Mitochondrial fatty acid oxidation in obesity

Significance: Current lifestyles with high-energy diets and little exercise are triggering an alarming growth in obesity. Excess of adiposity is leading to severe increases in associated pathologies, such as insulin resistance, type 2 diabetes, atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient obesity drugs, is the driving force behind much research. Recent Advances: Traditional anti-obesity strategies focused on reducing food intake and increasing physical activity. However, recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. Critical Issues: This review evaluates recent discoveries regarding mitochondrial fatty acid oxidation (FAO) and its potential as a therapy for obesity. We focus on the still controversial beneficial effects of increased FAO in liver and muscle, recent studies on how to potentiate adipose tissue energy expenditure, and the different hypotheses involving FAO and the reactive oxygen species production in the hypothalamic control of food intake. Future Directions: The present review aims to provide an overview of novel anti-obesity strategies that target mitochondrial FAO and that will definitively be of high interest in the future research to fight against obesity-related disorders.

Platelet-activating factor causes ventilation-perfusion mismatch in humans

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.

Effects of erythropoietin on muscle O2 transport during exercise in patients with chronic renal failure.

Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (CRF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not improved as much as the increase in hemoglobin concentration ([Hb)] would predict. We hypothesized that this discrepancy is due to failure of O2 transport rates to rise in a manner proportional to [Hb]. To test this, eight patients with CRF undergoing regular hemodialysis were studied pre- and post-rHuEPO ([Hb] = 7.5 +/- 1.0 vs. 12.5 +/- 1.0 g x dl-1) using a standard incremental cycle exercise protocol. A group of 12 healthy sedentary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flow (Qleg) by thermodilution to obtain O2 delivery and oxygen uptake (VO2). Despite a 68% increase in [Hb], peak VO2 increased by only 33%. This could be explained largely by reduced peak leg blood flow, limiting the gain in O2 delivery to 37%. At peak VO2, after rHuEPO, O2 supply limitation of maximal VO2 was found to occur, permitting the calculation of a value for muscle O2 conductance from capillary to mitochondria (DO2). While DO2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects. This kept maximal oxygen extraction at only 70%. Two important conclusions can be reached from this study. First, the increase in [Hb] produced by rHuEPO is accompanied by a significant reduction in peak blood flow to exercising muscle, which limits the gain in oxygen transport. Second, even after restoration of [Hb], O2 conductance from the muscle capillary to the mitochondria remains considerably below normal.

L’ús dels jocs de rol com a eina didàctica per a fomentar la participació i la reflexió crítica de tots els alumnes a la classe de ciències

Els jocs de rol són un recurs molt innovador que permeten un gran desenvolupament competencial i faciliten el treball de les qüestions sociocientífiques. Són dramatitzacions vertebrades al voltant d’una situació concreta en la qual els alumnes hauran d’argumentar la seva opinió en front a una qüestió sociocientífica. En el present treball s’analitza l’ús dels jocs de rol a l’aula de ciències a través de la posada en pràctica d’un joc de rol sobre les fonts d’energia a 1r Batxillerat. S’analitza qualitativament el disseny del joc de rol, la participació dels alumnes i el desenvolupament del pensament crític. Del treball se n’extreu que els jocs de rol afavoreixen la participació de l’alumnat, tot i que de manera heterogènia; i que desenvolupen la capacitat argumentativa, així com el pensament crític. Finalment es fan propostes de millora per tal de dinamitzar els jocs de rol de manera adequada.

Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction.

AIMS: Recent evidence suggests that cardiac progenitor cells (CPCs) may improve cardiac function after injury. The underlying mechanisms are indirect, but their mediators remain unidentified. Exosomes and other secreted membrane vesicles, hereafter collectively referred to as extracellular vesicles (EVs), act as paracrine signalling mediators. Here, we report that EVs secreted by human CPCs are crucial cardioprotective agents. METHODS AND RESULTS: CPCs were derived from atrial appendage explants from patients who underwent heart valve surgery. CPC-conditioned medium (CM) inhibited apoptosis in mouse HL-1 cardiomyocytic cells, while enhancing tube formation in human umbilical vein endothelial cells. These effects were abrogated by depleting CM of EVs. They were reproduced by EVs secreted by CPCs, but not by those secreted by human dermal fibroblasts. Transmission electron microscopy and nanoparticle tracking analysis showed most EVs to be 30-90 nm in diameter, the size of exosomes, although smaller and larger vesicles were also present. MicroRNAs most highly enriched in EVs secreted by CPCs compared with fibroblasts included miR-210, miR-132, and miR-146a-3p. miR-210 down-regulated its known targets, ephrin A3 and PTP1b, inhibiting apoptosis in cardiomyocytic cells. miR-132 down-regulated its target, RasGAP-p120, enhancing tube formation in endothelial cells. Infarcted hearts injected with EVs from CPCs, but not from fibroblasts, exhibited less cardiomyocyte apoptosis, enhanced angiogenesis, and improved LV ejection fraction (0.8 ± 6.8 vs. -21.3 ± 4.5%; P < 0.05) compared with those injected with control medium. CONCLUSION: EVs are the active component of the paracrine secretion by human CPCs. As a cell-free approach, EVs could circumvent many of the limitations of cell transplantation.

The promotion and assessment of generic skills from interdisciplinary teaching teams

The paper explains a teaching project financed by the University of Barcelona (UB). It focuses on ageneric skill of the University of Barcelona, which is defined as "the learning capability andresponsibility”, and in which analytical and synthesis skills are included. It follows a multidisciplinaryapproach including teachers of Mathematics, World Economics and Economic History. All of us sharethe same students during the first and the second course of the grade in Economics at the Faculty ofEconomics and Business. The project has been developed in three stages. The first one has beendone during the first semester of the course 2012/13, being applied to first year students on thesubjects of Mathematics and Economic History. The second phase is being to be done during thesecond semester only on the Economic History subject. A third stage is going to be done next course2013/14 to second year students on the subject of World Economics. Each different teaching teamhas developed specific materials and assessment tools for each one of the subjects included in theproject. The project emphasizes two teaching dimensions: the elaboration of teaching materials topromote the acquisition of generic skills from an interdisciplinary point of view, and the design ofspecific tools to assess such skills. The first results of the first phase of the project shows cleardeficiencies in the analytical skill regarding to first year students.

The promotion and assessment of generic skills from interdisciplinary teaching teams

The paper explains a teaching project financed by the University of Barcelona (UB). It focuses on ageneric skill of the University of Barcelona, which is defined as "the learning capability andresponsibility”, and in which analytical and synthesis skills are included. It follows a multidisciplinaryapproach including teachers of Mathematics, World Economics and Economic History. All of us sharethe same students during the first and the second course of the grade in Economics at the Faculty ofEconomics and Business. The project has been developed in three stages. The first one has beendone during the first semester of the course 2012/13, being applied to first year students on thesubjects of Mathematics and Economic History. The second phase is being to be done during thesecond semester only on the Economic History subject. A third stage is going to be done next course2013/14 to second year students on the subject of World Economics. Each different teaching teamhas developed specific materials and assessment tools for each one of the subjects included in theproject. The project emphasizes two teaching dimensions: the elaboration of teaching materials topromote the acquisition of generic skills from an interdisciplinary point of view, and the design ofspecific tools to assess such skills. The first results of the first phase of the project shows cleardeficiencies in the analytical skill regarding to first year students.

The promotion and assessment of generic skills from interdisciplinary teaching teams

The paper explains a teaching project financed by the University of Barcelona (UB). It focuses on ageneric skill of the University of Barcelona, which is defined as "the learning capability andresponsibility”, and in which analytical and synthesis skills are included. It follows a multidisciplinaryapproach including teachers of Mathematics, World Economics and Economic History. All of us sharethe same students during the first and the second course of the grade in Economics at the Faculty ofEconomics and Business. The project has been developed in three stages. The first one has beendone during the first semester of the course 2012/13, being applied to first year students on thesubjects of Mathematics and Economic History. The second phase is being to be done during thesecond semester only on the Economic History subject. A third stage is going to be done next course2013/14 to second year students on the subject of World Economics. Each different teaching teamhas developed specific materials and assessment tools for each one of the subjects included in theproject. The project emphasizes two teaching dimensions: the elaboration of teaching materials topromote the acquisition of generic skills from an interdisciplinary point of view, and the design ofspecific tools to assess such skills. The first results of the first phase of the project shows cleardeficiencies in the analytical skill regarding to first year students.

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

OBJECTIVE: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. DESIGN: Observational cohort study of patients initiating ART between January 2000 and December 2005. SETTING: The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. STUDY PARTICIPANTS: A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. MAIN OUTCOME MEASURES: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). RESULTS: Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). CONCLUSION: Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.

Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque.

High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4+ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4+ and CD8+ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4+ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

Proteínas del gluten y reología de trigos harineros mexicanos influeciados por factores ambientales y genotípicos

El objetivo de este estudio fue conocer el efecto de factores ambientales y genotípicos sobre los parámetros de calidad industrial y sobre la cantidad y relación de proteínas monoméricas y poliméricas del gluten en 24 líneas recombinantes de trigos harineros de temporal. El cultivo se desarrolló en cinco condiciones ambientales generadas por manejo agronómico, ciclo otoño-invierno 2006/2007, en Roque, Guanajuato, México. Se evaluaron el tiempo de amasado (TMA), fuerza (ALVW), extensibilidad (ALVPL) de la masa, fracción rica en gliadina (50PS) y en glutenina (50PI), y su relación (50PS/50PI). Las mejores combinaciones de gluteninas de alto y bajo peso molecular para TMA y ALVW fueron los genotipos con 1, 17+18, 5+10/Glu-A3c, Glu-B3g, Glu-D3b; 1, 17+18, 5+10/Glu-A3c, Glu-B3h, Glu-D3b, y 2*, 17+18, 5+10/Glu-A3c, Glu-B3g, Glu-D3b; para ALVPL, 2*, 17+18, 2+12/Glu-A3e, Glu-B3h, Glu-D3b; para 50PS, 2*, 17+18, 2+12/Glu-A3e, Glu-B3h, Glu-D3b; y 1, 17+18, 5+10/Glu-A3e, Glu-B3h, Glu-D3b. La relación 50PS/50PI fue mayor en genotipos con 2*, 17+18, 2+12/Glu-A3e, Glu-B3g, Glu-D3b. El TMA es mayor cuando aumenta la temperatura y la mejor ALVPL se obtiene en el ambiente bajo condiciones normales. La fracción 50PS y la relación 50PS/50PI son mayores cuando se realiza la fertilización con azufre, y se obtiene incremento de 50PI con riego limitado y aumento de temperaturas durante el llenado de grano.

Iowa Homeland Security and Emergency Management, 2015 Enhanced 911 Annual Report, January 14, 2016

The Iowa Department of Homeland Security and Emergency Management (HSEMD) submits this enhanced 911 (E911) annual report to the Iowa General Assembly’s standing committees on government oversight pursuant to Iowa Code § 34A.7A (3) (a). This section of the Code requires the E911 program manager to advise the General Assembly of the status of E911 wireline and wireless implementation and operations, the distribution of surcharge receipts, and an accounting of revenue and expenses of the E911 program.

Iowa Homeland Security and Emergency Management, 2014 Enhanced 911 Annual Report, January 15, 2015

The Iowa Department of Homeland Security and Emergency Management (HSEMD) submits this enhanced 911 (E911) annual report to the Iowa General Assembly’s standing committees on government oversight pursuant to Iowa Code § 34A.7A (3) (a). This section of the Code requires the E911 program manager to advise the General Assembly of the status of E911 wireline and wireless implementation and operations, the distribution of surcharge receipts, and an accounting of revenue and expenses of the E911 program.

La fantasia il·lustrada : la fantasia lliure en la segona meitat del segle XVIII

La Fantasia Il·lustrada és un treball d’investigació entorn la fantasia lliure, gènere compositiu de la segona meitat del segle XVIII. Aprofundeix, a partir d’un extens buidatge bibliogràfic, en els coneixements sobre aquest gènere oblidat, ubicant-lo en el seu entorn musical i social, i reconeix l’empremta que va deixar en l’estètica d’aquells anys, la qual justifica la seva vàlua i el clam per reivindicar el reconeixement que es mereix. Per tal d’aconseguir aquest fi, aquest treball elabora sobre les diferents realitats estètiques de meitat de segle, sobre l’art de la jardineria, sobre Carl Philipp Emanuel Bach, i sobre la pràctica improvisativa.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n ¼ 126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV 1 ) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n ¼ 125, 69 years) showed milder airflow limitation (FEV 1 63% predicted); and group 3 (n ¼ 91, 67 years) combined a similarly milder airflow limitation (FEV 1 58% predicted) with a high proportion of obesity, cardiovascular disorders, iabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p < 0.001) and higher all-cause mortality (HR 2.36, p ¼ 0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p ¼ 0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated:"severe respiratory COPD","moderate respiratory COPD", and"systemic COPD'