Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Objective]: This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism. [Methods]: Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed. [Results]: Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus. [Conclusions]: Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease. © 2012 Amigó-Correig et al.This work was supported by project no SAF 2006-07382 and grant no BES-2007-17284, both awarded by the Spanish Ministry of Education of Science, and by project noCP07/00152, financed by the Carlos III Health Institute (ISCIII). Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas is an initiative of ISCIII (Ministerio de Ciencia e Innovacion).Peer Reviewe

Dynamic Control of the Self-Assembling Properties of Cyclodextrins by the Interplay of Aromatic and Host-Guest Interactions

The presence of a doubly-linked naphthylene clip at the O-2I and O-3II positions in the secondary ring of β-cyclodextrin (βCD) derivatives promoted their self-assembly into head-to-head supramolecular dimers in which the aromatic modules act either as cavity extension walls (if the naphthalene moiety is 1,8-disubstituted) or as folding screens that separate the individual βCD units (if 2,3-disubstituted). Dimer architecture is governed by the conformational properties of the monomer constituents, as determined by NMR, fluorescence, circular dichroism, and computational techniques. In a second supramolecular organization level, the topology of the assembly directs host-guest interactions and, reciprocally, guest inclusion impacts the stability of the supramolecular edifice. Thus, inclusion of adamantane carboxylate, a well-known βCD cavity-fitting guest, was found to either preserve the dimeric arrangement, leading to multicomponent species, or elicit dimer disruption. The ensemble of results highlights the potential of the approach to program self-organization and external stimuli responsiveness of CD devices in a controlled manner while keeping full diastereomeric purity.Spanish Ministerio de Economía y Competitividad CTQ2015-64425-C2-1-R, CTQ2016-80600-P and SAF2016- 76083-RJunta de Andalucía contract number FQM2012-1467UAH CCGP2017-EXP/02

The ArDM Experiment

Presented at the Cracow Epiphany Conference on Physics in Underground Laboratories and Its Connection with LHC, Cracow, Poland, January 5–8, 2010.The aim of the ArDM project is the development and operation of a one ton double-phase liquid argon detector for direct Dark Matter searches. The detector measures both the scintillation light and the ionization charge from ionizing radiation using two independent readout systems. This paper briefly describes the detector concept and presents preliminary results from the ArDM R&D program, including a 3 l prototype developed to test the charge readout system

Social Comparison at Work: The Role of Culture, Type of Organization and Gender

The present study examined social comparisons among employees in Spain (Study 1) and The Netherlands (Study 2). We expected differences in social comparison frequency and dimension between employees from public and private organizations as well as between men and women. In addition, among Dutch workers, we expected social comparisons to be relatively unaffected by the type of organization they participated in and gender differences to be smaller. Several interesting findings emerged. For instance, in Spain, workers in private organizations were found to compare themselves more often than workers in public organizations, whereas, in The Netherlands, this was not the case. Results suggest that social comparisons are significantly affected by national culture, work context and gender. Key words: Social Comparison; Organizations; Gender, Culture Resumé: Dans la présente étude nous avons examiné les comparaisons sociales entre des employés en Espagne (Etude 1) et aux Pays-Bas (Etude 2). Nous nous attendions à des différences dans la fréquence des comparaisons sociales, dans les dimensions de comparaison (effort versus résultats) et dans les objectifs des comparaisons (hommes versus femmes) entre les employés d’organisations publiques et privées ainsi qu’entre les hommes et les femmes. Il s’est trouvé qu’en Espagne, les employés des organisations privées faisaient des comparaisons plus fréquentes que les employés des organisations publiques. En plus, ils comparaient leurs efforts plus souvent que les employés des organisations privés. En revanche, les employés des organisations publiques, et particulièrement les femmes, comparaient leurs résultats plus souvent avec ceux d’autres personnes. Surtout les femmes travaillant dans des organisations privées se comparaient avec des femmes aussi bien qu’avec des hommes. Aux Pays-Bas, ces différences étaient absentes ou beaucoup moins prononcées. Les résultats montrent que les comparaisons sociales sont significativement influencées par culture nationale, type d’organisation et sexe. Mots-clés: Comparaison Sociale; Organisations; Sexe; Cultur

Cross-industry innovation: A systematic literature review

Identificador de proyecto: UPO-1381152 (Programa Operativo FEDER Andalucía) y Proyecto de I+D+i: PID2020-114751RB-100 (Ministerio de Ciencia e Innovación)This article performs a systematic literature review of cross-industry innovation (CII), which is a specific case of open innovation (OI) that has proved to be especially relevant in a context of increasing digitalization and technological convergence. In spite of its interest, previous research on CII is disperse in studies adopting different perspectives. A bibliometric analysis and a content analysis were carried out on a sample of 45 articles about CII, published between the year 1997 and the end of 2021. We address five research questions about the conceptualization and types of CII, the main features of CII (types of innovation, industries and actors), the process of CII, its determinants and consequences, and the prevalent methodological trends. By answering our research questions, we present a comprehensive picture of the state of the art of CII and make valuable contributions. Among them, our research provides a new definition of CII and a delimitation of its types, an integration of the processes of CII described under various approaches, and a network map of the crossfertilization of knowledge among industries, showing the relationship between source and target industries. By identifying unexplored opportunities in the literature, a research agenda is proposed.Departamento de Organización de Empresas y Marketin

Pasaporte a la profesión en el Grado de Farmacia

La incorporació del sistema universitari espanyol al Espai Europeu d’Educació Superior (EEES) ha implicat una sèrie d’adaptacions dels graus. Entre aquests s’ha de destacar un període de pràctiques externes a la pròpia universitat, lo que ha comportar una sèrie de canvis considerables en els plans d’estudis de manera que s’aconsegueixi un balanç més equilibrat entre la formació teòrica i pràctica rebuda pels estudiants. Aquest nou marc de treball ha estat confirmat legalment pel Govern espanyol (Real Decreto 1393/2007, de 20 d’octubre i Real Decreto 1707/2011 de 18 de novembre) i en el cas de la Universitat de Barcelona amb la publicació d’una normativa de pràctiques (Normativa de pràctiques acadèmiques externes dels estudiants de la Universitat de Barcelona). Aprofitant aquesta oportunitat per adaptar el Grau de Farmàcia a la realitat social actual, l’equip deganal de la Facultat de Farmàcia amb el recolzament del personal administratiu i el Servei d’atenció a l’estudiant, va assumir el repte d’incloure una nova assignatura en el pla docent del Grau de Farmàcia, que es va denominar “Pràctiques en empreses”. En paral·lel a la posta en marxa d’aquesta assignatura, es va iniciar una nova activitat per assegurar que els estudiants escollirien adequadament la companyia/departament/lloc de treball i donar-los les nocions bàsiques per poder afrontar amb les millors garanties d’èxit l’entrevista laboral. Sota el nom “Passaport a la professió”, s’han programat una sèrie de deu sessions per cada any acadèmic. Aquestes sessions inclouen temes d’una amplia varietat per proveir als estudiants amb les eines bàsiques per aprofitar al màxim el període de practiques i afrontar amb èxit el seu futur professional quan acabin els estudis de grau. A més, s’han celebrat tres workshops i dos taules rodones per apropar el mon de l’empresa a la universitat. S’ha de destacar que el projecte s’ha ampliat a nivell internacional, ja que una empresa farmacèutica amb seu en el Regne Unit cada any contracta a dos o tres estudiants de grau durant un any. Les dades estadístiques obtingudes en el procés s’han analitzat per tenir una millor comprensió de l’activitat i poder millorar el programa

Diseño del instrumento de ayuda para la toma de decisiones: “alternativas de tratamiento para el cáncer de mama: ¿qué opción prefiero?”

Purpose: To design a Decision-making Aid within the ‘Breast cancer’ healthcare process modelling of the Andalusian Public Health System (SSPA) for the therapeutic approach of early-stage disease. Methods: The Decision Aid design was conducted in four phases: 1) Explore the receptiveness of users and professionals in the mainstream of the SSPA Decision Aid “Breast Cancer” process. 2) Select a Decision Aid from international experiences. 3) Transcultural adaptation of above selected Decision Aid. 4) Decision Aid Validation in the SSPA. Results: The Decision Aid “Alternative treatment for breast cancer: What option do I prefer?” designed for the SSPA includes innovative contents compared to other reviewed experiences. The results of the validation of Decision Aid have shown that the design is attractive for the patient, ideal size and suitable language, and that the clinical information it contains is of quality. The Decision Aid answers your questions (95%) and summarizes the essential information to make the decision (90%). The Decision Aid offers relevant information that help the patient in the decision making process (lack of decisional confl ict: 85.31), facilitates the work in the practice and doctor-patient communication. Conclusion: Patients and professionals agree to recommend the use of Decision Aid and to encourage participation in decisionmaking while recognizing that the time factor is the main obstacle to incorporate its use in the SSPA.Objetivo: Diseñar un Instrumento de Ayuda para la Toma de Decisiones (IATD) en el Proceso Asistencial Integrado ‘Cáncer de mama’ del Sistema Sanitario Público de Andalucía (SSPA) para el abordaje terapéutico de esta enfermedad en estadio inicial. Método: El diseño del IATD se realizó en cuatro fases: 1) Explorar la receptividad de las usuarias y los profesionales del SSPA sobre la incorporación de IATD en el proceso “Cáncer de mama”. 2). Seleccionar un IATD entre las experiencias internacionales.; 3) Adaptar transculturalmente del IATD seleccionado al entorno del SSPA. 4) Validar el IATD en el SSPA. Resultado: El IATD “Alternativas de tratamiento para el cáncer de mama: ¿Qué opción prefiero?” diseñado para el SSPA incluye contenidos innovadores frente a otras experiencias revisadas. Los resultados de la validación del IATD han mostrado que su diseño es atractivo para la paciente, su extensión y lenguaje idóneos, y la información clínica que contiene es de calidad. El Instrumento resuelve sus dudas (95%) y resume la información esencial para tomar la decisión (90%). El IATD ofrece información relevante que prepara a la paciente para la toma de decisiones (ausencia de conflicto decisional: 85,31), facilita la labor en consulta y la comunicación médico-paciente. Conclusiones: Pacientes y profesionales coinciden en recomendar la utilización del IATD y fomentar la participación en la toma de decisiones aunque reconocen que el factor tiempo es el principal obstáculo para incorporar su uso en el SSPA

Trifaceted Mickey Mouse Amphiphiles for Programmable Self-Assembly, DNA Complexation and Organ-Selective Gene Delivery

Instilling segregated cationic and lipophilic domains with an angular disposition in a trehalose-based trifaceted macrocyclic scaffold allows engineering patchy molecular nanoparticles leveraging directional interactions that emulate those controlling self-assembling processes in viral capsids. The resulting trilobular amphiphilic derivatives, featuring a Mickey Mouse architecture, can electrostatically interact with plasmid DNA (pDNA) and further engage in hydrophobic contacts to promote condensation into transfectious nanocomplexes. Notably, the topology and internal structure of the cyclooligosaccharide/pDNA co-assemblies can be molded by fine-tuning the valency and characteristics of the cationic and lipophilic patches, which strongly impacts the transfection efficacy in vitro and in vivo. Outstanding organ selectivities can then be programmed with no need of incorporating a biorecognizable motif in the formulation. The results provide a versatile strategy for the construction of fully synthetic and perfectly monodisperse nonviral gene delivery systems uniquely suited for optimization schemes by making cyclooligosaccharide patchiness the focus.Ministerio de Ciencia, Innovación y Universidades y Agencia Estatal de Investigación de España. RTI2018-097609-B-C21, RTI2018-097609-B-C22 y PID2019-105858RB-I00Universidad de Alcalá de Henares, Madrid. CCG19/CC-03

Clinical Management of COVID-19 in Cancer Patients with the STAT3 Inhibitor Silibinin

COVID-19 pathophysiology is caused by a cascade of respiratory and multiorgan failures arising, at least in part, from the SARS-CoV-2-driven dysregulation of the master transcriptional factor STAT3. Pharmacological correction of STAT3 over-stimulation, which is at the root of acute respiratory distress syndrome (ARDS) and coagulopathy/thrombosis events, should be considered for treatment of severe COVID-19. In this perspective, we first review the current body of knowledge on the role of STAT3 in the pathogenesis of severe COVID-19. We then exemplify the potential clinical value of treating COVID-19 disease with STAT3 inhibitors by presenting the outcomes of two hospitalized patients with active cancer and COVID-19 receiving oral Legalon(R)-a nutraceutical containing the naturally occurring STAT3 inhibitor silibinin. Both patients, which were recruited to the clinical trial SIL-COVID19 (EudraCT number: 2020-001794-77) had SARS-CoV-2 bilateral interstitial pneumonia and a high COVID-GRAM score, and showed systemic proinflammatory responses in terms of lymphocytopenia and hypoalbuminemia. Both patients were predicted to be at high risk of critical COVID-19 illness in terms of intensive care unit admission, invasive ventilation, or death. In addition to physician's choice of best available therapy or supportive care, patients received 1050 mg/day Legalon(R) for 10 days without side-effects. Silibinin-treated cancer/COVID-19+ patients required only minimal oxygen support (2-4 L/min) during the episode, exhibited a sharp decline of the STAT3-regulated C-reactive protein, and demonstrated complete resolution of the pulmonary lesions. These findings might inspire future research to advance our knowledge and improve silibinin-based clinical interventions aimed to target STAT3-driven COVID-19 pathophysiology

Zirconium Metal−Organic Polyhedra with Dual Behavior for Organophosphate Poisoning Treatment

Organophosphate nerve agents and pesticides are extremely toxic compounds because they result in acetylcholinesterase (AChE) inhibition and concomitant nerve system damage. Herein, we report the synthesis, structural characterization, and proof-of-concept utility of zirconium metal−organic polyhedra (Zr-MOPs) for organophosphate poisoning treatment. The results show the formation of robust tetrahedral cages [((n-butylCpZr)3(OH)3O)4L6]Cl6 (Zr-MOP-1; L = benzene-1,4- dicarboxylate, n-butylCp = n-butylcyclopentadienyl, Zr-MOP-10, and L = 4,4′-biphenyldicarboxylate) decorated with lipophilic alkyl residues and possessing accessible cavities of ∼9.8 and ∼10.7 Å inner diameters, respectively. These systems are able to both capture the organophosphate model compound diisopropylfluorophosphate (DIFP) and host and release the AChE reactivator drug pralidoxime (2-PAM). The resulting 2-PAM@ Zr-MOP-1(0) host−guest assemblies feature a sustained delivery of 2-PAM under simulated biological conditions, with a concomitant reactivation of DIFP-inhibited AChE. Finally, 2-PAM@Zr-MOP systems have been incorporated into biocompatible phosphatidylcholine liposomes with the resulting assemblies being non-neurotoxic, as proven using neuroblastoma cell viability assays.Spanish MCIN/AEI PID2020-113608RB-I00FEDER/Junta de Andalucia-Conserjeria de Economia y Conocimiento B-FQM-364-UGR18 B-FQM-006-UGR18FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades P18-RT-612 P20_00672Fondazione CRUIprograma Juan de la Cierva FormacionSpanish Government PID2020-118117RB-I00Center for Forestry Research & Experimentation (CIEF)European Commission SEJIGENT/2021/059 PROMETEU/2021/054La Caixa Foundation 100010434 LCF/BQ/PR20/11770014"Maria de Maeztu" Program for Centers of Excellence in RD CEX2019-000919-MH2020-MSCA-IF2019-888972-PSust-MO