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El presente artículo tiene como objeto dar a conocer distintas obras sobre lienzo de uno de los más destacados pintores de la segunda mitad del siglo XIX: José Cusachs y Cusachs (1851-1908), dos de gran formato, Muerte del teniente Rochera en Vic, de 1897 y La toma del fuerte del Collado de Alpuente firmada y fechada en 1900, y dos retratos de dos Capitanes de artillería, Don Juan Resino y Represa y Don Eduardo Temprado y Pérez, datados ambos en 1898. Esta compilación de obras estará expuesta en una sala dedicada a José Cusachs en el Museo Histórico Militar, sede del Acuartelamiento San Juan de Ribera desde 1898, situado en Valencia. Las obras de gran formato representan dos escenas militares y de batalla con un detallado programa iconográfico: La muerte del teniente Rochera en Vic, documenta el fallecimiento del teniente en la tercera guerra carlista. En La toma del fuerte del Collado de Alpuente se recrea la batalla de la conquista del castillo del Poyo. Las obras presentaban diferentes estados de conservación, apreciándose básicamente suciedad superficial, amarilleamiento de barniz y descohesiones puntuales alrededor de zonas con pérdidas ya tratadas en intervenciones anteriores.

SUMMARYAxolotl limb regeneration is accompanied by the transient induction of cellular senescence within the blastema, the structure which nucleates regeneration. The precise role of this blastemal senescent cell (bSC) population, however, remains unknown. Here, through a combination of gain- and loss-of-function assays, we elucidate the functions and molecular features of cellular senescence in vivo. We demonstrate that cellular senescence plays a positive role during axolotl regeneration, by creating a pro-proliferative niche that supports progenitor cell expansion and blastema outgrowth. Mechanistically, these effects are mediated by the provision of Wnt ligands by bSCs. Further, we uncover a link between Wnt signalling and senescence induction, and propose that bSC-derived Wnt signals facilitate the proliferation of neighbouring cells in part by preventing their induction into senescence. This work defines the roles of cellular senescence in regeneration of complex structures.

[EN] The induction of senescence produces a stable cell cycle arrest in cancer cells, thereby inhibiting tumor growth; however, the incomplete immune cell-mediated clearance of senescent cells may favor tumor relapse, limiting the long-term anti-tumorigenic effect of such drugs. A combination of senescence induction and the elimination of senescent cells may, therefore, represent an efficient means to inhibit tumor relapse. In this study, we explored the antitumor efficacy of a combinatory senogenic and targeted senolytic therapy in an immunocompetent orthotopic mouse model of the aggressive triple negative breast cancer subtype. Following palbociclib-induced senogenesis and senolysis by treatment with nano-encapsulated senolytic agent navitoclax, we observed inhibited tumor growth, reduced metastases, and a reduction in the systemic toxicity of navitoclax. We believe that this combination treatment approach may have relevance to other senescence-inducing chemotherapeutic drugs and additional tumor types. Significance: While the application of senescence inducers represents a successful treatment strategy in breast cancer patients, some patients still relapse, perhaps due to the subsequent accumulation of senescent cells in the body that can promote tumor recurrence. We now demonstrate that a combination treatment of a senescence inducer and a senolytic nanoparticle selectively eliminates senescent cells, delays tumor growth, and reduces metastases in a mouse model of aggressive breast cancer. Collectively, our results support targeted senolysis as a new therapeutic opportunity to improve outcomes in breast cancer patients., The M.O. laboratory members thank the financial support from the Spanish Government (project SAF2017-84689-R (MINECO/AEI/FEDER, EU)) and the Generalitat Valenciana (project PROMETEO/2019/065). The R.M. laboratory members thank the financial support from the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/FEDER, EU) and the Generalitat Valenciana (project PROMETEO 2018/024). Both I.G. and B.L-T. are grateful to the Generalitat Valenciana and the Spanish Ministry of Economy, respectively, for their Ph.D. grants. I.G. would like to thank I. Borreda and J. Forteza and the Instituto Valenciano de Patologia for their special collaboration and F. Sancenon for his appreciated help

Objective: To examine the dose-response relationship between overall and specific types of exercise with cognitive function in older adults. Design: Systematic Review and Bayesian Model-Based Network Meta-Analysis. Data sources: Systematic search of MEDLINE, Web of Science, Scopus, PsycINFO and SPORTDiscus. Eligibility criteria for selecting studies: Randomized controlled trials of exercise interventions in participants aged 50 years or over, and that reported on at least one global cognition outcome. Results: The search returned 1998 records, of which 44 studies (4793 participants; 102 different effect sizes) were included in this review with meta-analysis. There was a non-linear, dose-response association between overall exercise and cognition. We found no minimal threshold for the beneficial effect of exercise on cognition. The estimated minimal exercise dose associated with clinically relevant changes in cognition was 724 METs-min per week, and doses beyond 1200 METs-min per week provided less clear benefits. We also found that the dose-response association was exercise type dependent, and our results show that clinically important effects may occur at lower doses for many types of exercise. Our findings also highlighted the superior effects of resistance exercises over other modalities. Conclusions: If provided with the most potent modalities, older adults can get clinical meaningful benefits with lower doses than the WHO guidelines. Findings support the WHO recommendations to emphasise resistance training as a critical component of interventions for older adults.

Se realizó un estudio preliminar del proceso de producción de cerveza a partir de sorgo rojo CIAP R-132 a escala de laboratorio. Se obtuvo una germinación promedio de 75.15%, mientras que la cerveza obtenida tuvo un valor promedio de alcohol de 1.28%, de extracto original igual a 3.68%, y acidez de 4.26%. Se realizó una prueba a escala de banco, efectuando la etapa de cocción y agregando lúpulo durante la misma, obteniéndose un porcentaje de alcohol de 0.56%, extracto original igual a 3.46% y acidez de 1.29%. A partir de las conclusiones del estudio se recomienda realizar la etapa de remojo en solución de NaOH 0.1% m/m, llevar a cabo la etapa de cocción en el proceso productivo, añadir sacarosa o compuestos ricos en azúcares fermentables al mosto antes de la fermentación, y agregar la enzima exógena Fungamyl 800 l durante el proceso de maceración.

We report herein a gene-directed enzyme prodrug therapy (GDEPT) system using gated mesoporous silica nanoparticles (MSNs) in an attempt to combine the reduction of side effects characteristic of GDEPT with improved pharmacokinetics promoted by gated MSNs. The system consists of the transfection of cancer cells with a plasmid controlled by the cytomegalovirus promoter, which promotes β-galactosidase (β-gal) expression from the bacterial gene lacZ (CMV-lacZ). Moreover, dendrimer-like mesoporous silica nanoparticles (DMSNs) are loaded with the prodrug doxorubicin modified with a galactose unit through a self-immolative group (DOXO-Gal) and modified with a disulfide-containing polyethyleneglycol gatekeeper. Once in tumor cells, the reducing environment induces disulfide bond rupture in the gatekeeper with the subsequent DOXO-Gal delivery, which is enzymatically converted by β-gal into the cytotoxic doxorubicin drug, causing cell death. The combined treatment of the pair enzyme/DMSNs-prodrug are more effective in killing cells than the free prodrug DOXO-Gal alone in cells transfected with β-gal.

La combinación de anestesia general con analgesia epidural se considera como el gold-estándar para la cirugía abdominal por vía laparotómica. Ante la aparición de síntomas neurológicos en el postoperatorio inmediato de pacientes portadores de catéter epidural es preciso sospechar de complicaciones relacionadas con el mismo.En caso de presentar un hematoma epidural, es fundamental un diagnóstico precoz con prueba de imagen y la realización de una cirugía descompresiva urgente.

[EN] A bio-inspired nanodevice for the selective and sensitive fluorogenic detection of 3,4- methylenedioxypyrovalerone (MDPV), usually known as Cannibal drug, is reported. The sensing nanodevice is based on mesoporous silica nanoparticles (MSNs), loaded with a fluorescent reporter (rhodamine B) and functionalized on their external surface with a dopamine derivative (3), which specifically interacts with the recombinant human dopamine transporter (DAT), capping the pores. In the presence of MDPV, DAT detaches from the MSNs consequently causing rhodamine B release and allowing drug detection. The nanosensor shows a detection limit of 5.2 µM and it is able to detect the MDPV drug both in saliva and blood plasma samples., The authors thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and CTQ2017-87954-P) and the Generalitat Valencia (PROMETEO/2018/024) for support. E.G. is grateful to the Spanish MEC for her FPU grant. M.A. thanks her postdoctoral fellowship (PAID -10-17). The authors also thank the Electron Microscopy Service at the UPV for support.

[EN] Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. In the last years, navitoclax has emerged as a possible treatment for TNBC. Nevertheless, rapid navitoclax resistance onset has been observed thorough Mcl-1 overexpression. As a strategy to overcome Mcl-1-mediated resistance, herein we present a controlled drug co-delivery system based on mesoporous silica nanoparticles (MSNs) targeted to TNBC cells. The nanocarrier is loaded with navitoclax and the Mcl-1 inhibitor S63845 and capped with a MUC1-targeting aptamer (apMUC1-MSNs(Nav/S63845)). The apMUC1-capped nanoparticles effectively target TNBC cell lines and successfully induce apoptosis, overcoming navitoclax resistance. Moreover, navitoclax encapsulation protects platelets against apoptosis. These results point apMUC1-gated MSNs as suitable BH3 mimetics nanocarriers in the targeted treatment of MUC1-expressing TNBC., Gema Vivo-Llorca thanks the Generalitat Valenciana for her fellowship ACIF/2017/072. Vicente Candela-Noguera thanks the Spanish Government for his fellowship FPU15/02753. We would like to thank Servier for the workart used in the figures of this manuscript (Servier Medical Art ). We thank the Spanish Government (project RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE); SAF2017-84689-R-B (MCUI/AEI/FEDER, UE)) and the Generalitat Valenciana (project PROMETEO/2018/024 and PROMETEO/2019/065) for support.

[EN] Osteoporosis is an illness which appears when the osteoblast/osteoclast activities are unbalanced taking place bone resorption (caused by osteoclasts) in higher extension than bone formation (induced by osteoblasts). Alendronate is one of the most used drugs for osteoporosis treatment despite its scarce bioavailability. Here we present the synthesis and characterization of mesoporous gated nanoparticles (two sets) for the controlled release of alendronate. The first set of nanoparticles (S1) were loaded with sulforhodamine B and capped with a peptide that could be selectively hydrolyzed by cathepsin K enzyme (overexpressed in osteoclasts). The second set (S2) was functionalized with aminopropyl moieties, loaded with nitrobenzofurazan labelled alendronate and capped with the same peptide. Both nanoparticles were internalized by RAW 264.7 macrophages (which could differentiate in osteoclasts) and were able to release its entrapped cargo in the presence of cathepsin K added in the macrophage lysates. Using S2 nanoparticles 4.2% of the total alendronate amount in contact with the cells is liberated inside them and could produce its therapeutic effect., We thank the Spanish Government (RTI2018-100910-B-C41, RTI2018-100910-B-C42 (MCUI/AEI/FEDER, UE)) and the Generalitat Valenciana (PROMETEU/2018/024) for support. SCSIE (Universitat de Valencia) is gratefully acknowledged for all the equipment employed. NMR was registered at the U26 facility of ICTS "NANBIOSIS" at the Universitat of Valencia.

[EN] In vivo detection of cellular senescence is accomplished by using mesoporous silica nanoparticles loaded with the NIR-FDA approved Nile blue (NB) dye and capped with a galactohexasaccharide (S3). NB emission at 672 nm is highly quenched inside S3, yet a remarkable emission enhancement is observed upon cap hydrolysis in the presence of beta-galactosidase and dye release. The efficacy of the probe to detect cellular senescence is tested in vitro in melanoma SK-Mel-103 and breast cancer 4T1 cells and in vivo in palbociclib-treated BALB/cByJ mice bearing breast cancer tumor., R.M. thanks financial support from the Spanish Government (RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/AEI/FEDER, UE)) and the Generalitat Valenciana (PROMETEO 2018/024). M.O. thanks the financial support from SAF2017-84689-R project and MINECO/AEI/FEDER, UE and the Generalitat Valenciana (PROMETEO/2019/065). B.L.-T. is grateful to the Spanish Ministry of Economy for her PhD grant. I.G. thanks her contract from IDM. J.F.-B. and M.A. thank the UPV for their postdoctoral fellowship.

Background: The optimal management of major bleeding in patients receiving vitamin K antagonists (VKA) for venous thromboembolism (VTE) is unclear.Methods: We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the management and 30-day outcomes after major bleeding in patients receiving VKA for VTE.Results: From January 2013 to December 2017, 267 of 18,416 patients (1.4%) receiving long-term VKA for VTE had a major bleeding (in the gastrointestinal tract 78, intracranial 72, hematoma 50, genitourinary 20, other 47). Overall, 151 patients (57%) received blood transfusion; 110 (41%) vitamin K; 37 (14%) fresh frozen plasma; 29 (11%) pro-haemostatic agents and 20 (7.5%) a vena cava filter. During the first 30 days, 59 patients (22%) died (41 died of bleeding) and 13 (4.9%) had a thrombosis. On multivariable analysis, patients with intracranial bleeding (hazard ratio [HR]: 4.58; 95% CI: 2.40-8.72) and those with renal insufficiency at baseline (HR: 2.73; 95% CI: 1.45-5.15) had an increased mortality risk, whereas those receiving vitamin K had a lower risk (HR: 0.47; 0.24-0.92). On the other hand, patients receiving fresh frozen plasma were at increased risk for thrombotic events (HR: 4.22; 95% CI: 1.25-14.3).Conclusions: Major bleeding in VTE patients receiving VKA carries a high mortality rate. Intracranial bleeding and renal insufficiency increased the risk. Fresh frozen plasma seems to increase this risk for recurrent VTE.

[EN] This work reports the synthesis, characterization, and sensing behavior of a hybrid nanodevice for the detection of the potent abuse drug 25I-NBOMe. The system is based on mesoporous silica nanoparticles, loaded with a fluorescent dye, functionalized with a serotonin derivative and capped with the 5-HT2A receptor antibody. In the presence of 25I-NBOMe the capping antibody is displaced, leading to pore opening and rhodamine B release. This delivery was ascribed to 5-HT2A receptor antibody detachment from the surface due to its stronger coordination with 25I-NBOMe present in the solution. The prepared nanodevice allowed the sensitive (limit of detection of 0.6 mm) and selective recognition of the 25I-NBOMe drug (cocaine, heroin, mescaline, lysergic acid diethylamide, MDMA, and morphine were unable to induce pore opening and rhodamine B release). This nanodevice acts as a highly sensitive and selective fluorometric probe for the 25I-NBOMe illicit drug in artificial saliva and in sweets., The authors thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and CTQ2017-87954-P) and the Generalitat Valencia (PROMETEO/2018/024) for support. E.G. is grateful to the Spanish MEC for her FPU grant. The authors also thank the Electron Microscopy Service at the UPV for support.

[EN] Gold nanostars coated with a mesoporous silica shell and functionalized with poly(ethylene glycol) containing photolabile 2-nitrobenzyl moieties are able to release doxorubicin after NIR light irradiation at low power irradiance via a multiphoton absorption photo-dissociation process., The authors gratefully acknowledge financial support from the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/AEI/FEDER,UE)), the Generalitat Valenciana (Project PROMETEO2018/024) and the European Union (Programme European Union Action 2-Erasmus Mundus Partnerships, Grant Agreement Number-2014-0870/001-001). A.H.-M. thanks the Erasmus Mundus Programme for his PhD scholarship for the EuroInkaNet project.

[EN] Janus gold nanostar-mesoporous silica nanoparticle (AuNSt-MSNP) nanodevices able to release an entrapped payload upon irradiation with near infrared (NIR) light were prepared and characterized. The AuNSt surface was functionalized with a thiolated photolabile molecule (5), whereas the mesoporous silica face was loaded with a model drug (doxorubicin) and capped with proton-responsive benzimidazole-beta-cyclodextrin supramolecular gatekeepers (N 1). Upon irradiation with NIR-light, the photolabile compound 5 photodissociated, resulting in the formation of succinic acid, which induced the opening of the gatekeeper and cargo delivery. In the overall mechanism, the gold surface acts as a photochemical transducer capable of transforming the NIR-light input into a chemical messenger (succinic acid) that opens the supramolecular nanovalve. The prepared hybrid nanoparticles were non-cytotoxic to HeLa cells, until they were irradiated with a NIR laser, which led to intracellular doxorubicin release and hyperthermia. This induced a remarkable reduction in HeLa cells viability., The authors gratefully acknowledge financial support from the Spanish Government [Projects MAT2015-64139-C4-1-R, AGL2015-70235-C2-2-R and SAF2017-84689-R (MINECO/AEI/FEDER, UE)], the Generalitat Valenciana (Project PROMETEO2018/024) and European Union (Erasmus Mundus Programme, Action 2, grant agreement number 2014-0870/001001). A.H. thanks the Erasmus Mundus Programme for his PhD scholarship through the EuroInkaNet project. A.L.-L. thanks "La Caixa" Banking Foundation for his PhD scholarship.

This Digest traces the emergence of pyrrole-, imidazole-, and triazole-based receptors for ion-pairs recognition, and recent advances such as formation of ion-pair complexes in solid state, AND receptors, and multichannel detection of ion-pair complexes, are reviewed. The design of highly selective small molecules based on pyrrole, imidazole, and triazole core, as ion-pair receptors represents important advances in the field of the molecular recognition.

Fluorescent solid 5-pyridylimidazobenzothiadiazole displays a remarkable solvatofluorochromism and with Zn(AcO)2 and Cd(AcO)2, either in solution or under solvent-free conditions, forms ion-pair complexes that in the solid state can be discriminated and separated by fluorescence measurements and selective extraction with diethyl ether or chloroform.

Objetivo. En este estudió se pretendió un objetivo doble; 1) Constatar las diferencias entre niños asmáticos con sobrepeso y normopeso en cuanto a CVRS y cantidad de actividad física y sedentarismo y 2) Determinar la relación existente entre cantidad de actividad física, sedentarismo e IMC y su influencia en la CVRS de esta población en Sevilla. Método. Se usó un diseño de cohorte que incluyó a 69 niños en edad escolar con asma persistente controlado. Las medidas incluidas en el estudio fueron: el cuestionario PAQL(S), para evaluar la CVRS de los niños y el cuestionario IPAQ-A, para evaluar la cantidad de actividad física y sedentarismo de los niños. También se calculó el IMC y se determinó si el participante estaba en normopeso o sobrepeso. Resultados. Los niños con sobrepeso obtuvieron peores valores en CVRS e IPAQ-A que sus pares con normopeso. Además se observaron correlaciones positivas entre el IMC y la cantidad de sedentarismo y negativas entre el IMC y también entre éste y el valor en las escalas de valoración de la CVRS. Conclusión. El IMC afecta negativamente a la CVRS a los niños asmáticos en edad escolar. Palabras clave: niños asmáticos, enfermedad crónica, hábitos de vida, ejercicio físico.Abstract: Objective. The aim of this study was: 1) To determine the differences between normal-weight asthmatic children and overweight asthmatic children in terms of HRQoL and amount of physical activity and sedentary and 2) To determine the relationship between amount of physical activity, sedentary and BMI and their influence on the HRQoL of this population in Seville. Method. We used a cohort design study that included 69 school-age children with controlled persistent asthma. The measures included in the study were: the questionnaire PAQL (S), to assess the HRQoL of children and the IPAQ-A questionnaire to assess the amount of physical activity and sedentary lifestyle of children. BMI was also calculated and determined if the participant was of normal-weight or overweight. Results. Overweight children scored worse on HRQoL and IPAQ-A values than their peers with normal-weight. Positive correlations were also observed between BMI and the amount of sedentary lifestyle. Negative correlations were observed between BMI and the amount of physical activity and also negative correlations were observed between BMI and HRQoL. Conclusion. BMI negatively affect HRQoL in school- age asthmatic children. Key words: asthmatic children, chronic disease, lifestyles, physical exercise.

[Resumen] El objetivo del estudio fue describir y establecer las posibles relaciones entre la adherencia a la dieta mediterránea, rendimiento académico y nivel de actividad física en alumnos de educación primaria pertenecientes a un centro de la provincia de Sevilla. Se usó un diseño de corte transversal-observacional. La muestra estuvo compuesta por 50 sujetos (26 niños y 24 niñas) con edades comprendidas entre los 9 y 10 años. Para la recogida de datos se usó un cuestionario autorregistro, test Kidmed, cuestionario IPAQ-A y las calificaciones de las asignaturas comunes. Los resultados muestran que el 50% de los sujetos tuvieron una adherencia a la dieta mediterránea óptima, frente al 10% de los sujetos que tuvieron una adherencia baja. Por otro lado, el 40% de los sujetos reflejó la necesidad de mejorar el patrón alimentario para adecuarlo al modelo mediterráneo. Respecto al nivel de actividad física, el 60% de los sujetos eran inactivos o muy pocos activos, frente al 25% que fueron muy activos. Por último, se halló una asociación entre la adherencia a la dieta mediterránea y las calificaciones obtenidas en las diferentes asignaturas [educación artística (Coeficiente contingencia= ,442, p

Resumen En el entorno neumologico no es habitual conocer las normativas europeas y de EE. UU. que regulan la administracion de oxigeno durante los viajes en avion y la politica a tal respecto que cada compania aerea tiene. Este desconocimiento se debe en gran parte a la escasez de articulos que abordan este tema en las revistas especializadas y a la llamativamente limitada informacion que nos proporcionan las aerolineas en sus paginas web. En este articulo hemos abordado estas normativas, la politica que siguen algunas aerolineas y determinados aspectos practicos que deberiamos tener en cuenta, para que podamos responder de forma satisfactoria a las preguntas que, en un momento puntual, nos pueda plantear un paciente que necesite utilizar oxigeno durante los viajes en avion.

This Digest traces the emergence of pyrrole-, imidazole-, and triazole-based receptors for ion-pairs recognition, and recent advances such as formation of ion-pair complexes in solid state, AND receptors, and multichannel detection of ion-pair complexes, are reviewed. The design of highly selective small molecules based on pyrrole, imidazole, and triazole core, as ion-pair receptors represents important advances in the field of the molecular recognition.

La disminución de los niveles de práctica de actividad física, así como el incremento del sedentarismo repercute de forma muy negativa en los escolares, además de influir en factores como el rendimiento académico. El estudio presenta una muestra de 175 escolares de diferentes centros del sur de España. Se utilizaron variables sociodemográficas, practica de actividad física y diferentes calificaciones escolares. Los resultados indican que los escolares que practican actividad física extraescolar obtienen un mayor rendimiento. La práctica de actividad física extraescolar en escolares se asocia con mayor rendimiento académico. Decreasing physical activity levels and the incremental sedentary time affects negatively during primary school, and have a negative influence on academic performance. 175 students from different centers of southern Spain were included. Sociodemographic characteristics, physical activity practice and academic performance were evaluated. Results show how children who practice out of school have higher levels of academic performance. Therefore practice of sport and physical activity in adolescents is associated with higher academic performance

In the tricyclic bis(heteroaryl)substituted ferrocenyl-imidazo-quinoxalines 7 and 8, the presence of redox and fluorescent units at the heteroaromatic core, which can act as a ditopic binding site, made these molecules potential candidates as electro-optical ion-pair recognition receptors. In this context, both molecules behave as ion-pair receptors for cations and anions, which individually had demonstrated their ability to form the corresponding cationic and anionic complexes. These receptors also show an important enhancement of anion binding by co-bound cations, whereas no affinity of the free receptors by the anion is observed. Similarly, receptors 7 and 8 display a dramatic increase in the cation binding by the action of their anionic complexes, while no affinity of the free receptors by the cations was detected. Interestingly, both receptors exhibit a remarkable enhancement of anions and cations binding, although no affinity of the free receptors by the ions is observed. In all cases, the ion-pair formation is detected by a perturbation of the redox potential of the ferrocene moiety and a remarkable enhancement in the emission band.