challenging healthcare burden is minimized. Here, we review the prevalence of the metabolic syndrome, dyslipidemias, and CHD risk. Although changes in lifestyle are fundamental to reducing many of the CHD risk factors associated with the metabolic syndrome, pharmacologic interventions also play an important role. Retrospective subanalyses of the effects of statins on coronary event rates and lipid levels in patients with the metabolic syndrome included in clinical trials indicate that these agents are beneficial in correcting the extensive lipid abnormalities that are frequently present in these individuals. However, the optimal management of metabolic syndrome dyslipidemia will depend on the outcomes of future prospective clinical trials. This review examines the underlying causes and prevalence of the metabolic syndrome and its impact on CHD morbidity and mortality and discusses the role of statins in optimizing its management.

  16. Metabolic and cardiovascular outcomes in patients with Cushing's syndrome of different aetiologies during active disease and 1 year after remission.

    Science.gov (United States)

    Giordano, Roberta; Picu, Andreea; Marinazzo, Elisa; D'Angelo, Valentina; Berardelli, Rita; Karamouzis, Ioannis; Forno, Daniela; Zinnà, Domenico; Maccario, Mauro; Ghigo, Ezio; Arvat, Emanuela

    2011-09-01

    Cushing's syndrome is associated with several comorbidities responsible for the increased cardiovascular risk, not only during the active phase but also after disease remission. In 29 patients with Cushing's syndrome (14 Cushing's diseases and 15 adrenal adenomas), waist circumference, fasting and 2-h glucose after oral glucose tolerance test (OGTT), lipid profile and blood pressure were evaluated during the active disease and 1 year after remission and compared with those in 29 sex-, age- and BMI-matched controls. During the active disease, waist circumference, 2-h glucose after OGTT, total and LDL cholesterol were higher in patients with Cushing's syndrome than in controls (P Cushing's disease and adrenal adenomas. The prevalence of impaired glucose tolerance (IGT), diabetes mellitus, dyslipidaemia and hypertension was higher (P Cushing's syndrome (27%, 24%, 59% and 72%) than in controls (10%, 0%, 21% and 10%), with no significant difference between Cushing's disease and adrenal adenomas. One year following hormonal remission, waist circumference persisted higher than in controls (P Cushing's disease and adrenal adenomas. Metabolic and cardiovascular abnormalities were still present in both groups, although with a lower prevalence, as well as with a more marked decrease in adrenal adenomas (P Cushing's disease after hormonal remission. Pituitary hormonal deficiencies, hormonal replacement treatments and/or incomplete cure from Cushing's disease may account for these findings. © 2011 Blackwell Publishing Ltd.

  17. Favorable cardio-metabolic outcomes following high carbohydrate intake in accordance with the Daniel Fast: A review of available findings

    Directory of Open Access Journals (Sweden)

    Richard Bloomer

    2017-03-01

    Full Text Available The Daniel Fast is a biblically inspired dietary program rich in carbohydrate, most closely resembling a vegan diet but with additional restrictions, including the elimination of processed foods, white flour products, preservatives, additives, sweeteners, caffeine, and alcohol. While no specific requirements are placed on the ingestion of specific percentages of macronutrients, the mean daily carbohydrate intake is by default approximately 60%, while protein and fat intake are 15% and 25%, respectively. Despite a relatively high carbohydrate intake, multiple favorable cardio-metabolic effects are noted when following the plan, in as few as three weeks. This includes improvements in HOMA-IR, which may be at least in part due to the lower glycemic load and high dietary fiber content of the foods consumed. Other notable changes include reductions in systemic inflammation, total and LDL-cholesterol, oxidative stress, blood pressure, and body weight/body fat. Short and moderate-term compliance to the program is excellent-better than most dietary programs, perhaps due to the ad libitum nature of this plan. This paper presents an overview of the Daniel Fast, a carbohydrate-rich dietary program, including relevant findings from both human and animal investigations using this dietary model.

  18. Aryl hydrocarbon receptor signaling modulates antiviral immune responses: ligand metabolism rather than chemical source is the stronger predictor of outcome.

    Science.gov (United States)

    Boule, Lisbeth A; Burke, Catherine G; Jin, Guang-Bi; Lawrence, B Paige

    2018-01-29

    The aryl hydrocarbon receptor (AHR) offers a compelling target to modulate the immune system. AHR agonists alter adaptive immune responses, but the consequences differ across studies. We report here the comparison of four agents representing different sources of AHR ligands in mice infected with influenza A virus (IAV): TCDD, prototype exogenous AHR agonist; PCB126, pollutant with documented human exposure; ITE, novel pharmaceutical; and FICZ, degradation product of tryptophan. All four compounds diminished virus-specific IgM levels and increased the proportion of regulatory T cells. TCDD, PCB126 and ITE, but not FICZ, reduced virus-specific IgG levels and CD8 + T cell responses. Similarly, ITE, PCB126, and TCDD reduced Th1 and Tfh cells, whereas FICZ increased their frequency. In Cyp1a1-deficient mice, all compounds, including FICZ, reduced the response to IAV. Conditional Ahr knockout mice revealed that all four compounds require AHR within hematopoietic cells. Thus, differences in the immune response to IAV likely reflect variances in quality, magnitude, and duration of AHR signaling. This indicates that binding affinity and metabolism may be stronger predictors of immune effects than a compound's source of origin, and that harnessing AHR will require finding a balance between dampening immune-mediated pathologies and maintaining sufficient host defenses against infection.

  19. Optimizing cutoff scores for the Barthel Index and the modified Rankin Scale for defining outcome in acute stroke trials

    NARCIS (Netherlands)

    Uyttenboogaart, Maarten; Stewart, Roy E; Vroomen, Patrick C A J; De Keyser, Jacques; Luijckx, Gert-Jan

    Background and Purpose - There is little agreement on how to assess outcome in acute stroke trials. Cutoff scores for the Barthel Index (BI) and modified Rankin Scale (mRS) are frequently arbitrarily chosen to dichotomize favorable and unfavorable outcome. We investigated sensitivity and specificity

  20. PRECIPITATING FACTORS, CLINICAL PROFILE AND METABOLIC ABNORMALITIES OF DIABETIC KETOACIDOSIS IN CHILDREN WITH TYPE 1 DIABETES AND THEIR ROLE IN PREDICTING THE OUTCOME

    Directory of Open Access Journals (Sweden)

    Madhava Vijaya Kumar

    2017-01-01

    Full Text Available BACKGROUND The aim of the study is to study the clinical profile of diabetic ketoacidosis in children with type 1 diabetes to identify the precipitating factors, to assess the metabolic alterations due to this illness and to correlate these parameters with the outcome. MATERIALS AND METHODS This was a prospective observational study and 33 children admitted in PICU during the study period were recruited for the study. RESULTS 24 children were newly-diagnosed cases and 9 children were already established cases of type 1 diabetes. Mean age group was 10.7 years. Major precipitating causes of DKA in established cases were intercurrent respiratory infections and omission of insulin. Nausea, vomiting, thirst and polyuria were the most common symptoms. Mean duration of symptoms before diagnosing DKA were 20 days in newly-diagnosed cases and 4 days in established cases. ¾ of children had dehydration at the time of admission. Severity was more in younger children. Commonest biochemical abnormality was hypokalaemia. Late diagnosis and delay in the initiation of treatment were the commonest predisposing factors for the development of cerebral oedema. CONCLUSION DKA is a life-threatening complication of type 1 diabetes and the red flag signs of bad outcome were young age, late diagnosis, late referral and late initiation of treatment. Hence, a high index of suspicion is necessary to diagnose DKA in first presentation of diabetes as well as in established cases.

  1. TallyHO obese female mice experience poor reproductive outcomes and abnormal blastocyst metabolism that is reversed by metformin.

    Science.gov (United States)

    Louden, Erica D; Luzzo, Kerri M; Jimenez, Patricia T; Chi, Tiffany; Chi, Maggie; Moley, Kelle H

    2014-12-01

    Obese women experience worse reproductive outcomes than normal weight women, specifically infertility, pregnancy loss, fetal malformations and developmental delay of offspring. The aim of the present study was to use a genetic mouse model of obesity to recapitulate the human reproductive phenotype and further examine potential mechanisms and therapies. New inbred, polygenic Type 2 diabetic TallyHO mice and age-matched control C57BL/6 mice were superovulated to obtain morula or blastocyst stage embryos that were cultured in human tubal fluid (HTF) medium. Deoxyglucose uptake was determined for individual insulin-stimulated blastocysts. Apoptosis was detected by confocal microscopy using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay and Topro-3 nuclear dye. Embryos were scored for TUNEL-positive as a percentage of total nuclei. AMP-activated protein kinase (AMPK) activation, tumour necrosis factor (TNF)-α expression and adiponectin expression were analysed by western immunoblot and confocal immunofluorescent microscopy. Lipid accumulation was assayed by BODIPY. Comparisons were made between TallyHO morulae cultured to blastocyst embryos in either HTF medium or HTF medium with 25 μg mL(-1) metformin. TallyHO mice developed whole body abnormal insulin tolerance, had decreased litter sizes and increased non-esterified fatty acid levels. Blastocysts from TallyHO mice exhibited increased apoptosis, decreased insulin sensitivity and decreased AMPK. A possible cause for the insulin resistance and abnormal AMPK phosphorylation was the increased TNF-α expression and lipid accumulation, as detected by BODIPY, in TallyHO blastocysts and decreased adiponectin. Culturing TallyHO morulae with the AMPK activator metformin led to a reversal of all the abnormal findings, including increased AMPK phosphorylation, improved insulin-stimulated glucose uptake and normalisation of lipid accumulation. Women with obesity and

  2. Validity and reliability of the Turkish version of the Optimality Index-US (OI-US) to assess maternity care outcomes.

    Science.gov (United States)

    Yucel, Cigdem; Taskin, Lale; Low, Lisa Kane

    2015-12-01

    Although obstetrical interventions are used commonly in Turkey, there is no standardized evidence-based assessment tool to evaluate maternity care outcomes. The Optimality Index-US (OI-US) is an evidence-based tool that was developed for the purpose of measuring aggregate perinatal care processes and outcomes against an optimal or best possible standard. This index has been validated and used in Netherlands, USA and UK until now. The objective of this study was to adapt the OI-US to assess maternity care outcomes in Turkey. Translation and back translation were used to develop the Optimality Index-Turkey (OI-TR) version. To evaluate the content validity of the OI-TR, an expert panel group (n=10) reviewed the items and evidence-based quality of the OI-TR for application in Turkey. Following the content validity process, the OI-TR was used to assess 150 healthy and 150 high-risk pregnant women who gave birth at a high volume, urban maternity hospital in Turkey. The scores between the two groups were compared to assess the discriminant validity of the OI-TR. The percentage of agreement between two raters and the Kappa statistic were calculated to evaluate the reliability. Content validity was established for the OI-TR by an expert group. Discriminant validity was confirmed by comparing the OI scores of healthy pregnant women (mean OI score=77.65%) and those of high-risk pregnant women (mean OI score=78.60%). The percentage of agreement between the two raters was 96.19, and inter-rater agreement was provided for each item in the OI-TR. OI-TR is a valid and reliable tool that can be used to assess maternity care outcomes in Turkey. The results of this study indicate that although the risk statuses of the women differed, the type of care they received was essentially the same, as measured by the OI-TR. Care was not individualised based on risk and for a majority of items was inconsistent with evidence based practice, which is not optimal. Use of the OI-TR will help to

  3. The Association between Symptoms of Dry Eye Syndrome and Metabolic Outcome in a General Population in Korea.

    Science.gov (United States)

    Park, Hye Won; Park, Jong Woon

    2016-07-01

    Dry eye syndrome (DES) is recognized as a public health concern. One of the pathophysiologies in the development of DES is inflammation, and metabolic syndrome (MetS), which is highly prevalent in the general population, is a well-known chronic and systemic inflammatory condition. Despite the increasing interest regarding a relationship between DES and MetS, information is lacking on the association between DES and MetS and its individual components. We investigated the association between DES symptoms and MetS and its components among adults aged ≥ 19 years using population-based data from the Korea National Health and Nutrition Examination Survey V. A sample group of 15,294 adults (42.67% men and 57.33% women) completed household interviews in which they provided blood (for high-density lipoprotein cholesterol, triglyceride, and glucose) and anthropometric measurements (including waist circumference, weight, and height) to define MetS. We also collected information regarding sociodemographic and behavioral risk factors. The survey results showed that 11.50% of men and 22.35% of women experienced DES and 5.30% of patients had both DES and diagnosis of MetS, including 204 men and 606 women. Thus, no significant difference was observed between DES and the diagnosis of MetS according to sex (P = 0.4008 in men; P = 0.0804 in women); however, a significant association was observed between DES and hypertriglyceridemia in women (OR, 1.13; 95% CI, 1.01-1.29). Therefore, hypertriglyceridemia might be an important factor in the association between DES and MetS. Further longitudinal research is needed to evaluate this relationship.

  4. Optimism as predictor of patient-reported outcomes in patients with an implantable cardioverter defibrillator (data from the WEBCARE study)

    DEFF Research Database (Denmark)

    Habibović, M; Broers, E; Heumen, D

    2018-01-01

    OBJECTIVE: The implantable cardioverter defibrillator (ICD) is the treatment of choice for prevention of sudden cardiac death. However, a subgroup of ICD patients experiences psychological adjustment problems post implant. To date, positive psychological constructs (e.g. optimism) have been...... understudied in this population. Hence, we examined the association between optimism and anxiety, depression, and health status at 12-months post implant. METHODS: Patients (N=171) enrolled in the WEB-based distress management study for ICD patients were included in the analyses. Optimism and pessimism (LOT......), and Type D personality (DS14) were administered at baseline, while anxiety (GAD-7), depression (PHQ-9), and health status (SF-12) were assessed at 12-months. RESULTS: The mean age was 59.6±10.06 with 81% being male. After controlling for demographic, personality, and clinical variables, baseline optimism...

  5. Technology Education Using a Novel Approach in e-Learning-Towards Optimizing the Quality of Learning Outcomes

    Science.gov (United States)

    Malkawi, M. I.; Hawarey, M. M.

    2012-04-01

    Ever since the advent of the new era in presenting taught material in Electronic Form, international bodies, academic institutions, public sectors, as well as specialized entities in the private sector, globally, have all persevered to exploit the power of Distance Learning and e-Learning to disseminate the knowledge in Science and Art using the ubiquitous World Wide Web and its supporting Internet and Internetworking. Many Science & Education-sponsoring bodies, like UNESCO, the European Community, and the World Bank have been keen at funding multinational Distance Learning projects, many of which were directed at an educated audience in certain technical areas. Many countries around the Middle East have found a number of interested European partners to launch funding requests, and were generally successful in their solicitation efforts for the needed funds from these funding bodies. Albeit their intricacies in generating a wealth of knowledge in electronic form, many of the e-Learning schemas developed thus far, have only pursued their goals in the most conventional of ways; In essence, there had been little innovation introduced to gain anything, if any, above traditional classroom lecturing, other than, of course, the gained advantage of the simultaneous online testing and evaluation of the learned material by the examinees. In a sincere effort to change the way in which people look at the merits of e-Learning, and seek the most out of it, we shall propose a novel approach aimed at optimizing the learning outcomes of presented materials. In this paper we propose what shall henceforth be called as Iterative e-Learning. In Iterative e-Learning, as the name implies, a student uses some form of electronic media to access course material in a specific subject. At the end of each phase (Section, Chapter, Session, etc.) on a specific topic, the student is assessed online of how much he/she would have achieved before he/she would move on. If the student fails, due to

  6. IVF outcome is optimized when embryos are replaced between 5 and 15 mm from the fundal endometrial surface: a prospective analysis on 1184 IVF cycles

    Science.gov (United States)

    2013-01-01

    Background Some data suggest that the results of human in vitro fertilization (IVF) may be affected by the site of the uterine cavity where embryos are released. It is not yet clear if there is an optimal range of embryo-fundus distance (EFD) within which embryos should be transferred to optimize IVF outcome. Methods The present study included 1184 patients undergoing a blind, clinical-touch ET of 1–2 fresh embryos loaded in a soft catheter with a low amount of culture medium. We measured the EFD using transvaginal US performed immediately after ET, with the aim to assess (a) if EFD affects pregnancy and implantation rates, and (b) if an optimal EFD range can be identified. Results Despite comparable patients’ clinical characteristics, embryo morphological quality, and endometrial thickness, an EFD between 5 and 15 mm allowed to obtain significantly higher pregnancy and implantation rates than an EFD above 15 mm. The abortion rate was much higher (although not significantly) when EFD was below 5 mm than when it was between 5 and 15 mm. Combined together, these results produced an overall higher ongoing pregnancy rate in the group of patients whose embryos were released between 5 and 15 mm from the fundal endometrial surface. Conclusions The site at which embryos are released affects IVF outcome and an optimal EFD range exists; this observations suggest that US-guided ET could be advantageous vs. clinical-touch ET, as it allows to be more accurate in releasing embryos within the optimal EFD range. PMID:24341917

  7. An organizing framework for informal caregiver interventions: detailing caregiving activities and caregiver and care recipient outcomes to optimize evaluation efforts

    OpenAIRE

    Van Houtven, Courtney Harold; Voils, Corrine I; Weinberger, Morris

    2011-01-01

    Abstract Background Caregiver interventions may help improve the quality of informal care. Yet the lack of a systematic framework specifying the targets and outcomes of caregiver interventions hampers our ability to understand what has been studied, to evaluate existing programs, and to inform the design of future programs. Our goal was to develop an organizing framework detailing the components of the caregiving activities and the caregiver and care recipient outcomes that should be affected...

  8. Metabolic Surgery

    DEFF Research Database (Denmark)

    Pareek, Manan; Schauer, Philip R; Kaplan, Lee M

    2018-01-01

    The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown...... the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity....... Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further...

  9. Sex Effect on Obesity Indices and Metabolic Outcomes in Patients with Obese Obstructive Sleep Apnea and Type 2 Diabetes After Laparoscopic Roux-en-Y Gastric Bypass Surgery: a Preliminary Study.

    Science.gov (United States)

    Xu, Huajun; Zhang, Pin; Han, Xiaodong; Yu, Haoyong; Di, Jianzhong; Zou, Jianyin; Wang, Yuyu; Qian, Yingjun; Tu, Yinfang; Bao, Yuqian; Yi, Hongliang; Guan, Jian; Yin, Shankai; Jia, Weiping

    2016-11-01

    Roux-en-Y gastric bypass (RYGB) surgery is an effective therapy for obstructive sleep apnea (OSA). However, little attention has been paid to the treatment goals systematically stratified by sex. The objective of this study was to assess how sex differences affect obesity indices and metabolic outcomes after RYGB surgery. A sleep questionnaire was conducted and medical histories were taken. Full-night polysomnography (PSG), anthropometric variables, and blood samples were collected. Thirty-five consecutive patients with OSA who underwent laparoscopic RYGB surgery were prospectively examined for at least 6 months were included in the study. Significant improvements (p obesity indices, and metabolic outcomes [except low-density lipoprotein in men and high-density lipoprotein (HDL) in women] were obtained in men and women with OSA. Men had higher baseline triglyceride (TG) (p women. However, only TG in men improved more than in women (p = 0.02). Sleep parameters, obesity indices, and metabolic outcomes after RYGB surgery were of similar magnitude in women and men with OSA. Alleviating sleep and obesity problems was correlated with metabolic outcomes in men and women.

  10. Transcriptional and metabolic insights into the differential physiological responses of arabidopsis to optimal and supraoptimal atmospheric CO2.

    Directory of Open Access Journals (Sweden)

    Fatma Kaplan

    Full Text Available BACKGROUND: In tightly closed human habitats such as space stations, locations near volcano vents and closed culture vessels, atmospheric CO(2 concentration may be 10 to 20 times greater than Earth's current ambient levels. It is known that super-elevated (SE CO(2 (>1,200 µmol mol(-1 induces physiological responses different from that of moderately elevated CO(2 (up to 1,200 µmol mol(-1, but little is known about the molecular responses of plants to supra-optimal [CO(2]. METHODOLOGY/PRINCIPAL FINDINGS: To understand the underlying molecular causes for differential physiological responses, metabolite and transcript profiles were analyzed in aerial tissue of Arabidopsis plants, which were grown under ambient atmospheric CO(2 (400 µmol mol(-1, elevated CO(2 (1,200 µmol mol(-1 and SE CO(2 (4,000 µmol mol(-1, at two developmental stages early and late vegetative stage. Transcript and metabolite profiling revealed very different responses to elevated versus SE [CO(2]. The transcript profiles of SE CO(2 treated plants were closer to that of the control. Development stage had a clear effect on plant molecular response to elevated and SE [CO(2]. Photosynthetic acclimation in terms of down-regulation of photosynthetic gene expression was observed in response to elevated [CO(2], but not that of SE [CO(2] providing the first molecular evidence that there appears to be a fundamental disparity in the way plants respond to elevated and SE [CO(2]. Although starch accumulation was induced by both elevated and SE [CO(2], the increase was less at the late vegetative stage and accompanied by higher soluble sugar content suggesting an increased starch breakdown to meet sink strength resulting from the rapid growth demand. Furthermore, many of the elevated and SE CO(2-responsive genes found in the present study are also regulated by plant hormone and stress. CONCLUSIONS/SIGNIFICANCE: This study provides new insights into plant acclimation to elevated and SE [CO

  11. Outcome of focused pre-Ramadan education on metabolic and glycaemic parameters in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    El Toony, Lobna F; Hamad, Dina Ali; Omar, Omar Mohammed

    2018-04-25

    Ramadan fasting is associated with the risk of acute complications including hypoglycaemia. Therefore, patients' education before Ramadan and follow up during Ramadan is essential for safe fasting. To evaluate the effect of pre-Ramadan education program on biochemical parameters and the risk of hypoglycaemia in patients with type 2 diabetes mellitus. A prospective interventional controlled design was carried out on 320 Muslim patients with type 2 diabetes. They were divided into 2 groups; the control group (n = 200) who received standard diabetic care and the intervention group (n = 120) who received focused individualized diabetic education sessions before Ramadan. The study was carried out on 3 phases (before, during and after Ramadan). Post-education change of hypoglycaemia risk and biochemical parameters during Ramadan fasting were the primary outcomes. Fasting blood glucose decreased significantly during, and after Ramadan in both groups (P patients in the intervention group vs. 19.5% in the control group. Post Ramadan reduction of HbA1c patients before Ramadan to 55.8% after Ramadan). Low-density lipoprotein cholesterol decreased in the intervention group (P = 0.024). The body weight of the patients did not significantly change in both groups. There was a significant impact of pre-Ramadan educational program on reduction of hypoglycaemic risk and other acute complications, reduction of low-density lipoprotein cholesterol and improvement of high-density lipoprotein cholesterol. Therefore, it is recommended for the fasting patients especially those with high and very high risk during Ramadan. Copyright © 2018. Published by Elsevier Ltd.

  12. Impact of the level of metabolic control on the non-surgical periodontal therapy outcomes in diabetes mellitus type 2 patients: Clinical effects

    Directory of Open Access Journals (Sweden)

    Mirnić Jelena

    2013-01-01

    Full Text Available Introduction. Diabetes mellitus as a complex metabolic disease influences functioning of numerous organs. Chronic periodontitis is one of frequent diabetic complications. Objective. The aim of this study was to compare the clinical effects of non­surgical periodontal therapy between diabetes mellitus type 2 patients (DM type 2 and non­diabetic individuals (control group. Methods. Our study included 41 DM type 2 subjects and 21 non­diabetic individuals, all of them with chronic periodontitis. The diabetic group was divided into two subgroups based on the level of glycosylated hemoglobin (HbA1c as follows: D1 - 18 subjects with good metabolic control (HbA1c<7%, and D2 - 23 subjects with poor metabolic (HbA1c≥7%. State of oral hygiene and periodontal clinical parameters of subjects, such as: plaque index (PI, gingival index (GI, papilla bleeding index (PBI, probing pocket depth (PPD and clinical attachment level (CAL, were evaluated at the baseline and 3 months after scaling and root­planning. Results. ANOVA test showed that there was no statistically significant difference of treatment success between studied groups in relation to GI (p=0.52, PBI (p=0.36 and CAL (p=0.11. Reduction of PI and PPD in the control group (ΔPI=0.84; ΔPPD=0.35 mm was significantly higher (p<0.05 than the reduction of PI and PPD in patients with the diabetes (group D1 ΔPI=0.60, ΔPPD=0.11 mm; group D2 ΔPI=0.53, ΔPPD=0.11 mm. Conclusion. Although there were differences in treatment success between DM subjects and non­diabetic individuals, they were not significant for the most measured parameters. The results of this study did not absolutely support the assumption that the level of glycemic control significantly affected the periodontal therapy outcome in diabetics. [Projekat Ministarstva nauke Republike Srbije, br. 175075

  13. An organizing framework for informal caregiver interventions: detailing caregiving activities and caregiver and care recipient outcomes to optimize evaluation efforts

    Directory of Open Access Journals (Sweden)

    Van Houtven Courtney

    2011-11-01

    Full Text Available Abstract Background Caregiver interventions may help improve the quality of informal care. Yet the lack of a systematic framework specifying the targets and outcomes of caregiver interventions hampers our ability to understand what has been studied, to evaluate existing programs, and to inform the design of future programs. Our goal was to develop an organizing framework detailing the components of the caregiving activities and the caregiver and care recipient outcomes that should be affected by an intervention. In so doing, we characterize what has been measured in the published literature to date and what should be measured in future studies to enable comparisons across interventions and across time. Methods Our data set comprises 121 reports of caregiver interventions conducted in the United States and published between 2000 and 2009. We extracted information on variables that have been examined as primary and secondary outcomes. These variables were grouped into categories, which then informed the organizing framework. We calculated the frequency with which the interventions examined each framework component to identify areas about which we have the most knowledge and under-studied areas that deserve attention in future research. Results The framework stipulates that caregiver interventions seek to change caregiving activities, which in turn affect caregiver and care recipient outcomes. The most frequently assessed variables have been caregiver psychological outcomes (especially depression and burden and care recipient physical and health care use outcomes. Conclusions Based on the organizing framework, we make three key recommendations to guide interventions and inform research and policy. First, all intervention studies should assess quality and/or quantity of caregiving activities to help understand to what extent and how well the intervention worked. Second, intervention studies should assess a broad range of caregiver and care recipient

  14. Sex differences, endogenous sex-hormone hormones, sex-hormone binding globulin, and exogenous disruptors in diabetes and related metabolic outcomes.

    Science.gov (United States)

    Liu, Simin; Sun, Qi

    2016-12-19

    In assessing clinical and pathophysiological development of type 2 diabetes (T2D), the critical role of the sex steroids axis is underappreciated, particularly concerning the sex-specific relationships with many relevant cardiometabolic outcomes. In this issue of the Journal of Diabetes, we provide a comprehensive overview of these significant associations of germline variants in the genes governing the sex steroid pathways, plasma levels of steroid hormones, and sex hormone-binding globulin (SHBG) with T2D risk that have been observed in many clinical and high-quality large prospective cohorts of men and women across ethnic populations. Together, this body of evidence indicates that sex steroids and SHBG should be routinely incorporated into clinical characterization of T2D patients, particularly in screening prediabetic patients, such as those with metabolic syndrome, using plasma levels of SHBG. Given that several germline mutations in the SHBG gene have also been directly related to both plasma concentrations of SHBG and clinical manifestation of T2D, targeting signals in the sex steroid axis, particularly SHBG, may have significant utility in the prediction and treatment of T2D. Further, many of the environmental endocrine disrupting chemicals may exert their potential adverse effects on cardiometabolic outcomes via either estrogenic or androgenic signaling pathways, highlighting the importance of using the sex steroids and SHBG as important biochemical markers in both clinical and population studies in studying sex-specific mechanisms in the pathogenesis of T2D and its complications, as well as the need to equitably allocate resources in studying both men and women. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  15. Computational fluid dynamics simulation of an industrial P. chrysogenum fermentation with a coupled 9-pool metabolic model : Towards rational scale-down and design optimization

    NARCIS (Netherlands)

    Haringa, C.; Tang, W.; Wang, G.; Deshmukh, A.T.; van Winden, Wouter A.; Chu, Ju; van Gulik, W.M.; Heijnen, J.J.; Mudde, R.F.; Noorman, H.J.

    2018-01-01

    We assess the effect of substrate heterogeneity on the metabolic response of P. chrysogenum in industrial bioreactors via the coupling of a 9-pool metabolic model with Euler-Lagrange CFD simulations. In this work, we outline how this coupled hydrodynamic-metabolic modeling can be utilized in 5

  16. Challenged by cognition : toward optimal measurement and greater understanding of youth cognition in school refusal and cognitive behavioural therapy outcome

    NARCIS (Netherlands)

    Maric, Marija

    2010-01-01

    The main purpose of this dissertation was to highlight and address seven challenges related to the measurement of youth cognition, understanding the role of cognitive constructs in anxiety and school refusal, and the examination of cognitive mediators of cognitive-behavioural treatment outcomes. The

  17. Timing of Surgery and Rehabilitation to Optimize Outcome for Patients with Multiple Ligament Knee Injuries: A Multicenter Clinical Trial

    Science.gov (United States)

    2016-10-01

    contracture. Suboptimal outcomes for treatment of MLKIs include persistent pain , stiffness, residual instability and laxity, loss of motion and...a complete grade III injury of 2 or more ligaments) without a history of prior knee ligament reconstruction that do not have associated poly -trauma

  18. Effect of cerebral blood flow on consciousness and outcome after head injury. Assessment by jugular bulb venous metabolism and IMP-SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Imaizumi, Shigeki; Onuma, Takehide; Motohashi, Osamu; Kameyama, Motonobu; Ishii, Kiyoshi [Sendai City Hospital (Japan)

    2002-10-01

    This study was performed to elucidate the therapeutical value of arteriojugularvenous oxygen difference (AVDO{sub 2}) in the ultra-emergent period after head injury. Rational therapeutic strategy after severe head injury needs information concerning the dynamical change of cerebral blood flow (CBF) and metabolism. We monitored the cerebral venous metabolism within 6 hours after head injury until the day IMP-SPECT was performed. Whole brain cerebral blood flow detected by IMP-SPECT and AVDO{sub 2} at the same day was compared, which restored to the period within 6 hours after head injury. From this procedure, we could outline cerebral blood flow conditions by only AVDO{sub 2} without IMP-SPECT in the ultra-emergent period. Eighty-six patients with head injury who were carried to our emergency center in the period of recent 2 years aged ranging from 15 to 94 years were the subjects. They all performed jugular bulb cannulation within 6 hours after the accident (Martin's phase I: day 0) to know saturation of jugular vein (SjO{sub 2}), AVDO{sub 2} and AVL. They were monitored until the day IMP-SPECT was performed (Martin's phase II; day 1-3 or phase III; day 4-15). The correlation between CBF and AVDO{sub 2}. The effect of CBF and cerebral venous metabolism on consciousness and outcome was also analyzed. CBF and AVDO{sub 2} in phase II and III were reversely correlated (p<0.0001). Normal CBF corresponded with 5.0 vol% in AVDO{sub 2}. AVDO{sub 2} in all cases changed 6.2 vol% at phase I, 4.5 vol% at phase II and 5.1 vol% at phase III. Glasgow comascale (GCS) on admission under 8 (n=47) and over 9 (n=39) significantly differed in AVDO{sub 2} and CBF in the period of II and III. The patients with favorable consciousness showed low AVDO{sub 2} and hyperemia afterwards. Dead cases in phase I (n=19) showed high AVDO{sub 2} and low SjO{sub 2}. The patients with severe disability (SD) (n=13) showed high AVDO{sub 2} and low CBF and the patients with good recovery (GR

  19. Enhanced recovery pathways optimize health outcomes and resource utilization: A meta-analysis of randomized controlled trials in colorectal surgery

    DEFF Research Database (Denmark)

    Adamina, Michel; Kehlet, Henrik; Tomlinson, George A

    2011-01-01

    in costs that threatens the stability of health care systems. Enhanced recovery pathways (ERP) have been proposed as a means to reduce morbidity and improve effectiveness of care. We have reviewed the evidence supporting the implementation of ERP in clinical practice. Methods Medline, Embase...... of health care processes. Thus, while accelerating recovery and safely reducing hospital stay, ERPs optimize utilization of health care resources. ERPs can and should be routinely used in care after colorectal and other major gastrointestinal procedures....

  20. A Responsive Parenting Intervention: The Optimal Timing Across Early Childhood For Impacting Maternal Behaviors And Child Outcomes

    OpenAIRE

    Landry, Susan H.; Smith, Karen E.; Swank, Paul R.; Guttentag, Cathy

    2008-01-01

    This study examined the optimal timing (infancy, toddler–preschool, or both) for facilitating responsive parenting and the intervention effects on maternal behaviors and child social and communication skills for children who vary in biological risk. The intervention during infancy, Playing and Learning Strategies (PALS I), showed strong changes in maternal affective–emotional and cognitively responsive behaviors and infants’ development. However, it was hypothesized that a 2nd intervention do...

  1. Optimal medical outcomes with limited liability: risk management principles for medical practices at the intersection of medicine, law, and business.

    Science.gov (United States)

    Paterick, Timothy J; Paterick, Timothy E; Waterhouse, Blake E

    2007-01-01

    Physicians practice at the intersection of medicine, law, and business. Each discipline creates its own challenges for the practicing physician: to practice efficient, effective medicine; to limit potential liability; and to create a positive financial outcome. Those challenges increase with escalating costs and reduced reimbursements. In this paper, the common clinical presentation of chest pain has been used to create a paradigm to educate physicians to understand efficient and effective approaches to diagnosis and treatment, and how effective communication with patients and meticulous documentation of all medical encounters can limit the potential for liability. Ultimately, given today's reimbursement formulas, physicians must also understand the cost of testing, in relation to its benefits, in an attempt to yield a positive financial outcome.

  2. Predicting outcomes to optimize disease management in inflammatory bowel disease in Japan: their differences and similarities to Western countries.

    Science.gov (United States)

    Kobayashi, Taku; Hisamatsu, Tadakazu; Suzuki, Yasuo; Ogata, Haruhiko; Andoh, Akira; Araki, Toshimitsu; Hokari, Ryota; Iijima, Hideki; Ikeuchi, Hiroki; Ishiguro, Yoh; Kato, Shingo; Kunisaki, Reiko; Matsumoto, Takayuki; Motoya, Satoshi; Nagahori, Masakazu; Nakamura, Shiro; Nakase, Hiroshi; Tsujikawa, Tomoyuki; Sasaki, Makoto; Yokoyama, Kaoru; Yoshimura, Naoki; Watanabe, Kenji; Katafuchi, Miiko; Watanabe, Mamoru; Hibi, Toshifumi

    2018-04-01

    Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

  3. Outcome based state budget allocation for diabetes prevention programs using multi-criteria optimization with robust weights.

    Science.gov (United States)

    Mehrotra, Sanjay; Kim, Kibaek

    2011-12-01

    We consider the problem of outcomes based budget allocations to chronic disease prevention programs across the United States (US) to achieve greater geographical healthcare equity. We use Diabetes Prevention and Control Programs (DPCP) by the Center for Disease Control and Prevention (CDC) as an example. We present a multi-criteria robust weighted sum model for such multi-criteria decision making in a group decision setting. The principal component analysis and an inverse linear programming techniques are presented and used to study the actual 2009 budget allocation by CDC. Our results show that the CDC budget allocation process for the DPCPs is not likely model based. In our empirical study, the relative weights for different prevalence and comorbidity factors and the corresponding budgets obtained under different weight regions are discussed. Parametric analysis suggests that money should be allocated to states to promote diabetes education and to increase patient-healthcare provider interactions to reduce disparity across the US.

  4. Development of a Blended Learning Environment to Support Achievement of Graduate Outcomes through Optimal Learning in an Undergraduate Pharmacy Course

    Directory of Open Access Journals (Sweden)

    Alyson Brown

    2013-10-01

    Full Text Available The development of graduate attributes through health professional courses requires the opportunity to engage with learning and teaching activities that reflect the work-based role to which the student aspires. Such activities allow the contextualisation of discipline-specific knowledge, forging a critical understanding of the underpinning theory, and providing a firm foundation for the development of lifelong learning skills. A blended learning approach can be particularly valuable in supporting achievement of the learning outcomes in modules where performance is measured in terms of competency in work-based scenarios. An action research approach was taken to develop and evaluate a cardiovascular risk assessment as the basis for clinically and professionally relevant problem-based learning. Support for this was provided by means of blended learning including a number of online activities. Talking wall focus groups were used to evaluate the student experience, and this was combined with quantitative data regarding student examination performance. Student performance in the cardiovascular section of the examination paper was significantly higher than in other sections. Students reported very favorably on the use of this approach to support not only examination preparation, but also in terms of developing professional identity and enhancing employability skills.

  5. Mathematical modelling of metabolism

    DEFF Research Database (Denmark)

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

    Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology....... available. Both stoichiometric and kinetic models have been used to investigate the metabolism, which has resulted in defining the optimal fermentation conditions, as well as in directing the genetic changes to be introduced in order to obtain a good producer strain or cell line. With the increasing...

  6. Sub-optimal adherence to doxycycline and treatment outcomes among men with non-gonococcal urethritis: a prospective cohort study

    Science.gov (United States)

    Khosropour, Christine M.; Manhart, Lisa E.; Colombara, Danny V.; Gillespie, Catherine W.; Lowens, M. Sylvan; Totten, Patricia A.; Golden, Matthew R.; Simoni, Jane

    2014-01-01

    Objective Doxycycline, one of two recommended therapies for non-gonococcal urethritis (NGU), consists of a seven-day course of therapy (100mg BID). Since suboptimal adherence may contribute to poor treatment outcomes, we examined the association between self-reported imperfect adherence to doxycycline and clinical and microbiologic failure among men with NGU. Methods Men aged ≥16 years with NGU attending a Seattle, WA sexually transmitted diseases clinic were enrolled in a double-blind, parallel-group superiority trial from January 2007 to July 2011. Men were randomized to active doxycycline/placebo azithromycin or placebo doxycycline/active azithromycin. Imperfect adherence was defined as missing ≥1 dose in 7 days. Urine was tested for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and Ureaplasma urealyticum-biovar2 (UU-2) using nucleic acid amplification tests. Clinical failure (symptoms and ≥5 PMNs/HPF or discharge) and microbiologic failure (positive tests for CT, MG, and/or UU-2) were determined after 3-weeks. Results 184 men with NGU were randomized to active doxycycline and provided data on adherence. Baseline prevalence of CT, MG, and UU-2 was 26%, 13%, and 27%, respectively. 28% of men reported imperfect adherence and this was associated with microbiologic failure among men with CT (aRR=9.33; 95% CI=1.00–89.2) and UU-2 (aRR=3.08; 95% CI=1.31–7.26) but not MG. Imperfect adherence was not significantly associated with clinical failure overall or for any specific pathogens, but it was more common among imperfectly adherent men with CT (aRR=2.63; 0.93–7.41, p=0.07). Conclusions Adherence may be important for microbiologic cure of select pathogens. Factors other than adherence should be considered for CT-negative men with persistent NGU. PMID:24106340

  7. Dispositional Optimism

    Science.gov (United States)

    Carver, Charles S.; Scheier, Michael F.

    2014-01-01

    Optimism is a cognitive construct (expectancies regarding future outcomes) that also relates to motivation: optimistic people exert effort, whereas pessimistic people disengage from effort. Study of optimism began largely in health contexts, finding positive associations between optimism and markers of better psychological and physical health. Physical health effects likely occur through differences in both health-promoting behaviors and physiological concomitants of coping. Recently, the scientific study of optimism has extended to the realm of social relations: new evidence indicates that optimists have better social connections, partly because they work harder at them. In this review, we examine the myriad ways this trait can benefit an individual, and our current understanding of the biological basis of optimism. PMID:24630971

  8. Optimal healthcare delivery to care homes in the UK: a realist evaluation of what supports effective working to improve healthcare outcomes.

    Science.gov (United States)

    Gordon, Adam L; Goodman, Claire; Davies, Sue L; Dening, Tom; Gage, Heather; Meyer, Julienne; Schneider, Justine; Bell, Brian; Jordan, Jake; Martin, Finbarr C; Iliffe, Steve; Bowman, Clive; Gladman, John R F; Victor, Christina; Mayrhofer, Andrea; Handley, Melanie; Zubair, Maria

    2018-01-05

    care home residents have high healthcare needs not fully met by prevailing healthcare models. This study explored how healthcare configuration influences resource use. a realist evaluation using qualitative and quantitative data from case studies of three UK health and social care economies selected for differing patterns of healthcare delivery to care homes. Four homes per area (12 in total) were recruited. A total of 239 residents were followed for 12 months to record resource-use. Overall, 181 participants completed 116 interviews and 13 focus groups including residents, relatives, care home staff, community nurses, allied health professionals and General Practitioners. context-mechanism-outcome configurations were identified explaining what supported effective working between healthcare services and care home staff: (i) investment in care home-specific work that legitimises and values work with care homes; (ii) relational working which over time builds trust between practitioners; (iii) care which 'wraps around' care homes; and (iv) access to specialist care for older people with dementia. Resource use was similar between sites despite differing approaches to healthcare. There was greater utilisation of GP resource where this was specifically commissioned but no difference in costs between sites. activities generating opportunities and an interest in healthcare and care home staff working together are integral to optimal healthcare provision in care homes. Outcomes are likely to be better where: focus and activities legitimise ongoing contact between healthcare staff and care homes at an institutional level; link with a wider system of healthcare; and provide access to dementia-specific expertise. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Geriatrics Society.

  9. Connective tissue metabolism in patients with unclassified polyarthritis and early rheumatoid arthritis. Relationship to disease activity, bone mineral density, and radiographic outcome

    DEFF Research Database (Denmark)

    Jensen, Trine; Klarlund, Mette; Hansen, Michael

    2004-01-01

    tissue metabolism were measured in 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least 4 weeks and less than 2 years. At 2 years, 51 patients fulfilled the American College Rheumatology criteria for rheumatoid arthritis...

  10. Metabolic Engineering VII Conference

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  11. Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes

    Directory of Open Access Journals (Sweden)

    Kones R

    2013-10-01

    would be cardioprotective. When LDL cholesterol is aggressively lowered to targets, low HDL cholesterol levels are still inversely related to MCVE. The efflux capacity, or ability to relocate cholesterol out of macrophages, is believed to be a major antiatherogenic mechanism responsible for reduction in MCVE mediated in part by healthy HDL. HDL cholesterol is a complex molecule with antioxidative, anti-inflammatory, antithrombotic, antiplatelet, and vasodilatory properties, among which is protection of LDL from oxidation. HDL-associated paraoxonase-1 has a major effect on endothelial function. Further, HDL promotes endothelial repair and progenitor cell health, and supports production of nitric oxide. HDL from patients with cardiovascular disease, diabetes, and autoimmune disease may fail to protect or even become proinflammatory or pro-oxidant. Mendelian randomization and other clinical studies in which raising HDL cholesterol has not been beneficial suggest that high plasma levels do not necessarily reduce cardiovascular risk. These data, coupled with extensive preclinical information about the functional heterogeneity of HDL, challenge the “HDL hypothesis”, ie, raising HDL cholesterol per se will reduce MCVE. After the equivocal AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes study and withdrawal of two major cholesteryl ester transfer protein compounds, one for off-target adverse effects and the other for lack of efficacy, development continues for two other agents, ie, anacetrapib and evacetrapib, both of which lower LDL cholesterol substantially. The negative but controversial HPS2-THRIVE (the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events trial casts further doubt on the HDL cholesterol hypothesis. The growing impression that HDL functionality, rather than abundance, is clinically important is supported by experimental evidence highlighting

  12. Mycobacterium tuberculosis Metabolism

    Science.gov (United States)

    Warner, Digby F.

    2015-01-01

    Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host–pathogen interaction through modulation of metabolic functions. PMID:25502746

  13. DHA supplementation during pregnancy does not reduce BMI or body fat mass in children: follow-up of the DHA to Optimize Mother Infant Outcome randomized controlled trial.

    Science.gov (United States)

    Muhlhausler, Beverly S; Yelland, Lisa N; McDermott, Robyn; Tapsell, Linda; McPhee, Andrew; Gibson, Robert A; Makrides, Maria

    2016-06-01

    The omega-3 (n-3) long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) has proven effective at reducing fat storage in animal studies. However, a systematic review of human trials showed a lack of quality data to support or refute this hypothesis. We sought to determine whether maternal DHA supplementation during the second half of pregnancy results in a lower body mass index (BMI) and percentage of body fat in children. We conducted a follow-up at 3 and 5 y of age of children who were born to mothers enrolled in the DOMInO (DHA to Optimize Mother Infant Outcome) double-blind, randomized controlled trial, in which women with a singleton pregnancy were provided with DHA-rich fish-oil capsules (800 mg DHA/d) or vegetable-oil capsules (control group) in the second half of pregnancy. Primary outcomes were the BMI z score and percentage of body fat at 3 and 5 y of age. Potential interactions between prenatal DHA and the peroxisome proliferator-activated receptor-γ (PPARγ) genotype as a measure of the genetic predisposition to obesity were investigated. A total of 1614 children were eligible for the follow-up. Parent or caregiver consent was obtained for 1531 children (95%), and these children were included in the analysis. BMI z scores and percentages of body fat of children in the DHA group did not differ from those of children in the control group at either 3 y of age [BMI z score adjusted mean difference: 0.03 (95% CI: -0.07, 0.13; P = 0.61); percentage of body fat adjusted mean difference: -0.26 (95% CI: -0.99, 0.46; P = 0.47)] or 5 y of age [BMI z score adjusted mean difference: 0.02 (95% CI: -0.08, 0.12; P = 0.66); percentage of body fat adjusted mean difference: 0.11 (95% CI: -0.60, 0.82; P = 0.75)]. No treatment effects were modified by the PPARγ genotype of the child. Independent of a genetic predisposition to obesity, maternal intake of DHA-rich fish oil during the second half of pregnancy does not affect the growth or body composition

  14. Using optimal combination of teaching-learning methods (open book assignment and group tutorials) as revision exercises to improve learning outcome in low achievers in biochemistry.

    Science.gov (United States)

    Rajappa, Medha; Bobby, Zachariah; Nandeesha, H; Suryapriya, R; Ragul, Anithasri; Yuvaraj, B; Revathy, G; Priyadarssini, M

    2016-07-08

    Graduate medical students of India are taught Biochemistry by didactic lectures and they hardly get any opportunity to clarify their doubts and reinforce the concepts which they learn in these lectures. We used a combination of teaching-learning (T-L) methods (open book assignment followed by group tutorials) to study their efficacy in improving the learning outcome. About 143 graduate medical students were classified into low (75%: group 3, n = 46) achievers, based on their internal assessment marks. After the regular teaching module on the topics "Vitamins and Enzymology", all the students attempted an open book assignment without peer consultation. Then all the students participated in group tutorials. The effects on the groups were evaluated by pre and posttests at the end of each phase, with the same set of MCQs. Gain from group tutorials and overall gain was significantly higher in the low achievers, compared to other groups. High and medium achievers obtained more gain from open book assignment, than group tutorials. The overall gain was significantly higher than the gain obtained from open book assignment or group tutorials, in all three groups. All the three groups retained the gain even after 1 week of the exercise. Hence, optimal use of novel T-L methods (open book assignment followed by group tutorials) as revision exercises help in strengthening concepts in Biochemistry in this oft neglected group of low achievers in graduate medical education. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):321-325, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

  15. Single-gene testing combined with single nucleotide polymorphism microarray preimplantation genetic diagnosis for aneuploidy: a novel approach in optimizing pregnancy outcome.

    Science.gov (United States)

    Brezina, Paul R; Benner, Andrew; Rechitsky, Svetlana; Kuliev, Anver; Pomerantseva, Ekaterina; Pauling, Dana; Kearns, William G

    2011-04-01

    To describe a method of amplifying DNA from blastocyst trophectoderm cells (two or three cells) and simultaneously performing 23-chromosome single nucleotide polymorphism microarrays and single-gene preimplantation genetic diagnosis. Case report. IVF clinic and preimplantation genetic diagnostic centers. A 36-year-old woman, gravida 2, para 1011, and her husband who both were carriers of GM(1) gangliosidosis. The couple wished to proceed with microarray analysis for aneuploidy detection coupled with DNA sequencing for GM(1) gangliosidosis. An IVF cycle was performed. Ten blastocyst-stage embryos underwent trophectoderm biopsy. Twenty-three-chromosome microarray analysis for aneuploidy and specific DNA sequencing for GM(1) gangliosidosis mutations were performed. Viable pregnancy. After testing, elective single embryo transfer was performed followed by an intrauterine pregnancy with documented fetal cardiac activity by ultrasound. Twenty-three-chromosome microarray analysis for aneuploidy detection and single-gene evaluation via specific DNA sequencing and linkage analysis are used for preimplantation diagnosis for single-gene disorders and aneuploidy. Because of the minimal amount of genetic material obtained from the day 3 to 5 embryos (up to 6 pg), these modalities have been used in isolation of each other. The use of preimplantation genetic diagnosis for aneuploidy coupled with testing for single-gene disorders via trophectoderm biopsy is a novel approach to maximize pregnancy outcomes. Although further investigation is warranted, preimplantation genetic diagnosis for aneuploidy and single-gene testing seem destined to be used increasingly to optimize ultimate pregnancy success. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Obesity and metabolic syndrome in COPD: Is exercise the answer?

    Science.gov (United States)

    James, Benjamin D; Jones, Amy V; Trethewey, Ruth E; Evans, Rachael A

    2018-05-01

    Approximately half of all patients with chronic obstructive pulmonary disease (COPD) attending pulmonary rehabilitation (PR) programmes are overweight or obese which negatively impacts upon dyspnoea and exercise tolerance particularly when walking. Within the obese population (without COPD), the observed heterogeneity in prognosis is in part explained by the variability in the risk of developing cardiovascular disease or diabetes (cardiometabolic risk) leading to the description of metabolic syndrome. In obesity alone, high-intensity aerobic training can support healthy weight loss and improve the constituent components of metabolic syndrome. Those with COPD, obesity and/or metabolic syndrome undergoing PR appear to do as well in traditional outcomes as their normal-weight metabolically healthy peers in terms of improvement of symptoms, health-related quality of life and exercise performance, and should therefore not be excluded. To broaden the benefit of PR, for this complex population, we should learn from the extensive literature examining the effects of exercise in obesity and metabolic syndrome discussed in this review and optimize the exercise strategy to improve these co-morbid conditions. Standard PR outcomes could be expanded to include cardiometabolic risk reduction to lower future morbidity and mortality; to this end exercise may well be the answer.

  17. Natural selection and optimality

    International Nuclear Information System (INIS)

    Torres, J.L.

    1989-01-01

    It is assumed that Darwin's principle translates into optimal regimes of operation along metabolical pathways in an ecological system. Fitness is then defined in terms of the distance of a given individual's thermodynamic parameters from their optimal values. The method is illustrated testing maximum power as a criterion of merit satisfied in ATP synthesis. (author). 26 refs, 2 figs

  18. Metabolic syndrome X as a clinical outcome of hormonal changes on the liquidators of the Chernobyl accident consequences (the problem analysis)

    International Nuclear Information System (INIS)

    Kovalenko, A.N.

    1999-01-01

    An analysis of hormonal changes in the liquidators of the Chernobyl accident consequences, which promote the metabolic syndrome X development, was carried out on the base of clinical and experimental data. The system insulin-glucose, the mechanisms of insulinresistance and gyperinslinemia forming, the pathogenetical role of hyperinsulinemia interaction with others hormomes, some aspects of hormone - receptor interaction, an interconnection of hyperinsulinemia and vascular pathology, peculiarities of radiobiological stress as a non-classic adaptive reaction, which frequently resulting with a pathology, were discussed in the article

  19. Diabetes Destiny in our Hands: Achieving Metabolic Karma.

    Science.gov (United States)

    Kalra, Sanjay; Ved, Jignesh; Baruah, Manash P

    2017-01-01

    Karma is the ancient Indian philosophy of cause and effect, which implies that an individual's intentions, and actions, both have consequences. None can escape the consequences of one's actions. Applying the principle of karma to medicine and healthcare, the significance of optimal and timely interventions at various stages of disease, may be realized. A holistic approach to metabolic control in diabetes translates into improved clinical outcomes, as evident from the result of STENO-2, EMPA-REG OUTCOME, or LEADER trials. The principle of karma in the management of diabetes may have implications at the transgenerational level during pregnancy and nursing, at the individual patient-level based on phenotype, and at the community level in preventive medicine. The concept of metabolic karma can be used as an effective motivational tool to encourage better health care seeking behavior and adherence to prescribed interventions.

  20. Diabetes destiny in our hands: Achieving metabolic karma

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2017-01-01

    Full Text Available Karma is the ancient Indian philosophy of cause and effect, which implies that an individual's intentions, and actions, both have consequences. None can escape the consequences of one's actions. Applying the principle of karma to medicine and healthcare, the significance of optimal and timely interventions at various stages of disease, may be realized. A holistic approach to metabolic control in diabetes translates into improved clinical outcomes, as evident from the result of STENO-2, EMPA-REG OUTCOME, or LEADER trials. The principle of karma in the management of diabetes may have implications at the transgenerational level during pregnancy and nursing, at the individual patient-level based on phenotype, and at the community level in preventive medicine. The concept of metabolic karma can be used as an effective motivational tool to encourage better health care seeking behavior and adherence to prescribed interventions.

  1. Three-year follow-up comparing metabolic surgery versus medical weight management in patients with type 2 diabetes and BMI 30-35. The role of sRAGE biomarker as predictor of satisfactory outcomes.

    Science.gov (United States)

    Horwitz, Daniel; Saunders, John K; Ude-Welcome, Aku; Marie Schmidt, Ann; Dunn, Van; Leon Pachter, H; Parikh, Manish

    2016-08-01

    Patients with type 2 diabetes (T2D) and body mass index (BMI)<35 may benefit from metabolic surgery. The soluble form of the receptor for advanced glycation end products (sRAGE) may identify patients at greater chance for T2D remission. To study long-term outcomes of patients with T2D and BMI 30-35 treated with metabolic surgery or medical weight management (MWM) and search for predictors of T2D remission. University METHODS: Retrospective review of the original cohort, including patients who crossed over from MWM to surgery. Repeated-measures linear models were used to model weight loss (%WL), change in glycated hemoglobin (HbA1C) and association with baseline sRAGE. Fifty-seven patients with T2D and BMI 30-35 were originally randomly assigned to metabolic surgery versus MWM. Mean BMI and HbA1C was 32.6% and 7.8%, respectively. A total of 30 patients underwent surgery (19 sleeves, 8 bypasses, 3 bands). Three-year follow-up in the surgery group and MWM group was 75% and 86%, respectively. Surgery resulted in higher T2D remission (63% versus 0%; P<.001) and lower HbA1C (6.9% versus 8.4%; P<.001) for up to 3 years. There was no difference in %WL in those with versus those without T2D remission (21.7% versus 20.6%, P = .771), suggesting that additional mechanisms other than %WL play an important role for the studied outcome. Higher baseline sRAGE was associated with greater change in HbA1C and greater %WL after surgery (P< .001). Metabolic surgery was effective in promoting remission of T2D in 63% of patients with BMI 30-35; higher baseline sRAGE predicted T2D remission with surgery. Larger-scale randomly assigned trials are needed in this patient population. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  2. Effects of fish oil on lipid profile and other metabolic outcomes in HIV-infected patients on antiretroviral therapy: a randomized placebo-controlled trial.

    Science.gov (United States)

    Oliveira, Julicristie M; Rondó, Patrícia H C; Yudkin, John S; Souza, José M P; Pereira, Tatiane N; Catalani, Andrea W; Picone, Camila M; Segurado, Aluisio A C

    2014-02-01

    Although antiretroviral therapy has revolutionized the care of HIV-infected patients, it has been associated with metabolic abnormalities. Hence, this study was planned to investigate the effects of fish oil on lipid profile, insulin resistance, and body fat distribution in HIV-infected Brazilian patients on antiretroviral therapy, considering that marine omega-3 fatty acids seem to improve features of the metabolic syndrome. We conducted a randomized, parallel, placebo-controlled trial that assessed the effects of 3 g fish oil/day (540 mg of eicosapentaenoic acid plus 360 mg of docosahexaenoic acid) or 3 g soy oil/day (placebo) on 83 HIV-infected Brazilian men and non-pregnant women on antiretroviral therapy. No statistically significant relationships between fish oil supplementation and longitudinal changes in triglyceride (p = 0.335), low-density lipoprotein cholesterol (p = 0.078), high-density lipoprotein cholesterol (p = 0.383), total cholesterol (p = 0.072), apolipoprotein B (p = 0.522), apolipoprotein A1 (p = 0.420), low-density lipoprotein cholesterol/apolipoprotein B ratio (p = 0.107), homeostasis model assessment for insulin resistance index (p = 0.387), body mass index (p = 0.068), waist circumference (p = 0.128), and waist/hip ratio (p = 0.359) were observed. A low dose of fish oil did not alter lipid profile, insulin resistance, and body fat distribution in HIV-infected patients on antiretroviral therapy.

  3. Optimal cut-off of homeostasis model assessment of insulin resistance (HOMA-IR) for the diagnosis of metabolic syndrome: third national surveillance of risk factors of non-communicable diseases in Iran (SuRFNCD-2007).

    Science.gov (United States)

    Esteghamati, Alireza; Ashraf, Haleh; Khalilzadeh, Omid; Zandieh, Ali; Nakhjavani, Manouchehr; Rashidi, Armin; Haghazali, Mehrdad; Asgari, Fereshteh

    2010-04-07

    We have recently determined the optimal cut-off of the homeostatic model assessment of insulin resistance for the diagnosis of insulin resistance (IR) and metabolic syndrome (MetS) in non-diabetic residents of Tehran, the capital of Iran. The aim of the present study is to establish the optimal cut-off at the national level in the Iranian population with and without diabetes. Data of the third National Surveillance of Risk Factors of Non-Communicable Diseases, available for 3,071 adult Iranian individuals aging 25-64 years were analyzed. MetS was defined according to the Adult Treatment Panel III (ATPIII) and International Diabetes Federation (IDF) criteria. HOMA-IR cut-offs from the 50th to the 95th percentile were calculated and sensitivity, specificity, and positive likelihood ratio for MetS diagnosis were determined. The receiver operating characteristic (ROC) curves of HOMA-IR for MetS diagnosis were depicted, and the optimal cut-offs were determined by two different methods: Youden index, and the shortest distance from the top left corner of the curve. The area under the curve (AUC) (95%CI) was 0.650 (0.631-0.670) for IDF-defined MetS and 0.683 (0.664-0.703) with the ATPIII definition. The optimal HOMA-IR cut-off for the diagnosis of IDF- and ATPIII-defined MetS in non-diabetic individuals was 1.775 (sensitivity: 57.3%, specificity: 65.3%, with ATPIII; sensitivity: 55.9%, specificity: 64.7%, with IDF). The optimal cut-offs in diabetic individuals were 3.875 (sensitivity: 49.7%, specificity: 69.6%) and 4.325 (sensitivity: 45.4%, specificity: 69.0%) for ATPIII- and IDF-defined MetS, respectively. We determined the optimal HOMA-IR cut-off points for the diagnosis of MetS in the Iranian population with and without diabetes.

  4. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  5. Lifestyle changes and prevention of metabolic syndrome in the Heart of New Ulm Project

    Directory of Open Access Journals (Sweden)

    Jeffrey J. VanWormer

    2017-06-01

    Full Text Available Prior research has shown that unhealthy lifestyles increase the risk for developing a number of chronic diseases, but there are few studies examining how lifestyle changes impact metabolic syndrome. This study analyzed the association between two-year changes in key lifestyle risk metrics and incident metabolic syndrome in adults. A retrospective cohort study was conducted using data from metabolic syndrome free adults in the Heart of New Ulm Project (New Ulm, MN. The outcome was incident metabolic syndrome observed two years after baseline in 2009. The primary predictor was change in optimal lifestyle score based on four behavioral risk factors, including smoking, alcohol use, fruit/vegetable consumption, and physical activity. In the analytical sample of 1059 adults, 12% developed metabolic syndrome by 2011. Multivariable regression models (adjusted for baseline lifestyle score, age, sex, education, cardiovascular disease, and diabetes revealed that a two-year decrease in optimal lifestyle score was associated with significantly greater odds of incident metabolic syndrome (OR = 2.92; 95% CI: 1.69, 5.04; p < 0.001. This association was primarily driven by changes in obesity, fruit/vegetable consumption, and alcohol intake. As compared to improving poor lifestyle habits, maintaining a healthy lifestyle seemed to be most helpful in avoiding metabolic syndrome over the two-year study timeframe.

  6. Correlating tumor metabolic progression index measured by serial FDG PET-CT, apparent diffusion coefficient measured by magnetic resonance imaging (MRI) and blood genomics to patient’s outcome in advanced colorectal cancer: the CORIOLAN study

    International Nuclear Information System (INIS)

    Deleporte, Amelie; Charette, Nicolas; Machiels, Godelieve; Piccart, Martine; Flamen, Patrick; Hendlisz, Alain; Paesmans, Marianne; Garcia, Camilo; Vandeputte, Caroline; Lemort, Marc; Engelholm, Jean-Luc; Hoerner, Frederic; Aftimos, Philippe; Awada, Ahmad

    2014-01-01

    Metastatic colorectal cancer (mCRC) may present various behaviours that define different courses of tumor evolution. There is presently no available tool designed to assess tumor aggressiveness, despite the fact that this is considered to have a major impact on patient outcome. CORIOLAN is a single-arm prospective interventional non-therapeutic study aiming mainly to assess the natural tumor metabolic progression index (TMPI) measured by serial FDG PET-CT without any intercurrent antitumor therapy as a prognostic factor for overall survival (OS) in patients with mCRC. Secondary objectives of the study aim to test the TMPI as a prognostic marker for progression-free survival (PFS), to assess the prognostic value of baseline tumor FDG uptake on PFS and OS, to compare TMPI to classical clinico-biological assessment of prognosis, and to test the prognostic value on OS and PFS of MRI-based apparent diffusion coefficient (ADC) and variation of vADC using voxel-based diffusion maps. Additionally, this study intends to identify genomic and epigenetic factors that correlate with progression of tumors and the OS of patients with mCRC. Consequently, this analysis will provide information about the signaling pathways that determine the natural and therapy-free course of the disease. Finally, it would be of great interest to investigate whether in a population of patients with mCRC, for which at present no known effective therapy is available, tumor aggressiveness is related to elevated levels of circulating tumor cells (CTCs) and to patient outcome. Tumor aggressiveness is one of the major determinants of patient outcome in advanced disease. Despite its importance, supported by findings reported in the literature of extreme outcomes for patients with mCRC treated with chemotherapy, no objective tool allows clinicians to base treatment decisions on this factor. The CORIOLAN study will characterize TMPI using FDG-PET-based metabolic imaging of patients with chemorefractory m

  7. The favorable effects of garlic intake on metabolic profiles, hs-CRP, biomarkers of oxidative stress and pregnancy outcomes in pregnant women at risk for pre-eclampsia: randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Aalami-Harandi, Rezvan; Karamali, Maryam; Asemi, Zatollah

    2015-01-01

    This study was performed to determine the favorable effects of garlic on metabolic status and pregnancy outcomes among pregnant women at risk for pre-eclampsia. This randomized, double-blind, placebo-controlled trial was conducted among 44 pregnant women, primigravida, aged 18-40 years old at 27 weeks' gestation with positive roll-over test. Participants were randomly assigned to receive either one garlic tablet (equal to 400 mg garlic and 1 mg allicin) (n = 22) or placebo (n = 22) once daily for 9 weeks. Fasting blood samples were taken at baseline and after 9 weeks' intervention to measure metabolic profiles and biomarkers of oxidative stress. Administration of garlic compared with the placebo resulted in decreased levels of serum high sensitivity C-reactive protein (hs-CRP) (-1425.90 versus 1360.50 ng/mL, p = 0.01) and increased plasma glutathione (GSH) (+98.10 versus. -49.87 µmol/l, p = 0.03). A trend toward a significant effect of garlic intake on reducing fasting plasma glucose (FPG) (p = 0.07), insulin (p = 0.09) and increasing quantitative insulin sensitivity check (QUICKI) (p = 0.05) was also observed. Consumption of garlic for 9 weeks among pregnant women at risk for pre-eclampsia led to decreased hs-CRP and increased GSH, but did not affect lipid profiles, total antioxidant capacity (TAC) and pregnancy outcomes.

  8. Perspectives on the Nutritional Management of Metabolic Syndrome in Asia: People, Practice and Programmes

    Directory of Open Access Journals (Sweden)

    Phing Chee Huei

    2017-03-01

    Full Text Available Numerous Asian countries have a high prevalence of metabolic syndrome, also associated with cardiovascular disease and diabetes mellitus. Healthcare expenditure varies among Asian countries, and is influenced by poverty factor and large populations. The effect of metabolic syndrome on nutritional management in Asia demonstrates the essential for clinicians to equalize the needs for higher standards of dietetics practice; as they execute optimal care processes with the aim of improving outcomes, alongside setting of workforce limitations, inadequate expertise in metabolic syndrome nutrition practice, as well as ethnic diversity among Asians. This paper presents some aspects of dietetics practice and the possibility that an alteration in practice is mandatory if dietitians are to play an active role in preventing or decelerating the evolution of the metabolic syndrome.

  9. Inulin-type fructan degradation capacity of Clostridium cluster IV and XIVa butyrate-producing colon bacteria and their associated metabolic outcomes.

    Science.gov (United States)

    Moens, F; De Vuyst, L

    2017-05-30

    Four selected butyrate-producing colon bacterial strains belonging to Clostridium cluster IV (Butyricicoccus pullicaecorum DSM 23266 T and Faecalibacterium prausnitzii DSM 17677 T ) and XIVa (Eubacterium hallii DSM 17630 and Eubacterium rectale CIP 105953 T ) were studied as to their capacity to degrade inulin-type fructans and concomitant metabolite production. Cultivation of these strains was performed in bottles and fermentors containing a modified medium for colon bacteria, including acetate, supplemented with either fructose, oligofructose, or inulin as the sole energy source. Inulin-type fructan degradation was not a general characteristic among these strains. B. pullicaecorum DSM 23266 T and E. hallii DSM 17630 could only ferment fructose and did not degrade oligofructose or inulin. E. rectale CIP 105953 T and F. prausnitzii DSM 17677 T fermented fructose and could degrade both oligofructose and inulin. All chain length fractions of oligofructose were degraded simultaneously (both strains) and both long and short chain length fractions of inulin were degraded either simultaneously (E. rectale CIP 105953 T ) or consecutively (F. prausnitzii DSM 17677 T ), indicating an extracellular polymer degradation mechanism. B. pullicaecorum DSM 23266 T and E. hallii DSM 17630 produced high concentrations of butyrate, CO 2 , and H 2 from fructose. E. rectale CIP 105953 T produced lactate, butyrate, CO 2 , and H 2 , from fructose, oligofructose, and inulin, whereas F. prausnitzii DSM 17677 T produced butyrate, formate, CO 2 , and traces of lactate from fructose, oligofructose, and inulin. Based on carbon recovery and theoretical metabolite production calculations, an adapted stoichiometrically balanced metabolic pathway for butyrate, formate, lactate, CO 2 , and H 2 production by members of both Clostridium cluster IV and XIVa butyrate-producing bacteria was constructed.

  10. Determination of the Optimal Cutoff Values for Pain Sensitivity Questionnaire Scores and the Oswestry Disability Index for Favorable Surgical Outcomes in Subjects With Lumbar Spinal Stenosis.

    Science.gov (United States)

    Kim, Ho-Joong; Park, Jong-Woong; Kang, Kyoung-Tak; Chang, Bong-Soon; Lee, Choon-Ki; Kang, Sung-Shik; Yeom, Jin S

    2015-10-15

    Retrospective analysis of prospectively collected data (NCT02134821). The aim of this study was to elucidate the cutoff values for significant predictors for favorable outcomes after lumbar spine surgery in patients with lumbar spinal stenosis (LSS). Various factors are associated with the surgical outcomes for patients with LSS. However, we did not know the odds ratio and/or cutoff values of a predictive factor for a favorable surgical outcome for LSS. A total of 157 patients who underwent spine surgery due to LSS between June 2012 and April 2013 were included in this study. The patients were dichotomized into 2 groups on the basis of an Oswestry Disability Index (ODI) score of 22 or less (favorable outcome group) or more than 22 (unfavorable outcome group) at 12 months after surgery. Regarding favorable outcomes, the odds ratio for each preoperative variable including demographic data, preoperative symptom severity, and pain sensitivity questionnaire (PSQ) score was calculated using univariate and multivariate logistic regression analyses. For the significant variables for surgical outcome, receiver operating characteristic (ROC) curve was plotted with calculation of the area under the ROC curve. Multivariate analysis revealed that the ODI and total PSQ scores were significantly associated with a greater likelihood of an unfavorable surgical outcome [odds ratio (95% confidence interval) of ODI, 1.289 (1.028-1.616); odds ratio (95% confidence interval) of total PSQ, 1.060 (1.009-1.113)]. ROC analysis revealed area under the ROC curves for the total PSQ and ODI scores of 0.638 (P = 0.005) and 0.692 (P disability and pain sensitivity can be predictors of the functional level achieved after spine surgery in patients with LSS, and the ideal cutoff values for the total PSQ and ODI scores were 6.6 and 45.0, respectively.

  11. Modelling of the metabolism of Zymomonas mobilis

    Energy Technology Data Exchange (ETDEWEB)

    Posten, C; Thoma, M

    1986-01-01

    In order to optimize fermentations with respect to media, reactor configuration, and control a structured model of the metabolism of Zymononas mobilis has been developed. The model is based on structure of metabolism, rate limiting steps, energy balance and metabolic elemental balances. A three-fold effect of ethanol has been observed concerning substrate-turnover, ammonia uptake and energy consumption. In addition to the metabolic view a structured cell-membrane-model should be considered.

  12. The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids.

    Science.gov (United States)

    Cassidy, Aedín; Minihane, Anne-Marie

    2017-01-01

    At a population level, there is growing evidence of the beneficial effects of dietary flavonoids on health. However, there is extensive heterogeneity in the response to increased intake, which is likely mediated via wide interindividual variability in flavonoid absorption and metabolism. Flavonoids are extensively metabolized by phase I and phase II metabolism (which occur predominantly in the gastrointestinal tract and liver) and colonic microbial metabolism. A number of factors, including age, sex, and genotype, may affect these metabolic processes. In addition, food composition and flavonoid source are likely to affect bioavailability, and emerging data suggest a critical role for the microbiome. This review will focus on the current knowledge for the main subclasses of flavonoids, including anthocyanins, flavonols, flavan-3-ols, and flavanones, for which there is growing evidence from prospective studies of beneficial effects on health. The identification of key factors that govern metabolism and an understanding of how the differential capacity to metabolize these bioactive compounds affect health outcomes will help establish how to optimize intakes of flavonoids for health benefits and in specific subgroups. We identify research areas that need to be addressed to further understand important determinants of flavonoid bioavailability and metabolism and to advance the knowledge base that is required to move toward the development of dietary guidelines and recommendations for flavonoids and flavonoid-rich foods.

  13. Use of BMI as marker of adiposity in a metabolic syndrome severity score: derivation and validation in predicting long-term disease outcomes.

    Science.gov (United States)

    Gurka, Matthew J; Filipp, Stephanie L; Musani, Solomon K; Sims, Mario; DeBoer, Mark D

    2018-02-01

    Estimates of adiposity in evaluating the metabolic syndrome (MetS) have traditionally utilized measures of waist circumference (WC), whereas body mass index (BMI) is more commonly used clinically. Our objective was to determine if a MetS severity Z-score employing BMI as its measure of adiposity (MetS-Z-BMI) would perform similarly to a WC-based score (MetS-Z-WC) in predicting future disease. To formulate the MetS-Z-BMI, we performed confirmatory factor analysis on a sex- and race/ethnicity-specific basis on MetS-related data for 6870 adult participants of the National Health and Nutrition Survey 1999-2010. We then validated this score and compared it to MetS-Z-WC in assessing correlations with future coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM) using Cox proportional hazard analysis of 13,094 participants of the Atherosclerosis Risk in Communities study and Jackson Heart Study. Loading factors, which represent the relative contribution of each component to the latent MetS factor, were lower for BMI than for WC in formulating the two respective scores (MetS-Z-BMI and MetS-Z-WC). Nevertheless, MetS-Z-BMI and MetS-Z-WC exhibited similar hazard ratios (HR) toward future disease. For each one standard-deviation-unit increase in MetS-Z-BMI, HR for CHD was 1.76 (95% confidence interval [CI]: 1.65, 1.88) and HR for T2DM was 3.39 (CI 3.16, 3.63) (both p BMI scores in their associations with future CHD and T2DM. A MetS severity Z-score utilizing BMI as its measure of adiposity operated similarly to a WC-based score in predicting future CHD and T2DM, suggesting overall similarity in MetS-based risk as estimated by both measures of adiposity. This indicates potential clinical usefulness of MetS-Z-BMI in assessing and following MetS-related risk over time. Copyright © 2018. Published by Elsevier Inc.

  14. Student performance study: the outcomes of metabolic, molecular and physical-chemical characterization of intestinal tract microbiome on a four mammalian species model

    Directory of Open Access Journals (Sweden)

    Nataša CIBER

    2015-11-01

    Full Text Available Many environmental factors influence the structure of microbial communities, their activity and properties of the environment of the digestive tract. Contrary to constant disturbances, the system provides the basis for energy conversion and thus the long-term stable coexistence of different hosts and their specific intestinal microbiota over geological timescales. Since the methodological approaches proved to be the largest source of systematic errors in comparisons of microbial communities among different organisms of the same species or between different species, we tested a number of methods on samples from different species of mammals in order to verify the feasibility of this approach for future routine analysis of microbiomes:(i analyses of physical-chemical parameters;(iithe metabolic properties of attached, planktonic fractions in comparison to the total;(iiistructure of microbial communities of bacteria and archaea; (ivdata analysis. We used a model of intestinal samples from four species of mammals, encompassing the differences between the various types of intestinal tracts: ruminants and rodents (such as pre- and post- peptic fermentors, omnivores and carnivores. The second purpose of the study was to(iassess the extent of spread of data due to the cooperation of the various operators on the data obtained, and(ii to evaluate the skills of the students to carry out industry-oriented investigations and measurements in 1st year of MSc study Microbiology; and(iii to promote awareness of the importance of routine laboratory work day and the corresponding duties. The results suggest(ithat the operators independently organized and shared tasks;(iisuccessfully completed all methods;(iiiobtain relevant information;(ivcritically evaluated and interpreted within the extent of their knowledge;(v that relative standard deviation(RSD typically could be compared to those of the automated analytical procedures(<10 % and therefore represented the

  15. Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dholakia, Avani S. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chaudhry, Muhammad; Leal, Jeffrey P. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chang, Daniel T. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Raman, Siva P. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hacker-Prietz, Amy [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Su, Zheng; Pai, Jonathan [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Oteiza, Katharine E.; Griffith, Mary E. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Wahl, Richard L. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Pawlik, Timothy [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Laheru, Daniel A. [Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Wolfgang, Christopher L. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); and others

    2014-07-01

    Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV{sub max} and SUV{sub peak}) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver{sub mean} + [2 × Liver{sub sd}]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm{sup 3} or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in

  16. Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

    International Nuclear Information System (INIS)

    Dholakia, Avani S.; Chaudhry, Muhammad; Leal, Jeffrey P.; Chang, Daniel T.; Raman, Siva P.; Hacker-Prietz, Amy; Su, Zheng; Pai, Jonathan; Oteiza, Katharine E.; Griffith, Mary E.; Wahl, Richard L.; Tryggestad, Erik; Pawlik, Timothy; Laheru, Daniel A.; Wolfgang, Christopher L.; Koong, Albert C.

    2014-01-01

    Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV max and SUV peak ) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver mean + [2 × Liver sd ]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm 3 or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in tailoring therapy

  17. Noise effect in metabolic networks

    International Nuclear Information System (INIS)

    Zheng-Yan, Li; Zheng-Wei, Xie; Tong, Chen; Qi, Ouyang

    2009-01-01

    Constraint-based models such as flux balance analysis (FBA) are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution and natural selection, this model successfully predicts most cellular behaviours in growth rate. However, the model ignores the fact that cells can change their cellular metabolic states during evolution, leaving optimal metabolic states unstable. Here, we consider all the cellular processes that change metabolic states into a single term 'noise', and assume that cells change metabolic states by randomly walking in feasible solution space. By simulating a state of a cell randomly walking in the constrained solution space of metabolic networks, we found that in a noisy environment cells in optimal states tend to travel away from these points. On considering the competition between the noise effect and the growth effect in cell evolution, we found that there exists a trade-off between these two effects. As a result, the population of the cells contains different cellular metabolic states, and the population growth rate is at suboptimal states. (cross-disciplinary physics and related areas of science and technology)

  18. Metabolic syndrome, diet and exercise.

    Science.gov (United States)

    De Sousa, Sunita M C; Norman, Robert J

    2016-11-01

    Polycystic ovary syndrome (PCOS) is associated with a range of metabolic complications including insulin resistance (IR), obesity, dyslipidaemia, hypertension, obstructive sleep apnoea (OSA) and non-alcoholic fatty liver disease. These compound risks result in a high prevalence of metabolic syndrome and possibly increased cardiovascular (CV) disease. As the cardiometabolic risk of PCOS is shared amongst the different diagnostic systems, all women with PCOS should undergo metabolic surveillance though the precise approach differs between guidelines. Lifestyle interventions consisting of increased physical activity and caloric restriction have been shown to improve both metabolic and reproductive outcomes. Pharmacotherapy and bariatric surgery may be considered in resistant metabolic disease. Issues requiring further research include the natural history of PCOS-associated metabolic disease, absolute CV risk and comparative efficacy of lifestyle interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Congenital adrenal hyperplasia: Treatment and outcomes

    Directory of Open Access Journals (Sweden)

    Mahdi Kamoun

    2013-01-01

    Full Text Available Congenital adrenal hyperplasia (CAH describes a group of autosomal recessive disorders where there is impairment of cortisol biosynthesis. CAH due to 21-hydroxylase deficiency accounts for 95% of cases and shows a wide range of clinical severity. Glucocorticoid and mineralocorticoid replacement therapies are the mainstays of treatment of CAH. The optimal treatment for adults with CAH continues to be a challenge. Important long-term health issues for adults with CAH affect both men and women. These issues may either be due to the disease or to steroid treatment and may affect final height, fertility, cardiometabolic risk, bone metabolism, neuro-cognitive development and the quality-of-life. Patients with CAH should be regularly followed-up from childhood to adulthood by multidisciplinary teams who have knowledge of CAH. Optimal replacement therapy, close clinical and laboratory monitoring, early life-style interventions, early and regular fertility assessment and continuous psychological management are needed to improve outcome.

  20. Optimal use of directional coronary atherectomy is required to ensure long-term angiographic benefit: a study with matched procedural outcome after atherectomy and angioplasty

    NARCIS (Netherlands)

    V.A.W.M. Umans (Victor); D.T.J. Keane (David); R. Melkert (Rein); P.W.J.C. Serruys (Patrick); D.P. Foley (David); H. Boersma (Eric)

    1994-01-01

    textabstractOBJECTIVES. This study was designed to examine whether restenosis is related to the extent or mechanism of lumen improvement and to explore angiographic determinants of optimal atherectomy. BACKGROUND. Directional atherectomy induces a greater extent of immediate gain and late loss but

  1. What is Metabolic Syndrome?

    Science.gov (United States)

    ... Intramural Research Home / Metabolic Syndrome Metabolic Syndrome Also known as What Is Metabolic syndrome ... metabolic risk factors to be diagnosed with metabolic syndrome. Metabolic Risk Factors A Large Waistline Having a large ...

  2. What is the optimal time point to assess patient-reported recovery after hip and knee replacement? A systematic review and analysis of routinely reported outcome data from the English patient-reported outcome measures programme.

    Science.gov (United States)

    Browne, John Patrick; Bastaki, Hamad; Dawson, Jill

    2013-07-30

    It is unclear if there is a clinically important improvement in the six to 12-month recovery period after hip and knee replacement. This is an obvious gap in the evidence required by patients undergoing these procedures. It is also an issue for the English PROMs (Patient-Reported Outcome Measures) Programme which uses 6-month outcome data to compare the results of hospitals that perform hip and knee replacements. A systematic review of studies reporting the Oxford Hip Score (OHS) or Oxford Knee Score (OKS) at 12 months after surgery was performed. This was compared with six-month outcome data collected for 60, 160 patients within the English PROMs programme. A minimally important difference of one standard error of the measurement, equivalent to 2.7 for the OHS and 2.1 for the OKS, was adopted. Six studies reported OHS data for 10 different groups containing 8,308 patients in total. In eight groups the change scores reported were at least 2.7 points higher than the six-month change observed in the PROMs programme (20.2 points). Nine studies reported OKS data for 13 different groups containing 4,369 patients in total. In eight groups the change scores reported were at least 2.1 points higher than the six-month change observed in the PROMs programme (15.0 points). There is some evidence from this systematic review that clinically important improvement in the Oxford hip and knee scores occurs in the six to 12 month recovery period. This trend is more apparent for hip than knee replacement. Therefore we recommend that the English Department of Health study the impact on hospital comparisons of using 12- rather than six-month outcome data.

  3. Optimization and Optimal Control

    CERN Document Server

    Chinchuluun, Altannar; Enkhbat, Rentsen; Tseveendorj, Ider

    2010-01-01

    During the last four decades there has been a remarkable development in optimization and optimal control. Due to its wide variety of applications, many scientists and researchers have paid attention to fields of optimization and optimal control. A huge number of new theoretical, algorithmic, and computational results have been observed in the last few years. This book gives the latest advances, and due to the rapid development of these fields, there are no other recent publications on the same topics. Key features: Provides a collection of selected contributions giving a state-of-the-art accou

  4. Optimally Stopped Optimization

    Science.gov (United States)

    Vinci, Walter; Lidar, Daniel

    We combine the fields of heuristic optimization and optimal stopping. We propose a strategy for benchmarking randomized optimization algorithms that minimizes the expected total cost for obtaining a good solution with an optimal number of calls to the solver. To do so, rather than letting the objective function alone define a cost to be minimized, we introduce a further cost-per-call of the algorithm. We show that this problem can be formulated using optimal stopping theory. The expected cost is a flexible figure of merit for benchmarking probabilistic solvers that can be computed when the optimal solution is not known, and that avoids the biases and arbitrariness that affect other measures. The optimal stopping formulation of benchmarking directly leads to a real-time, optimal-utilization strategy for probabilistic optimizers with practical impact. We apply our formulation to benchmark the performance of a D-Wave 2X quantum annealer and the HFS solver, a specialized classical heuristic algorithm designed for low tree-width graphs. On a set of frustrated-loop instances with planted solutions defined on up to N = 1098 variables, the D-Wave device is between one to two orders of magnitude faster than the HFS solver.

  5. Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS–NSTEMI randomized trial

    Science.gov (United States)

    Layland, Jamie; Oldroyd, Keith G.; Curzen, Nick; Sood, Arvind; Balachandran, Kanarath; Das, Raj; Junejo, Shahid; Ahmed, Nadeem; Lee, Matthew M.Y.; Shaukat, Aadil; O'Donnell, Anna; Nam, Julian; Briggs, Andrew; Henderson, Robert; McConnachie, Alex; Berry, Colin; Hannah, Andrew; Stewart, Andrew; Metcalfe, Malcolm; Norrie, John; Chowdhary, Saqib; Clark, Andrew; Henderson, Robert; Balachandran, Kanarath; Berry, Colin; Baird, Gordon; O'Donnell, Anna; Sood, Arvind; Curzen, Nick; Das, Raj; Ford, Ian; Layland, Jamie; Junejo, Shahid; Oldroyd, Keith

    2015-01-01

    Aim We assessed the management and outcomes of non-ST segment elevation myocardial infarction (NSTEMI) patients randomly assigned to fractional flow reserve (FFR)-guided management or angiography-guided standard care. Methods and results We conducted a prospective, multicentre, parallel group, 1 : 1 randomized, controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% of the lumen diameter assessed visually (threshold for FFR measurement) (NCT01764334). Enrolment took place in six UK hospitals from October 2011 to May 2013. Fractional flow reserve was disclosed to the operator in the FFR-guided group (n = 176). Fractional flow reserve was measured but not disclosed in the angiography-guided group (n = 174). Fractional flow reserve ≤0.80 was an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The median (IQR) time from the index episode of myocardial ischaemia to angiography was 3 (2, 5) days. For the primary outcome, the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [40 (22.7%) vs. 23 (13.2%), difference 95% (95% CI: 1.4%, 17.7%), P = 0.022]. Fractional flow reserve disclosure resulted in a change in treatment between medical therapy, PCI or CABG in 38 (21.6%) patients. At 12 months, revascularization remained lower in the FFR-guided group [79.0 vs. 86.8%, difference 7.8% (−0.2%, 15.8%), P = 0.054]. There were no statistically significant differences in health outcomes and quality of life between the groups. Conclusion In NSTEMI patients, angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management. A larger trial is necessary to assess health outcomes and cost-effectiveness. PMID:25179764

  6. Optimizing utilization of kidneys from deceased donors over 60 years: five-year outcomes after implementation of a combined clinical and histological allocation algorithm.

    Science.gov (United States)

    Pierobon, Elisa Sefora; Sefora, Pierobon Elisa; Sandrini, Silvio; Silvio, Sandrini; De Fazio, Nicola; Nicola, De Fazio; Rossini, Giuseppe; Giuseppe, Rossini; Fontana, Iris; Iris, Fontana; Boschiero, Luigino; Luigino, Boschiero; Gropuzzo, Maria; Maria, Gropuzzo; Gotti, Eliana; Eliana, Gotti; Donati, Donato; Donato, Donati; Minetti, Enrico; Enrico, Minetti; Gandolfo, Maria Teresa; Teresa, Gandolfo Maria; Brunello, Anna; Anna, Brunello; Libetta, Carmelo; Carmelo, Libetta; Secchi, Antonio; Antonio, Secchi; Chiaramonte, Stefano; Stefano, Chiaramonte; Rigotti, Paolo; Paolo, Rigotti

    2013-08-01

    This 5 year observational multicentre study conducted in the Nord Italian Transplant programme area evaluated outcomes in patients receiving kidneys from donors over 60 years allocated according to a combined clinical and histological algorithm. Low-risk donors 60-69 years without risk factors were allocated to single kidney transplant (LR-SKT) based on clinical criteria. Biopsy was performed in donors over 70 years or 60-69 years with risk factors, allocated to Single (HR-SKT) or Dual kidney transplant (HR-DKT) according to the severity of histological damage. Forty HR-DKTs, 41 HR-SKTs and 234 LR-SKTs were evaluated. Baseline differences generally reflected stratification and allocation criteria. Patient and graft (death censored) survival were 90% and 92% for HR-DKT, 85% and 89% for HR-SKT, 88% and 87% for LR-SKT. The algorithm appeared user-friendly in daily practice and was safe and efficient, as demonstrated by satisfactory outcomes in all groups at 5 years. Clinical criteria performed well in low-risk donors. The excellent outcomes observed in DKTs call for fine-tuning of cut-off scores for allocation to DKT or SKT in high-risk patients. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

  7. Comparing wavefront-optimized, wavefront-guided and topography-guided laser vision correction: clinical outcomes using an objective decision tree.

    Science.gov (United States)

    Stonecipher, Karl; Parrish, Joseph; Stonecipher, Megan

    2018-05-18

    This review is intended to update and educate the reader on the currently available options for laser vision correction, more specifically, laser-assisted in-situ keratomileusis (LASIK). In addition, some related clinical outcomes data from over 1000 cases performed over a 1-year are presented to highlight some differences between the various treatment profiles currently available including the rapidity of visual recovery. The cases in question were performed on the basis of a decision tree to segregate patients on the basis of anatomical, topographic and aberrometry findings; the decision tree was formulated based on the data available in some of the reviewed articles. Numerous recent studies reported in the literature provide data related to the risks and benefits of LASIK; alternatives to a laser refractive procedure are also discussed. The results from these studies have been used to prepare a decision tree to assist the surgeon in choosing the best option for the patient based on the data from several standard preoperative diagnostic tests. The data presented here should aid surgeons in understanding the effects of currently available LASIK treatment profiles. Surgeons should also be able to appreciate how the findings were used to create a decision tree to help choose the most appropriate treatment profile for patients. Finally, the retrospective evaluation of clinical outcomes based on the decision tree should provide surgeons with a realistic expectation for their own outcomes should they adopt such a decision tree in their own practice.

  8. Metabolic crisis in severely head-injured patients: is ischemia just the tip of the iceberg?

    Science.gov (United States)

    Carre, Emilie; Ogier, Michael; Boret, Henry; Montcriol, Ambroise; Bourdon, Lionel; Jean-Jacques, Risso

    2013-10-11

    Ischemia and metabolic crisis are frequent post-traumatic secondary brain insults that negatively influence outcome. Clinicians commonly mix up these two types of insults, mainly because high lactate/pyruvate ratio (LPR) is the common marker for both ischemia and metabolic crisis. However, LPR elevations during ischemia and metabolic crisis reflect two different energetic imbalances: ischemia (Type 1 LPR elevations with low oxygenation) is characterized by a drastic deprivation of energetic substrates, whereas metabolic crisis (Type 2 LPR elevations with normal or high oxygenation) is associated with profound mitochondrial dysfunction but normal supply of energetic substrates. The discrimination between ischemia and metabolic crisis is crucial because conventional recommendations against ischemia may be detrimental for patients with metabolic crisis. Multimodal monitoring, including microdialysis and brain tissue oxygen monitoring, allows such discrimination, but these techniques are not easily accessible to all head-injured patients. Thus, a new "gold standard" and adapted medical education are required to optimize the management of patients with metabolic crisis.

  9. Metabolic crisis in severely head-injured patients: is ischemia just the tip of the iceberg?

    Directory of Open Access Journals (Sweden)

    Emilie eCarre

    2013-10-01

    Full Text Available Ischemia and metabolic crisis are frequent post-traumatic secondary brain insults that negatively influence outcome. Clinicians commonly mix up these two types of insults, mainly because high lactate/pyruvate ratio (LPR is the common marker for both ischemia and metabolic crisis. However, LPR elevations during ischemia and metabolic crisis reflect two different energetic imbalances: ischemia (Type 1 LPR elevations with low oxygenation is characterized by a drastic deprivation of energetic substrates, whereas metabolic crisis (Type 2 LPR elevations with normal or high oxygenation is associated with profound mitochondrial dysfunction but normal supply of energetic substrates. The discrimination between ischemia and metabolic crisis is crucial because conventional recommendations against ischemia may be detrimental for patients with metabolic crisis. Multimodal monitoring, including microdialysis and brain tissue oxygen monitoring, allows such discrimination, but these techniques are not easily accessible to all head-injured patients. Thus, a new gold standard and adapted medical education are required to optimize the management of patients with metabolic crisis.

  10. Model-based design of bistable cell factories for metabolic engineering.

    Science.gov (United States)

    Srinivasan, Shyam; Cluett, William R; Mahadevan, Radhakrishnan

    2018-04-15

    Metabolism can exhibit dynamic phenomena like bistability due to the presence of regulatory motifs like the positive feedback loop. As cell factories, microorganisms with bistable metabolism can have a high and a low product flux at the two stable steady states, respectively. The exclusion of metabolic regulation and network dynamics limits the ability of pseudo-steady state stoichiometric models to detect the presence of bistability, and reliably assess the outcomes of design perturbations to metabolic networks. Using kinetic models of metabolism, we assess the change in the bistable characteristics of the network, and suggest designs based on perturbations to the positive feedback loop to enable the network to produce at its theoretical maximum rate. We show that the most optimal production design in parameter space, for a small bistable metabolic network, may exist at the boundary of the bistable region separating it from the monostable region of low product fluxes. The results of our analysis can be broadly applied to other bistable metabolic networks with similar positive feedback network topologies. This can complement existing model-based design strategies by providing a smaller number of feasible designs that need to be tested in vivo. http://lmse.biozone.utoronto.ca/downloads/. krishna.mahadevan@utoronto.ca. Supplementary data are available at Bioinformatics online.

  11. Urban metabolism: A review of research methodologies

    International Nuclear Information System (INIS)

    Zhang, Yan

    2013-01-01

    Urban metabolism analysis has become an important tool for the study of urban ecosystems. The problems of large metabolic throughput, low metabolic efficiency, and disordered metabolic processes are a major cause of unhealthy urban systems. In this paper, I summarize the international research on urban metabolism, and describe the progress that has been made in terms of research methodologies. I also review the methods used in accounting for and evaluating material and energy flows in urban metabolic processes, simulation of these flows using a network model, and practical applications of these methods. Based on this review of the literature, I propose directions for future research, and particularly the need to study the urban carbon metabolism because of the modern context of global climate change. Moreover, I recommend more research on the optimal regulation of urban metabolic systems. Highlights: •Urban metabolic processes can be analyzed by regarding cities as superorganisms. •Urban metabolism methods include accounting, assessment, modeling, and regulation. •Research methodologies have improved greatly since this field began in 1965. •Future research should focus on carbon metabolism and optimal regulation. -- The author reviews research progress in the field of urban metabolism, and based on her literature review, proposes directions for future research

  12. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  13. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  14. Metabolic Myopathies.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2016-12-01

    Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

  15. Animal metabolism

    International Nuclear Information System (INIS)

    Walburg, H.E.

    1977-01-01

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144 Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95 Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  16. Long-Term Outcome in Patients With Ductal Carcinoma In Situ Treated With Breast-Conserving Therapy: Implications for Optimal Follow-up Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Shaitelman, Simona F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wilkinson, J. Ben [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Kestin, Larry L. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ye Hong [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Goldstein, Neal S. [Advanced Diagnostics Laboratory, Redford, Michigan (United States); Martinez, Alvaro A. [Michigan HealthCare Professionals, Pontiac, Michigan (United States); Vicini, Frank A., E-mail: fvicini@pol.net [Michigan HealthCare Professionals, Pontiac, Michigan (United States)

    2012-07-01

    Purpose: To determine 20-year rates of local control and outcome-associated factors for ductal carcinoma in situ (DCIS) after breast-conserving therapy (BCT). Methods and Materials: All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. Results: One hundred forty-five cases were evaluated; the median follow-up time was 19.3 years. IBTR developed in 25 patients, for 5-, 10-, 15-, and 20-year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. One third of IBTRs were elsewhere failures, and 68% of IBTRs occurred <10 years after diagnosis. Young age and cancerization of lobules predicted for IBTR at <10 years, and increased slide involvement and atypical ductal hyperplasia were associated with IBTR at later time points. Conclusions: Patients with DCIS treated with BCT have excellent long-term rates of local control. Predictors of IBTR vary over time, and the risk of recurrence seems highest within 10 to 12 years after diagnosis.

  17. Long-Term Outcome in Patients With Ductal Carcinoma In Situ Treated With Breast-Conserving Therapy: Implications for Optimal Follow-up Strategies

    International Nuclear Information System (INIS)

    Shaitelman, Simona F.; Wilkinson, J. Ben; Kestin, Larry L.; Ye Hong; Goldstein, Neal S.; Martinez, Alvaro A.; Vicini, Frank A.

    2012-01-01

    Purpose: To determine 20-year rates of local control and outcome-associated factors for ductal carcinoma in situ (DCIS) after breast-conserving therapy (BCT). Methods and Materials: All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. Results: One hundred forty-five cases were evaluated; the median follow-up time was 19.3 years. IBTR developed in 25 patients, for 5-, 10-, 15-, and 20-year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. One third of IBTRs were elsewhere failures, and 68% of IBTRs occurred <10 years after diagnosis. Young age and cancerization of lobules predicted for IBTR at <10 years, and increased slide involvement and atypical ductal hyperplasia were associated with IBTR at later time points. Conclusions: Patients with DCIS treated with BCT have excellent long-term rates of local control. Predictors of IBTR vary over time, and the risk of recurrence seems highest within 10 to 12 years after diagnosis.

  18. (Too) optimistic about optimism: the belief that optimism improves performance.

    Science.gov (United States)

    Tenney, Elizabeth R; Logg, Jennifer M; Moore, Don A

    2015-03-01

    A series of experiments investigated why people value optimism and whether they are right to do so. In Experiments 1A and 1B, participants prescribed more optimism for someone implementing decisions than for someone deliberating, indicating that people prescribe optimism selectively, when it can affect performance. Furthermore, participants believed optimism improved outcomes when a person's actions had considerable, rather than little, influence over the outcome (Experiment 2). Experiments 3 and 4 tested the accuracy of this belief; optimism improved persistence, but it did not improve performance as much as participants expected. Experiments 5A and 5B found that participants overestimated the relationship between optimism and performance even when their focus was not on optimism exclusively. In summary, people prescribe optimism when they believe it has the opportunity to improve the chance of success-unfortunately, people may be overly optimistic about just how much optimism can do. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  19. Optimal waist circumference cut-off points and ability of different metabolic syndrome criteria for predicting diabetes in Japanese men and women: Japan Epidemiology Collaboration on Occupational Health Study

    Directory of Open Access Journals (Sweden)

    Huanhuan Hu

    2016-03-01

    Full Text Available Abstract Background We sought to establish the optimal waist circumference (WC cut-off point for predicting diabetes mellitus (DM and to compare the predictive ability of the metabolic syndrome (MetS criteria of the Joint Interim Statement (JIS and the Japanese Committee of the Criteria for MetS (JCCMS for DM in Japanese. Methods Participants of the Japan Epidemiology Collaboration on Occupational Health Study, who were aged 20–69 years and free of DM at baseline (n = 54,980, were followed-up for a maximum of 6 years. Time-dependent receiver operating characteristic analysis was used to determine the optimal cut-off points of WC for predicting DM. Time-dependent sensitivity, specificity, and positive and negative predictive values for the prediction of DM were compared between the JIS and JCCMS MetS criteria. Results During 234,926 person-years of follow-up, 3180 individuals developed DM. Receiver operating characteristic analysis suggested that the most suitable cut-off point of WC for predicting incident DM was 85 cm for men and 80 cm for women. MetS was associated with 3–4 times increased hazard for developing DM in men and 7–9 times in women. Of the MetS criteria tested, the JIS criteria using our proposed WC cut-off points (85 cm for men and 80 cm for women had the highest sensitivity (54.5 % for men and 43.5 % for women for predicting DM. The sensitivity and specificity of the JCCMS MetS criteria were ~37.7 and 98.9 %, respectively. Conclusion Data from the present large cohort of workers suggest that WC cut-offs of 85 cm for men and 80 cm for women may be appropriate for predicting DM for Japanese. The JIS criteria can detect more people who later develop DM than does the JCCMS criteria.

  20. Toward a feline-optimized culture medium: impact of ions, carbohydrates, essential amino acids, vitamins, and serum on development and metabolism of in vitro fertilization-derived feline embryos relative to embryos grown in vivo.

    Science.gov (United States)

    Herrick, Jason R; Bond, Jennifer B; Magarey, Genevieve M; Bateman, Helen L; Krisher, Rebecca L; Dunford, Susan A; Swanson, William F

    2007-05-01

    The objective of this study was to define the physiologic needs of domestic cat embryos to facilitate development of a feline-specific culture medium. In a series of factorial experiments, in vivo-matured oocytes (n = 2040) from gonadotropin-treated domestic cats were inseminated in vitro to generate embryos (n = 1464) for culture. In the initial study, concentrations of NaCl (100.0 vs. 120.0 mM), KCl (4.0 vs. 8.0 mM), KH(2)PO(4) (0.25 vs. 1.0 mM), and the ratio of CaCl(2) to MgSO(4)-7H(2)O (1.0:2.0 mM vs. 2.0:1.0 mM) in the medium were evaluated during Days 1-6 (Day 0: oocyte recovery and in vitro fertilization [IVF]) of culture. Subsequent experiments assessed the effects of varying concentrations of carbohydrate (glucose, 1.5, 3.0, or 6.0 mM; l-lactate, 3.0, 6.0, or 12.0 mM; and pyruvate, 0.1 or 1.0 mM) and essential amino acids (EAAs; 0, 0.5, or 1.0x) in the medium during Days 1-3 and Days 3-6 of culture. Inclusion of vitamins (0 vs. 1.0x) and fetal calf serum (FCS; 0 vs. 5% [v/v]) in the medium also was evaluated during Days 3-6. Development and metabolism of IVF embryos on Day 3 or Day 6 were compared to age-matched in vivo embryos recovered from naturally mated queens. A feline-optimized culture medium (FOCM) was formulated based on these results (100.0 mM NaCl, 8.0 mM KCl, 1.0 mM KH(2)PO(4), 2.0 mM CaCl(2), 1.0 mM MgSO(4), 1.5 mM glucose, 6.0 mM L-lactate, 0.1 mM pyruvate, and 0x EAAs with 25.0 mM NaHCO(3), 1.0 mM alanyl-glutamine, 0.1 mM taurine, and 1.0x nonessential amino acids) with 0.4% (w/v) BSA from Days 0-3 and 5% FCS from Days 3-6. Using this medium, ~70% of cleaved embryos developed into blastocysts with profiles of carbohydrate metabolism similar to in vivo embryos. Our results suggest that feline embryos have stage-specific responses to carbohydrates and are sensitive to EAAs but are still reliant on one or more unidentified components of FCS for optimal blastocyst development.

  1. Sci-Thur AM: YIS – 05: Prediction of lung tumor motion using a generalized neural network optimized from the average prediction outcome of a group of patients

    Energy Technology Data Exchange (ETDEWEB)

    Teo, Troy; Alayoubi, Nadia; Bruce, Neil; Pistorius, Stephen [University of Manitoba/ CancerCare Manitoba, University of Manitoba, University of Manitoba, University of Manitoba / CancerCare Manitoba (Canada)

    2016-08-15

    Purpose: In image-guided adaptive radiotherapy systems, prediction of tumor motion is required to compensate for system latencies. However, due to the non-stationary nature of respiration, it is a challenge to predict the associated tumor motions. In this work, a systematic design of the neural network (NN) using a mixture of online data acquired during the initial period of the tumor trajectory, coupled with a generalized model optimized using a group of patient data (obtained offline) is presented. Methods: The average error surface obtained from seven patients was used to determine the input data size and number of hidden neurons for the generalized NN. To reduce training time, instead of using random weights to initialize learning (method 1), weights inherited from previous training batches (method 2) were used to predict tumor position for each sliding window. Results: The generalized network was established with 35 input data (∼4.66s) and 20 hidden nodes. For a prediction horizon of 650 ms, mean absolute errors of 0.73 mm and 0.59 mm were obtained for method 1 and 2 respectively. An average initial learning period of 8.82 s is obtained. Conclusions: A network with a relatively short initial learning time was achieved. Its accuracy is comparable to previous studies. This network could be used as a plug-and play predictor in which (a) tumor positions can be predicted as soon as treatment begins and (b) the need for pretreatment data and optimization for individual patients can be avoided.

  2. Sci-Thur AM: YIS – 05: Prediction of lung tumor motion using a generalized neural network optimized from the average prediction outcome of a group of patients

    International Nuclear Information System (INIS)

    Teo, Troy; Alayoubi, Nadia; Bruce, Neil; Pistorius, Stephen

    2016-01-01

    Purpose: In image-guided adaptive radiotherapy systems, prediction of tumor motion is required to compensate for system latencies. However, due to the non-stationary nature of respiration, it is a challenge to predict the associated tumor motions. In this work, a systematic design of the neural network (NN) using a mixture of online data acquired during the initial period of the tumor trajectory, coupled with a generalized model optimized using a group of patient data (obtained offline) is presented. Methods: The average error surface obtained from seven patients was used to determine the input data size and number of hidden neurons for the generalized NN. To reduce training time, instead of using random weights to initialize learning (method 1), weights inherited from previous training batches (method 2) were used to predict tumor position for each sliding window. Results: The generalized network was established with 35 input data (∼4.66s) and 20 hidden nodes. For a prediction horizon of 650 ms, mean absolute errors of 0.73 mm and 0.59 mm were obtained for method 1 and 2 respectively. An average initial learning period of 8.82 s is obtained. Conclusions: A network with a relatively short initial learning time was achieved. Its accuracy is comparable to previous studies. This network could be used as a plug-and play predictor in which (a) tumor positions can be predicted as soon as treatment begins and (b) the need for pretreatment data and optimization for individual patients can be avoided.

  3. Preoperative Optimization of Total Joint Arthroplasty Surgical Risk: Obesity.

    Science.gov (United States)

    Fournier, Matthew N; Hallock, Justin; Mihalko, William M

    2016-08-01

    Obesity is a problem that is increasing in prevalence in the United States and in other countries, and it is a common comorbidity in patients seeking total joint arthroplasty for degenerative musculoskeletal diseases. Obesity, as well as commonly associated comorbidities such as diabetes mellitus, cardiovascular disease, and those contributing to the diagnosis of metabolic syndrome, have been shown to have detrimental effects on total joint arthroplasty outcomes. Although there are effective surgical and nonsurgical interventions which can result in weight loss in these patients, concomitant benefit on arthroplasty outcomes is not clear. Preoperative optimization of surgical risk in obese total joint arthroplasty patients is an important point of intervention to improve arthroplasty outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Prolonged platelet preservation by transient metabolic suppression

    NARCIS (Netherlands)

    Badlou, Bahram Alamdary

    2006-01-01

    Introduction: Different clinical studies have shown that transfusion of stored platelets results in better haemostasis in patients with thrombocytopenia with and without a platelet function defect. Objectives: Current preservation procedures aim to optimally preserve the metabolic status of

  5. Optimal Skin-to-Stone Distance Is a Positive Predictor for Successful Outcomes in Upper Ureter Calculi following Extracorporeal Shock Wave Lithotripsy: A Bayesian Model Averaging Approach.

    Directory of Open Access Journals (Sweden)

    Kang Su Cho

    Full Text Available To investigate whether skin-to-stone distance (SSD, which remains controversial in patients with ureter stones, can be a predicting factor for one session success following extracorporeal shock wave lithotripsy (ESWL in patients with upper ureter stones.We retrospectively reviewed the medical records of 1,519 patients who underwent their first ESWL between January 2005 and December 2013. Among these patients, 492 had upper ureter stones that measured 4-20 mm and were eligible for our analyses. Maximal stone length, mean stone density (HU, and SSD were determined on pretreatment non-contrast computed tomography (NCCT. For subgroup analyses, patients were divided into four groups. Group 1 consisted of patients with SSD<25th percentile, group 2 consisted of patients with SSD in the 25th to 50th percentile, group 3 patients had SSD in the 50th to 75th percentile, and group 4 patients had SSD≥75th percentile.In analyses of group 2 patients versus others, there were no statistical differences in mean age, stone length and density. However, the one session success rate in group 2 was higher than other groups (77.9% vs. 67.0%; P = 0.032. The multivariate logistic regression model revealed that shorter stone length, lower stone density, and the group 2 SSD were positive predictors for successful outcomes in ESWL. Using the Bayesian model-averaging approach, longer stone length, lower stone density, and group 2 SSD can be also positive predictors for successful outcomes following ESWL.Our data indicate that a group 2 SSD of approximately 10 cm is a positive predictor for success following ESWL.

  6. [Metabolic myopathies].

    Science.gov (United States)

    Papazian, Óscar; Rivas-Chacón, Rafael

    2013-09-06

    To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

  7. Tumor macroenvironment and metabolism.

    Science.gov (United States)

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Optimizing antiretroviral product selection: a sample approach to improving patient outcomes, saving money, and scaling-up health services in developing countries.

    Science.gov (United States)

    Amole, Carolyn D; Brisebois, Catherine; Essajee, Shaffiq; Koehler, Erin; Levin, Andrew D; Moore, Meredith C; Brown Ripin, David H; Sickler, Joanna J; Singh, Inder R

    2011-08-01

    Over the last decade, increased funding to support HIV treatment programs has enabled millions of new patients in developing countries to access the medications they need. Today, although demand for antiretrovirals continues to grow, the financial crisis has severely constrained funding leaving countries with difficult choices on program prioritization. Product optimization is one solution countries can pursue to continue to improve patient care while also uncovering savings that can be used for further scale up or other health system needs. Program managers can make procurement decisions that actually reduce program costs by considering additional factors beyond World Health Organization guidelines when making procurement decisions. These include in-country product availability, convenience, price, and logistics such as supply chain implications and laboratory testing requirements. Three immediate product selection opportunities in the HIV space include using boosted atazanavir in place of lopinovir for second-line therapy, lamivudine instead of emtricitabine in both first-line and second-line therapy, and tenofovir + lamivudine over abacavir + didanosine in second-line therapy. If these 3 opportunities were broadly implemented in sub-Saharan Africa and India today, approximately $300 million of savings would be realized over the next 5 years, enabling hundreds of thousands of additional patients to be treated. Although the discussion herein is specific to antriretrovirals, the principles of product selection are generalizable to diseases with multiple treatment options and fungible commodity procurement. Identifying and implementing approaches to overcome health system inefficiencies will help sustain and may expand quality care in resource-limited settings.

  9. Effects of a multicentre teamwork and communication programme on patient outcomes: results from the Triad for Optimal Patient Safety (TOPS) project.

    Science.gov (United States)

    Auerbach, Andrew D; Sehgal, Niraj L; Blegen, Mary A; Maselli, Judith; Alldredge, Brian K; Vittinghoff, Eric; Wachter, Robert M

    2012-02-01

    Improving communication between caregivers is an important approach to improving safety. To implement teamwork and communication interventions and evaluate their impact on patient outcomes. A prospective, interrupted time series of a three-phase a run-in period (phase 1), during which a training programme was given to providers and staff on each unit; phase 2, which focused on unit-based safety teams to identify and address care problems using skills from phase 1; and phase 3, which focused on engaging patients in communication efforts. General medical inpatient units at three northern California hospitals. Administrative data were collected from all adults admitted to the target units, and a convenience sample of patients interviewed during and after hospitalisation. Readmission, length of stay and patient reports of teamwork, problems with care, and overall satisfaction. 10 977 patients were admitted; 581 patients (5.3% of total sample) were interviewed in hospital, and 313 (2.9% overall, 53.8% of interviewed patients) completed 1-month surveys. No phase of the study was associated with adjusted differences in readmission or length of stay. The phase 2 intervention appeared to be associated with improvement in reports of whether physicians treated them with respect, whether nurses treated them with respect or understood their needs (pcommunication may improve patients' perception of team functions, but may also increase patients' perception of safety gaps.

  10. Is metabolic syndrome predictive of prevalence, extent, and risk of coronary artery disease beyond its components? results from the multinational coronary ct angiography evaluation for clinical outcome: An international multicenter registry (confirm) : An international multicenter registry (confirm)

    NARCIS (Netherlands)

    A. Ahmadi (Amir); J. Leipsic (Jonathon); G.M. Feuchtner (Gudrun); H. Gransar (Heidi); Kalra, D. (Dan); R. Heo (Ran); S. Achenbach (Stephan); D. Andreini (Daniele); M. Al-Mallah (Mouaz); D.S. Berman (Daniel S.); M.J. Budoff (Matthew); F. Cademartiri (Filippo); T.Q. Callister (Tracy); H.-J. Chang (Hyuk-Jae); K. Chinnaiyan (Kavitha); B.J.W. Chow (Benjamin); R.C. Cury (Ricardo); A. Delago (Augustin); M. Gomez (Millie); M. Hadamitzky (Martin); J. Hausleiter (Jörg); N. Hindoyan (Niree); P.A. Kaufmann (Philipp); Y.-J. Kim (Yong-Jin); F.Y. Lin (Fay); E. Maffei (Erica); G. Pontone (Gianluca); G.L. Raff (Gilbert); L.J. Shaw (Leslee); T.C. Villines (Todd); A.M. Dunning (Allison M.); J.K. Min (James)

    2015-01-01

    textabstractAlthough metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic

  11. Lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative and postoperatively prolonged extracorporeal membrane oxygenation provides optimally controlled reperfusion and excellent outcome.

    Science.gov (United States)

    Moser, Bernhard; Jaksch, Peter; Taghavi, Shahrokh; Muraközy, Gabriella; Lang, Georg; Hager, Helmut; Krenn, Claus; Roth, Georg; Faybik, Peter; Bacher, Andreas; Aigner, Clemens; Matilla, José R; Hoetzenecker, Konrad; Hacker, Philipp; Lang, Irene; Klepetko, Walter

    2018-01-01

    Lung transplantation for idiopathic pulmonary arterial hypertension has the highest reported postoperative mortality of all indications. Reasons lie in the complexity of treatment of these patients and the frequent occurrence of postoperative left ventricular failure. Transplantation on intraoperative extracorporeal membrane oxygenation support instead of cardiopulmonary bypass and even more the prolongation of extracorporeal membrane oxygenation into the postoperative period helps to overcome these problems. We reviewed our experience with this concept. All patients undergoing bilateral lung transplantation for idiopathic pulmonary arterial hypertension on intraoperative extracorporeal membrane oxygenation with or without prophylactic extracorporeal membrane oxygenation prolongation into the postoperative period between January 2000 and December 2014 were retrospectively analysed. Forty-one patients entered the study. Venoarterial extracorporeal membrane oxygenation support was prolonged into the postoperative period for a median of 2.5 days (range 1-40). Ninety-day, 1-, 3- and 5-year survival rates for the patient collective were 92.7%, 90.2%, 87.4% and 87.4%, respectively. When compared with 31 patients with idiopathic pulmonary arterial hypertension transplanted in the same period of time without prolongation of extracorporeal membrane oxygenation into the postoperative period, the results compared favourably (83.9%, 77.4%, 77.4%, and 77.4%; P = 0.189). Furthermore, these results are among the best results ever reported for this particularly difficult patient population. Bilateral lung transplantation for idiopathic pulmonary arterial hypertension with intraoperative venoarterial extracorporeal membrane oxygenation support seems to provide superior outcome compared with the results reported about the use of cardiopulmonary bypass. Prophylactic prolongation of venoarterial extracorporeal membrane oxygenation into the early postoperative period provides

  12. Clinical and radiographic outcomes of femoral head fractures: excision vs. fixation of fragment in Pipkin type I: what is the optimal choice for femoral head fracture?

    Science.gov (United States)

    Park, Kyung-Soon; Lee, Keun-Bae; Na, Bo-Ram; Yoon, Taek-Rim

    2015-07-01

    In this work, we present relatively long-term results of femoral head fractures with a specific focus on Pipkin type I fractures. Fifty-nine femoral head fractures were treated according to modified Pipkin's classification as follows: type I, small fragment distal to the fovea centralis (FC); type II, large fragment distal to the FC; type III, large fragment proximal to the FC; type IV, comminuted fracture. There were 15 cases of type I, 28 of type II, 9 of type III, and 7 of type IV fractures. Conservative treatment with skeletal traction was performed in 4 type II cases, excision of the fragment in 15 type I and 10 type II cases, fixation of the fragment in 14 type II and all 9 type III cases, and total hip replacement in all 7 type IV cases. The overall clinical and radiographic outcomes were evaluated using previously published criteria, focusing on the results in Pipkin type I fractures with relatively large fragments. Based on Epstein criteria, in type II fractures, excellent or good clinical results were seen in 6 of 10 patients (60.0 %) treated by excision of the fragment and 12 of 14 patients (85.7 %) treated by internal fixation (p = 0.05). Also, excellent or good radiologic results were seen in 4 of 10 (40.0 %) patients treated by excision of the fragment and 12 of 14 (85.7 %) patients treated by internal fixation (p = 0.03). Even in Pipkin type I fractures, if the fragment is large (modified Pipkin type II), early reduction and internal fixation can produce good results.

  13. Comparison of clinical outcomes in PRK with a standard and aspherical optimized profile: a full case analysis of 100 eyes with 1-year follow-up.

    Science.gov (United States)

    Dausch, Dieter; Dausch, Burglinde; Wottke, Matthias; Sluyterman van Langeweyde, Georg

    2014-01-01

    One hundred eyes from 55 adult patients with myopia were retrospectively studied to determine the comparative safety, efficacy, and predictability of aberration smart ablation (ASA) and a new advanced ablation algorithm (Triple-A) using the MEL(®) 80 excimer laser. Fifty myopic eyes with a manifest refraction spherical equivalent (MRSE) between -1.0 diopters (D) and -9.75 D were consecutively treated with photorefractive keratec-tomy ASA, and 50 myopic eyes with an MRSE between -1.38 D and -11.0 D with photorefractive keratectomy Triple-A. Uncorrected distance visual acuity, MRSE, the absolute value of the cylinder, corrected distance visual acuity, and postoperative complications at 1 month, 3 months, 6 months, and 12 months (1 year) were descriptively analyzed and compared at 1 year. After 12 months, the MRSE variance was statistically significantly better in patients triaged to receive Triple-A compared with patients receiving ASA (ASA, ±0.7 D; Triple-A, ±0.15 D; P<0.001). Furthermore, no patient in the Triple-A group had any cylinder postoperatively. Patients in the Triple-A treatment arm achieved a superior result. No statistically significant difference in the two treatment arms was noted for the analysis of the mean MRSE at 12 months (P=0.78). Triple-A was more effective than standard aspherical surgical intervention in a number of treatment outcome parameters (eg, MRSE, astigmatism, efficacy index). The two surgical procedures were equivalent in terms of safety.

  14. Comparison of clinical outcomes in PRK with a standard and aspherical optimized profile: a full case analysis of 100 eyes with 1-year follow-up

    Directory of Open Access Journals (Sweden)

    Dausch D

    2014-11-01

    Full Text Available Dieter Dausch,1,2 Burglinde Dausch,2 Matthias Wottke,3 Georg Sluyterman van Langeweyde31Chung-Ang University, Seoul, South Korea; 2Augen-Laser-Klinik Nürnberg, Nuremberg, Germany; 3Carl Zeiss Meditec AG, Jena, Germany Purpose: One hundred eyes from 55 adult patients with myopia were retrospectively studied to determine the comparative safety, efficacy, and predictability of aberration smart ablation (ASA and a new advanced ablation algorithm (Triple-A using the MEL® 80 excimer laser.Methods: Fifty myopic eyes with a manifest refraction spherical equivalent (MRSE between -1.0 diopters (D and -9.75 D were consecutively treated with photorefractive keratectomy ASA, and 50 myopic eyes with an MRSE between -1.38 D and -11.0 D with photorefractive keratectomy Triple-A. Uncorrected distance visual acuity, MRSE, the absolute value of the cylinder, corrected distance visual acuity, and postoperative complications at 1 month, 3 months, 6 months, and 12 months (1 year were descriptively analyzed and compared at 1 year.Results: After 12 months, the MRSE variance was statistically significantly better in patients triaged to receive Triple-A compared with patients receiving ASA (ASA, ±0.7 D; Triple-A, ±0.15 D; P<0.001. Furthermore, no patient in the Triple-A group had any cylinder postoperatively. Patients in the Triple-A treatment arm achieved a superior result. No statistically significant difference in the two treatment arms was noted for the analysis of the mean MRSE at 12 months (P=0.78.Conclusion: Triple-A was more effective than standard aspherical surgical intervention in a number of treatment outcome parameters (eg, MRSE, astigmatism, efficacy index. The two surgical procedures were equivalent in terms of safety. Keywords: aberration smart ablation (ASA, manifest refraction spherical equivalent, Triple-A advanced ablation algorithm, uncorrected distance visual acuity, corrected distance visual acuity, excimer laser, PRK, ablation profile

  15. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolis...

  16. Cancer cell metabolism: one hallmark, many faces.

    Science.gov (United States)

    Cantor, Jason R; Sabatini, David M

    2012-10-01

    Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes within the metabolic program of a cancer cell can dictate by what means proliferative rewiring is driven, and can also impart heterogeneity in the metabolic dependencies of the cell. A better understanding of this heterogeneity may enable the development and optimization of therapeutic strategies that target tumor metabolism.

  17. Genome-scale modeling for metabolic engineering.

    Science.gov (United States)

    Simeonidis, Evangelos; Price, Nathan D

    2015-03-01

    We focus on the application of constraint-based methodologies and, more specifically, flux balance analysis in the field of metabolic engineering, and enumerate recent developments and successes of the field. We also review computational frameworks that have been developed with the express purpose of automatically selecting optimal gene deletions for achieving improved production of a chemical of interest. The application of flux balance analysis methods in rational metabolic engineering requires a metabolic network reconstruction and a corresponding in silico metabolic model for the microorganism in question. For this reason, we additionally present a brief overview of automated reconstruction techniques. Finally, we emphasize the importance of integrating metabolic networks with regulatory information-an area which we expect will become increasingly important for metabolic engineering-and present recent developments in the field of metabolic and regulatory integration.

  18. A Metabolic Race

    Directory of Open Access Journals (Sweden)

    A.M.S. Costa et al.

    2017-07-01

    Full Text Available Metabolic Syndrome describes a set of metabolic risk factors that manifest in an individual and some aspects contribute to its appearance: genetic, overweight and the absence of physical activity. So, a board game was created to simulate the environment and routine experienced by UFF students that could contribute  to the development of Metabolic Syndrome. Players move along a simplified map of Niterói city, where places as Antônio Pedro Hospital (HUAP are pointed out. OBJECTIVES: This project aimed to develop an educational game to consolidate Metabolic Syndrome biochemical events. MATERIAL E METHODS: Each group receives a board, pins, dice, question, challenge and diagnostics cards. One student performs the family doctor function, responsable for delivering cards, reading activities and providing diagnosis to players when game is over.The scoring system is based on 3 criteria for Metabolic Syndrome diagnosis: glycemia, abdominal obesity and HDL cholesterol. At the end of game, it is possible to calculate the rates of each player and provide proportional diagnosis. The winner is the healthiest that first arrives at HUAP. RESULTS AND DISCUSSION: The game was applied to 50 students and only 10% classified the subject-matter as difficult. This finding highlight the need to establish new methods to enhance the teaching and learning process and decrease the students’ dificulties. Students evaluated the game as an important educational support and 85% of them agreed it complements  and consolidate the content discussed in classroom. Finally, the game was very highly rated by students according to their perception about their own performance while playing.  In addition, 95 % students pointed they would play again and 98% said they think games are able to optimize learning. CONCLUSIONS: It was possible not only to approximate biochemical phenomena to the students’ daily life, but also to solidify the theoretical concepts in a dynamic and fun

  19. A randomised trial of a psychosocial intervention for cancer patients integrated into routine care: the PROMPT study (promoting optimal outcomes in mood through tailored psychosocial therapies

    Directory of Open Access Journals (Sweden)

    Jolley Damien

    2011-02-01

    Full Text Available Abstract Background Despite evidence that up to 35% of patients with cancer experience significant distress, access to effective psychosocial care is limited by lack of systematic approaches to assessment, a paucity of psychosocial services, and patient reluctance to accept treatment either because of perceived stigma or difficulties with access to specialist psycho-oncology services due to isolation or disease burden. This paper presents an overview of a randomised study to evaluate the effectiveness of a brief tailored psychosocial Intervention delivered by health professionals in cancer care who undergo focused training and participate in clinical supervision. Methods/design Health professionals from the disciplines of nursing, occupational therapy, speech pathology, dietetics, physiotherapy or radiation therapy will participate in training to deliver the psychosocial Intervention focusing on core concepts of supportive-expressive, cognitive and dignity-conserving care. Health professional training will consist of completion of a self-directed manual and participation in a skills development session. Participating health professionals will be supported through structured clinical supervision whilst delivering the Intervention. In the stepped wedge design each of the 5 participating clinical sites will be allocated in random order from Control condition to Training then delivery of the Intervention. A total of 600 patients will be recruited across all sites. Based on level of distress or risk factors eligible patients will receive up to 4 sessions, each of up to 30 minutes in length, delivered face-to-face or by telephone. Participants will be assessed at baseline and 10-week follow-up. Patient outcome measures include anxiety and depression, quality of life, unmet psychological and supportive care needs. Health professional measures include psychological morbidity, stress and burnout. Process evaluation will be conducted to assess perceptions

  20. Guided randomness in optimization

    CERN Document Server

    Clerc, Maurice

    2015-01-01

    The performance of an algorithm used depends on the GNA. This book focuses on the comparison of optimizers, it defines a stress-outcome approach which can be derived all the classic criteria (median, average, etc.) and other more sophisticated.   Source-codes used for the examples are also presented, this allows a reflection on the ""superfluous chance,"" succinctly explaining why and how the stochastic aspect of optimization could be avoided in some cases.

  1. Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Sevil Ikinci

    2010-10-01

    Full Text Available Metabolic Syndrome is a combination of risk factors including common etiopathogenesis. These risk factors play different roles in occurence of atherosclerotic diseases, type 2 diabetes, and cancers. Although a compromise can not be achieved on differential diagnosis for MS, the existence of any three criterias enable to diagnose MS. These are abdominal obesity, dislipidemia (hypertrigliceridemia, hypercholesterolemia, and reduced high density lipoprotein hypertension, and elevated fasting blood glucose. According to the results of Metabolic Syndrome Research (METSAR, the overall prevalence of MS in Turkey is 34%; in females 40%, and in males it is 28%. As a result of “Western” diet, and increased frequency of obesity, MS is observed in children and in adolescents both in the world and in Turkey. Resulting in chronic diseases, it is thought that the syndrome can be prevented by healthy lifestyle behaviours. [TAF Prev Med Bull 2010; 9(5.000: 535-540

  2. Cellular metabolism

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  3. Circadian physiology of metabolism.

    Science.gov (United States)

    Panda, Satchidananda

    2016-11-25

    A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

  4. Impact of Dietary Carbohydrate and Protein Levels on Carbohydrate Metabolism

    Science.gov (United States)

    Lasker, Denise Ann

    2009-01-01

    The goal of this dissertation was to investigate the impact of changing dietary carbohydrate (CARB) intakes within recommended dietary guidelines on metabolic outcomes specifically associated with glycemic regulations and carbohydrate metabolism. This research utilized both human and animal studies to examine changes in metabolism across a wide…

  5. Clinical neurogenetics: neurologic presentations of metabolic disorders.

    Science.gov (United States)

    Kwon, Jennifer M; D'Aco, Kristin E

    2013-11-01

    This article reviews aspects of the neurologic presentations of selected treatable inborn errors of metabolism within the category of small molecule disorders caused by defects in pathways of intermediary metabolism. Disorders that are particularly likely to be seen by neurologists include those associated with defects in amino acid metabolism (organic acidemias, aminoacidopathies, urea cycle defects). Other disorders of small molecule metabolism are discussed as additional examples in which early treatments have the potential for better outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Comparison of early clinical outcomes following transcatheter aortic valve implantation versus surgical aortic valve replacement versus optimal medical therapy in patients older than 80 years with symptomatic severe aortic stenosis.

    Science.gov (United States)

    Im, Eui; Hong, Myeong-Ki; Ko, Young-Guk; Shin, Dong-Ho; Kim, Jung-Sun; Kim, Byeong-Keuk; Choi, Donghoon; Shim, Chi Young; Chang, Hyuk-Jae; Shim, Jae-Kwang; Kwak, Young-Lan; Lee, Sak; Chang, Byung-Chul; Jang, Yangsoo

    2013-05-01

    Transcatheter aortic valve implantation (TAVI) has become an attractive therapeutic strategy for severe aortic stenosis (AS) in elderly patients due to its minimally-invasive nature. Therefore, early results of its clinical outcomes in elderly Korean patients were evaluated. We compared early clinical outcomes of TAVI, surgical aortic valve replacement (SAVR), and optimal medical therapy (OMT) in patients aged≥80 years with symptomatic severe AS. Treatment groups were allocated as follows: TAVI (n=10), SAVR (n=14), and OMT (n=42). Baseline clinical characteristics including predicted operative mortality were similar among the three groups. However, patients with New York Heart Association functional class III or IV symptoms and smaller aortic valve area were treated with TAVI or SAVR rather than OMT. In-hospital combined safety endpoints (all-cause mortality, major stroke, peri-procedural myocardial infarction, life-threatening bleeding, major vascular complication, and acute kidney injury) after TAVI or SAVR were significantly lower in the TAVI group than in the SAVR group (10.0% vs. 71.4%, respectively, p=0.005), along with an acceptable rate of symptom improvement and device success. During the follow-up period, the TAVI group showed the lowest rate of 3-month major adverse cardiovascular and cerebrovascular events, a composite of all-cause mortality, myocardial infarction, major stroke, and re-hospitalization (TAVI 0.0% vs. SAVR 50.0% vs. OMT 42.9%, p=0.017). Treatment with TAVI was associated with lower event rates compared to SAVR or OMT. Therefore, TAVI may be considered as the first therapeutic strategy in selected patients aged≥80 years with symptomatic severe AS.

  7. Optimization an optimal artificial diet for the predatory bug Orius sauteri (hemiptera: anthocoridae.

    Directory of Open Access Journals (Sweden)

    Xiao-Ling Tan

    Full Text Available BACKGROUND: The flower bug Orius sauteri is an important polyphagous predator that is widely used for the biological control of mites and aphids. However, the optimal conditions for mass rearing of this insect are still unclear, thus limiting its application. METHODOLOGY: In this study, we investigated the optimal ingredients of an artificial diet for raising O. sauteri using a microencapsulation technique. The ingredients included egg yolk (vitellus, whole-pupa homogenate of the Tussah silk moth (Antheraea paphia, honey, sucrose, rapeseed (Brassica napus pollen and sinkaline. We tested 25 combinations of the above ingredients using an orthogonal experimental design. Using statistical analysis, we confirmed the main effect factors amongst the components, and selected five optimal combinations based on different biological and physiological characters. PRINCIPAL FINDINGS: The results showed that, although different artificial diet formats significantly influenced the development and reproductive ability of O. sauteri, the complete development of O. sauteri to sexual maturity could only be achieved by optimizing the artificial diet according to specific biological characters. In general, pupae of A. paphia had more influence on O sauteri development than did artificial components. The results of a follow-up test of locomotory and respiratory capacity indicated that respiratory quotient, metabolic rate and average creeping speed were all influenced by different diets. Furthermore, the field evaluations of mating preference, predatory consumption and population dispersion also demonstrated the benefits that could be provided by optimal artificial diets. CONCLUSIONS: A microencapsulated artificial diet overcame many of the difficulties highlighted by previous studies on the mass rearing of O. sauteri. Optimization of the microencapsulated artificial diet directly increased the biological and physiological characters investigated. Successive

  8. Metabolic Surgery in Korea: What to Consider before Surgery

    Directory of Open Access Journals (Sweden)

    Mi-Kyung Kim

    2017-09-01

    Full Text Available Obesity is increasing globally and represents a significant global health problem because it predisposes towards various diseases, such as type 2 diabetes mellitus, cardiovascular disease, degenerative joint disease, and certain types of cancer. Numerous studies have shown that bariatric surgery reduces body mass and ameliorates obesity-related complications, such as hypertension and hyperglycemia, suggesting that surgery is the most effective therapeutic option for severely obese and obese diabetic patients. Recent international guidelines recommend surgical treatment for diabetic patients with class III obesity (body mass index [BMI] >40 kg/m2, regardless of their level of glycemic control or the complexity of their glucose-lowering regimens, and for patients with class II obesity (BMI 35.0 to 39.9 kg/m2 and hyperglycemia that is poorly controlled despite appropriate lifestyle and pharmacological therapy. The most popular procedures are Roux-en-Y gastric bypass and sleeve gastrectomy, but new procedures with better outcomes have been reported. For optimal surgical outcome, comprehensive management including assessments of a medical condition, nutrition, mental health, and social support is needed before and after surgery. However, there is still a lack of understanding regarding metabolic surgery in Korea. Therefore, this article reviews indications for metabolic surgery in patients with a specific focus on the situation in Korea.

  9. Optimizing Outcomes of Colorectal Cancer Screening

    NARCIS (Netherlands)

    R.G.S. Meester (Reinier)

    2017-01-01

    markdownabstractColorectal cancer is a leading cause of cancer deaths. Screening for colorectal cancer is implemented in an increasing number of settings, but performance of programs is often suboptimal. In this thesis, advanced modeling, informed by empirical data, was used to identify areas for

  10. Metabolically Healthy Obesity and Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Hansen, Louise; Netterstrom, Marie K.; Johansen, Nanna B.

    2017-01-01

    Context: Recent studies have suggested that a subgroup of obese individuals is not at increased risk of obesity-related complications. This subgroup has been referred to as metabolically healthy obese. Objective: To investigate whether obesity is a risk factor for development of ischemic heart...... risk factors (low high-density lipoprotein cholesterol, elevated blood pressure, triglycerides, and fasting plasma glucose). Metabolically healthy individuals were defined as having no metabolic risk factors, and metabolically unhealthy individuals were defined as having a minimum of one. Main Outcome...... Measures: IHD. Results: During follow-up, 323 participants developed IHD. Metabolically healthy obese men had increased risk of IHD compared with metabolically healthy normal-weight men [hazard ratio (HR), 3.1; 95% confidence interval (CI), 1.1 to 8.2)]. The corresponding results for women were less...

  11. Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

    Science.gov (United States)

    McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

    2015-09-01

    Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  12. Optimism and Adaptation to Multiple Sclerosis: What Does Optimism Mean?

    NARCIS (Netherlands)

    Fournier, M.; Ridder, D.T.D. de; Bensing, J.

    1999-01-01

    The aim of the present study was to determine the meaning of optimism by explicating the dimensions underlying the notion and their links to adjusting to MS. Seventy-three patients responded to optimism questionnaire s (i.e., the LOT, Generalized Self-Efficacy Scale) and outcome questionnaires.

  13. Optimism and adaptation to multiple sclerosis: what does optimism mean?

    NARCIS (Netherlands)

    Fournier, M.; Ridder, D. de; Bensing, J.

    1999-01-01

    The aim of the present study was to determine the meaning of optimism by explicating the dimensions underlying the notion and their links to adjusting to MS. Seventy-three patients responded to optimism questionnaires (i.e., the LOT, Generalized Self-Efficacy Scale) and outcome questionnaires. In

  14. Degradation Rate of 5-Fluorouracil in Metastatic Colorectal Cancer: A New Predictive Outcome Biomarker?

    Directory of Open Access Journals (Sweden)

    Andrea Botticelli

    Full Text Available 5-FU based chemotherapy is the most common first line regimen used for metastatic colorectal cancer (mCRC. Identification of predictive markers of response to chemotherapy is a challenging approach for drug selection. The present study analyzes the predictive role of 5-FU degradation rate (5-FUDR and genetic polymorphisms (MTHFR, TSER, DPYD on survival.Genetic polymorphisms of MTHFR, TSER and DPYD, and the 5-FUDR of homogenous patients with mCRC were retrospectively studied. Genetic markers and the 5-FUDR were correlated with clinical outcome.133 patients affected by mCRC, treated with fluoropyrimidine-based chemotherapy from 2009 to 2014, were evaluated. Patients were classified into three metabolic classes, according to normal distribution of 5-FUDR in more than 1000 patients, as previously published: poor-metabolizer (PM with 5-FU-DR ≤ 0,85 ng/ml/106 cells/min (8 pts; normal metabolizer with 0,85 < 5-FU-DR < 2,2 ng/ml/106 cells/min (119 pts; ultra-rapid metabolizer (UM with 5-FU-DR ≥ 2,2 ng/ml/106 cells/min (6 pts. PM and UM groups showed a longer PFS respect to normal metabolizer group (14.5 and 11 months respectively vs 8 months; p = 0.029. A higher G3-4 toxicity rate was observed in PM and UM, respect to normal metabolizer (50% in both PM and UM vs 18%; p = 0.019. No significant associations between genes polymorphisms and outcomes or toxicities were observed.5-FUDR seems to be significantly involved in predicting survival of patients who underwent 5-FU based CHT for mCRC. Although our findings require confirmation in large prospective studies, they reinforce the concept that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes.

  15. A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

    DEFF Research Database (Denmark)

    Hefzi, Hooman; Ang, Kok Siong; Hanscho, Michael

    2016-01-01

    Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways...

  16. Carbohydrate Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose (a type of sugar). If ...

  17. Comprehensive metabolic panel

    Science.gov (United States)

    Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... Chernecky CC, Berger BJ. Comprehensive metabolic panel (CMP) - blood. In: ... Tests and Diagnostic Procedures . 6th ed. St Louis, MO: ...

  18. Metabolic syndrome: nature, therapeutic solutions and options.

    Science.gov (United States)

    Onat, Altan

    2011-08-01

    Metabolic syndrome (MetS) defines the clustering in an individual of multiple metabolic abnormalities, based on central obesity and insulin resistance. In addition to its five components, prothrombotic and proinflammatory states are essential features. The significance of MetS lies in its close association with the risk of type 2 diabetes and cardiovascular disease (CVD). This field being an evolving one necessitated the current review. The areas covered in this review include the so far unproven concept that enhanced low-grade inflammation often leads to dysfunction of the anti-inflammatory and atheroprotective properties of apolipoprotein A-I (apoA-I) and HDL particles, which further increases the risk of diabetes and CVD. It was emphasized that lifestyle modification is essential in the prevention and management of MetS, which includes maintenance of optimal weight by caloric restriction, adherence to a diet that minimizes postprandial glucose and triglyceride fluctuations, restricting alcohol consumption, smoking cessation and engaging in regular exercise. Drug therapy should target the dyslipoproteinemia and the often associated hypertension or dysglycemia.Statins are the drugs of first choice, to be initiated in patients with MetS at high 10-year cardiovascular risk. Such treatment is inadequate if fasting serum triglycerides remain at > 150 mg/dl, when niacin should be combined. Fibrates, omega 3 fatty acids, metformin, angiotensin-converting enzyme inhibitors and pioglitazone are additional options in drug therapy. Research on MetS in subpopulations prone to impaired glucose tolerance and insulin resistance has indicated that proinflammatory state and oxidative stress are often prominently involved in MetS, to the extent that evidence of impaired function of HDL and apo A-I particles is discernible by biological evidence of functional defectiveness via outcomes studies and/or correlations with inflammatory and anti-inflammatory biomarkers. A sex difference

  19. Adherence issues in inherited metabolic disorders treated by low natural protein diets

    DEFF Research Database (Denmark)

    MaCdonald, A; van Rijn, M; Feillet, F

    2012-01-01

    Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor......-free or essential L-AAs are important in all these conditions. Optimal long-term outcome depends on early diagnosis and good metabolic control, but because of the rarity and severity of conditions, randomized controlled trials are scarce. In all of these disorders, it is commonly described that dietary adherence...... on their neuropsychological profile. There are little data about their ability to self-manage their own diet or the success of any formal educational programs that may have been implemented. Trials conducted in non-phenylketonuria (PKU) patients are rare, and the development of specialist L-AAs for non-PKU AA disorders has...

  20. Availability of public goods shapes the evolution of competing metabolic strategies.

    Science.gov (United States)

    Bachmann, Herwig; Fischlechner, Martin; Rabbers, Iraes; Barfa, Nakul; Branco dos Santos, Filipe; Molenaar, Douwe; Teusink, Bas

    2013-08-27

    Tradeoffs provide a rationale for the outcome of natural selection. A prominent example is the negative correlation between the growth rate and the biomass yield in unicellular organisms. This tradeoff leads to a dilemma, where the optimization of growth rate is advantageous for an individual, whereas the optimization of the biomass yield would be advantageous for a population. High-rate strategies are observed in a broad variety of organisms such as Escherichia coli, yeast, and cancer cells. Growth in suspension cultures favors fast-growing organisms, whereas spatial structure is of importance for the evolution of high-yield strategies. Despite this realization, experimental methods to directly select for increased yield are lacking. We here show that the serial propagation of a microbial population in a water-in-oil emulsion allows selection of strains with increased biomass yield. The propagation in emulsion creates a spatially structured environment where the growth-limiting substrate is privatized for populations founded by individual cells. Experimental evolution of several isogenic Lactococcus lactis strains demonstrated the existence of a tradeoff between growth rate and biomass yield as an apparent Pareto front. The underlying mutations altered glucose transport and led to major shifts between homofermentative and heterofermentative metabolism, accounting for the changes in metabolic efficiency. The results demonstrated the impact of privatizing a public good on the evolutionary outcome between competing metabolic strategies. The presented approach allows the investigation of fundamental questions in biology such as the evolution of cooperation, cell-cell interactions, and the relationships between environmental and metabolic constraints.

  1. Disturbance by optimal discrimination

    Science.gov (United States)

    Kawakubo, Ryûitirô; Koike, Tatsuhiko

    2018-03-01

    We discuss the disturbance by measurements which unambiguously discriminate between given candidate states. We prove that such an optimal measurement necessarily changes distinguishable states indistinguishable when the inconclusive outcome is obtained. The result was previously shown by Chefles [Phys. Lett. A 239, 339 (1998), 10.1016/S0375-9601(98)00064-4] under restrictions on the class of quantum measurements and on the definition of optimality. Our theorems remove these restrictions and are also applicable to infinitely many candidate states. Combining with our previous results, one can obtain concrete mathematical conditions for the resulting states. The method may have a wide variety of applications in contexts other than state discrimination.

  2. Inherited metabolic liver diseases in infants and children: an overview

    Directory of Open Access Journals (Sweden)

    Ivo Barić

    2013-10-01

    damage into portal cirrhosis, this classisfication is still very useful. Diagnostic work-up in an unexplained liver disease can be very complex and tricky, particularly in patients with (subacute liver failure, when the time for interventions is limited, many pathological laboratory results can be a secondary abnormality, and many specific tests should be done and interpreted properly in parallel with various treatment measures. In such clinical setting, specific knowledge, skills, experience, special drugs and properly equiped diagnostic laboratories are, as a rule, necessary for good clinical outcome. Therefore, it is highly recommended to transfer the patient as soon as possible to a specialized center where all these requirements can be fulfilled by an experienced specialized team comprising pediatric gastroenterologist, subspecialist in metabolic diseases, intensivist, surgeon, biochemist and others. Such an approach is the only way to decrease the still high proportion of patients with inherited metabolic liver diseases who remain causally undiagnosed and whose outcome is far from optimal.

  3. Nonlinear optimization

    CERN Document Server

    Ruszczynski, Andrzej

    2011-01-01

    Optimization is one of the most important areas of modern applied mathematics, with applications in fields from engineering and economics to finance, statistics, management science, and medicine. While many books have addressed its various aspects, Nonlinear Optimization is the first comprehensive treatment that will allow graduate students and researchers to understand its modern ideas, principles, and methods within a reasonable time, but without sacrificing mathematical precision. Andrzej Ruszczynski, a leading expert in the optimization of nonlinear stochastic systems, integrates the theory and the methods of nonlinear optimization in a unified, clear, and mathematically rigorous fashion, with detailed and easy-to-follow proofs illustrated by numerous examples and figures. The book covers convex analysis, the theory of optimality conditions, duality theory, and numerical methods for solving unconstrained and constrained optimization problems. It addresses not only classical material but also modern top...

  4. Website Optimization

    CERN Document Server

    King, Andrew

    2008-01-01

    Remember when an optimized website was one that merely didn't take all day to appear? Times have changed. Today, website optimization can spell the difference between enterprise success and failure, and it takes a lot more know-how to achieve success. This book is a comprehensive guide to the tips, techniques, secrets, standards, and methods of website optimization. From increasing site traffic to maximizing leads, from revving up responsiveness to increasing navigability, from prospect retention to closing more sales, the world of 21st century website optimization is explored, exemplified a

  5. Optimally frugal foraging

    Science.gov (United States)

    Bénichou, O.; Bhat, U.; Krapivsky, P. L.; Redner, S.

    2018-02-01

    We introduce the frugal foraging model in which a forager performs a discrete-time random walk on a lattice in which each site initially contains S food units. The forager metabolizes one unit of food at each step and starves to death when it last ate S steps in the past. Whenever the forager eats, it consumes all food at its current site and this site remains empty forever (no food replenishment). The crucial property of the forager is that it is frugal and eats only when encountering food within at most k steps of starvation. We compute the average lifetime analytically as a function of the frugality threshold and show that there exists an optimal strategy, namely, an optimal frugality threshold k* that maximizes the forager lifetime.

  6. Optimality Conditions in Vector Optimization

    CERN Document Server

    Jiménez, Manuel Arana; Lizana, Antonio Rufián

    2011-01-01

    Vector optimization is continuously needed in several science fields, particularly in economy, business, engineering, physics and mathematics. The evolution of these fields depends, in part, on the improvements in vector optimization in mathematical programming. The aim of this Ebook is to present the latest developments in vector optimization. The contributions have been written by some of the most eminent researchers in this field of mathematical programming. The Ebook is considered essential for researchers and students in this field.

  7. Medicinsk Optimering

    DEFF Research Database (Denmark)

    Birkholm, Klavs

    2010-01-01

    En undersøgelse af anvendelsen af medicin til optimering af koncentration, hukommelse og følelsestonus. Efterfulgt af etiske overvejelser og anbefalinger til det politiske system......En undersøgelse af anvendelsen af medicin til optimering af koncentration, hukommelse og følelsestonus. Efterfulgt af etiske overvejelser og anbefalinger til det politiske system...

  8. Structural optimization

    CERN Document Server

    MacBain, Keith M

    2009-01-01

    Intends to supplement the engineer's box of analysis and design tools making optimization as commonplace as the finite element method in the engineering workplace. This title introduces structural optimization and the methods of nonlinear programming such as Lagrange multipliers, Kuhn-Tucker conditions, and calculus of variations.

  9. Metabolic engineering in methanotrophic bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Kalyuzhnaya, MG; Puri, AW; Lidstrom, ME

    2015-05-01

    Methane, as natural gas or biogas, is the least expensive source of carbon for (bio)chemical synthesis. Scalable biological upgrading of this simple alkane to chemicals and fuels can bring new sustainable solutions to a number of industries with large environmental footprints, such as natural gas/petroleum production, landfills, wastewater treatment, and livestock. Microbial biocatalysis with methane as a feedstock has been pursued off and on for almost a half century, with little enduring success. Today, biological engineering and systems biology provide new opportunities for metabolic system modulation and give new optimism to the concept of a methane-based bio-industry. Here we present an overview of the most recent advances pertaining to metabolic engineering of microbial methane utilization. Some ideas concerning metabolic improvements for production of acetyl-CoA and pyruvate, two main precursors for bioconversion, are presented. We also discuss main gaps in the current knowledge of aerobic methane utilization, which must be solved in order to release the full potential of methane-based biosystems. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  10. Synthetic biology and metabolic engineering.

    Science.gov (United States)

    Stephanopoulos, Gregory

    2012-11-16

    Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

  11. Topology Optimization

    DEFF Research Database (Denmark)

    A. Kristensen, Anders Schmidt; Damkilde, Lars

    2007-01-01

    . A way to solve the initial design problem namely finding a form can be solved by so-called topology optimization. The idea is to define a design region and an amount of material. The loads and supports are also fidefined, and the algorithm finds the optimal material distribution. The objective function...... dictates the form, and the designer can choose e.g. maximum stiness, maximum allowable stresses or maximum lowest eigenfrequency. The result of the topology optimization is a relatively coarse map of material layout. This design can be transferred to a CAD system and given the necessary geometrically...... refinements, and then remeshed and reanalysed in other to secure that the design requirements are met correctly. The output of standard topology optimization has seldom well-defined, sharp contours leaving the designer with a tedious interpretation, which often results in less optimal structures. In the paper...

  12. Next-generation genome-scale models for metabolic engineering

    DEFF Research Database (Denmark)

    King, Zachary A.; Lloyd, Colton J.; Feist, Adam M.

    2015-01-01

    Constraint-based reconstruction and analysis (COBRA) methods have become widely used tools for metabolic engineering in both academic and industrial laboratories. By employing a genome-scale in silico representation of the metabolic network of a host organism, COBRA methods can be used to predict...... examples of applying COBRA methods to strain optimization are presented and discussed. Then, an outlook is provided on the next generation of COBRA models and the new types of predictions they will enable for systems metabolic engineering....

  13. Evolutionary programming as a platform for in silico metabolic engineering

    DEFF Research Database (Denmark)

    Patil, Kiran Raosaheb; Rocha, Isabel; Förster, Jochen

    2005-01-01

    , and it is therefore interesting to develop new faster algorithms. Results In this study we report an evolutionary programming based method to rapidly identify gene deletion strategies for optimization of a desired phenotypic objective function. We illustrate the proposed method for two important design parameters...... of close to optimal solutions. The identified metabolic engineering strategies suggest that non-intuitive genetic modifications span several different pathways and may be necessary for solving challenging metabolic engineering problems....

  14. Adherence to two methods of education and metabolic control in ...

    African Journals Online (AJOL)

    BACKGROUND: Education in diabetes optimizes metabolic control, prevents acute and chronic complications, and improves quality of life. Our main objective was to evaluate if a better metabolic control is achieved in diabetic patients undergoing a program of intensive interactive care than in those with traditional care and ...

  15. Evaluation of empowerment model on indicators of metabolic control in patients with type 2 diabetes, a randomized clinical trial study.

    Science.gov (United States)

    Ebrahimi, Hossein; Sadeghi, Mahdi; Amanpour, Farzaneh; Vahedi, Hamid

    2016-04-01

    Diabetes education is a major subject in achieving optimal glycemic control. Effective empowerment approach can be beneficial for improving patients' health. The aim of this study was to evaluate the effect of empowerment model on indicators of metabolic control in patients with type 2 diabetes. a randomized controlled trial of 103 patients with type 2 diabetes were randomly assigned to either the intervention (empowerment approach training) or the control group (conventional training) 2014. Empowerment approach training were performed for the experimental group for eight weeks. Data collection tool included demographic information form and indicators of metabolic control checklist. Analysis was performed by one-way analysis of variance, chi-square test, paired t-test, independent t-test and multiple linear regression. Before the intervention, two groups were homogeneous in terms of demographic variables, glycosylated hemoglobin (HbA1C), and other indicators of metabolic control. After the intervention, average HbA1C and other metabolic indicators except for LDL showed significant differences in the experimental group compared to the control group. study results indicated the positive effects of applying the empowerment model on the metabolic control indicators. Therefore, applying this model is recommended to nurses and the relevant authorities in order to improve clinical outcomes in diabetic patients. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  16. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection.

    Science.gov (United States)

    Gilliland, Taylor M; Villafane-Ferriol, Nicole; Shah, Kevin P; Shah, Rohan M; Tran Cao, Hop S; Massarweh, Nader N; Silberfein, Eric J; Choi, Eugene A; Hsu, Cary; McElhany, Amy L; Barakat, Omar; Fisher, William; Van Buren, George

    2017-03-07

    Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995-2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate treatment to improve the patient's quality of life.

  17. Mineral Metabolic Abnormalities and Mortality in Dialysis Patients

    Directory of Open Access Journals (Sweden)

    Masanori Abe

    2013-03-01

    Full Text Available The survival rate of dialysis patients, as determined by risk factors such as hypertension, nutritional status, and chronic inflammation, is lower than that of the general population. In addition, disorders of bone mineral metabolism are independently related to mortality and morbidity associated with cardiovascular disease and fracture in dialysis patients. Hyperphosphatemia is an important risk factor of, not only secondary hyperparathyroidism, but also cardiovascular disease. On the other hand, the risk of death reportedly increases with an increase in adjusted serum calcium level, while calcium levels below the recommended target are not associated with a worsened outcome. Thus, the significance of target levels of serum calcium in dialysis patients is debatable. The consensus on determining optimal parathyroid function in dialysis patients, however, is yet to be established. Therefore, the contribution of phosphorus and calcium levels to prognosis is perhaps more significant. Elevated fibroblast growth factor 23 levels have also been shown to be associated with cardiovascular events and death. In this review, we examine the associations between mineral metabolic abnormalities including serum phosphorus, calcium, and parathyroid hormone and mortality in dialysis patients.

  18. Weight Changes and Metabolic Outcomes in Calorie-Restricted Obese Mice Fed High-Fat Diets Containing Corn or Flaxseed Oil: Physiological Role of Sugar Replacement with Polyphenol-Rich Grape.

    Science.gov (United States)

    Ansar, Hastimansooreh; Zamaninour, Negar; Djazayery, Abolghassem; Pishva, Hamideh; Vafa, Mohammadreza; Mazaheri Nezhad Fard, Ramin; Dilmaghanian, Aydin; Mirzaei, Khadijeh; Shidfar, Farzad

    2017-08-01

    Because diet components are important during dieting in obesity treatment, we examined possible beneficial effects of substituting corn oil and sugar with flaxseed oil and grape in calorie-restricted high-fat diets on weight changes as well as improvement in some metabolic markers and related gene expression. Seventy-five C57BL/6J male mice were given free access to a high-fat (36% of energy from fat) diet containing corn oil plus sugar (CO + S). After 11 weeks, 15 mice were sacrificed and another 60 were divided among 4 high-fat diet groups with 30% calorie restriction (CR) for the next 12 weeks. The diets contained corn oil (CO) or flaxseed oil (FO) with sugar (S) or grape (G). Despite CR, a weight loss trend was observed only during the first 4 weeks in all groups. CR did not significantly increase SIRT1 gene expression. Higher liver weight was observed in mice consuming FO (p sugar (FBS) was significantly higher than in CO + G-CR. Grape intake increased Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression and decreased insulin resistance in CO + G-CR. Sugar replacement with polyphenol-rich grape along with CR improved glucose homeostasis, and substituting corn oil with flaxseed oil in obese mice reduced fat mass, but even with no change in adiponectin levels it could not decrease insulin resistance. However, none of the food item combinations facilitated weight reduction in the long-term CR. Therefore, regardless of the total calorie intake, different diet components and fat contents may have unexpected effects on metabolic regulation.

  19. Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling.

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava

    2018-01-11

    Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies.

  20. Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava

    2018-01-01

    Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies. PMID:29324649

  1. Metabolic Effects of Intermittent Fasting.

    Science.gov (United States)

    Patterson, Ruth E; Sears, Dorothy D

    2017-08-21

    The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.

  2. Intermittent metabolic switching, neuroplasticity and brain health

    Science.gov (United States)

    Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu

    2018-01-01

    During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease. PMID:29321682

  3. Partisan Optimism and Political Bargaining

    DEFF Research Database (Denmark)

    Jensen, Thomas; Madum, Andreas

    Partisan voters are optimistic about electoral outcomes: their estimates of the probability of electoral success for their party or candidate are substantially higher than the average among the electorate. This has large potential implications for political bargaining. Optimism about future...... electoral outcomes can make costly bargaining delay look more favorable, which may induce partisans to punish their party for agreeing to a compromise rather than waiting, for example by not turning out to vote. Therefore, party decision makers should take optimism among partisans into account when...... bargaining. In this paper we use game theoretic modeling to explore the implications of partisan optimism for political bargaining. We show that increased optimism among a partisan group leads to a stronger bargaining position for their party, but may hurt its electoral prospects. Another main finding...

  4. Portfolio Optimization

    OpenAIRE

    Issagali, Aizhan; Alshimbayeva, Damira; Zhalgas, Aidana

    2015-01-01

    In this paper Portfolio Optimization techniques were used to determine the most favorable investment portfolio. In particular, stock indices of three companies, namely Microsoft Corporation, Christian Dior Fashion House and Shevron Corporation were evaluated. Using this data the amounts invested in each asset when a portfolio is chosen on the efficient frontier were calculated. In addition, the Portfolio with minimum variance, tangency portfolio and optimal Markowitz portfolio are presented.

  5. Protein design in systems metabolic engineering for industrial strain development.

    Science.gov (United States)

    Chen, Zhen; Zeng, An-Ping

    2013-05-01

    Accelerating the process of industrial bacterial host strain development, aimed at increasing productivity, generating new bio-products or utilizing alternative feedstocks, requires the integration of complementary approaches to manipulate cellular metabolism and regulatory networks. Systems metabolic engineering extends the concept of classical metabolic engineering to the systems level by incorporating the techniques used in systems biology and synthetic biology, and offers a framework for the development of the next generation of industrial strains. As one of the most useful tools of systems metabolic engineering, protein design allows us to design and optimize cellular metabolism at a molecular level. Here, we review the current strategies of protein design for engineering cellular synthetic pathways, metabolic control systems and signaling pathways, and highlight the challenges of this subfield within the context of systems metabolic engineering. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. The metabolic consequences of thyroxine replacement in adult hypopituitary patients

    DEFF Research Database (Denmark)

    Filipsson Nyström, Helena; Feldt-Rasmussen, Ulla; Kourides, Ione

    2012-01-01

    The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database...

  7. Drug discovery strategies in the field of tumor energy metabolism: Limitations by metabolic flexibility and metabolic resistance to chemotherapy.

    Science.gov (United States)

    Amoedo, N D; Obre, E; Rossignol, R

    2017-08-01

    The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro. Such contradictory findings raised several questions concerning the optimization of drug discovery strategies in the field of cancer metabolism. For instance, the cell culture models in 2D or 3D might already show strong limitations to mimic the tumor micro- and macro-environment. The microenvironment of tumors is composed of cancer cells of variegated metabolic profiles, supporting local metabolic exchanges and symbiosis, but also of immune cells and stroma that further interact with and reshape cancer cell metabolism. The macroenvironment includes the different tissues of the organism, capable of exchanging signals and fueling the tumor 'a distance'. Moreover, most metabolic targets were identified from their increased expression in tumor transcriptomic studies, or from targeted analyses looking at the metabolic impact of particular oncogenes or tumor suppressors on selected metabolic pathways. Still, very few targets were identified from in vivo analyses of tumor metabolism in patients because such studies are difficult and adequate imaging methods are only currently being developed for that purpose. For instance, perfusion of patients with [ 13 C]-glucose allows deciphering the metabolomics of tumors and opens a new area in the search for effective targets. Metabolic imaging with positron emission tomography and other techniques that do not involve [ 13 C] can also be used to evaluate tumor

  8. Labor Supply and Optimization Frictions

    DEFF Research Database (Denmark)

    Søgaard, Jakob Egholt

    In this paper I investigate the nature of optimization frictions by studying the labor market of Danish students. This particular labor market is an interesting case study as it features a range of special institutional settings that affect students’ incentive to earn income and comparing outcomes...... theory. More concretely I find the dominate optimization friction to be individuals’ inattention about their earnings during the year, while real adjustment cost and gradual learning appears to be of less importance....

  9. The risk of metabolic syndrome and nutrition

    Directory of Open Access Journals (Sweden)

    Aleksandr Konstantinovich Kuntsevich

    2015-02-01

    Full Text Available In the present literature review modern epidemiological studies the role of nutrition in the prevalence of the metabolic syndrome. Were analyzed mainly work on the association of certain types of dietary intake of the population to the risk of metabolic syndrome in several Western and Asian countries. The purpose of these studies was to determine deemed "good" type and the "bad" type of food, risk assessment and exchange of metabolic disorders to determine the optimal dietary recommendations.  Application of factor and cluster analysis allowed in a number of studies to identify groups of products associated with a decrease in the prevalence of metabolic syndrome and to estimate the odds ratios of metabolic syndrome when compared with the "bad" diet.  A number of papers were obtained confirm the effectiveness of the Mediterranean diet in the prevention of metabolic disorders. Commitment to the traditional Western diet is associated with deterioration in health, compared with the recommended "healthy" diet.  Data from epidemiological studies nutrition and metabolic disorders associated with a number of diseases, may be useful in determining how the recommendations on the best type of feeding the population, so to identify ways to further research.

  10. Metabolism and disease

    National Research Council Canada - National Science Library

    Grodzicker, Terri; Stewart, David J; Stillman, Bruce

    2011-01-01

    ...), cellular, organ system (cardiovascular, bone), and organismal (timing and life span) scales. Diseases impacted by metabolic imbalance or dysregulation that were covered in detail included diabetes, obesity, metabolic syndrome, and cancer...

  11. Pathway Design, Engineering, and Optimization.

    Science.gov (United States)

    Garcia-Ruiz, Eva; HamediRad, Mohammad; Zhao, Huimin

    The microbial metabolic versatility found in nature has inspired scientists to create microorganisms capable of producing value-added compounds. Many endeavors have been made to transfer and/or combine pathways, existing or even engineered enzymes with new function to tractable microorganisms to generate new metabolic routes for drug, biofuel, and specialty chemical production. However, the success of these pathways can be impeded by different complications from an inherent failure of the pathway to cell perturbations. Pursuing ways to overcome these shortcomings, a wide variety of strategies have been developed. This chapter will review the computational algorithms and experimental tools used to design efficient metabolic routes, and construct and optimize biochemical pathways to produce chemicals of high interest.

  12. Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes

    Directory of Open Access Journals (Sweden)

    Nuernberg Karin

    2011-08-01

    Full Text Available Abstract Background Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue. Methods The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6 leading to rapid obesity development, or selected for high treadmill performance (DUhTP leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.2% fat, 25.7% protein, or a high-fat diet rich in n-3 PUFA (n-3 HFD, 27.7% fat, 19% protein or a high-fat diet rich in n-6 PUFA (n-6 HFD, 27.7% fat, 18.6% protein for 8 weeks. The aim of the study was to determine the effect of these PUFA-rich high-fat diets on the fatty acid profile and on the protein expression of key components of insulin signalling pathways. Results Plasma concentrations of leptin and insulin were higher in DU6 in comparison with DUhTP mice. The high-fat diets stimulated a strong increase in leptin levels and body fat only in DU6 mice. Muscle and liver fatty acid composition were clearly changed by dietary lipid composition. In both lines of mice n-3 HFD feeding significantly reduced the hepatic insulin receptor β protein concentration which may explain decreased insulin action in liver. In contrast, protein kinase C ζ expression increased strongly in abdominal fat of n-3 HFD fed DUhTP mice, indicating enhanced insulin sensitivity in adipose tissue. Conclusions A diet high in n-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary n-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.

  13. Unrealistic optimism and decision making

    Directory of Open Access Journals (Sweden)

    Božović Bojana

    2009-01-01

    Full Text Available One of the leading descriptive theories of decision-making under risk, Tversky & Kahneman's Prospect theory, reveals that normative explanation of decisionmaking, based only on principle of maximizing outcomes expected utility, is unsustainable. It also underlines the effect of alternative factors on decision-making. Framing effect relates to an influence that verbal formulation of outcomes has on choosing between certain and risky outcomes; in negative frame people tend to be risk seeking, whereas in positive frame people express risk averse tendencies. Individual decisions are not based on objective probabilities of outcomes, but on subjective probabilities that depend on outcome desirability. Unrealistically pessimistic subjects assign lower probabilities (than the group average to the desired outcomes, while unrealistically optimistic subjects assign higher probabilities (than the group average to the desired outcomes. Experiment was conducted in order to test the presumption that there's a relation between unrealistic optimism and decision-making under risk. We expected optimists to be risk seeking, and pessimist to be risk averse. We also expected such cognitive tendencies, if they should become manifest, to be framing effect resistant. Unrealistic optimism scale was applied, followed by the questionnaire composed of tasks of decision-making under risk. Results within the whole sample, and results of afterwards extracted groups of pessimists and optimists both revealed dominant risk seeking tendency that is resistant to the influence of subjective probabilities as well as to the influence of frame in which the outcome is presented.

  14. Metabolic Engineering X Conference

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  15. The venom optimization hypothesis revisited.

    Science.gov (United States)

    Morgenstern, David; King, Glenn F

    2013-03-01

    Animal venoms are complex chemical mixtures that typically contain hundreds of proteins and non-proteinaceous compounds, resulting in a potent weapon for prey immobilization and predator deterrence. However, because venoms are protein-rich, they come with a high metabolic price tag. The metabolic cost of venom is sufficiently high to result in secondary loss of venom whenever its use becomes non-essential to survival of the animal. The high metabolic cost of venom leads to the prediction that venomous animals may have evolved strategies for minimizing venom expenditure. Indeed, various behaviors have been identified that appear consistent with frugality of venom use. This has led to formulation of the "venom optimization hypothesis" (Wigger et al. (2002) Toxicon 40, 749-752), also known as "venom metering", which postulates that venom is metabolically expensive and therefore used frugally through behavioral control. Here, we review the available data concerning economy of venom use by animals with either ancient or more recently evolved venom systems. We conclude that the convergent nature of the evidence in multiple taxa strongly suggests the existence of evolutionary pressures favoring frugal use of venom. However, there remains an unresolved dichotomy between this economy of venom use and the lavish biochemical complexity of venom, which includes a high degree of functional redundancy. We discuss the evidence for biochemical optimization of venom as a means of resolving this conundrum. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Radiological optimization

    International Nuclear Information System (INIS)

    Zeevaert, T.

    1998-01-01

    Radiological optimization is one of the basic principles in each radiation-protection system and it is a basic requirement in the safety standards for radiation protection in the European Communities. The objectives of the research, performed in this field at the Belgian Nuclear Research Centre SCK-CEN, are: (1) to implement the ALARA principles in activities with radiological consequences; (2) to develop methodologies for optimization techniques in decision-aiding; (3) to optimize radiological assessment models by validation and intercomparison; (4) to improve methods to assess in real time the radiological hazards in the environment in case of an accident; (5) to develop methods and programmes to assist decision-makers during a nuclear emergency; (6) to support the policy of radioactive waste management authorities in the field of radiation protection; (7) to investigate existing software programmes in the domain of multi criteria analysis. The main achievements for 1997 are given

  17. Optimizing detectability

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    HPLC is useful for trace and ultratrace analyses of a variety of compounds. For most applications, HPLC is useful for determinations in the nanogram-to-microgram range; however, detection limits of a picogram or less have been demonstrated in certain cases. These determinations require state-of-the-art capability; several examples of such determinations are provided in this chapter. As mentioned before, to detect and/or analyze low quantities of a given analyte at submicrogram or ultratrace levels, it is necessary to optimize the whole separation system, including the quantity and type of sample, sample preparation, HPLC equipment, chromatographic conditions (including column), choice of detector, and quantitation techniques. A limited discussion is provided here for optimization based on theoretical considerations, chromatographic conditions, detector selection, and miscellaneous approaches to detectability optimization. 59 refs

  18. Optimizing DMPK Properties: Experiences from a Big Pharma DMPK Department.

    Science.gov (United States)

    Sohlenius-Sternbeck, Anna-Karin; Janson, Juliette; Bylund, Johan; Baranczewski, Pawel; Breitholtz-Emanuelsson, Anna; Hu, Yin; Tsoi, Carrie; Lindgren, Anders; Gissberg, Olle; Bueters, Tjerk; Briem, Sveinn; Juric, Sanja; Johansson, Jenny; Bergh, Margareta; Hoogstraate, Janet

    2016-01-01

    The disposition of a drug is dependent on interactions between the body and the drug, its molecular properties and the physical and biological barriers presented in the body. In order for a drug to have a desired pharmacological effect it has to have the right properties to be able to reach the target site in sufficient concentration. This review details how drug metabolism and pharmacokinetics (DMPK) and physicochemical deliveries played an important role in data interpretation and compound optimization at AstraZeneca R&D in Södertälje, Sweden. A selection of assays central in the evaluation of the DMPK properties of new chemical entities is presented, with guidance and consideration on assay outcome interpretation. Early in projects, solubility, LogD, permeability and metabolic stability were measured to support effective optimization of DMPK properties. Changes made to facilitate high throughput, efficient bioanalysis and the handling of large amounts of samples are described. Already early in drug discovery, we used an integrated approach for the prediction of the fate of drugs in human (early dose to man) based on data obtained from in vitro experiments. The early dose to man was refined with project progression, which triggered more intricate assays and experiments. At later stages, preclinical in vivo pharmacokinetic (PK) data was integrated with pharmacodynamics (PD) to allow predictions of required dose, dose intervals and exposure profile to achieve the desired effect in man. A well-defined work flow of DMPK activities from early lead identification up to the selection of a candidate drug was developed. This resulted in a cost effective and efficient optimization of chemical series, and facilitated informed decision making throughout project progress.

  19. Computer-aided design for metabolic engineering.

    Science.gov (United States)

    Fernández-Castané, Alfred; Fehér, Tamás; Carbonell, Pablo; Pauthenier, Cyrille; Faulon, Jean-Loup

    2014-12-20

    The development and application of biotechnology-based strategies has had a great socio-economical impact and is likely to play a crucial role in the foundation of more sustainable and efficient industrial processes. Within biotechnology, metabolic engineering aims at the directed improvement of cellular properties, often with the goal of synthesizing a target chemical compound. The use of computer-aided design (CAD) tools, along with the continuously emerging advanced genetic engineering techniques have allowed metabolic engineering to broaden and streamline the process of heterologous compound-production. In this work, we review the CAD tools available for metabolic engineering with an emphasis, on retrosynthesis methodologies. Recent advances in genetic engineering strategies for pathway implementation and optimization are also reviewed as well as a range of bionalytical tools to validate in silico predictions. A case study applying retrosynthesis is presented as an experimental verification of the output from Retropath, the first complete automated computational pipeline applicable to metabolic engineering. Applying this CAD pipeline, together with genetic reassembly and optimization of culture conditions led to improved production of the plant flavonoid pinocembrin. Coupling CAD tools with advanced genetic engineering strategies and bioprocess optimization is crucial for enhanced product yields and will be of great value for the development of non-natural products through sustainable biotechnological processes. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

    Science.gov (United States)

    Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2013-10-16

    Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

  1. Unconstrained Optimization

    DEFF Research Database (Denmark)

    Frandsen, P. E.; Jonasson, K.; Nielsen, Hans Bruun

    1999-01-01

    This lecture note is intended for use in the course 04212 Optimization and Data Fitting at the Technincal University of Denmark. It covers about 25% of the curriculum. Hopefully, the note may be useful also to interested persons not participating in that course. The aim of the note is to give...... an introduction to algorithms for unconstrained optimization. We present Conjugate Gradient, Damped Newton and Quasi Newton methods together with the relevant theoretical background. The reader is assumed to be familiar with algorithms for solving linear and nonlinear system of equations, at a level corresponding...

  2. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  3. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  4. Optimal management strategies in variable environments: Stochastic optimal control methods

    Science.gov (United States)

    Williams, B.K.

    1985-01-01

    Dynamic optimization was used to investigate the optimal defoliation of salt desert shrubs in north-western Utah. Management was formulated in the context of optimal stochastic control theory, with objective functions composed of discounted or time-averaged biomass yields. Climatic variability and community patterns of salt desert shrublands make the application of stochastic optimal control both feasible and necessary. A primary production model was used to simulate shrub responses and harvest yields under a variety of climatic regimes and defoliation patterns. The simulation results then were used in an optimization model to determine optimal defoliation strategies. The latter model encodes an algorithm for finite state, finite action, infinite discrete time horizon Markov decision processes. Three questions were addressed: (i) What effect do changes in weather patterns have on optimal management strategies? (ii) What effect does the discounting of future returns have? (iii) How do the optimal strategies perform relative to certain fixed defoliation strategies? An analysis was performed for the three shrub species, winterfat (Ceratoides lanata), shadscale (Atriplex confertifolia) and big sagebrush (Artemisia tridentata). In general, the results indicate substantial differences among species in optimal control strategies, which are associated with differences in physiological and morphological characteristics. Optimal policies for big sagebrush varied less with variation in climate, reserve levels and discount rates than did either shadscale or winterfat. This was attributed primarily to the overwintering of photosynthetically active tissue and to metabolic activity early in the growing season. Optimal defoliation of shadscale and winterfat generally was more responsive to differences in plant vigor and climate, reflecting the sensitivity of these species to utilization and replenishment of carbohydrate reserves. Similarities could be seen in the influence of both

  5. Optimization of sodium hydroxide pretreatment and enzyme loading for efficient hydrolysis of rice straw to improve succinate production by metabolically engineered Escherichia coli KJ122 under simultaneous saccharification and fermentation.

    Science.gov (United States)

    Sawisit, Apichai; Jampatesh, Surawee; Jantama, Sirima Suvarnakuta; Jantama, Kaemwich

    2018-07-01

    Rice straw was pretreated with sodium hydroxide (NaOH) before subsequent use for succinate production by Escherichia coli KJ122 under simultaneous saccharification and fermentation (SSF). The NaOH pretreated rice straw was significantly enhanced lignin removal up to 95%. With the optimized enzyme loading of 4% cellulase complex + 0.5% xylanase (endo-glucanase 67 CMC-U/g, β-glucosidase 26 pNG-U/g and xylanase 18 CMC-U/g dry biomass), total sugar conversion reached 91.7 ± 0.8% (w/w). The physicochemical analysis of NaOH pretreated rice straw indicated dramatical changes in its structure, thereby favoring enzymatic saccharification. In batch SSF, succinate production of 69.8 ± 0.3 g/L with yield and productivity of 0.84 g/g pretreated rice straw and 0.76 ± 0.02 g/L/h, respectively, was obtained. Fed-batch SSF significantly improved succinate concentration and productivity to 103.1 ± 0.4 g/L and 1.37 ± 0.07 g/L/h with a comparable yield. The results demonstrated a feasibility of sequential saccharification and fermentation of rice straw as a promising process for succinate production in industrial scale. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Optimal transport

    CERN Document Server

    Eckmann, B

    2008-01-01

    At the close of the 1980s, the independent contributions of Yann Brenier, Mike Cullen and John Mather launched a revolution in the venerable field of optimal transport founded by G Monge in the 18th century, which has made breathtaking forays into various other domains of mathematics ever since. The author presents a broad overview of this area.

  7. Topology optimization

    DEFF Research Database (Denmark)

    Bendsøe, Martin P.; Sigmund, Ole

    2007-01-01

    Taking as a starting point a design case for a compliant mechanism (a force inverter), the fundamental elements of topology optimization are described. The basis for the developments is a FEM format for this design problem and emphasis is given to the parameterization of design as a raster image...

  8. Sample size calculation in metabolic phenotyping studies.

    Science.gov (United States)

    Billoir, Elise; Navratil, Vincent; Blaise, Benjamin J

    2015-09-01

    The number of samples needed to identify significant effects is a key question in biomedical studies, with consequences on experimental designs, costs and potential discoveries. In metabolic phenotyping studies, sample size determination remains a complex step. This is due particularly to the multiple hypothesis-testing framework and the top-down hypothesis-free approach, with no a priori known metabolic target. Until now, there was no standard procedure available to address this purpose. In this review, we discuss sample size estimation procedures for metabolic phenotyping studies. We release an automated implementation of the Data-driven Sample size Determination (DSD) algorithm for MATLAB and GNU Octave. Original research concerning DSD was published elsewhere. DSD allows the determination of an optimized sample size in metabolic phenotyping studies. The procedure uses analytical data only from a small pilot cohort to generate an expanded data set. The statistical recoupling of variables procedure is used to identify metabolic variables, and their intensity distributions are estimated by Kernel smoothing or log-normal density fitting. Statistically significant metabolic variations are evaluated using the Benjamini-Yekutieli correction and processed for data sets of various sizes. Optimal sample size determination is achieved in a context of biomarker discovery (at least one statistically significant variation) or metabolic exploration (a maximum of statistically significant variations). DSD toolbox is encoded in MATLAB R2008A (Mathworks, Natick, MA) for Kernel and log-normal estimates, and in GNU Octave for log-normal estimates (Kernel density estimates are not robust enough in GNU octave). It is available at http://www.prabi.fr/redmine/projects/dsd/repository, with a tutorial at http://www.prabi.fr/redmine/projects/dsd/wiki. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Metabolic engineering tools in model cyanobacteria.

    Science.gov (United States)

    Carroll, Austin L; Case, Anna E; Zhang, Angela; Atsumi, Shota

    2018-03-26

    Developing sustainable routes for producing chemicals and fuels is one of the most important challenges in metabolic engineering. Photoautotrophic hosts are particularly attractive because of their potential to utilize light as an energy source and CO 2 as a carbon substrate through photosynthesis. Cyanobacteria are unicellular organisms capable of photosynthesis and CO 2 fixation. While engineering in heterotrophs, such as Escherichia coli, has result in a plethora of tools for strain development and hosts capable of producing valuable chemicals efficiently, these techniques are not always directly transferable to cyanobacteria. However, recent efforts have led to an increase in the scope and scale of chemicals that cyanobacteria can produce. Adaptations of important metabolic engineering tools have also been optimized to function in photoautotrophic hosts, which include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9, 13 C Metabolic Flux Analysis (MFA), and Genome-Scale Modeling (GSM). This review explores innovations in cyanobacterial metabolic engineering, and highlights how photoautotrophic metabolism has shaped their development. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  10. Effect of Volume of Fluid Resuscitation on Metabolic Normalization in Children Presenting in Diabetic Ketoacidosis: A Randomized Controlled Trial.

    Science.gov (United States)

    Bakes, Katherine; Haukoos, Jason S; Deakyne, Sara J; Hopkins, Emily; Easter, Josh; McFann, Kim; Brent, Alison; Rewers, Arleta

    2016-04-01

    The optimal rate of fluid administration in pediatric diabetic ketoacidosis (DKA) is unknown. Our aim was to determine whether the volume of fluid administration in children with DKA influences the rate of metabolic normalization. We performed a randomized controlled trial conducted in a tertiary pediatric emergency department from December 2007 until June 2010. The primary outcome was time to metabolic normalization; secondary outcomes were time to bicarbonate normalization, pH normalization, overall length of hospital treatment, and adverse outcomes. Children between 0 and 18 years of age were eligible if they had type 1 diabetes mellitus and DKA. Patients were randomized to receive intravenous (IV) fluid at low volume (10 mL/kg bolus + 1.25 × maintenance rate) or high volume (20 mL/kg bolus + 1.5 × maintenance rate) (n = 25 in each). After adjusting for initial differences in bicarbonate levels, time to metabolic normalization was significantly faster in the higher-volume infusion group compared to the low-volume infusion group (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.0-3.9; p = 0.04). Higher-volume IV fluid infusion appeared to hasten, to a greater extent, normalization of pH (HR = 2.5; 95% CI 1.2-5.0; p = 0.01) than normalization of serum bicarbonate (HR = 1.2; 95% CI 0.6-2.3; p = 0.6). The length of hospital treatment HR (0.8; 95% CI 0.4-1.5; p = 0.5) and time to discharge HR (0.8; 95% CI 0.4-1.5; p = 0.5) did not differ between treatment groups. Higher-volume fluid infusion in the treatment of pediatric DKA patients significantly shortened metabolic normalization time, but did not change overall length of hospital treatment. ClinicalTrials.gov ID NCT01701557. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The cut-off values of dietary energy intake for determining metabolic syndrome in hemodialysis patients: A clinical cross-sectional study

    Science.gov (United States)

    Duong, Tuyen Van; Wong, Te-Chih; Chen, Hsi-Hsien; Chen, Tzen-Wen; Chen, Tso-Hsiao; Hsu, Yung-Ho; Peng, Sheng-Jeng; Kuo, Ko-Lin; Wang, Chi-Sin; Tseng, I-Hsin; Feng, Yi-Wei; Chang, Tai-Yue; Su, Chien-Tien

    2018-01-01

    Dietary energy intake strongly linked to dialysis outcomes. We aimed to explore the optimal cut-off point of energy intake (EI) for identification of metabolic syndrome (MetS) in hemodialysis patients. The cross-sectional data of 243 hemodialysis patients from multi-dialysis centers in Taiwan was used. The dietary intake was assessed by using the three-day dietary questionnaire, and a 24-hour dietary recall, clinical and biochemical data were also evaluated. The MetS was diagnosed by the Harmonized Metabolic Syndrome criteria. The receiver operating characteristic (ROC) curve was to depict the optimal cut-off value of EI for the diagnosis of MetS. The logistic regression was also used to explore the association between inadequate EI and MetS. The optimal cut-off points of EI for identifying the MetS were 26.7 kcal/kg/day for patients aged less than 60 years, or with non-diabetes, and 26.2 kcal/kg/day for patients aged 60 years and above, or with diabetes, respectively. The likelihood of the MetS increased with lower percentiles of energy intake in hemodialysis patients. In the multivariate analysis, the inadequate dietary energy intake strongly determined 3.24 folds of the MetS. The assessment of dietary EI can help healthcare providers detecting patients who are at risk of metabolic syndrome. PMID:29538427

  12. Demographic and personal factors associated with metabolic control and self-care in youth with type 1 diabetes

    DEFF Research Database (Denmark)

    Neylon, Orla M.; O'Connell, Michele A.; Skinner, Timothy C.

    2013-01-01

    Optimal use of recent technological advances in insulin delivery and glucose monitoring remain limited by the impact of behaviour on self-care. In recent years, there has been a resurgence of interest in psychosocial methods of optimizing care in youth with type 1 diabetes. We therefore sought...... studies fulfilled the inclusion criteria. These studies have indicated that identifiable individual characteristics in each domain are robustly associated with metabolic control and/or self-care in children and adolescents. We present these characteristics and propose a theoretical model...... of their interactions and effect on diabetes outcomes. There is currently no consensus regarding patient selection for insulin pump therapy. In this era of scarce healthcare resources, it may be prudent to identify youth requiring increased psychosocial support prior to regimen intensification. The importance...

  13. Isolated human islets require hyperoxia to maintain islet mass, metabolism, and function.

    Science.gov (United States)

    Komatsu, Hirotake; Kang, Dongyang; Medrano, Leonard; Barriga, Alyssa; Mendez, Daniel; Rawson, Jeffrey; Omori, Keiko; Ferreri, Kevin; Tai, Yu-Chong; Kandeel, Fouad; Mullen, Yoko

    2016-02-12

    Pancreatic islet transplantation has been recognized as an effective treatment for Type 1 diabetes; however, there is still plenty of room to improve transplantation efficiency. Because islets are metabolically active they require high oxygen to survive; thus hypoxia after transplant is one of the major causes of graft failure. Knowing the optimal oxygen tension for isolated islets would allow a transplant team to provide the best oxygen environment during pre- and post-transplant periods. To address this issue and begin to establish empirically determined guidelines for islet maintenance, we exposed in vitro cultured islets to different partial oxygen pressures (pO2) and assessed changes in islet volume, viability, metabolism, and function. Human islets were cultured for 7 days in different pO2 media corresponding to hypoxia (90 mmHg), normoxia (160 mmHg), and hyerpoxia (270 or 350 mmHg). Compared to normoxia and hypoxia, hyperoxia alleviated the loss of islet volume, maintaining higher islet viability and metabolism as measured by oxygen consumption and glucose-stimulated insulin secretion responses. We predict that maintaining pre- and post-transplanted islets in a hyperoxic environment will alleviate islet volume loss and maintain islet quality thereby improving transplant outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Optimal control

    CERN Document Server

    Aschepkov, Leonid T; Kim, Taekyun; Agarwal, Ravi P

    2016-01-01

    This book is based on lectures from a one-year course at the Far Eastern Federal University (Vladivostok, Russia) as well as on workshops on optimal control offered to students at various mathematical departments at the university level. The main themes of the theory of linear and nonlinear systems are considered, including the basic problem of establishing the necessary and sufficient conditions of optimal processes. In the first part of the course, the theory of linear control systems is constructed on the basis of the separation theorem and the concept of a reachability set. The authors prove the closure of a reachability set in the class of piecewise continuous controls, and the problems of controllability, observability, identification, performance and terminal control are also considered. The second part of the course is devoted to nonlinear control systems. Using the method of variations and the Lagrange multipliers rule of nonlinear problems, the authors prove the Pontryagin maximum principle for prob...

  15. [Menopause and metabolic syndrome].

    Science.gov (United States)

    Meirelles, Ricardo M R

    2014-03-01

    The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.

  16. Numerical Optimization Algorithms and Software for Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Saunders, Michael

    2013-02-02

    The basic aims of this work are: to develop reliable algorithms for solving optimization problems involving large stoi- chiometric matrices; to investigate cyclic dependency between metabolic and macromolecular biosynthetic networks; and to quantify the significance of thermodynamic constraints on prokaryotic metabolism.

  17. SU-F-T-195: Systematic Constraining of Contralateral Parotid Gland Led to Improved Dosimetric Outcomes for Multi-Field Optimization with Scanning Beam Proton Therapy: Promising Results From a Pilot Study in Patients with Base of Tongue Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, R; Liu, A; Poenisch, F; Palmer, M; Gillin, M; Zhu, X [Department of Radiation Physics, UT MD Anderson Cancer Center, Houston, TX (United States); Crowford, C; Georges, R; Amin, M [Department of Medical Dosimetry, MD Anderson Cancer Ctr, Houston, TX (United States); Sio, T; Gunn, B; Frank, S [Radiation Oncology Department MD Anderson Cancer Ctr, Houston, TX (United States)

    2016-06-15

    Purpose: Treatment planning for Intensity Modulated Proton Therapy (IMPT) for head and neck cancer is time-consuming due to the large number of organs-at-risk (OAR) to be considered. As there are many competing objectives and also wide range of acceptable OAR constraints, the final approved plan may not be most optimal for the given structures. We evaluated the dose reduction to the contralateral parotid by implementing standardized constraints during optimization for scanning beam proton therapy planning. Methods: Twenty-four (24) consecutive patients previously treated for base of tongue carcinoma were retrospectively selected. The doses were 70Gy, 63Gy and 57Gy (SIB in 33 fractions) for high-, intermediate-, and standard-risk clinical target volumes (CTV), respectively; the treatment included bilateral neck. Scanning beams using MFO with standardized bilateral anterior oblique and PA fields were applied. New plans where then developed and optimized by employing additional contralateral parotid constraints at multiple defined dose levels. Using a step-wise iterative process, the volume-based constraints at each level were then further reduced until known target coverages were compromised. The newly developed plans were then compared to the original clinically approved plans using paired student t-testing. Results: All 24 newly optimized treatment plans maintained initial plan quality as compared to the approved plans, and the 98% prescription dose coverage to the CTV’s were not compromised. Representative DVH comparison is shown in FIGURE 1. The contralateral parotid doses were reduced at all levels of interest when systematic constraints were applied to V10, V20, V30 and V40Gy (All P<0.0001; TABLE 1). Overall, the mean contralateral parotid doses were reduced by 2.26 Gy on average, a ∼13% relative improvement. Conclusion: Applying systematic and volume-based contralateral parotid constraints for IMPT planning significantly reduced the dose at all dosimetric

  18. Metabolic syndrome and menopause

    OpenAIRE

    Jouyandeh, Zahra; Nayebzadeh, Farnaz; Qorbani, Mostafa; Asadi, Mojgan

    2013-01-01

    Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3) criteria t...

  19. Maternal Preeclampsia and Neonatal Outcomes

    Directory of Open Access Journals (Sweden)

    Carl H. Backes

    2011-01-01

    Full Text Available Preeclampsia is a multiorgan, heterogeneous disorder of pregnancy associated with significant maternal and neonatal morbidity and mortality. Optimal strategies in the care of the women with preeclampsia have not been fully elucidated, leaving physicians with incomplete data to guide their clinical decision making. Because preeclampsia is a progressive disorder, in some circumstances, delivery is needed to halt the progression to the benefit of the mother and fetus. However, the need for premature delivery has adverse effects on important neonatal outcomes not limited to the most premature infants. Late-preterm infants account for approximately two thirds of all preterm deliveries and are at significant risk for morbidity and mortality. Reviewed is the current literature in the diagnosis and obstetrical management of preeclampsia, the outcomes of late-preterm infants, and potential strategies to optimize fetal outcomes in pregnancies complicated by preeclampsia.

  20. Understanding Regulation of Metabolism through Feasibility Analysis

    Science.gov (United States)

    Nikerel, Emrah; Berkhout, Jan; Hu, Fengyuan; Teusink, Bas; Reinders, Marcel J. T.; de Ridder, Dick

    2012-01-01

    Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but through non-obvious combinations of hierarchical (gene and enzyme levels) and metabolic regulation (mass action and allosteric interaction). Quantitative analyses relating changes in metabolic fluxes to changes in transcript or protein levels have revealed a remarkable lack of understanding of the regulation of these networks. We study metabolic regulation via feasibility analysis (FA). Inspired by the constraint-based approach of Flux Balance Analysis, FA incorporates a model describing kinetic interactions between molecules. We enlarge the portfolio of objectives for the cell by defining three main physiologically relevant objectives for the cell: function, robustness and temporal responsiveness. We postulate that the cell assumes one or a combination of these objectives and search for enzyme levels necessary to achieve this. We call the subspace of feasible enzyme levels the feasible enzyme space. Once this space is constructed, we can study how different objectives may (if possible) be combined, or evaluate the conditions at which the cells are faced with a trade-off among those. We apply FA to the experimental scenario of long-term carbon limited chemostat cultivation of yeast cells, studying how metabolism evolves optimally. Cells employ a mixed strategy composed of increasing enzyme levels for glucose uptake and hexokinase and decreasing levels of the remaining enzymes. This trade-off renders the cells specialized in this low-carbon flux state to compete for the available glucose and get rid of over-overcapacity. Overall, we show that FA is a powerful tool for systems biologists to study regulation of metabolism, interpret experimental data and evaluate hypotheses. PMID

  1. [Metabolic functions and sport].

    Science.gov (United States)

    Riviere, Daniel

    2004-01-01

    Current epidemiological studies emphasize the increased of metabolic diseases of the adults, such as obesity, type-2 diabetes and metabolic syndromes. Even more worrying is the rising prevalence of obesity in children. It is due more to sedentariness, caused more by inactivity (television, video, games, etc.) than by overeating. Many studies have shown that regular physical activities benefit various bodily functions including metabolism. After dealing with the major benefits of physical exercise on some adult metabolic disorders, we focus on the prime role played by physical activity in combating the public health problem of childhood obesity.

  2. Constraint based modeling of metabolism allows finding metabolic cancer hallmarks and identifying personalized therapeutic windows.

    Science.gov (United States)

    Bordel, Sergio

    2018-04-13

    In order to choose optimal personalized anticancer treatments, transcriptomic data should be analyzed within the frame of biological networks. The best known human biological network (in terms of the interactions between its different components) is metabolism. Cancer cells have been known to have specific metabolic features for a long time and currently there is a growing interest in characterizing new cancer specific metabolic hallmarks. In this article it is presented a method to find personalized therapeutic windows using RNA-seq data and Genome Scale Metabolic Models. This method is implemented in the python library, pyTARG. Our predictions showed that the most anticancer selective (affecting 27 out of 34 considered cancer cell lines and only 1 out of 6 healthy mesenchymal stem cell lines) single metabolic reactions are those involved in cholesterol biosynthesis. Excluding cholesterol biosynthesis, all the considered cell lines can be selectively affected by targeting different combinations (from 1 to 5 reactions) of only 18 metabolic reactions, which suggests that a small subset of drugs or siRNAs combined in patient specific manners could be at the core of metabolism based personalized treatments.

  3. Adaptive Evolution of Phosphorus Metabolism in Prochlorococcus

    DEFF Research Database (Denmark)

    Casey, John R; Mardinoglu, Adil; Nielsen, Jens

    2016-01-01

    Inorganic phosphorus is scarce in the eastern Mediterranean Sea, where the high-light-adapted ecotype HLI of the marine picocyanobacterium Prochlorococcus marinus thrives. Physiological and regulatory control of phosphorus acquisition and partitioning has been observed in HLI both in culture...... and in the field; however, the optimization of phosphorus metabolism and associated gains for its phosphorus-limited-growth (PLG) phenotype have not been studied. Here, we reconstructed a genome-scale metabolic network of the HLI axenic strain MED4 (iJC568), consisting of 568 metabolic genes in relation to 794...... through drastic depletion of phosphorus-containing biomass components but also through network-wide reductions in phosphate-reaction participation and the loss of a key enzyme, succinate dehydrogenase. These alterations occur despite the stringency of having relatively few pathway redundancies...

  4. Fluoroacetylcarnitine: metabolism and metabolic effects in mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, J; Davis, E J

    1973-01-01

    The metabolism and metabolic effects of fluoroacetylcarnitine have been investigated. Carnitineacetyltransferase transfers the fluoro-acetyl group of fluoroacetylcarnitine nearly as rapidly to CoA as the acetyl group of acetylcarnitine. Fluorocitrate is then formed by citrate synthase, but this second reaction is relatively slow. The fluorocitrate formed intramitochondrially inhibits the metabolism of citrate. In heart and skeletal muscle mitochondria the accumulated citrate inhibits citrate synthesis and the ..beta..-oxidation of fatty acids. Free acetate is formed, presumably because accumulated acetyl-CoA is hydrolyzed. In liver mitochondria the accumulation of citrate leads to a relatively increased rate of ketogenesis. Increased ketogenesis is obtained also upon the addition of citrate to the reaction mixture.

  5. Metabolic Diet App Suite for inborn errors of amino acid metabolism.

    Science.gov (United States)

    Ho, Gloria; Ueda, Keiko; Houben, Roderick F A; Joa, Jeff; Giezen, Alette; Cheng, Barbara; van Karnebeek, Clara D M

    2016-03-01

    An increasing number of rare inborn errors of metabolism (IEMs) are amenable to targeted metabolic nutrition therapy. Daily adherence is important to attain metabolic control and prevent organ damage. This is challenging however, given the lack of information of disorder specific nutrient content of foods, the limited availability and cost of specialty products as well as difficulties in reliable calculation and tracking of dietary intake and targets. To develop apps for all inborn errors of amino acid metabolism for which the mainstay of treatment is a medical diet, and obtain patient and family feedback throughout the process to incorporate this into subsequent versions. The Metabolic Diet App Suite was created with input from health care professionals as a free, user-friendly, online tool for both mobile devices and desktop computers (http://www.metabolicdietapp.org) for 15 different IEMs. General information is provided for each IEM with links to useful online resources. Nutrient information is based on the MetabolicPro™, a North American food database compiled by the Genetic Metabolic Dietitians International (GMDI) Technology committee. After user registration, a personalized dashboard and management plan including specific nutrient goals are created. Each Diet App has a user-friendly interface and the functions include: nutrient intake counts, adding your own foods and homemade recipes and, managing a daily food diary. Patient and family feedback was overall positive and specific suggestions were used to further improve the App Suite. The Metabolic Diet App Suite aids individuals affected by IEMs to track and plan their meals. Future research should evaluate its impact on patient adherence, metabolic control, quality of life and health-related outcomes. The Suite will be updated and expanded to Apps for other categories of IEMs. Finally, this Suite is a support tool only, and does not replace medical/metabolic nutrition professional advice. Copyright

  6. Fatty acid metabolism: target for metabolic syndrome

    OpenAIRE

    Wakil, Salih J.; Abu-Elheiga, Lutfi A.

    2009-01-01

    Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They...

  7. Discrete optimization

    CERN Document Server

    Parker, R Gary

    1988-01-01

    This book treats the fundamental issues and algorithmic strategies emerging as the core of the discipline of discrete optimization in a comprehensive and rigorous fashion. Following an introductory chapter on computational complexity, the basic algorithmic results for the two major models of polynomial algorithms are introduced--models using matroids and linear programming. Further chapters treat the major non-polynomial algorithms: branch-and-bound and cutting planes. The text concludes with a chapter on heuristic algorithms.Several appendixes are included which review the fundamental ideas o

  8. Investigation of metabolic encephalopathy

    African Journals Online (AJOL)

    cycle defects is the X-linked recessive disorder, ornithine ... life, or if the child is fed the compounds that they are unable .... as learning difficulties, drowsiness and avoidance of ... Table 2. Laboratory investigation of suspected metabolic encephalopathy. Laboratory .... Clinical approach to treatable inborn metabolic diseases:.

  9. Metabolic regulation of inflammation.

    Science.gov (United States)

    Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

    2017-05-01

    Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

  10. Metabolic syndrome and menopause

    Directory of Open Access Journals (Sweden)

    Jouyandeh Zahra

    2013-01-01

    Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

  11. Balancing cellular redox metabolism in microbial electrosynthesis and electro fermentation - A chance for metabolic engineering.

    Science.gov (United States)

    Kracke, Frauke; Lai, Bin; Yu, Shiqin; Krömer, Jens O

    2018-01-01

    More and more microbes are discovered that are capable of extracellular electron transfer, a process in which they use external electrodes as electron donors or acceptors for metabolic reactions. This feature can be used to overcome cellular redox limitations and thus optimizing microbial production. The technologies, termed microbial electrosynthesis and electro-fermentation, have the potential to open novel bio-electro production platforms from sustainable energy and carbon sources. However, the performance of reported systems is currently limited by low electron transport rates between microbes and electrodes and our limited ability for targeted engineering of these systems due to remaining knowledge gaps about the underlying fundamental processes. Metabolic engineering offers many opportunities to optimize these processes, for instance by genetic engineering of pathways for electron transfer on the one hand and target product synthesis on the other hand. With this review, we summarize the status quo of knowledge and engineering attempts around chemical production in bio-electrochemical systems from a microbe perspective. Challenges associated with the introduction or enhancement of extracellular electron transfer capabilities into production hosts versus the engineering of target compound synthesis pathways in natural exoelectrogens are discussed. Recent advances of the research community in both directions are examined critically. Further, systems biology approaches, for instance using metabolic modelling, are examined for their potential to provide insight into fundamental processes and to identify targets for metabolic engineering. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  12. Drug metabolism in birds

    Science.gov (United States)

    Pan, Huo Ping; Fouts, James R.

    1979-01-01

    Papers published over 100 years since the beginning of the scientific study of drug metabolism in birds were reviewed. Birds were found to be able to accomplish more than 20 general biotransformation reactions in both functionalization and conjugation. Chickens were the primary subject of study but over 30 species of birds were used. Large species differences in drug metabolism exist between birds and mammals as well as between various birds, these differences were mostly quantitative. Qualitative differences were rare. On the whole, drug metabolism studies in birds have been neglected as compared with similar studies on insects and mammals. The uniqueness of birds and the advantages of using birds in drug metabolism studies are discussed. Possible future studies of drug metabolism in birds are recommended.

  13. Metabolic imaging using SPECT

    International Nuclear Information System (INIS)

    Taki, Junichi; Matsunari, Ichiro

    2007-01-01

    In normal condition, the heart obtains more than two-thirds of its energy from the oxidative metabolism of long chain fatty acids, although a wide variety of substrates such as glucose, lactate, ketone bodies and amino acids are also utilised. In ischaemic myocardium, on the other hand, oxidative metabolism of free fatty acid is suppressed and anaerobic glucose metabolism plays a major role in residual oxidative metabolism. Therefore, metabolic imaging can be an important technique for the assessment of various cardiac diseases and conditions. In SPECT, several iodinated fatty acid traces have been introduced and studied. Of these, 123 I-labelled 15-(p-iodophenyl)3-R, S-methylpentadecanoic acid (BMIPP) has been the most commonly used tracer in clinical studies, especially in some of the European countries and Japan. In this review article, several fatty acid tracers for SPECT are characterised, and the mechanism of uptake and clinical utility of BMIPP are discussed in detail. (orig.)

  14. Metabolic imaging using PET

    International Nuclear Information System (INIS)

    Kudo, Takashi

    2007-01-01

    There is growing evidence that myocardial metabolism plays a key role not only in ischaemic heart disease but also in a variety of diseases which involve myocardium globally, such as heart failure and diabetes mellitus. Understanding myocardial metabolism in such diseases helps to elucidate the pathophysiology and assists in making therapeutic decisions. As well as providing information on regional changes, PET can deliver quantitative information about both regional and global changes in metabolism. This capability of quantitative measurement is one of the major advantages of PET along with physiological positron tracers, especially relevant in evaluating diseases which involve the whole myocardium. This review discusses major PET tracers for metabolic imaging and their clinical applications and contributions to research regarding ischaemic heart disease and other diseases such as heart failure and diabetic heart disease. Future applications of positron metabolic tracers for the detection of vulnerable plaque are also highlighted briefly. (orig.)

  15. Astrocytes and energy metabolism.

    Science.gov (United States)

    Prebil, Mateja; Jensen, Jørgen; Zorec, Robert; Kreft, Marko

    2011-05-01

    Astrocytes are glial cells, which play a significant role in a number of processes, including the brain energy metabolism. Their anatomical position between blood vessels and neurons make them an interface for effective glucose uptake from blood. After entering astrocytes, glucose can be involved in different metabolic pathways, e.g. in glycogen production. Glycogen in the brain is localized mainly in astrocytes and is an important energy source in hypoxic conditions and normal brain functioning. The portion of glucose metabolized into glycogen molecules in astrocytes is as high as 40%. It is thought that the release of gliotransmitters (such as glutamate, neuroactive peptides and ATP) into the extracellular space by regulated exocytosis supports a significant part of communication between astrocytes and neurons. On the other hand, neurotransmitter action on astrocytes has a significant role in brain energy metabolism. Therefore, understanding the astrocytes energy metabolism may help understanding neuron-astrocyte interactions.

  16. Cell-free protein synthesis enabled rapid prototyping for metabolic engineering and synthetic biology

    Directory of Open Access Journals (Sweden)

    Lihong Jiang

    2018-06-01

    Full Text Available Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade. However, due to complexity of cellular metabolism, the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering. Recently, cell-free protein synthesis system (CFPS has been emerging as an enabling alternative to address challenges in biomanufacturing. This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits (biosensors to speed up design-build-test (DBT cycles of metabolic engineering and synthetic biology. Keywords: Cell-free protein synthesis, Metabolic pathway optimization, Genetic circuits, Metabolic engineering, Synthetic biology

  17. Investigation of Fat Metabolism during Antiobesity Interventions by Magnetic Resonance Imaging and Spectroscopy

    Directory of Open Access Journals (Sweden)

    Arunima Pola

    2014-01-01

    Full Text Available The focus of current treatments for obesity is to reduce the body weight or visceral fat, which requires longer duration to show effect. In this study, we investigated the short-term changes in fat metabolism in liver, abdomen, and skeletal muscle during antiobesity interventions including Sibutramine treatment and diet restriction in obese rats using magnetic resonance imaging, magnetic resonance spectroscopy, and blood chemistry. Sibutramine is an antiobesity drug that results in weight loss by increasing satiety and energy expenditure. The Sibutramine-treated rats showed reduction of liver fat and intramyocellular lipids on day 3. The triglycerides (TG decreased on day 1 and 3 compared to baseline (day 0. The early response/nonresponse in different fat depots will permit optimization of treatment for better clinical outcome rather than staying with a drug for longer periods.

  18. Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome.

    Science.gov (United States)

    Wimalawansa, Sunil J

    2018-01-01

    The aim of this study is to determine the relationships of vitamin D with diabetes, insulin resistance obesity, and metabolic syndrome. Intra cellular vitamin D receptors and the 1-α hydroxylase enzyme are distributed ubiquitously in all tissues suggesting a multitude of functions of vitamin D. It plays an indirect but an important role in carbohydrate and lipid metabolism as reflected by its association with type 2 diabetes (T2D), metabolic syndrome, insulin secretion, insulin resistance, polycystic ovarian syndrome, and obesity. Peer-reviewed papers, related to the topic were extracted using key words, from PubMed, Medline, and other research databases. Correlations of vitamin D with diabetes, insulin resistance and metabolic syndrome were examined for this evidence-based review. In addition to the well-studied musculoskeletal effects, vitamin D decreases the insulin resistance, severity of T2D, prediabetes, metabolic syndrome, inflammation, and autoimmunity. Vitamin D exerts autocrine and paracrine effects such as direct intra-cellular effects via its receptors and the local production of 1,25(OH) 2 D 3 , especially in muscle and pancreatic β-cells. It also regulates calcium homeostasis and calcium flux through cell membranes, and activation of a cascade of key enzymes and cofactors associated with metabolic pathways. Cross-sectional, observational, and ecological studies reported inverse correlations between vitamin D status with hyperglycemia and glycemic control in patients with T2D, decrease the rate of conversion of prediabetes to diabetes, and obesity. However, no firm conclusions can be drawn from current studies, because (A) studies were underpowered; (B) few were designed for glycemic outcomes, (C) the minimum (or median) serum 25(OH) D levels achieved are not measured or reported; (D) most did not report the use of diabetes medications; (E) some trials used too little (F) others used too large, unphysiological and infrequent doses of vitamin D; and

  19. Further analysis of multicentre cystathionine beta synthase deficiency thrombosis data and metabolic pathways suggests potentially better treatment via improved cysteine supplementation, diet, antioxidant supplementation, follow-up and testing for thrombophilic mutations

    Directory of Open Access Journals (Sweden)

    David Vance

    2017-01-01

    Full Text Available Background Homozygous or compound heterozygous Cystathionine-beta-synthase deficiency (CBS-- may result in thrombosis. Treatment has included various combinations of: low-methionine diets, cystine (cystine dimer-enriched amino acid supplementation, vitamin B6, folic acid, vitamin B12 and betaine. Treatment compliance and outcomes even in the most-developed countries are mostly sub-optimal and variable, and the differing theoretical metabolic ramifications due to differing treatments have not been well addressed. The aim of this work was to further analyse the thrombosis events data of Yap et al (2001/2003, and to compare these with the rate of thrombosis in the general population, and to examine the theoretical significance of the metabolic pathways affected by CBS-- and its treatments, and so find any potential improvements in treatments, considering also less-developed areas. Methods Yap et al’s (2001/2003 data of the thrombosis outcomes of five major (CBS---treating centers: in Dublin, Sydney, Nijmegen, Manchester and London; were statistically compared with outcomes predicted by Mudd et al’s (1985 untreated natural history outcomes, and then Dublin versus the others; these rates were then compared with those of general populations; and treatments were examined regarding their theoretical metabolic ramifications. Results There were less thrombosis outcomes (P<.05 in the treated and followed CBS-- patient groups of each of the five centers, even when considered singly, than that expected in the absence of treatment by reference to the natural history data of Mudd et al (1985, but the reduction was less than half that claimed by Yap et al, and the remaining level of thrombosis is roughly 10 times that of the general population. The thromboses outcome (nil of the Dublin group is better than that of the other four groups, but only at P ~ 0.16 with the other four groups combined, or P = 0.14 to 0.23 singly. Treatment regimens differ, including

  20. Influence of diabetes mellitus on heart failure risk and outcome

    Directory of Open Access Journals (Sweden)

    Van Belle Eric

    2003-01-01

    Full Text Available Abstract Our aim is to summarize and discuss the recent literature linking diabetes mellitus with heart failure, and to address the issue of the optimal treatment for diabetic patients with heart failure. The studies linking diabetes mellitus (DM with heart failure (HF The prevalence of diabetes mellitus in heart failure populations is close to 20% compared with 4 to 6% in control populations. Epidemiological studies have demonstrated an increased risk of heart failure in diabetics; moreover, in diabetic populations, poor glycemic control has been associated with an increased risk of heart failure. Various mechanisms may link diabetes mellitus to heart failure: firstly, associated comorbidities such as hypertension may play a role; secondly, diabetes accelerates the development of coronary atherosclerosis; thirdly, experimental and clinical studies support the existence of a specific diabetic cardiomyopathy related to microangiopathy, metabolic factors or myocardial fibrosis. Subgroup analyses of randomized trials demonstrate that diabetes is also an important prognostic factor in heart failure. In addition, it has been suggested that the deleterious impact of diabetes may be especially marked in patients with ischemic cardiomyopathy. Treatment of heart failure in diabetic patients The knowledge of the diabetic status may help to define the optimal therapeutic strategy for heart failure patients. Cornerstone treatments such as ACE inhibitors or beta-blockers appear to be uniformly beneficial in diabetic and non diabetic populations. However, in ischemic cardiomyopathy, the choice of the revascularization technique may differ according to diabetic status. Finally, clinical studies are needed to determine whether improved metabolic control might favorably influence the outcome of diabetic heart failure patients.

  1. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

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    Taylor M. Gilliland

    2017-03-01

    Full Text Available Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL. The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016 addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC. We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1 patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2 patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3 enteral nutrition (EN should be preferred as a nutritional intervention over total parenteral nutrition (TPN postoperatively; and, (4 a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of

  2. It must be my metabolism: Metabolic control of mind

    Directory of Open Access Journals (Sweden)

    Dana M Small

    2014-07-01

    Full Text Available For millennia it was advantageous to overeat whenever food was available in order to create reserves of energy for likely future episodes of famine. Neural circuits thus evolved to promote eating in the absence of hunger when cues signaling food availability were encountered. In today’s food environment, this once adaptive behavior may fuel the obesity epidemic. An oft-used index of one’s propensity to eat in the absence of hunger is “food cue reactivity”. How “reactive” one is to a food cue can be assessed in a variety of ways. Food intake can be measured subsequent to initial exposures to the sight, taste or smell of a palatable food. Not surprisingly, overweight and obese individuals are more likely to eat or to eat more than their lean counterparts when presented with food cues (1. Measuring brain response to food cues can also assess food cue reactivity. Heightened responses in dopamine source and target regions are associated with increased food consumption (2-5, weight gain (6-9, and poor outcomes in weight loss programs (10. Paralleling the behavioral data, overweight and obese individuals also show heightened responses to food cues, as do individuals at risk for overeating (11-14. Despite the reliable relationship between brain response to food cues and obesity the mechanism by which food cues drive brain response is unknown. To identify factors that regulate food cue reactivity in humans we have employed a flavor nutrient conditioning protocol in which associations are formed between a novel flavor and calorie content. In the rodent model, it is well established that pairing a novel flavor with intra-gastric infusion of glucose conditions a strong preference for that flavor when later consumed in the absence of calories (15. This implies that a peripheral signal generated by the glucose infusion is critical for flavor preference formation. Recent work also performed in the rodent model demonstrates that there is a close

  3. Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

    Science.gov (United States)

    Yadav, Saveg; Pandey, Shrish Kumar; Singh, Vinay Kumar; Goel, Yugal; Kumar, Ajay; Singh, Sukh Mahendra

    2017-01-01

    Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP), with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA) and propionic acid (PA), with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

  4. Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

    Directory of Open Access Journals (Sweden)

    Saveg Yadav

    Full Text Available Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP, with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA and propionic acid (PA, with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

  5. Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

    Directory of Open Access Journals (Sweden)

    Huss M

    2017-07-01

    Full Text Available Michael Huss,1 Praveen Duhan,2 Preetam Gandhi,3 Chien-Wei Chen,4 Carsten Spannhuth,3 Vinod Kumar5 1Child and Adolescent Psychiatry, University Medicine, Mainz, Germany; 2Global Medical Affairs, Novartis Healthcare Pvt. Ltd., Hyderabad, India; 3Development Franchise, Established Medicine Neuroscience, Novartis Pharma AG, Basel, Switzerland; 4Biostatistics Cardio-Metabolic & Established Medicine, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 5Established Medicines, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Abstract: Attention-deficit/hyperactivity disorder (ADHD is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH, a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD. Keywords: methylphenidate, dose optimization, attention-deficit/hyperactivity disorder, ADHD

  6. Metabolic disorders in menopause

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    Grzegorz Stachowiak

    2015-04-01

    Full Text Available Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance – IGT, type 2 diabetes mellitus – T2DM or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women’s life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases in menopause, including the role of a tailored menopausal hormone therapy (HT. According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy. Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities.

  7. Metabolic Reprogramming During Multidrug Resistance in Leukemias

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    Raphael Silveira Vidal

    2018-04-01

    Full Text Available Cancer outcome has improved since introduction of target therapy. However, treatment success is still impaired by the same drug resistance mechanism of classical chemotherapy, known as multidrug resistance (MDR phenotype. This phenotype promotes resistance to drugs with different structures and mechanism of action. Recent reports have shown that resistance acquisition is coupled to metabolic reprogramming. High-gene expression, increase of active transport, and conservation of redox status are one of the few examples that increase energy and substrate demands. It is not clear if the role of this metabolic shift in the MDR phenotype is related to its maintenance or to its induction. Apart from the nature of this relation, the metabolism may represent a new target to avoid or to block the mechanism that has been impairing treatment success. In this mini-review, we discuss the relation between metabolism and MDR resistance focusing on the multiple non-metabolic functions that enzymes of the glycolytic pathway are known to display, with emphasis with the diverse activities of glyceraldehyde-3-phosphate dehydrogenase.

  8. Endothelial dysfunction in metabolic and vascular disorders.

    Science.gov (United States)

    Polovina, Marija M; Potpara, Tatjana S

    2014-03-01

    Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in the maintenance of vascular health and metabolic homeostasis. It has long been recognized that endothelial dysfunction participates in the pathogenesis of atherosclerosis from early, preclinical lesions to advanced, thrombotic complications. In addition, endothelial dysfunction has been recently implicated in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering that states of insulin resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, and T2DM) represent the most prevalent metabolic disorders and risk factors for atherosclerosis, it is of considerable scientific and clinical interest that both metabolic and vascular disorders have endothelial dysfunction as a common background. Importantly, endothelial dysfunction has been associated with adverse outcomes in patients with established cardiovascular disease, and a growing body of evidence indicates that endothelial dysfunction also imparts adverse prognosis in states of insulin resistance. In this review, we discuss the association of insulin resistance and T2DM with endothelial dysfunction and vascular disease, with a focus on the underlying mechanisms and prognostic implications of the endothelial dysfunction in metabolic and vascular disorders. We also address current therapeutic strategies for the improvement of endothelial dysfunction.

  9. Long-Term Outcome After Radiotherapy in Patients With Atypical and Malignant Meningiomas—Clinical Results in 85 Patients Treated in a Single Institution Leading to Optimized Guidelines for Early Radiation Therapy

    International Nuclear Information System (INIS)

    Adeberg, Sebastian; Hartmann, Christian; Welzel, Thomas; Rieken, Stefan; Habermehl, Daniel; Deimling, Andreas von; Debus, Jürgen; Combs, Stephanie E.

    2012-01-01

    Purpose: Previously, we could show that the new World Health Organization (WHO) classification of meningiomas significantly correlated with outcome in patients with atypical and anaplastic histology. In the present work, we analyzed our long-term experience in radiotherapy for atypical and malignant meningioma diagnosed according to the most recent WHO categorization system. Patients and Methods: Sixty-two patients with atypical and 23 patients with malignant meningioma have been treated with radiotherapy. Sixty percent of all patients received radiotherapy (RT) after surgical resection, 19% at disease progression and 8.3% as a primary treatment. Radiation was applied using different techniques including fractionated stereotactic RT (FSRT), intensity-modulated RT, and combination treatment with carbon ions. The median PTV was 156.0 mL. An average dose of 57.6 Gy (range, 30–68.4 Gy) in 1.8–3 Gy fractions was applied. All patients were followed regularly including clinical-neurological follow-up as well as computed tomographies or magnetic resonance imaging. Results: Overall survival was impacted significantly by histological grade, with 81% and 53% at 5 years for atypical or anaplastic meningiomas, respectively. This difference was significant at p = 0.022. Eighteen patients died of tumor progression during follow-up. Progression-free survival was 95% and 50% for atypical, and 63% and 13% for anaplastic histology at 2 and 5 years. This difference was significant at p = 0.017. Despite histology, we could not observe any prognostic factors including age, resection status, or Karnofsky performance score. However, preexisting clinical symptoms observed in 63 patients improved in 29.3% of these patients. Conclusion: RT resulted in improvement of preexisting clinical symptoms; outcome is comparable to other series reported in the literature. RT should be offered after surgical resection after initial diagnosis to increase progression-free survival as well as overall

  10. Metabolic syndrome induced by anticancer treatment in childhood cancer survivors.

    Science.gov (United States)

    Chueh, Hee Won; Yoo, Jae Ho

    2017-06-01

    The number of childhood cancer survivors is increasing as survival rates improve. However, complications after treatment have not received much attention, particularly metabolic syndrome. Metabolic syndrome comprises central obesity, dyslipidemia, hypertension, and insulin resistance, and cancer survivors have higher risks of cardiovascular events compared with the general population. The mechanism by which cancer treatment induces metabolic syndrome is unclear. However, its pathophysiology can be categorized based on the cancer treatment type administered. Brain surgery or radiotherapy may induce metabolic syndrome by damaging the hypothalamic-pituitary axis, which may induce pituitary hormone deficiencies. Local therapy administered to particular endocrine organs directly damages the organs and causes hormone deficiencies, which induce obesity and dyslipidemia leading to metabolic syndrome. Chemotherapeutic agents interfere with cell generation and growth, damage the vascular endothelial cells, and increase the cardiovascular risk. Moreover, chemotherapeutic agents induce oxidative stress, which also induces metabolic syndrome. Physical inactivity caused by cancer treatment or the cancer itself, dietary restrictions, and the frequent use of antibiotics may also be risk factors for metabolic syndrome. Since childhood cancer survivors with metabolic syndrome have higher risks of cardiovascular events at an earlier age, early interventions should be considered. The optimal timing of interventions and drug use has not been established, but lifestyle modifications and exercise interventions that begin during cancer treatment might be beneficial and tailored education and interventions that account for individual patients' circumstances are needed. This review evaluates the recent literature that describes metabolic syndrome in cancer survivors, with a focus on its pathophysiology.

  11. VRML metabolic network visualizer.

    Science.gov (United States)

    Rojdestvenski, Igor

    2003-03-01

    A successful date collection visualization should satisfy a set of many requirements: unification of diverse data formats, support for serendipity research, support of hierarchical structures, algorithmizability, vast information density, Internet-readiness, and other. Recently, virtual reality has made significant progress in engineering, architectural design, entertainment and communication. We experiment with the possibility of using the immersive abstract three-dimensional visualizations of the metabolic networks. We present the trial Metabolic Network Visualizer software, which produces graphical representation of a metabolic network as a VRML world from a formal description written in a simple SGML-type scripting language.

  12. Human Body Exergy Metabolism

    OpenAIRE

    Mady, Carlos Eduardo Keutenedjian

    2013-01-01

    The exergy analysis of the human body is a tool that can provide indicators of health and life quality. To perform the exergy balance it is necessary to calculate the metabolism on an exergy basis, or metabolic exergy, although there is not yet consensus in its calculation procedure. Hence, the aim of this work is to provide a general method to evaluate this physical quantity for human body based on indirect calorimetry data. To calculate the metabolism on an exergy basis it is necessary to d...

  13. Altered drug metabolism during pregnancy: hormonal regulation of drug-metabolizing enzymes.

    Science.gov (United States)

    Jeong, Hyunyoung

    2010-06-01

    Medication use during pregnancy is prevalent, but pharmacokinetic information of most drugs used during pregnancy is lacking in spite of known effects of pregnancy on drug disposition. Accurate pharmacokinetic information is essential for optimal drug therapy in mother and fetus. Thus, understanding how pregnancy influences drug disposition is important for better prediction of pharmacokinetic changes of drugs in pregnant women. Pregnancy is known to affect hepatic drug metabolism, but the underlying mechanisms remain unknown. Physiological changes accompanying pregnancy are probably responsible for the reported alteration in drug metabolism during pregnancy. These include elevated concentrations of various hormones such as estrogen, progesterone, placental growth hormones and prolactin. This review covers how these hormones influence expression of drug-metabolizing enzymes (DMEs), thus potentially responsible for altered drug metabolism during pregnancy. The reader will gain a greater understanding of the altered drug metabolism in pregnant women and the regulatory effects of pregnancy hormones on expression of DMEs. In-depth studies in hormonal regulatory mechanisms as well as confirmatory studies in pregnant women are warranted for systematic understanding and prediction of the changes in hepatic drug metabolism during pregnancy.

  14. INO80 Chromatin Remodeling Coordinates Metabolic Homeostasis with Cell Division

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    Graeme J. Gowans

    2018-01-01

    Full Text Available Adaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the yeast metabolic cycle (YMC. Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here, we demonstrate that the INO80 chromatin-remodeling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC1-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin to restrict proliferation to metabolically optimal states.

  15. Emerging health problems among women: Inactivity, obesity, and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Yi-Ju Tsai

    2014-02-01

    Full Text Available The increase in obesity and metabolic syndrome has been documented worldwide. However, few studies have investigated the risk of inactivity, obesity, and metabolic syndrome specifically in women. Hormone balance plays a crucial role in regulating metabolism and helps to maintain optimal health. It is likely that the sex difference in obesity may be due to the variation in hormone concentration throughout a woman's life, which predisposes them to weight gain. This paper reviews previous literature and discusses factors that influence the risk of adiposity-related health consequences among women for three critical biological transitions throughout a woman's life: puberty, menopause, and pregnancy. To improve quality of life and metabolic health for women, interventions are needed to target women at different transition stages and provide tailored health education programs. Interventions should raise awareness of physical inactivity, obesity, and metabolic syndrome, and promote healthy behavioral change in women.

  16. [SIAM conference on optimization

    Energy Technology Data Exchange (ETDEWEB)

    1992-05-10

    Abstracts are presented of 63 papers on the following topics: large-scale optimization, interior-point methods, algorithms for optimization, problems in control, network optimization methods, and parallel algorithms for optimization problems.

  17. Physical activity and metabolic disease among people with affective disorders: Prevention, management and implementation.

    Science.gov (United States)

    Vancampfort, Davy; Stubbs, Brendon

    2017-12-15

    One in ten and one in three of people with affective disorders experience diabetes and metabolic syndrome respectively. Physical activity (PA) and sedentary behaviour (SB) are key risk factors that can ameliorate the risk of metabolic disease among this population. However, PA is often seen as luxury and/or a secondary component within the management of people with affective disorders. The current article provides a non-systematic best-evidence synthesis of the available literature, detailing a number of suggestions for the implementation of PA into clinical practice. Whilst the evidence is unequivocal for the efficacy of PA to prevent and manage metabolic disease in the general population, it is in its infancy in this patient group. Nonetheless, action must be taken now to ensure that PA and reducing SB are given a priority to prevent and manage metabolic diseases and improve wider health outcomes. PA should be treated as a vital sign and all people with affective disorders asked about their activity levels and if appropriate advised to increase this. There is a need for investment in qualified exercise specialists in clinical practice such as physiotherapists to undertake and oversee PA in practice. Behavioural strategies such as the self-determined theory should be employed to encourage adherence. Funding is required to develop the evidence base and elucidate the optimal intervention characteristics. PA interventions should form an integral part of the multidisciplinary management of people with affective disorders and our article outlines the evidence and strategies to implement this in practice. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. METABOLIC THERAPY IN PATIENTS WITH ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    L. B. Zavaliy

    2018-01-01

    Full Text Available The article shows the world experience of metabolic therapy use in the treatment of ischemic stroke. The issue still remains prominent. The reasonability of prescribing metabolic drugs is not completely clear, its effectiveness has not been fully proved, despite numerous studies which show only trends. The article presents an overview of the most popular drugs of different pharmacological groups with a metabolic effect which affect different parts of the ischemic cascade. Ethylmethylhydroxypyridine succinate and cytoflavin have predominantly antihypoxic effect, improve functional outcome and neurological functions, and normalize overall well-being and adaptation. Cerebrolysin is a complex of low molecular weight biologically active peptides derived from the pig’s brain. It has a multimodal effect on the brain, helps to reduce the volume of cerebral infarction, restores neurologic functions and improves the functional outcome. Cortexin is a mixture of cattle brain polypeptides, also has a complex action that provides the most complete reversion of neurological deficit, improves cognitive functions and the functional outcome, reduces the level of paroxysmal convulsive readiness and improves bioelectric activity of the brain. Citicoline is a precursor of cell membrane key ultrastructures, contributes to significant reduction in the volume of cortical brain damage, improves cholinergic transmission, which results in better clinical outcome, even despite the questionable impact on the neurological status. Choline Alfoscerate is a precursor of choline, and the use of the drug significantly limits the growth of the cerebral infarction area starting from the first day of therapy, leads to reversion of neurological symptoms and achievement of rehabilitation goals. Actovegin is deproteinized derivative of calf blood, activates metabolism in tissues, improves trophism and stimulates regeneration. In a large study, it was shown that Actovegin improved

  19. Predicting outcome of status epilepticus.

    Science.gov (United States)

    Leitinger, M; Kalss, G; Rohracher, A; Pilz, G; Novak, H; Höfler, J; Deak, I; Kuchukhidze, G; Dobesberger, J; Wakonig, A; Trinka, E

    2015-08-01

    Status epilepticus (SE) is a frequent neurological emergency complicated by high mortality and often poor functional outcome in survivors. The aim of this study was to review available clinical scores to predict outcome. Literature review. PubMed Search terms were "score", "outcome", and "status epilepticus" (April 9th 2015). Publications with abstracts available in English, no other language restrictions, or any restrictions concerning investigated patients were included. Two scores were identified: "Status Epilepticus Severity Score--STESS" and "Epidemiology based Mortality score in SE--EMSE". A comprehensive comparison of test parameters concerning performance, options, and limitations was performed. Epidemiology based Mortality score in SE allows detailed individualization of risk factors and is significantly superior to STESS in a retrospective explorative study. In particular, EMSE is very good at detection of good and bad outcome, whereas STESS detecting bad outcome is limited by a ceiling effect and uncertainty of correct cutoff value. Epidemiology based Mortality score in SE can be adapted to different regions in the world and to advances in medicine, as new data emerge. In addition, we designed a reporting standard for status epilepticus to enhance acquisition and communication of outcome relevant data. A data acquisition sheet used from patient admission in emergency room, from the EEG lab to intensive care unit, is provided for optimized data collection. Status Epilepticus Severity Score is easy to perform and predicts bad outcome, but has a low predictive value for good outcomes. Epidemiology based Mortality score in SE is superior to STESS in predicting good or bad outcome but needs marginally more time to perform. Epidemiology based Mortality score in SE may prove very useful for risk stratification in interventional studies and is recommended for individual outcome prediction. Prospective validation in different cohorts is needed for EMSE, whereas

  20. Metabolic engineering of Saccharomyces cerevisiae for optimizing 3HP production

    DEFF Research Database (Denmark)

    Jensen, Niels Bjerg; Maury, Jerome; Oberg, Fredrik

    2012-01-01

    . Polyacrylates are a substantial part of the different plastic varieties found on the market. This kind of plastic is derived from acrylic acid, which is currently produced from propylene, a by-product of ethylene and gasoline production. Annually, more than one billion kilograms of acrylic acid is produced...

  1. Optimality principles in the regulation of metabolic networks

    NARCIS (Netherlands)

    Berkhout, J.; Bruggeman, F.J.; Teusink, B.

    2012-01-01

    One of the challenging tasks in systems biology is to understand how molecular networks give rise to emergent functionality and whether universal design principles apply to molecular networks. To achieve this, the biophysical, evolutionary and physiological constraints that act on those networks

  2. Soldier Health Habits and the Metabolically Optimized Brain.

    Science.gov (United States)

    Friedl, Karl E; Breivik, Torbjorn J; Carter, Robert; Leyk, Dieter; Opstad, Per Kristian; Taverniers, John; Trousselard, Marion

    2016-11-01

    Human performance enhancement was the subject of a NATO workshop that considered the direct benefits of individual soldier health and fitness habits to brain health and performance. Some of the important health and fitness include physical activity and purposeful exercise, nutritional intake, sleep and rest behaviors, psychological outlook and mindfulness, and other physiologically based systemic challenges such as thermal exposure. These influences were considered in an integrated framework with insights contributed by each of five participating NATO member countries using representative research to highlight relevant interrelationships. Key conclusions are that (1) understanding the neurobiological bases and consequences of personal health behaviors is a priority for soldier performance research, and this also involves long-term brain health consequences to veterans and (2) health and fitness habits have been underappreciated as reliably effective performance enhancers and these should be preferred targets in the development of scientifically based recommendations for soldier brain health and performance. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  3. In silico strain optimization by adding reactions to metabolic models

    Directory of Open Access Journals (Sweden)

    Correia Sara

    2012-12-01

    Full Text Available Nowadays, the concerns about the environment and the needs to increase the productivity at low costs, demand for the search of new ways to produce compounds with industrial interest. Based on the increasing knowledge of biological processes, through genome sequencing projects, and high-throughput experimental techniques as well as the available computational tools, the use of microorganisms has been considered as an approach to produce desirable compounds. However, this usually requires to manipulate these organisms by genetic engineering and/ or changing the enviromental conditions to make the production of these compounds possible. In many cases, it is necessary to enrich the genetic material of those microbes with hereologous pathways from other species and consequently adding the potential to produce novel compounds.

  4. What is Nutrition & Metabolism?

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2004-08-01

    Full Text Available Abstract A new Open Access journal, Nutrition & Metabolism (N&M will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.

  5. Epigenetics and Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wenyi Xu

    2016-01-01

    Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  6. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... this process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form ...

  7. The metabolic radiotherapy

    International Nuclear Information System (INIS)

    Begon, F.; Gaci, M.

    1993-01-01

    In this article, the authors recall the principles of the metabolic radiotherapy and present these main applications in the treatment of thyroid cancers, hyperthyroidism, polycythemia, arthritis, bone metastases, adrenergic neoplasms. They also present the radioimmunotherapy

  8. Engineering of metabolic control

    Science.gov (United States)

    Liao, James C.

    2004-03-16

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  9. Accessing Autonomic Function Can Early Screen Metabolic Syndrome

    Science.gov (United States)

    Dai, Meng; Li, Mian; Yang, Zhi; Xu, Min; Xu, Yu; Lu, Jieli; Chen, Yuhong; Liu, Jianmin; Ning, Guang; Bi, Yufang

    2012-01-01

    Background Clinical diagnosis of the metabolic syndrome is time-consuming and invasive. Convenient instruments that do not require laboratory or physical investigation would be useful in early screening individuals at high risk of metabolic syndrome. Examination of the autonomic function can be taken as a directly reference and screening indicator for predicting metabolic syndrome. Methodology and Principal Findings The EZSCAN test, as an efficient and noninvasive technology, can access autonomic function through measuring electrochemical skin conductance. In this study, we used EZSCAN value to evaluate autonomic function and to detect metabolic syndrome in 5,887 participants aged 40 years or older. The EZSCAN test diagnostic accuracy was analyzed by receiver operating characteristic curves. Among the 5,815 participants in the final analysis, 2,541 were diagnosed as metabolic syndrome and the overall prevalence was 43.7%. Prevalence of the metabolic syndrome increased with the elevated EZSCAN risk level (p for trend metabolic syndrome components (p for trend metabolic syndrome after the multiple adjustments. The area under the curve of the EZSCAN test was 0.62 (95% confidence interval [CI], 0.61–0.64) for predicting metabolic syndrome. The optimal operating point for the EZSCAN value to detect a high risk of prevalent metabolic syndrome was 30 in this study, while the sensitivity and specificity were 71.2% and 46.7%, respectively. Conclusions and Significance In conclusion, although less sensitive and accurate when compared with the clinical definition of metabolic syndrome, we found that the EZSCAN test is a good and simple screening technique for early predicting metabolic syndrome. PMID:22916265

  10. Accessing autonomic function can early screen metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Kan Sun

    Full Text Available BACKGROUND: Clinical diagnosis of the metabolic syndrome is time-consuming and invasive. Convenient instruments that do not require laboratory or physical investigation would be useful in early screening individuals at high risk of metabolic syndrome. Examination of the autonomic function can be taken as a directly reference and screening indicator for predicting metabolic syndrome. METHODOLOGY AND PRINCIPAL FINDINGS: The EZSCAN test, as an efficient and noninvasive technology, can access autonomic function through measuring electrochemical skin conductance. In this study, we used EZSCAN value to evaluate autonomic function and to detect metabolic syndrome in 5,887 participants aged 40 years or older. The EZSCAN test diagnostic accuracy was analyzed by receiver operating characteristic curves. Among the 5,815 participants in the final analysis, 2,541 were diagnosed as metabolic syndrome and the overall prevalence was 43.7%. Prevalence of the metabolic syndrome increased with the elevated EZSCAN risk level (p for trend <0.0001. Moreover, EZSCAN value was associated with an increase in the number of metabolic syndrome components (p for trend <0.0001. Compared with the no risk group (EZSCAN value 0-24, participants at the high risk group (EZSCAN value: 50-100 had a 2.35 fold increased risk of prevalent metabolic syndrome after the multiple adjustments. The area under the curve of the EZSCAN test was 0.62 (95% confidence interval [CI], 0.61-0.64 for predicting metabolic syndrome. The optimal operating point for the EZSCAN value to detect a high risk of prevalent metabolic syndrome was 30 in this study, while the sensitivity and specificity were 71.2% and 46.7%, respectively. CONCLUSIONS AND SIGNIFICANCE: In conclusion, although less sensitive and accurate when compared with the clinical definition of metabolic syndrome, we found that the EZSCAN test is a good and simple screening technique for early predicting metabolic syndrome.

  11. Oxidative metabolism in muscle.

    OpenAIRE

    Ferrari, M; Binzoni, T; Quaresima, V

    1997-01-01

    Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantage...

  12. Tumor Macroenvironment and Metabolism

    OpenAIRE

    Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-01-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organ...

  13. Cerebral tryptophan metabolism and outcome of tuberculous meningitis

    NARCIS (Netherlands)

    Laarhoven, van Arjan; Dian, Sofiati; Aguirre-Gamboa, Raúl; Avila-Pacheco, Julian; Ricaño-Ponce, Isis; Ruesen, Carolien; Annisa, Jessi; Koeken, Valerie A.C.M.; Chaidir, Lidya; Li, Yang; Achmad, Tri Hanggono; Joosten, Leo A.B.; Notebaart, Richard A.; Ruslami, Rovina; Netea, Mihai G.; Verbeek, Marcel M.; Alisjahbana, Bachti; Kumar, Vinod; Clish, Clary B.; Ganiem, A.R.; Crevel, van Reinout

    2018-01-01

    Background: Immunopathology contributes to the high mortality of tuberculous meningitis, but the biological pathways involved are mostly unknown. We aimed to compare cerebrospinal fluid (CSF) and serum metabolomes of patients with tuberculous meningitis with that of controls without tuberculous

  14. Ca-48 metabolism studies

    International Nuclear Information System (INIS)

    Van der Merwe, D.G.

    1987-03-01

    Calcium metabolism has been studied in depth physiologically and is a relatively well-understood element in biochemistry and medicine. There is still only restricted knowledge of the metabolic fate of calcium in normal and abnormal paediatric subjects. The latter is partially owing to inadequate techniques for tracing and modelling calcium pathways in children. The advent of radioactive tracers has unquestionably enhanced medical research and improved the quality of many metabolic studies. The present study was aimed at the development, promotion and justification of a new tracer technique using the stable isotope, calcium-48. The obvious advantages of such a technique are its harmlessness tothe subject, its applicability to both short- and long-term studies as well as its usefulness to the study for which it was originally motivated, viz research defining the actual relationship between a calcium-deficient diet and the occurrence of rickets in rural Black children in South Africa. Exploratory instrumental