Antitumor Activity and Reductive Stress by Platinum(II) N-Heterocyclic Carbenes based on Guanosine.

Platinum(II) complexes bearing N-heterocyclic carbenes based guanosine and caffeine have been synthesized by unassisted C-H oxidative addition, leading to the corresponding trans-hydride complexes. Platinum guanosine derivatives bearing triflate as counterion or bromide instead of hydride as co-ligand were also synthesized to facilitate correlation between structure and activity. The hydride compounds show high antiproliferative activity against all cell lines (TC-71, MV-4-11, U-937 and A-172). Methyl Guanosine complex 3, bearing a hydride ligand, is up to 30 times more active than compound 4, with a bromide in the same position. Changing the counterion has no significant effect in antiproliferative activity. Increasing bulkiness at N7, with an isopropyl group (compound 6), allows to maintain the antiproliferative activity while decreasing toxicity for non-cancer cells. Compound 6 leads to an increase in endoplasmic reticulum and autophagy markers on TC71 and MV-4-11 cancer cells, induces reductive stress and increases glutathione levels in cancer cells but not in non-cancer cell line HEK-293.

Involvement of autophagy in melatonin-induced cytotoxicity in glioma-initiating cells.

Glioblastoma-initiating cells (GICs) represent a stem cell-like subpopulation within malignant glioblastomas responsible for tumor development, progression, therapeutic resistance, and tumor relapse. Thus, eradication of this subpopulation is essential to achieve stable, long-lasting remission. We have previously reported that melatonin decreases cell proliferation of glioblastoma cells both in vitro and in vivo and synergistically increases effectiveness of drugs in glioblastoma cells and also in GICs. In this study, we evaluated the effect of the indolamine alone in GICs and found that melatonin treatment reduces GICs proliferation and induces a decrease in self-renewal and clonogenic ability accompanied by a reduction in the expression of stem cell markers. Moreover, our results also indicate that melatonin treatment, by modulating stem cell properties, induces cell death with ultrastructural features of autophagy. Thus, data reported here reinforce the therapeutic potential of melatonin as a treatment of malignant glioblastoma both by inhibiting tumor bulk proliferation or killing GICs, and simultaneously enhancing the effect of chemotherapy.

Mechanisms involved in the pro-apoptotic effect of melatonin in cancer cells.

It is well established that melatonin exerts antitumoral effects in many cancer types, mostly decreasing cell proliferation at low concentrations. On the other hand, induction of apoptosis by melatonin has been described in the last few years in some particular cancer types. The cytotoxic effect occurs after its administration at high concentrations, and the molecular pathways involved have been only partially determined. Moreover, a synergistic effect has been found in several cancer types when it is administered in combination with chemotherapeutic agents. In the present review, we will summarize published work on the pro-apoptotic effect of melatonin in cancer cells and the reported mechanisms involved in such action. We will also construct a hypothesis on how different cell signaling pathways may relate each other on account for such effect.

The Impact of COVID-19 Outbreak on Camping Tourism in Spain: A Spatial Approach to Tourist Destinations.

The COVID-19 health crisis has wreaked devastation on the world economy, especially on the tourism sector. The camping sector has been little studied despite its high economic impact and participation rate. Moreover, the observable effects of phenomena such as the COVID-19 pandemic have received little research attention. Consequently, the objective of this paper is therefore to analyse the effects of the pandemic on camping tourism by characterising the factors that determine it. The study is carried out by providing a geographical perspective of the sector by tourist areas, whereby two types of tourist destinations are considered: campsites located in coastal areas, and campsites located in natural areas. This is the main contribution of the work, as the proposed geographical analysis studies smaller territorial units than those usually used in tourism research. For the study, Multivariate Analysis techniques are applied, specifically Factor Analysis and Cluster Analysis. The results show that there is a balance between supply and demand in the sector, with a significant economic impact, especially on employment and the performance of the sector. The impact of the COVID-19 pandemic has led to nature tourism gaining greater popularity, and shows an evolution in travellers' preferences for tourist destinations in favour of campsites located in natural areas over those located in coastal destinations. The geographical location of the tourist destination, therefore, plays a key role in the characterisation of Spanish campsites. This has practical implications for both camping companies and institutions, as the fact that some areas are more attractive than others is a decisive factor in deciding on the location of new campsites.

One more step in the study of children's daily stress: The spillover effect as the transfer of tension in family and school environments.

Introduction: The spillover effect is the psychological overflow due to daily stress in one context and the transfer of its consequences to another close environment. The aim is to explore the spillover effect in conflicts within the family, on the one hand, and school with peers on the other hand, as an inferred measure of daily stress according to the literature. Method: The study consisted of a sample of 208 6-year-old students and their families. A methodology based on daily report records was used, by means of two ad hoc checklists with simultaneous measurements, for 2 consecutive weeks and 3 academic years, for both family and school contexts. A repeated measures design, together with a nonparametric statistical data analysis with Friedman's test and contrast measures, was used. Results: Daily stress shows significant differences in the family setting throughout the week (χ 2 = 32.44; p = 0.000) and at different times of the day (χ 2 = 29.65; p = 0.000). In the school setting, differences were found across the different days of the week (χ 2 = 36.96; p = 0.000). Spillover effect has been discovered between conflicts at home in the evening and conflicts at school. At the same time, conflicts at school are related to conflicts at home from Wednesday onward. Discussion: The results suggest further research on daily stress through the interrelation of the different contexts, as well as the impact that moments of conflict may have on the psychological and emotional development of the child.

Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin.

Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antiproliferative, oncolytic and neuroprotective properties. Here, we present evidence that the N-acetyl side chain plays a key role in melatonin's antiproliferative effect in HT22 and sw-1353 cells, but it does so at the expense of antioxidant and neuroprotective properties. Removal of the N-acetyl group enhances the antioxidant and neuroprotective properties of the indole, but it can lead to toxic methamphetamine-like effects in several cell lines. Inhibition of NFkB mimicked melatonin's antiproliferative and antioxidant effects, but not neuroprotection. Our results strongly suggest that neuroprotective and antiproliferative effects of melatonin rely on different parts of the molecule and are likely mediated by different mechanisms. We also predict that melatonin metabolism by target cells could determine whether melatonin inhibits cell proliferation, prevents toxicity or induces cell death (e.g. apoptosis or autophagy). These observations could have important implications for the rational use of melatonin in personalized medicine.

Riesgos laborales en las empresas de residuos sólidos en Andalucía: una perspectiva de género / Labour risks in solid waste companies in Andalusia: a gender perspective

Resumen El sector de Residuos Sólidos Urbanos tiene amplia trayectoria en la implementación de planes de prevención en riesgos laborales. Analizamos dos aspectos: cuáles son los factores de riesgos laborales a los que se encuentran expuestos los empleados y que pueden afectar fundamentalmente a su salud dentro del sector analizado; y diferencias en la prevención de riesgos laborales por las empresas del sector que presentaron enfermedades profesionales en función del género de los trabajadores. El procedimiento metodológico consistió en el análisis descriptivo transversal en ocho provincias de Andalucía (España). Como herramienta de estudio se ha utilizado el cuestionario de 75 preguntas para la elaboración del informe sobre "condiciones de trabajo y gestión preventiva en las empresas de gestión de residuos sólidos urbanos en Andalucía" realizado por el Instituto Andaluz de Prevención de Riesgos Laborales. Como técnica estadística se ha usado el análisis de correspondencias múltiple y el test Chi-Cuadrado de independencia. En los resultados se han encontrado dos percepciones bien diferenciadas sobre los riesgos laborales en las organizaciones que vienen fijadas por la jerarquía en la organización. Se puede establecer relación directa entre los puestos de mando de la empresa y la preocupación por los riesgos laborales. A mayor distancia a puestos de dirección mayor es la preocupación de los empleados respecto a los riesgos laborales a los que están expuestos. En cuanto a los riesgos psicosociales se identifica que las mujeres se ven más afectadas que los hombres.

Abstract The Urban Solid Waste sector has a great trajectory in the implementation of preventive plans in workplace risks. We analyzed two aspects: which are the factors of workplace risks to what the employees are exposed and can essentially affect their health inside of the analyzed sector; and the differences in preventive management performed in companies that had informed their workers about occupational diseases, and analyzed these differences according to workers' gender. The method used was cross-sectional analysis in eight provinces of Andalusia (Spain). As research tool, a 75-question questionnaire was used to prepare the report on "Working conditions and safety management in enterprises specialized in management of urban solid wastes in Andalusia" by the Andalusian Institute of Occupational Health and Safety. As statistical technique, it has been used multiple correspondence analysis and the Chi-Squared test of independence. In the results there are two different perceptions of workplace risks in organizations that are fixed by the hierarchy in the company. It is possible to establish a direct relationship between the Team Management of the company and the concerning about workplace risks. The greater the distance between leadership's positions, the greater concern of employees exposed to the workplace risks. Regarding psychosocial risks, we concluded that women are more affected than men.

Adenoma de conductos biliares (hamartoma de glándulas peribiliares): la importancia de su adecuado reconocimiento / Bile duct adenoma (hamartoma of peribiliary glands): Importance of an adequate diagnosis

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