MetaNetX/MNXref - reconciliation of metabolites and biochemical reactions to bring together genome-scale metabolic networks.

MetaNetX is a repository of genome-scale metabolic networks (GSMNs) and biochemical pathways from a number of major resources imported into a common namespace of chemical compounds, reactions, cellular compartments-namely MNXref-and proteins. The MetaNetX.org website (http://www.metanetx.org/) provides access to these integrated data as well as a variety of tools that allow users to import their own GSMNs, map them to the MNXref reconciliation, and manipulate, compare, analyze, simulate (using flux balance analysis) and export the resulting GSMNs. MNXref and MetaNetX are regularly updated and freely available.

Screening premorbid metabolic syndrome in community pharmacies: a cross-sectional descriptive study

Background: Premorbid metabolic syndrome (pre-MetS) is a cluster of cardiometabolic risk factors characterised by central obesity, elevated fasting glucose, atherogenic dyslipidaemia and hypertension without established cardiovascular disease or diabetes. Community pharmacies are in an excellent position to develop screening programmes because of their direct contact with the population. The main aim of the study was to determine the prevalence of pre-MetS in people who visited community pharmacies for measurement of any of its five risk factors to detect the presence of other risk factors. The secondary aims were to study the presence of other cardiovascular risk factors and determine patients" cardiovascular risk. Methods: Cross-sectional, descriptive, multicentre study. Patients meeting selection criteria aged between 18 and 65 years who visited participating community pharmacies to check any of five pre-MetS diagnostic factors were included. The study involved 23 community pharmacies in Catalonia (Spain). Detection criteria for pre-MetS were based on the WHO proposal following IDF and AHA/NHBI consensus. Cardiovascular risk (CVR) was calculated by Regicor and Score methods. Other variables studied were smoking habit, physical activity, body mass index (BMI), and pharmacological treatment of dyslipidemia and hypertension. The data were collected and analysed with the SPSS programme. Comparisons of variables were carried out using the Student"s T-test, Chi-Squared test or ANOVA test. Level of significance was 5% (0.05). Results: The overall prevalence of pre-MetS was 21.9% [95% CI 18.7-25.2]. It was more prevalent in men, 25.5% [95% CI 22.1-28.9], than in women, 18.6% [95% CI 15.5-21.7], and distribution increased with age. The most common risk factors were high blood pressure and abdominal obesity. About 70% of people with pre-MetS were sedentary and over 85% had a BMI ≥25 Kg/m2 . Some 22.4% had two metabolic criteria and 27.2% of patients with pre-MetS had no previous diagnosis. Conclusions: The prevalence of pre-MetS in our study (21.9%) was similar to that found in other studies carried out in Primary Care in Spain. The results of this study confirm emergent cardiometabolic risk factors such as hypertension, obesity and physical inactivity. Our study highlights the strategic role of the community pharmacy in the detection of pre-MetS in the apparently healthy population.

Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.

[(18)F]FDG-PET/CT metabolic parameters as useful prognostic factors in cervical cancer patients treated with chemo-radiotherapy.

BACKGROUND: To compare the prognostic value of different anatomical and functional metabolic parameters determined using [(18)F]FDG-PET/CT with other clinical and pathological prognostic parameters in cervical cancer (CC). METHODS: Thirty-eight patients treated with standard curative doses of chemo-radiotherapy (CRT) underwent pre- and post-therapy [(18)F]FDG-PET/CT. [(18)F]FDG-PET/CT parameters including mean tumor standardized uptake values (SUV), metabolic tumor volume (MTV) and tumor glycolytic volume (TGV) were measured before the start of CRT. The post-treatment tumor metabolic response was evaluated. These parameters were compared to other clinical prognostic factors. Survival curves were estimated by using the Kaplan-Meier method. Cox regression analysis was performed to determine the independent contribution of each prognostic factor. RESULTS: After 37 months of median follow-up (range, 12-106), overall survival (OS) was 71 % [95 % confidence interval (CI), 54-88], disease-free survival (DFS) 61 % [95 % CI, 44-78] and loco-regional control (LRC) 76 % [95 % CI, 62-90]. In univariate analyses the [(18)F]FDG-PET/CT parameters unfavorably influencing OS, DFS and LRC were pre-treatment TGV-cutoff ≥562 (37 vs. 76 %, p = 0.01; 33 vs. 70 %, p = 0.002; and 55 vs. 83 %, p = 0.005, respectively), mean pre-treatment tumor SUV cutoff ≥5 (57 vs. 86 %, p = 0.03; 36 vs. 88 %, p = 0.004; 65 vs. 88 %, p = 0.04, respectively) and a partial tumor metabolic response after treatment (9 vs. 29 %, p = 0.0008; 0 vs. 83 %, p < 0.0001; 22 vs. 96 %, p < 0.0001, respectively). After multivariate analyses a partial tumor metabolic response after treatment remained as an independent prognostic factor unfavorably influencing DFS and LRC (RR 1:7.7, p < 0.0001, and RR 1:22.6, p = 0.0003, respectively) while the pre-treatment TGV-cutoff ≥562 negatively influenced OS and DFS (RR 1:2, p = 0.03, and RR 1:2.75, p = 0.05). CONCLUSIONS: Parameters capturing the pre-treatment glycolytic volume and metabolic activity of [(18)F]FDG-positive disease provide important prognostic information in patients with CC treated with CRT. The post-therapy [(18)F]FDG-PET/CT uptake (partial tumor metabolic response) is predictive of disease outcome.

Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL).

BACKGROUND: Most peripheral T-cell lymphoma (PTCL) patients have a poor outcome and the identification of prognostic factors at diagnosis is needed. PATIENTS AND METHODS: The prognostic impact of total metabolic tumor volume (TMTV0), measured on baseline [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography, was evaluated in a retrospective study including 108 PTCL patients (27 PTCL not otherwise specified, 43 angioimmunoblastic T-cell lymphomas and 38 anaplastic large-cell lymphomas). All received anthracycline-based chemotherapy. TMTV0 was computed with the 41% maximum standardized uptake value threshold method and an optimal cut-off point for binary outcomes was determined and compared with others prognostic factors. RESULTS: With a median follow-up of 23 months, 2-year progression-free survival (PFS) was 49% and 2-year overall survival (OS) was 67%. High TMTV0 was significantly associated with a worse prognosis. At 2 years, PFS was 26% in patients with a high TMTV0 (>230 cm(3), n = 53) versus 71% for those with a low TMTV0, [P < 0.0001, hazard ratio (HR) = 4], whereas OS was 50% versus 80%, respectively, (P = 0.0005, HR = 3.1). In multivariate analysis, TMTV0 was the only significant independent parameter for both PFS and OS. TMTV0, combined with PIT, discriminated even better than TMTV0 alone, patients with an adverse outcome (TMTV0 >230 cm(3) and PIT >1, n = 33,) from those with good prognosis (TMTV0 ≤230 cm(3) and PIT ≤1, n = 40): 19% versus 73% 2-year PFS (P < 0.0001) and 43% versus 81% 2-year OS, respectively (P = 0.0002). Thirty-one patients (other TMTV0-PIT combinations) had an intermediate outcome, 50% 2-year PFS and 68% 2-year OS. CONCLUSION: TMTV0 appears as an independent predictor of PTCL outcome. Combined with PIT, it could identify different risk categories at diagnosis and warrants further validation as a prognostic marker.

Toxic and metabolic encephalopathies: iconographic essay

Generally, toxic-metabolic diseases affecting the central nervous system can hardly be differentiated just on the basis of their clinical presentation. However, some typical neuroradiological features can guide the correct diagnosis. In this context, magnetic resonance imaging is an important tool which, in association with clinical and laboratory data, can establish an early and specific treatment. The present pictorial essay with selected cases from the archives of the authors' institution describes imaging findings which might help in the etiologic diagnosis of toxic-metabolic diseases.

Profound hyperglycemia in knockout mutant mice identifies novel function for POU4F2/Brn-3b in regulating metabolic processes.

The POU4F2/Brn-3b transcription factor has been identified as a potentially novel regulator of key metabolic processes. Loss of this protein in Brn-3b knockout (KO) mice causes profound hyperglycemia and insulin resistance (IR), normally associated with type 2 diabetes (T2D), whereas Brn-3b is reduced in tissues taken from obese mice fed on high-fat diets (HFD), which also develop hyperglycemia and IR. Furthermore, studies in C2C12 myocytes show that Brn-3b mRNA and proteins are induced by glucose but inhibited by insulin, suggesting that this protein is itself highly regulated in responsive cells. Analysis of differential gene expression in skeletal muscle from Brn-3b KO mice showed changes in genes that are implicated in T2D such as increased glycogen synthase kinase-3β and reduced GLUT4 glucose transporter. The GLUT4 gene promoter contains multiple Brn-3b binding sites and is directly transactivated by this transcription factor in cotransfection assays, whereas chromatin immunoprecipitation assays confirm that Brn-3b binds to this promoter in vivo. In addition, correlation between GLUT4 and Brn-3b in KO tissues or in C2C12 cells strongly supports a close association between Brn-3b levels and GLUT4 expression. Since Brn-3b is regulated by metabolites and insulin, this may provide a mechanism for controlling key genes that are required for normal metabolic processes in insulin-responsive tissues and its loss may contribute to abnormal glucose uptake.

The unfathomable secret remains: a reverse engineering study of SEO factors on Google's search engine

The vast majority of users don’t seek results beyond the second page offered by the search engine, so if a site fails to be among the top 20 (second page), it says that this page does not have good SEO and, therefore, is not visible to the user. The overall objective of this project is to conduct a study to discover the factors that determine (or not) the positioning of websites in a search engine.

International journal of engineering education

This work presents an analysis of the assessment tools used by professors at the Universitat Politécnica de Catalunya to assess the generic competencies introduced in the Bachelor’s Degrees in Engineering. In order to conduct this study, a survey was designed and administered anonymously to a sample of the professors most receptive to educational innovation at their own university. All total, 80 professors responded to this survey, of whom 26% turned out to be members of the university’s own evaluation innovation group (https://www.upc.edu/rima/grups/grapa), GRAPA. This percentage represents 47% of the total GRAPA membership, meaning that nearly half of the professors most concerned about evaluation at the university chose to participate. The analysis of the variables carried out using the statistical program SPSS v19 shows that for practically 49% of those surveyed, rubrics are the tools most commonly used to assess generic competencies integrated in more specific ones. Of those surveyed, 60% use them either frequently or always. The most frequently evaluated generic competencies were teamwork (28%), problem solving (26%), effective oral and written communication (24%) and autonomous learning (13%), all of which constitute commonly recognized competencies in the engineering profession. A two-dimensional crosstabs analysis with SPSS v19 shows a significant correlation (Asymp. Sig. 0.001) between the type of tool used and the competencies assessed. However, no significant correlation was found between the type of assessment tool used and the type of subject, type of evaluation (formative or summative), frequency of feedback given to the students or the degree of student satisfaction, and thus none of these variables can be considered to have an influence on the kind of assessment tool used. In addition, the results also indicate that there are no significant differences between the instructors belonging to GRAPA and the rest of those surveyed

Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes.

The 16p11.2 600 kb BP4-BP5 deletion and duplication syndromes have been associated with developmental delay; autism spectrum disorders; and reciprocal effects on the body mass index, head circumference and brain volumes. Here, we explored these relationships using novel engineered mouse models carrying a deletion (Del/+) or a duplication (Dup/+) of the Sult1a1-Spn region homologous to the human 16p11.2 BP4-BP5 locus. On a C57BL/6N inbred genetic background, Del/+ mice exhibited reduced weight and impaired adipogenesis, hyperactivity, repetitive behaviors, and recognition memory deficits. In contrast, Dup/+ mice showed largely opposite phenotypes. On a F1 C57BL/6N × C3B hybrid genetic background, we also observed alterations in social interaction in the Del/+ and the Dup/+ animals, with other robust phenotypes affecting recognition memory and weight. To explore the dosage effect of the 16p11.2 genes on metabolism, Del/+ and Dup/+ models were challenged with high fat and high sugar diet, which revealed opposite energy imbalance. Transcriptomic analysis revealed that the majority of the genes located in the Sult1a1-Spn region were sensitive to dosage with a major effect on several pathways associated with neurocognitive and metabolic phenotypes. Whereas the behavioral consequence of the 16p11 region genetic dosage was similar in mice and humans with activity and memory alterations, the metabolic defects were opposite: adult Del/+ mice are lean in comparison to the human obese phenotype and the Dup/+ mice are overweight in comparison to the human underweight phenotype. Together, these data indicate that the dosage imbalance at the 16p11.2 locus perturbs the expression of modifiers outside the CNV that can modulate the penetrance, expressivity and direction of effects in both humans and mice.

A virtual mathematics learning environment for engineering students

Teachers of the course Introduction to Mathematics for Engineers at the UOC, an online distance-learning university, have designed,developed and tested an online studymaterial. It includes basic pre-university mathematics, indications for correct follow-up of this content and recommendations for finding appropriate support and complementarymaterials. Many different resources are used,depending on the characteristics of thecontents: Flash sequences, interactive applets, WIRIS calculators and PDF files.During the last semester, the new study material has been tested with 119 students. The academic results and student satisfaction have allowed us to outline and prioritise future lines of action.

A Virtual Mathematics Learning Environment for Engineering Students

Teachers of the course Introduction to Mathematics for Engineers at the UOC, an online distance-learning university, have designed and produced online study material which includes basic pre-university mathematics, instructions for correct follow-up of this content and recommendations for finding appropiate support and complementary materials.