Deciphering the H-Bonding Preference on Nucleoside Molecular Recognition through Model Copper(II) Compounds

This research was funded by Agencia Estatal de Investigación, Ministerio de Ciencia, Innovación y Universidades (MICIU) from Spain and co-funded with FEDER-EU (Projects No. PGC2018-102047-B-I00 and CTQ2017-85821-R); Junta de Andalucía (FQM-283), and University of Granada (Project ref. PPJIA2019-03).The data presented in this study are available in this article or supplementary material.The contribution of the undergraduate student Elisabet J. Muela Morales as well as the technical and human support provided by SGIker (UPV/EHU) is gratefully acknowledged. A.D.-M. and M.B.-O. acknowledge support from Cost Action CA18202—Network for Equilibria and Chemical Thermodynamics Advanced Research.The synthetic nucleoside acyclovir is considered an outstanding model of the natural nucleoside guanosine. With the purpose of deepening on the influence and nature of non-covalent interactions regarding molecular recognition patterns, three novel Cu(II) complexes, involving acyclovir (acv) and the ligand receptor N-(2-hydroxyethyl)ethylenediamine (hen), have been synthesized and thoroughly characterized. The three novel compounds introduce none, one or two acyclovir molecules, respectively. Molecular recognition has been evaluated using single crystal X-ray diffraction. Furthermore, theoretical calculations and other physical methods such as thermogravimetric analysis, infrared and UV-Vis spectroscopy, electron paramagnetic resonance and magnetic measurements have been used. Theoretical calculations are in line with experimental results, supporting the relevance of the [metal-N7(acv) + H-bond] molecular recognition pattern. It was also shown that (hen)O-H group is used as preferred H-donor when it is found within the basal coordination plane, since the higher polarity of the terminal (hen)O-H versus the N-H group favours its implication. Otherwise, when (hen)O-H occupies the distal coordination site, (hen)N-H groups can take over.Agencia Estatal de Investigacion, Ministerio de Ciencia, Innovacion y Universidades (MICIU) from SpainEuropean Commission PGC2018-102047-B-I00 CTQ2017-85821-RJunta de Andalucia FQM-283University of Granada PPJIA2019-0

Aprender Historia de la Educación Contemporánea a través del teatro

Historia de la Educación Contemporánea es una materia enclavada en la Universidad de Sevilla, en segundo curso del Grado de Pedagogía, de 6 créditos ECTS, que está concebida para contribuir al desarrollo de la formación básica del estudiante, a través del estudio del hecho educativo desde el punto de vista histórico. Esta asignatura, que suele resultar densa y difícil a quienes la cursan, ha sido concebida desde el punto de vista metodológico durante el curso escolar 2012/13, como un viaje por la contemporaneidad de la educación, que juntos han realizado profesorado y alumnado. En el transcurso de este trayecto, nos hemos apoyado en el uso del teatro como recurso didáctico para el aprendizaje de ciertas pedagogías, ligadas a determinados autores objeto de estudio. Este trabajo trata de exponer algunas de las potencialidades del teatro como medio pedagógico para en equipo, aprender, conocer, reflexionar, estudiar, reconstruir y ampliar el conocimiento histórico educativo contemporáneo

New Metformin–Citric Acid Pharmaceutical Molecular Salt: Improving Metformin Physicochemical Properties

Crystal engineering and, more specifically, the development of multicomponent materials has become an effective technique to rationally modify important physicochemical properties of solids, such as solubility and thermal stability. In this work, in order to overcome some of the problems that metformin has as a pharmaceutical, a new metformin base salt with citric acid (MTF–CIT) has been developed, which improves the thermal stability and solubility (two-fold) compared to metformin base (MTF). A complete characterization of the new crystalline form through PXRD, DSC, SCXRD, and FT–IR was conducted to ensure the purity of the new phase and provide a comprehensive view of its physicochemical behavior, thus correlating the improvement in stability and solubility with the crystal structure. The MTF–CIT salt crystallizes in the monoclinic P21/c1 spacegroup with z0 = 1. Intermolecular interactions found in MTF–CIT structure and simulated crystal morphology suggest a steric protection effect on the metformin ion that leads to the enhancement of stability in several orders of magnitude compared with MTF, as well as an improvement in solubility due to the exposition of polar groups in the biggest facets, making this new multicomponent salt a promising pharmaceutical solid.MCIU/AEI/FEDER, UE PGC2018-102047-B-I00FEDER-Universidad de Granada, Spain B-FQM-478-UGR2

Rational Coformer Selection in the Development of 6-Propyl-2-thiouracil Pharmaceutical Cocrystals

The following supporting information can be downloaded at: https://www. mdpi.com/article/10.3390/ph16030370/s1This research was funded by Project B-FQM-478-UGR20 (FEDER-Universidad de Granada, Spain). A.F. thanks MICIU/AEI of Spain (project PID2020-115637GB-I00, FEDER) for financial support.Pharmaceutical multicomponent solids have proved to efficiently modulate the physico- chemical properties of active pharmaceutical ingredients. In this context, polyphenols are interesting coformers for designing pharmaceutical cocrystals due to their wide safety profile and interesting antioxidant properties. The novel 6-propyl-2-thiouracil multicomponent solids have been obtained by mechanochemical synthesis and fully characterized by powder and single-crystal X-ray diffraction methods. The analysis of supramolecular synthons has been further performed with computational methods, with both results revealing a robust supramolecular organization influenced by the different positions of the hydroxyl groups within the polyphenolic coformers. All novel 6-propyl-2-thiouracil cocrystals show an enhanced solubility profile, but unfortunately, their thermodynamic stability in aqueous media is limited to 24 h.FEDER-Universidad de Granada, Spain B-FQM-478-UGR20Spanish Government PID2020-115637GB-I0

The activation of citizenship as a strategy for tourism sustainability in heritage sites near the big city. The case of Madrid region

Aunque el Patrimonio Cultural es fuente reconocida de bienestar, su sobreexplotación turística genera fuertes impactos negativos, agravados en las grandes ciudades por la concentración de efectos en el espacio. Este trabajo aborda el caso de Madrid, ciudad que cuenta en su periferia metropolitana con activos patrimoniales de primer nivel, cuyo mejor aprovechamiento turístico ayudaría a mitigar el impacto negativo en la capital, a la vez que contribuiría al desarrollo económico y social de la periferia. En la investigación se aplicó un planteamiento metodológico dinámico con cuatro planos de análisis complementarios: documental y de redes, cualitativo, cuantitativo y procesos participativos. Los resultados evidencian la necesidad de adoptar estrategias de gestión cultural y de planificación turística orientadas al reequilibrio de los flujos de visitantes. La activación de los propios vecinos se revela como un recurso especialmente valioso para fortalecer un turismo de proximidad, experiencial y más sostenible. El impacto de la Covid‐19, por una parte, y la declaración del Paseo del Prado y el Retiro como Patrimonio de la Humanidad, por otra, han puesto aún más de actualidad esta situación.Although Cultural Heritage is a recognized source of well‐being, its touristic overexploitation gen‐ erates strong negative impacts, aggravated in large cities due to the concentration of effects in space. This work addresses the case of Madrid, a city that has first‐rate heritage assets in its metropolitan periphery, whose better touristic use would help to mitigate the negative impact on the capital, while contributing to the economic and social development of the periphery. In the research, a dynamic methodological approach was applied with four complementary analysis planes: documentary and networks, qualitative, quantitative and participatory processes. The results show the need to adopt cultural management and tourism planning strategies aimed at rebalancing visitor flows. The activation of the neighbors themselves is revealed as an especially valuable resource to strengthen proximity, experiential and more sustainable tourism. The The impact of Covid‐19, on the one hand, and the declaration of Paseo del Prado and El Retiro as World Heritage Sites, on the other, have made this situation even more topical

Evaluation of synthon influence on ethenzamide– polyphenol pharmaceutical cocrystals

The pharmaceutical cocrystal landscape of ethenzamide has been addressed during the past years with the aim of improving its physicochemical properties, mainly solubility and dissolution rate. Herein four novel ethenzamide cocrystals have been isolated by mechanochemical synthesis and thoroughly characterized by powder and single-crystal X-ray diffraction. Polyphenols have been selected as coformers based on ethenzamide synthon preference as well as their safety profile and antioxidant character. Besides crystallographic analysis, theoretical calculations have been made to evaluate the strength of intermolecular interactions and their role in crystal packing. The results evidence differences in the supramolecular architecture depending on the different polyphenolic isomers used as coformers. Finally, the physicochemical properties of the novel compounds were assessed and compared to those of ethenzamide alone. Although the solubility profile is significantly enhanced, the thermodynamic stability of the novel cocrystals in aqueous medium is restricted to 24 hours. These findings have been correlated with the crystal structure.FEDER-Universidad de Granada, Spain B-FQM-478-UGR20Spanish Government PID2020-115637GB-I00European CommissionSpanish Government PRE2019-08883

Specific bioelectrical impedance vector analysis (BIVA) is more accurate than classic BIVA to detect changes in body composition and in nutritional status in institutionalised elderly with dementia

A new analytical variation of bioelectrical impedance vector analysis (BIVA), called specific BIVA, has shown to be more accurate in detecting changes in fat mass than classic BIVA.To compare classic and specific BIVA in order to identify which is more strongly associated with psycho-functional and nutritional indicators in a group of institutionalised elderly patients with dementia.Cross-sectional study. Fifty-four patients (34 women, 20 men) with dementia in moderately severe to very severe stages and aged 60–95years underwent geriatric nutritional assessment, including body mass index calculations, the Mini Nutritional Assessment, the Geriatric Nutritional Risk Index, and whole body composition analysis.With specific BIVA (unlike with classic BIVA), significant differences were found between women with moderately severe and very severe dementia. In the BIVA conducted for body mass index, the confidence ellipses produced with the classic BIVA approach were highly overlapping; but with specific BIVA, significant differences were observed between the women in different nutritional categories (malnutrition, risk of malnutrition, normal weight and obesity). On the other hand, both approaches distinguished malnourished women from those who were at risk of malnutrition, according to the Mini Nutritional Assessment; and men with a moderate-high risk of malnutrition from men with no risk, on the basis of the Geriatric Nutritional Risk Index.Overall, the findings of the present study suggest that specific BIVA is more effective than classic BIVA in identifying bioelectrical changes associated with psycho-functional and nutritional indicators in institutionalised elderly with dementia

Towards the Development of Novel Diclofenac Multicomponent Pharmaceutical Solids

Multicomponent pharmaceutical materials offer new opportunities to address drug physicochemical issues and to obtain improved drug formulation, especially on oral administration drugs. This work reports three new multicomponent pharmaceutical crystals of the non-steroidal antiinflammatory drug diclofenac and the nucleobases adenine, cytosine, and isocytosine. They have been synthesized by mechanochemical methods and been characterized in-depth in solid-state by powder and single crystal X-ray diffraction, as well as other techniques such as thermal analyses and infrared spectroscopy. Stability and solubility tests were also performed on these materials. This work aimed to evaluate the physicochemical properties of these solid forms, which revealed thermal stability improvement. Dissociation of the new phases was observed in water, though. This fact is consistent with the reported observed layered structures and BFDH morphology calculations.Spanish Agencia Estatal de Investigacion of the Ministerio de Ciencia, Innovacion y Universidades (MICIU)European Commission PGC2018-102047-B-I00FEDER-Universidad de Granada, Spain B-FQM-478-UGR2

Phenformin as an Anticancer Agent: Challenges and Prospects

Currently, there is increasing evidence linking diabetes mellitus (especially type 2 diabetes mellitus) with carcinogenesis through various biological processes, such as fat-induced chronic inflammation, hyperglycemia, hyperinsulinemia, and angiogenesis. Chemotherapeutic agents are used in the treatment of cancer, but in most cases, patients develop resistance. Phenformin, an oral biguanide drug used to treat type 2 diabetes mellitus, was removed from the market due to a high risk of fatal lactic acidosis. However, it has been shown that phenformin is, with other biguanides, an authentic tumor disruptor, not only by the production of hypoglycemia due to caloric restriction through AMP-activated protein kinase with energy detection (AMPK) but also as a blocker of the mTOR regulatory complex. Moreover, the addition of phenformin eliminates resistance to antiangiogenic tyrosine kinase inhibitors (TKI), which prevent the uncontrolled metabolism of glucose in tumor cells. In this review, we evidence the great potential of phenformin as an anticancer agent. We thoroughly review its mechanism of action and clinical trial assays, specially focusing on current challenges and future perspectives of this promising drug.This research was supported by the Fundación Mutua Madrileña (project FMM-AP16683-2017), Consejería de Salud Junta de Andalucía (PI-0089-2017), the MNat Scientitc Unit of Excellence (UCE.PP2017.0f) and the Chair “Doctors Galera-Requena in cancer stem cell research”

Deciphering the H-Bonding Preference on Nucleoside Molecular Recognition through Model Copper(II) Compounds

The synthetic nucleoside acyclovir is considered an outstanding model of the natural nucleoside guanosine. With the purpose of deepening on the influence and nature of non-covalent interactions regarding molecular recognition patterns, three novel Cu(II) complexes, involving acyclovir (acv) and the ligand receptor N-(2-hydroxyethyl)ethylenediamine (hen), have been synthesized and thoroughly characterized. The three novel compounds introduce none, one or two acyclovir molecules, respectively. Molecular recognition has been evaluated using single crystal X-ray diffraction. Furthermore, theoretical calculations and other physical methods such as thermogravimetric analysis, infrared and UV-Vis spectroscopy, electron paramagnetic resonance and magnetic measurements have been used. Theoretical calculations are in line with experimental results, supporting the relevance of the [metal-N7(acv) + H-bond] molecular recognition pattern. It was also shown that (hen)O-H group is used as preferred H-donor when it is found within the basal coordination plane, since the higher polarity of the terminal (hen)O-H versus the N-H group favours its implication. Otherwise, when (hen)O-H occupies the distal coordination site, (hen)N-H groups can take overThis research was funded by Agencia Estatal de Investigación, Ministerio de Ciencia, Innovación y Universidades (MICIU) from Spain and co-funded with FEDER-EU (Projects No. PGC2018-102047-B-I00 and CTQ2017-85821-R); Junta de Andalucía (FQM-283), and University of Granada (Project ref. PPJIA2019-03)S