Effectiveness of Mediterranean Diet Implementation in Dry Eye Parameters: A Study of PREDIMED-PLUS Trial

This study was cofounded by grants from the Spanish Ministry of Science-Instituto de Salud Carlos III (PI17/00764) and FEDER funds. The authors wish to thank Ingrid de Ruiter, MBChB, Ph.D., for English language support.The purpose of this study is to evaluate the effect of a Mediterranean diet supplemented with extra virgin olive oil and nuts on dry eye parameters. The participants in this study were randomized into one of the two interventional arms: (1) a standard intervention group, a Mediterranean diet supplemented with extra virgin olive oil and nuts; and (2) an intensive intervention group, based on a hypocaloric Mediterranean diet and an intensive lifestyle program with physical activity and weight-loss goals. In both groups, common dry eye tests were conducted at baseline and after six months: the Ocular Surface Disease Index (OSDI), the Dry Eye Scoring System (DESS), tear break-up time (TBUT), the Schirmer’s test, and the Oxford staining grade. Sixty-seven eyes were examined. After six months, dry eye parameters improved in both groups; differences between groups were favorable for the intensive intervention group. The implementation of a Mediterranean diet pattern was beneficial for the selected patients with dry eye, and could be beneficial for patients with dry eye in general. Behavioral support for diet adherence and the promotion of healthy lifestyles (exercise) and weight loss (calorie restriction) have an added positive effect.Instituto de Salud Carlos III Spanish Government PI17/00764European Union (EU

New physics searches using ProtoDUNE and the CERN SPS accelerator

The exquisite capabilities of liquid Argon Time Projection Chambers make them ideal to search for weakly interacting articles in Beyond the Standard Model scenarios. Given their location at CERN the ProtoDUNE detectors may be exposed to a flux of such particles, produced in the collisions of 400 GeV protons (extracted from the Super Proton Synchrotron accelerator) on a target. Here we point out the interesting possibilities that such a setup offers to search for both long-lived unstable particles (Heavy Neutral Leptons, axion-like particles, etc) and stable particles (e.g. light dark matter, or millicharged particles). Our results show that, under conservative assumptions regarding the expected luminosity, this setup has the potential to improve over present bounds for some of the scenarios considered. This could be done within a short timescale, using facilities that are already in place at CERN, and without interfering with the experimental program in the North Area at CERN

The multifaceted roles of gasdermins in cancer biology and oncologic therapies

The involvement of the Gasdermin (GSDM) protein family in cancer and other pathologies is one of the hottest topics in biomedical research. There are six GSDMs in humans (GSDMA, B, C, D, GSDME/DFNA5 and PJVK/DFNB59) and, except PJVK, they can trigger cell death mostly by pyroptosis (a form of lytic and pro-inflammatory cell death) but also other mechanisms. The exact role of GSDMs in cancer is intricate, since depending on the biological context, these proteins have diverse cell-death dependent and independent functions, exhibit either pro-tumor or anti-tumor functions, and promote either sensitization or resistance to oncologic treatments. In this review we provide a comprehensive overview on the multifaceted roles of the GSDMs in cancer, and we critically discuss the possibilities of exploiting GSDM functions as determinants of anti-cancer treatment and as novel therapeutic targets, with special emphasis on innovative GSDM-directed nano-therapies. Finally, we discuss the issues to be resolved before GSDM-mediated oncologic therapies became a reality at the clinical levelThis study was supported by the Ministerio de Ciencia e Innovaci´on (PID2019-104644RB-I00 -GMB-), the Instituto de Salud Carlos III (CIBERONC, CB16/12/00295 –GMB-; partly supported by FEDER funds) and by the Fundaci´on Científica de la AECC (FC_AECC PROYE19036MOR -GMB-

The multifaceted roles of gasdermins in cancer biology and oncologic therapies

The involvement of the Gasdermin (GSDM) protein family in cancer and other pathologies is one of the hottest topics in biomedical research. There are six GSDMs in humans (GSDMA, B, C, D, GSDME/DFNA5 and PJVK/ DFNB59) and, except PJVK, they can trigger cell death mostly by pyroptosis (a form of lytic and proinflammatory cell death) but also other mechanisms. The exact role of GSDMs in cancer is intricate, since depending on the biological context, these proteins have diverse cell-death dependent and independent functions, exhibit either pro-tumor or anti-tumor functions, and promote either sensitization or resistance to oncologic treatments. In this review we provide a comprehensive overview on the multifaceted roles of the GSDMs in cancer, and we critically discuss the possibilities of exploiting GSDM functions as determinants of anti-cancer treatment and as novel therapeutic targets, with special emphasis on innovative GSDM-directed nano-therapies. Finally, we discuss the issues to be resolved before GSDM-mediated oncologic therapies became a reality at the clinical level.This study was supported by the Ministerio de Ciencia e Innovación (PID2019-104644RB-I00 -GMB-), the Instituto de Salud Carlos III (CIBERONC, CB16/12/00295 –GMB-; partly supported by FEDER funds) and by the Fundación Científica de la AECC (FC_AECC PROYE19036MOR -GMB-).S

Depth of maximum of air-shower profiles at the Pierre Auger Observatory. I. Measurements at energies above 10(17.8) eV

The successful installation, commissioning, and operation of the Pierre Auger Observatory would not have been possible without the strong commitment and effort from the technical and administrative staff in Malargue. We are very grateful to the following agencies and organizations for financial support: Comision Nacional de Energia Atomica, Fundacion Antorchas, Gobierno De La Provincia de Mendoza, Municipalidad de Malargue, NDM Holdings and Valle Las Lenas, in gratitude for their continuing cooperation over land access, Argentina; the Australian Research Council; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Financiadora de Estudos e Projetos (FINEP), Fundacao de Amparo a Pesquisa do Estado de Rio de Janeiro (FAPERJ), Sao Paulo Research Foundation (FAPESP) Grants No. 2010/07359-6, No. 1999/05404-3, Ministerio de Ciencia e Tecnologia (MCT), Brazil; MSMT-CR LG13007, 7AMB14AR005, CZ.1.05/2.1.00/03.0058 and the Czech Science Foundation Grant No. 14-17501S, Czech Republic; Centre de Calcul IN2P3/CNRS, Centre National de la Recherche Scientifique (CNRS), Conseil Regional Ile-de-France, Departement Physique Nucleaire et Corpusculaire (PNC-IN2P3/CNRS), Departement Sciences de l'Univers (SDU-INSU/CNRS), Institut Lagrange de Paris, ILP LABEX ANR-10-LABX-63, within the Investissements d'Avenir Programme ANR-11-IDEX-0004-02, France; Bundesministerium fur Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), Finanzministerium Baden-Wurttemberg, Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF), Ministerium fur Wissenschaft und Forschung, Nordrhein Westfalen, Ministerium fur Wissenschaft, Forschung und Kunst, Baden-Wurttemberg, Germany; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR), Gran Sasso Center for Astroparticle Physics (CFA), CETEMPS Center of Excellence, Italy; Consejo Nacional de Ciencia y Tecnologia (CONACYT), Mexico; Ministerie van Onderwijs, Cultuur en Wetenschap, Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO), Stichting voor Fundamenteel Onderzoek der Materie (FOM), Netherlands; National Centre for Research and Development, Grants No. ERA-NET-ASPERA/01/11 and No. ERA-NET-ASPERA/02/11, National Science Centre, Grants No. 2013/08/M/ST9/00322, No. 2013/08/M/ST9/00728 and No. HARMONIA 5 - 2013/10/M/ST9/00062, Poland; Portuguese national funds and FEDER funds within COMPETE - Programa Operacional Factores de Competitividade through Fundacao para a Ciencia e a Tecnologia, Portugal; Romanian Authority for Scientific Research ANCS, CNDI-UEFISCDI partnership projects nr. 20/2012 and nr. 194/2012, project nr. 1/ASPERA2/2012 ERA-NET, PN-II-RU-PD-2011-3-0145-17, and PN-II-RU-PD-2011-3-0062, the Minister of National Education, Programme for research - Space Technology and Advanced Research - STAR, project no. 83/2013, Romania; Slovenian Research Agency, Slovenia; Comunidad de Madrid, FEDER funds, Ministerio de Educacion y Ciencia, Xunta de Galicia, European Community 7th Framework Program, Grant No. FP7-PEOPLE-2012-IEF-328826, Spain; Science and Technology Facilities Council, U.K.; Department of Energy, Contracts No. DE-AC02-07CH11359, No. DE-FR02-04ER41300, No. DE-FG02-99ER41107 and No. DE-SC0011689, National Science Foundation, Grant No. 0450696, The Grainger Foundation, USA; NAFOSTED, Vietnam; Marie Curie-IRSES/EPLANET, European Particle Physics Latin American Network, European Union 7th Framework Program, Grant No. PIRSES-2009-GA-246806; and UNESCO.We report a study of the distributions of the depth of maximum, Xmax, of extensive air-shower profiles with energies above 1017.8  eV as observed with the fluorescence telescopes of the Pierre Auger Observatory. The analysis method for selecting a data sample with minimal sampling bias is described in detail as well as the experimental cross-checks and systematic uncertainties. Furthermore, we discuss the detector acceptance and the resolution of the Xmax measurement and provide parametrizations thereof as a function of energy. The energy dependence of the mean and standard deviation of the Xmax distributions are compared to air-shower simulations for different nuclear primaries and interpreted in terms of the mean and variance of the logarithmic mass distribution at the top of the atmosphere.Comision Nacional de Energia AtomicaFundacion AntorchasGobierno De La Provincia de MendozaMunicipalidad de MalargueNDM HoldingsValle Las LenasAustralian Research CouncilNational Council for Scientific and Technological Development (CNPq)Ciencia Tecnologia e Inovacao (FINEP)Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) 2010/07359-6 1999/05404-3Ministerio de Ciencia e Tecnologia (MCT), BrazilGrant Agency of the Czech Republic Czech Republic Government 14-17501SCentre National de la Recherche Scientifique (CNRS)Region Ile-de-FranceDepartement Sciences de l'Univers (SDU-INSU/CNRS)Institut Lagrange de ParisFrench National Research Agency (ANR) ANR-10-LABX-63 ANR-11-IDEX-0004-02Federal Ministry of Education & Research (BMBF)German Research Foundation (DFG)Finanzministerium Baden-WurttembergHelmholtz AssociationMinisterium fur Wissenschaft und ForschungNordrhein WestfalenMinisterium fur WissenschaftForschung und KunstBaden-Wurttemberg, GermanyIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Universities and Research (MIUR)Gran Sasso Center for Astroparticle Physics (CFA)CETEMPS Center of Excellence, ItalyConsejo Nacional de Ciencia y Tecnologia (CONACyT)Ministerie van Onderwijs, Cultuur en WetenschapNetherlands Organization for Scientific Research (NWO)FOM (The Netherlands) Netherlands GovernmentNational Centre for Research and Development ERA-NET-ASPERA/01/11 ERA-NET-ASPERA/02/11National Science Centre, Poland 2013/08/M/ST9/00322 2013/08/M/ST9/00728 HARMONIA 5 - 2013/10/M/ST9/00062Portuguese national funds within COMPETE - Programa Operacional Factores de Competitividade through Fundacao para a Ciencia e a Tecnologia, PortugalFEDER funds within COMPETE - Programa Operacional Factores de Competitividade through Fundacao para a Ciencia e a Tecnologia, PortugalRomanian Authority for Scientific Research ANCSCNDI-UEFISCDI 20/2012 194/2012 1/ASPERA2/2012 ERA-NET PN-II-RU-PD-2011-3-0145-17 PN-II-RU-PD-2011-3-0062Minister of National Education, Programme for research - Space Technology and Advanced Research - STAR, Romania 83/2013Slovenian Research Agency - SloveniaComunidad de Madrid Instituto de Salud Carlos IIIEuropean Union (EU)Spanish GovernmentXunta de GaliciaEuropean Community 7th Framework Program, Spain FP7-PEOPLE-2012-IEF-328826Science & Technology Facilities Council (STFC)United States Department of Energy (DOE) DE-AC02-07CH11359 DE-FR02-04ER41300 DE-FG02-99ER41107 DE-SC0011689National Science Foundation (NSF) 0450696Grainger Foundation, USANational Foundation for Science & Technology Development (NAFOSTED)European Union (EU) PIRSES-2009-GA-246806UNESCOMSMT-CR LG130077AMB14AR005CZ.1.05/2.1.00/03.005

Undercarboxylated Osteocalcin: A Promising Target for Early Diagnosis of Cardiovascular and Glycemic Disorders in Patients with Metabolic Syndrome: A Pilot Study

Lifestyle changes are causing an exponential increase in the prevalence of obesity and metabolic syndrome (MetS) worldwide. The most frequent complications of these are the development of diabetes (T2D) and cardiovascular disease (CVD). Accurate tools are needed to classify the cardiovascular risk (CVR) in the MetS population. In recent years, numerous biomarkers of bone metabolism have been associated with CVR. The aim of this study was to determine the levels of undercarboxylated osteocalcin (ucOC) in a cohort of patients with MetS and to analyse its association with MetS parameters and CVR as well as with T2D prevalence. A longitudinal study was conducted in which a MetS population was followed for one year. Weight change, adherence to the Mediterranean diet (MedDiet), ucOC levels, MetS parameters and CVR were analysed and CVR was calculated using different scores. Our results showed a decrease of CVR associated with a better adherence to the MetDiet resulting in higher HDL-C and ucOC levels though the improvement of MetS risk factors. This bone protein appeared as a potential biomarker to classify CVR in the MetS population, especially for MetS patients without prevalent T2D. Furthermore, ucOC serum levels could be good predictors of T2D prevalence.Instituto de Salud Carlos III European Commission PI18-00803 PI21/01069 PI18-01235 FI19/00118 CD20/00022European CommissionJunta de Andalucia CD20/00022 PI-0268-2019 RH-0069202

Control of the extractable content of bioactive compounds in coffee beans by near infrared hyperspectral imaging

Control of coffee quality has a great importance for being one of the most important raw materials within the international trade. The extractable composition of coffee has been studied in recent decades and the use of non-destructive methodologies is being continuously promoted. In this study, near infrared hyperspectral imaging has been applied to develop non-destructive methods for the control of extractable contents of caffeine, chlorogenic acid, total phenolics and melanoidins in coffee beans. Extractable contents and trends obtained among the different coffee types analysed are similar to those obtained previously in other studies. Moreover, modified partial least square (MPLS) regressions produced prediction models with standard errors of prediction in external validation of 12.01%, 15.61% and 17.61% for caffeine, chlorogenic acid and total phenolics, respectively. Therefore, results obtained for these three parameters indicate that NIR spectroscopy has a great potential for their control in coffee beans

Adecuación Nutricional y Adherencia a la Dieta Mediterránea y su Asociación con Hábitos de Vida de Estudiantes de Medicina: Un Estudio Transversal Descriptivo

Introducción. A pesar de que la etapa universitaria es crucial para la adquisición de hábitos de vida que pueden repercutir en el estado de salud, se ha evidenciado una alimentación inadecuada en esta población. Objetivos. (1) Estudiar el nivel de adecuación a las recomendaciones de ingesta alimentarias en estudiantes de medicina, (2) determinar la adhesión a la Dieta Mediterránea (Diet Med) y (3) determinar las variables asociadas con el cumplimiento de las recomendaciones dietéticas. Metodología. Estudio descriptivo transversal. Se analizó la ingesta dietética de 225 estudiantes de medicina mediante un cuestionario de frecuencia de alimentos. Se calculó la ingesta de nutrientes mediante la utilización de tablas de composición de alimentos y el porcentaje de cumplimiento de micronutrientes (RDI para población adulta española). Se determinó la adhesión a la Diet Med y el riesgo cardiovascular. Se realizaron modelos regresión logística múltiple con objeto de determinar las variables asociadas con la adecuación nutricional. Resultados. Los estudiantes de medicina muestran una baja adhesión a la Diet Med así como una baja frecuencia del cumplimiento de las RDI de vitamina A, D y calcio. El cumplimiento con las recomendaciones se asoció positivamente con variables como el sexo femenino y la Diet Med en el caso de las recomendaciones de vitamina A, mientras que un mayor IMC y sedentarismo se asociaron negativamente con las de vitamina D. Conclusiones. Los hábitos alimentarios de los estudiantes de medicina pueden considerarse poco saludables, por lo que deben priorizarse intervenciones educativas y conductuales para mejorar el estilo de vida de esta población.  Financiación. B.R.-G. is a Postdoctoral Investigator funded by the Junta de Andalucía (ref. RH-0069-2021)

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO