The Decreased Growth Hormone Response to Growth Hormone Releasing Hormone in Obesity Is Associated to Cardiometabolic Risk Factors

The aim of the present study was to evaluate the relationship between GHRH-induced GH secretion in obese premenopausal women and cardiovascular risk markers or insulin resistance. Premenopausal obese women, aged 35–52 years, were studied. GH secretion, IGF-I, serum cardiovascular risk markers, insulin, leptin, mid-waist and hip circumference, total body fat, and truncal fat were measured. Subjects were classified as meeting the criteria for GH deficiency (GHD) when peak GH after stimulation with GHRH was ≤3 μg/L. Mean total and LDL cholesterol, fasting insulin, and HOMA-IR were all higher, in subjects who would have been classified as GH-deficient compared with GH-sufficient. Peak GH secretion after stimulation was inversely associated with fasting insulin (R = −0.650, P = .012), HOMA-IR (R = −0.846, P = .001), total cholesterol (R = −0.532, P = .034), and LDL cholesterol (R = −0.692, P = .006) and positively associated with HDL cholesterol (R = 0.561, P = .037). These data strongly suggest a role for insulin resistance in the decreased GH secretion of obesity and that the blunted GH secretion of central obesity could be the pituitary expression of the metabolic syndrome

Host-Guest and Guest-Guest Interactions of P- and N-Containing Structure Directing Agents Entrapped inside MFI-Type Zeolite by Multinuclear NMR Spectroscopy

"This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Physical Chemistry C, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.jpcc.9b05689".[EN] Highly crystalline pure silica MFI zeolites have been synthesized using tetraethylammonium (TEA), tetraethylphosphonium (TEP), or a mixture of both cations in different proportions as organic structure directing agents (OSDAs). The zeolites have been deeply characterized in order to get insight about the guest guest interactions involving the OSDAs and the guest host interactions involving the OSDAs and the inorganic framework, as well as the main features of the resulting materials. The results show that the average size of the MFI crystals decreases when TEP is present within the zeolite and that this cation is homogeneously distributed throughout the crystallites. The multinuclear NMR investigation (H-1, C-13, N-14, F-19, Si-29, P-31) indicates that TEP interacts with the zeolite host creating higher heterogeneity of the SiO4 crystallographic sites and a diminution on the mobility of fluorine atoms incorporated into the zeolite. Moreover, the presence of TEP influences the dynamics of the nitrogen atoms of the TEA molecules, and 2D heteronuclear correlation experiments give evidence on the spatial proximity of the TEA and TEP molecules in the MFI zeolites. Then, it is concluded that TEA and TEP are intimately mixed within the zeolite voids of the pure silica MFI samples synthesized by the dual template route.Financial support by the MINECO of Spain through the Severo Ochoa (SEV-2016-0683) and RTI2018-101784-B-I00 projects is gratefully acknowledged. The authors also thank the Microscopy Service of the Universitat Politecnica de Valencia for its assistance in microscopy characterization (FESEM equipment preparation). J.M.-O. (SEV-2012-0267-02) is grateful to the Severo Ochoa Program for a predoctoral fellowship.Martinez-Ortigosa, J.; Simancas-Coloma, J.; Vidal Moya, JA.; Gaveau, P.; Rey Garcia, F.; Alonso, B.; Blasco Lanzuela, T. (2019). Host-Guest and Guest-Guest Interactions of P- and N-Containing Structure Directing Agents Entrapped inside MFI-Type Zeolite by Multinuclear NMR Spectroscopy. The Journal of Physical Chemistry C. 123(36):22324-22334. https://doi.org/10.1021/acs.jpcc.9b05689S223242233412336Davis, M. E., & Lobo, R. F. (1992). Zeolite and molecular sieve synthesis. Chemistry of Materials, 4(4), 756-768. doi:10.1021/cm00022a005Cundy, C. S., & Cox, P. A. (2003). The Hydrothermal Synthesis of Zeolites:  History and Development from the Earliest Days to the Present Time. Chemical Reviews, 103(3), 663-702. doi:10.1021/cr020060iWilson, S. T., Lok, B. M., Messina, C. A., Cannan, T. R., & Flanigen, E. M. (1982). Aluminophosphate molecular sieves: a new class of microporous crystalline inorganic solids. Journal of the American Chemical Society, 104(4), 1146-1147. doi:10.1021/ja00368a062Liu, X., Yan, N., Wang, L., Ma, C., Guo, P., Tian, P., … Liu, Z. (2019). Landscape of AlPO-based structures and compositions in the database of zeolite structures. Microporous and Mesoporous Materials, 280, 105-115. doi:10.1016/j.micromeso.2019.01.047McCusker, L. B., Liebau, F., & Engelhardt, G. (2003). Nomenclature of structural and compositional characteristics of ordered microporous and mesoporous materials with inorganic hosts. Microporous and Mesoporous Materials, 58(1), 3-13. doi:10.1016/s1387-1811(02)00545-0Davis, M. E. (2013). Zeolites from a Materials Chemistry Perspective. Chemistry of Materials, 26(1), 239-245. doi:10.1021/cm401914uCorma, A., & Martinez, A. (1995). Zeolites and Zeotypes as catalysts. Advanced Materials, 7(2), 137-144. doi:10.1002/adma.19950070206Corma, A. (1997). From Microporous to Mesoporous Molecular Sieve Materials and Their Use in Catalysis. Chemical Reviews, 97(6), 2373-2420. doi:10.1021/cr960406nBurton, A. W., & Zones, S. I. (2007). Organic Molecules in Zeolite Synthesis: Their Preparation and Structure-Directing Effects. Introduction to Zeolite Science and Practice, 137-179. doi:10.1016/s0167-2991(07)80793-2Moliner, M., Rey, F., & Corma, A. (2013). Towards the Rational Design of Efficient Organic Structure-Directing Agents for Zeolite Synthesis. Angewandte Chemie International Edition, 52(52), 13880-13889. doi:10.1002/anie.201304713Martínez, C., & Corma, A. (2011). Inorganic molecular sieves: Preparation, modification and industrial application in catalytic processes. Coordination Chemistry Reviews, 255(13-14), 1558-1580. doi:10.1016/j.ccr.2011.03.014Sastre, G., Vidal-Moya, J. A., Blasco, T., Rius, J., Jordá, J. L., Navarro, M. T., … Corma, A. (2002). Preferential Location of Ge Atoms in Polymorph C of Beta Zeolite (ITQ-17) and Their Structure-Directing Effect: A Computational, XRD, and NMR Spectroscopic Study. Angewandte Chemie International Edition, 41(24), 4722-4726. doi:10.1002/anie.200290028Chauhan, N. L., Das, J., Jasra, R. V., Parikh, P. A., & Murthy, Z. V. P. (2012). Synthesis of small-sized ZSM-5 zeolites employing mixed structure directing agents. Materials Letters, 74, 115-117. doi:10.1016/j.matlet.2012.01.094Mitani, E., Yamasaki, Y., Tsunoji, N., Sadakane, M., & Sano, T. (2018). Synthesis of phosphorus-modified AFX zeolite using a dual-template method with tetraethylphosphonium hydroxide as phosphorus modification agent. Microporous and Mesoporous Materials, 267, 192-197. doi:10.1016/j.micromeso.2018.03.033Blasco, T., Corma, A., Díaz-Cabañas, M. J., Rey, F., Vidal-Moya, J. A., & Zicovich-Wilson, C. M. (2002). Preferential Location of Ge in the Double Four-Membered Ring Units of ITQ-7 Zeolite. The Journal of Physical Chemistry B, 106(10), 2634-2642. doi:10.1021/jp013302bCamblor, M. A., Villaescusa, L. A., & Díaz‐Cabañas, M. J. (1999). Topics in Catalysis, 9(1/2), 59-76. doi:10.1023/a:1019154304344Koller, H., Wölker, A., Villaescusa, L. A., Díaz-Cabañas, M. J., Valencia, S., & Camblor, M. A. (1999). Five-Coordinate Silicon in High-Silica Zeolites. Journal of the American Chemical Society, 121(14), 3368-3376. doi:10.1021/ja9840549Koller, H., Wölker, A., Eckert, H., Panz, C., & Behrens, P. (1997). Five-Coordinate Silicon in Zeolites: Probing SiO4/2F− Sites in Nonasil and ZSM-5 with29Si Solid-State NMR Spectroscopy. Angewandte Chemie International Edition in English, 36(24), 2823-2825. doi:10.1002/anie.199728231Dědeček, J., Tabor, E., & Sklenak, S. (2018). Tuning the Aluminum Distribution in Zeolites to Increase their Performance in Acid-Catalyzed Reactions. ChemSusChem, 12(3), 556-576. doi:10.1002/cssc.201801959Li, C., Vidal-Moya, A., Miguel, P. J., Dedecek, J., Boronat, M., & Corma, A. (2018). Selective Introduction of Acid Sites in Different Confined Positions in ZSM-5 and Its Catalytic Implications. ACS Catalysis, 8(8), 7688-7697. doi:10.1021/acscatal.8b02112Gallego, E. M., Portilla, M. T., Paris, C., León-Escamilla, A., Boronat, M., Moliner, M., & Corma, A. (2017). «Ab initio» synthesis of zeolites for preestablished catalytic reactions. Science, 355(6329), 1051-1054. doi:10.1126/science.aal0121Simancas, J., Simancas, R., Bereciartua, P. J., Jorda, J. L., Rey, F., Corma, A., … Mugnaioli, E. (2016). Ultrafast Electron Diffraction Tomography for Structure Determination of the New Zeolite ITQ-58. Journal of the American Chemical Society, 138(32), 10116-10119. doi:10.1021/jacs.6b06394Yun, Y., Hernández, M., Wan, W., Zou, X., Jordá, J. L., Cantín, A., … Corma, A. (2015). The first zeolite with a tri-directional extra-large 14-ring pore system derived using a phosphonium-based organic molecule. Chemical Communications, 51(36), 7602-7605. doi:10.1039/c4cc10317cSonoda, T., Maruo, T., Yamasaki, Y., Tsunoji, N., Takamitsu, Y., Sadakane, M., & Sano, T. (2015). Synthesis of high-silica AEI zeolites with enhanced thermal stability by hydrothermal conversion of FAU zeolites, and their activity in the selective catalytic reduction of NOx with NH3. Journal of Materials Chemistry A, 3(2), 857-865. doi:10.1039/c4ta05621cKakiuchi, Y., Tanigawa, T., Tsunoji, N., Takamitsu, Y., Sadakane, M., & Sano, T. (2019). Phosphorus modified small-pore zeolites and their catalytic performances in ethanol conversion and NH3-SCR reactions. Applied Catalysis A: General, 575, 204-213. doi:10.1016/j.apcata.2019.02.026Van der Bij, H. E., & Weckhuysen, B. M. (2015). Phosphorus promotion and poisoning in zeolite-based materials: synthesis, characterisation and catalysis. Chemical Society Reviews, 44(20), 7406-7428. doi:10.1039/c5cs00109aBLASCO, T., CORMA, A., & MARTINEZTRIGUERO, J. (2006). Hydrothermal stabilization of ZSM-5 catalytic-cracking additives by phosphorus addition. Journal of Catalysis, 237(2), 267-277. doi:10.1016/j.jcat.2005.11.011Liu, X., & Luo, Q. (2017). Solid State NMR Spectroscopy Studies of the Nature of Structure Direction of OSDAs in Pure-Silica Zeolites ZSM-5 and Beta. The Journal of Physical Chemistry C, 121(24), 13211-13217. doi:10.1021/acs.jpcc.7b03350Fyfe, C. A., & Brouwer, D. H. (2006). Optimization, Standardization, and Testing of a New NMR Method for the Determination of Zeolite Host−Organic Guest Crystal Structures. Journal of the American Chemical Society, 128(36), 11860-11871. doi:10.1021/ja060744yDib, E., Gimenez, A., Mineva, T., & Alonso, B. (2015). Preferential orientations of structure directing agents in zeolites. Dalton Transactions, 44(38), 16680-16683. doi:10.1039/c5dt02558cDib, E., Mineva, T., Gaveau, P., & Alonso, B. (2013). 14N solid-state NMR: a sensitive probe of the local order in zeolites. Physical Chemistry Chemical Physics, 15(42), 18349. doi:10.1039/c3cp51845kDib, E., Mineva, T., Gaveau, P., Véron, E., Sarou-Kanian, V., Fayon, F., & Alonso, B. (2017). Probing Disorder in Al-ZSM-5 Zeolites by 14N NMR Spectroscopy. The Journal of Physical Chemistry C, 121(29), 15831-15841. doi:10.1021/acs.jpcc.7b04861Tuel, A., Ben Taǎrit, Y., & Naccache, C. (1993). Characterization of TS-1 synthesized using mixtures of tetrabutyl and tetraethyl ammonium hydroxides. Zeolites, 13(6), 454-461. doi:10.1016/0144-2449(93)90120-rDing, J., Xue, T., Wu, H., & He, M. (2017). One-step post-synthesis treatment for preparing hydrothermally stable hierarchically porous ZSM-5. Chinese Journal of Catalysis, 38(1), 48-57. doi:10.1016/s1872-2067(16)62549-4Schmidt-Rohr, K., Clauss, J., & Spiess, H. W. (1992). Correlation of structure, mobility, and morphological information in heterogeneous polymer materials by two-dimensional wideline-separation NMR spectroscopy. Macromolecules, 25(12), 3273-3277. doi:10.1021/ma00038a037Massiot, D., Fayon, F., Capron, M., King, I., Le Calvé, S., Alonso, B., … Hoatson, G. (2001). Modelling one- and two-dimensional solid-state NMR spectra. Magnetic Resonance in Chemistry, 40(1), 70-76. doi:10.1002/mrc.984Chen, X., Yan, W., Cao, X., Yu, J., & Xu, R. (2009). Fabrication of silicalite-1 crystals with tunable aspect ratios by microwave-assisted solvothermal synthesis. Microporous and Mesoporous Materials, 119(1-3), 217-222. doi:10.1016/j.micromeso.2008.10.015Schmidt, J. E., Fu, D., Deem, M. W., & Weckhuysen, B. M. (2016). Template–Framework Interactions in Tetraethylammonium‐Directed Zeolite Synthesis. Angewandte Chemie International Edition, 55(52), 16044-16048. doi:10.1002/anie.201609053Baerlocher, Ch.; McCusker, L. B. Database of Zeolite Structures. http://www.iza-structure.org/databases/.Fyfe, C. A., Brouwer, D. H., Lewis, A. R., Villaescusa, L. A., & Morris, R. E. (2002). Combined Solid State NMR and X-ray Diffraction Investigation of the Local Structure of the Five-Coordinate Silicon in Fluoride-Containing As-Synthesized STF Zeolite. Journal of the American Chemical Society, 124(26), 7770-7778. doi:10.1021/ja012558sFyfe, C. A., Brouwer, D. H., Lewis, A. R., & Chézeau, J.-M. (2001). Location of the Fluoride Ion in Tetrapropylammonium Fluoride Silicalite-1 Determined by 1H/19F/29Si Triple Resonance CP, REDOR, and TEDOR NMR Experiments. Journal of the American Chemical Society, 123(28), 6882-6891. doi:10.1021/ja010532vBrunklaus, G., Koller, H., & Zones, S. I. (2016). Defect Models of As-Made High-Silica Zeolites: Clusters of Hydrogen-Bonds and Their Interaction with the Organic Structure-Directing Agents Determined from1H Double and Triple Quantum NMR Spectroscopy. Angewandte Chemie International Edition, 55(46), 14459-14463. doi:10.1002/anie.201607428Koller, H., Lobo, R. F., Burkett, S. L., & Davis, M. E. (1995). SiO-.cntdot. .cntdot. .cntdot.HOSi Hydrogen Bonds in As-Synthesized High-Silica Zeolites. The Journal of Physical Chemistry, 99(33), 12588-12596. doi:10.1021/j100033a036Dib, E., Grand, J., Mintova, S., & Fernandez, C. (2015). Structure-Directing Agent Governs the Location of Silanol Defects in Zeolites. Chemistry of Materials, 27(22), 7577-7579. doi:10.1021/acs.chemmater.5b03668Losch, P., Pinar, A. B., Willinger, M. G., Soukup, K., Chavan, S., Vincent, B., … Louis, B. (2017). H-ZSM-5 zeolite model crystals: Structure-diffusion-activity relationship in methanol-to-olefins catalysis. Journal of Catalysis, 345, 11-23. doi:10.1016/j.jcat.2016.11.005Dib, E., Alonso, B., & Mineva, T. (2014). DFT-D Study of 14N Nuclear Quadrupolar Interactions in Tetra-n-alkyl Ammonium Halide Crystals. The Journal of Physical Chemistry A, 118(19), 3525-3533. doi:10.1021/jp502858nMineva, T., Gaveau, P., Galarneau, A., Massiot, D., & Alonso, B. (2011). 14N: A Sensitive NMR Probe for the Study of Surfactant–Oxide Interfaces. The Journal of Physical Chemistry C, 115(39), 19293-19302. doi:10.1021/jp206567

A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect

Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis.Seventh Framework Programme (European Commission) (Grant HEALTH-F5-2010-258236-SYSCOL)Seventh Framework Programme (European Commission) (Grant HEALTH-F2-2011-259015-COLTHERES)Cellex FoundationOlga Torres FoundationEuropean Research Council (EPINORC Project Grant Agreement 268626)Spain. Ministerio de Economia y Competividad (MINECO Project SAF2011-22803)Institute of Health Carlos III (RTICC Grant RD12/0036/0039

The Prometastatic Microenvironment of the Liver

The liver is a major metastasis-susceptible site and majority of patients with hepatic metastasis die from the disease in the absence of efficient treatments. The intrahepatic circulation and microvascular arrest of cancer cells trigger a local inflammatory reaction leading to cancer cell apoptosis and cytotoxicity via oxidative stress mediators (mainly nitric oxide and hydrogen peroxide) and hepatic natural killer cells. However, certain cancer cells that resist or even deactivate these anti-tumoral defense mechanisms still can adhere to endothelial cells of the hepatic microvasculature through proinflammatory cytokine-mediated mechanisms. During their temporary residence, some of these cancer cells ignore growth-inhibitory factors while respond to proliferation-stimulating factors released from tumor-activated hepatocytes and sinusoidal cells. This leads to avascular micrometastasis generation in periportal areas of hepatic lobules. Hepatocytes and myofibroblasts derived from portal tracts and activated hepatic stellate cells are next recruited into some of these avascular micrometastases. These create a private microenvironment that supports their development through the specific release of both proangiogenic factors and cancer cell invasion- and proliferation-stimulating factors. Moreover, both soluble factors from tumor-activated hepatocytes and myofibroblasts also contribute to the regulation of metastatic cancer cell genes. Therefore, the liver offers a prometastatic microenvironment to circulating cancer cells that supports metastasis development. The ability to resist anti-tumor hepatic defense and to take advantage of hepatic cell-derived factors are key phenotypic properties of liver-metastasizing cancer cells. Knowledge on hepatic metastasis regulation by microenvironment opens multiple opportunities for metastasis inhibition at both subclinical and advanced stages. In addition, together with metastasis-related gene profiles revealing the existence of liver metastasis potential in primary tumors, new biomarkers on the prometastatic microenvironment of the liver may be helpful for the individual assessment of hepatic metastasis risk in cancer patients

Highly efficient full-wave electromagnetic analysis of 3D arbitrarily-shaped waveguide microwave devices using an integral equation technique

A novel technique for the full-wave analysis of 3-D complex waveguide devices is presented. This new formulation, based on the Boundary Integral-Resonant Mode Expansion (BI-RME) method, allows the rigorous full-wave electromagnetic characterization of 3-D arbitrarily shaped metallic structures making use of extremely low CPU resources (both time and memory). The unknown electric current density on the surface of the metallic elements is represented by means of Rao-Wilton-Glisson basis functions, and an algebraic procedure based on a singular value decomposition is applied to transform such functions into the classical solenoidal and nonsolenoidal basis functions needed by the original BI-RME technique. The developed tool also provides an accurate computation of the electromagnetic fields at an arbitrary observation point of the considered device, so it can be used for predicting high-power breakdown phenomena. In order to validate the accuracy and efficiency of this novel approach, several new designs of band-pass waveguides filters are presented. The obtained results (S-parameters and electromagnetic fields) are successfully compared both to experimental data and to numerical simulations provided by a commercial software based on the finite element technique. The results obtained show that the new technique is specially suitable for the efficient full-wave analysis of complex waveguide devices considering an integrated coaxial excitation, where the coaxial probes may be in contact with the metallic insets of the component.This work was supported by the Ministerio de Economia y Competitividad, Spanish Government, under the Research Projects TEC2013-47037-C5-1-R and TEC2013-47037-C5-4-R.Vidal Pantaleoni, A.; San Blas Oltra, ÁA.; Quesada Pereira, FD.; Pérez Soler, FJ.; Gil Raga, J.; Vicente Quiles, CP.; Gimeno Martinez, B.... (2015). Highly efficient full-wave electromagnetic analysis of 3D arbitrarily-shaped waveguide microwave devices using an integral equation technique. Radio Science. 50(7):642-655. https://doi.org/10.1002/2015RS005685S64265550

Multisensor System for Isotemporal Measurements to Assess Indoor Climatic Conditions in Poultry Farms

The rearing of poultry for meat production (broilers) is an agricultural food industry with high relevance to the economy and development of some countries. Periodic episodes of extreme climatic conditions during the summer season can cause high mortality among birds, resulting in economic losses. In this context, ventilation systems within poultry houses play a critical role to ensure appropriate indoor climatic conditions. The objective of this study was to develop a multisensor system to evaluate the design of the ventilation system in broiler houses. A measurement system equipped with three types of sensors: air velocity, temperature and differential pressure was designed and built. The system consisted in a laptop, a data acquisition card, a multiplexor module and a set of 24 air temperature, 24 air velocity and two differential pressure sensors. The system was able to acquire up to a maximum of 128 signals simultaneously at 5 second intervals. The multisensor system was calibrated under laboratory conditions and it was then tested in field tests. Field tests were conducted in a commercial broiler farm under four different pressure and ventilation scenarios in two sections within the building. The calibration curves obtained under laboratory conditions showed similar regression coefficients among temperature, air velocity and pressure sensors and a high goodness fit (R2 = 0.99) with the reference. Under field test conditions, the multisensor system showed a high number of input signals from different locations with minimum internal delay in acquiring signals. The variation among air velocity sensors was not significant. The developed multisensor system was able to integrate calibrated sensors of temperature, air velocity and differential pressure and operated succesfully under different conditions in a mechanically-ventilated broiler farm. This system can be used to obtain quasi-instantaneous fields of the air velocity and temperature, as well as differential pressure maps to assess the design and functioning of ventilation system and as a verification and validation (V&V) system of Computational Fluid Dynamics (CFD) simulations in poultry farms.This work was funded by the project GV04B-511 (Generalitat Valenciana, Spain). The authors would like to thank Victoria Blanes-Vidal of the Southern Denmark University, for her helpful comments and suggestions. We are also grateful for the comments and assistance provided by anonymous referees of earlier versions of this paper.Bustamante García, E.; Guijarro Estelles, ED.; García Diego, FJ.; Balasch Parisi, S.; Hospitaler Pérez, A.; Torres Martínez, AJ. (2012). Multisensor System for Isotemporal Measurements to Assess Indoor Climatic Conditions in Poultry Farms. Sensors. 12(5):5752-5774. doi:10.3390/s120505752S5752577412

Measurement of ISR-FSR interference in the processes e+ e- --> mu+ mu- gamma and e+ e- --> pi+ pi- gamma

Charge asymmetry in processes e+ e- --> mu+ mu- gamma and e+ e- --> pi+ pi- gamma is measured using 232 fb-1 of data collected with the BABAR detector at center-of-mass energies near 10.58 GeV. An observable is introduced and shown to be very robust against detector asymmetries while keeping a large sensitivity to the physical charge asymmetry that results from the interference between initial and final state radiation. The asymmetry is determined as afunction of the invariant mass of the final-state tracks from production threshold to a few GeV/c2. It is compared to the expectation from QED for e+ e- --> mu+ mu- gamma and from theoretical models for e+ e- --> pi+ pi- gamma. A clear interference pattern is observed in e+ e- --> pi+ pi- gamma, particularly in the vicinity of the f_2(1270) resonance. The inferred rate of lowest order FSR production is consistent with the QED expectation for e+ e- --> mu+ mu- gamma, and is negligibly small for e+ e- --> pi+ pi- gamma.Comment: 32 pages,29 figures, to be submitted to Phys. Rev.

Effect of a Nutritional and Behavioral Intervention on Energy-Reduced Mediterranean Diet Adherence Among Patients With Metabolic Syndrome: Interim Analysis of the PREDIMED-Plus Randomized Clinical Trial

Key PointsQuestionWhat is the effect of a nutritional and behavioral intervention focused on encouraging an energy-reduced Mediterranean diet and physical activity on the dietary pattern of participants after 12 months? FindingsIn this preliminary analysis of an ongoing randomized clinical trial involving 6874 participants, an intervention focused on encouraging an energy-reduced Mediterranean diet and promoting physical activity, compared with advice to follow an energy-unrestricted Mediterranean diet, resulted in a significant increase in a measure of diet adherence, the 17-item energy-reduced Mediterranean diet score, at 12 months (4.7 points vs 2.5 points; score range, 0-17; minimal clinically important difference, 1 point). MeaningA nutritional and behavioral intervention focused on encouraging an energy-reduced Mediterranean diet and physical activity led to a significant improvement in a measure of diet adherence at 12 months. Further evaluation of the effects on long-term cardiovascular and other health outcomes is needed. ImportanceHigh-quality dietary patterns may help prevent chronic disease, but limited data exist from randomized trials about the effects of nutritional and behavioral interventions on dietary changes. ObjectiveTo assess the effect of a nutritional and physical activity education program on dietary quality. Design, Setting, and ParticipantsPreliminary exploratory interim analysis of an ongoing randomized trial. In 23 research centers in Spain, 6874 men and women aged 55 to 75 years with metabolic syndrome and no cardiovascular disease were enrolled in the trial between September 2013 and December 2016, with final data collection in March 2019. InterventionsParticipants were randomized to an intervention group that encouraged an energy-reduced Mediterranean diet, promoted physical activity, and provided behavioral support (n=3406) or to a control group that encouraged an energy-unrestricted Mediterranean diet (n=3468). All participants received allotments of extra-virgin olive oil (1 L/mo) and nuts (125 g/mo) for free. Main Outcomes and MeasuresThe primary outcome was 12-month change in adherence based on the energy-reduced Mediterranean diet (er-MedDiet) score (range, 0-17; higher scores indicate greater adherence; minimal clinically important difference, 1 point). ResultsAmong 6874 randomized participants (mean [SD] age, 65.0 [4.9] years; 3406 [52%] men), 6583 (96%) completed the 12-month follow-up and were included in the main analysis. The mean (SD) er-MedDiet score was 8.5 (2.6) at baseline and 13.2 (2.7) at 12 months in the intervention group (increase, 4.7 [95% CI, 4.6-4.8]) and 8.6 (2.7) at baseline and 11.1 (2.8) at 12 months in the control group (increase, 2.5 [95% CI, 2.3-2.6]) (between-group difference, 2.2 [95% CI, 2.1-2.4]; P<.001). Conclusions and RelevanceIn this preliminary analysis of an ongoing trial, an intervention that encouraged an energy-reduced Mediterranean diet and physical activity, compared with advice to follow an energy-unrestricted Mediterranean diet, resulted in a significantly greater increase in diet adherence after 12 months. Further evaluation of long-term cardiovascular effects is needed. Trial Registrationisrctn.com Identifier: ISRCTN89898870 This preliminary exploratory analysis of the ongoing PREDIMED-Plus randomized trial reports dietary adherence among Spanish community-dwelling participants with metabolic syndrome randomized to an energy-reduced Mediterranean diet, physical activity, and behavioral support vs an energy-unrestricted Mediterranean diet alone