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Abstract Cutaneous and Head and Neck squamous cell carcinoma (CSCC, HNSCC) are among the most prevalent cancers. Both types of cancer can be treated with photodynamic therapy (PDT) by using the photosensitizer Temoporfin in HNSCC and the prodrug methyl-aminolevulinate (MAL) in CSCC. However, PDT is not always effective. Therefore, it is mandatory to correctly approach the therapy according to the characteristics of the tumour cells. For this reason, we have used cell lines of CSCC (A431 and SCC13) and HNSCC (HN5 and SCC9). The results obtained indicated that the better response to MAL-PDT was related to its localization in the plasma membrane (A431 and HN5 cells). However, with Temoporfin all cell lines showed lysosome localization, even the most sensitive ones (HN5). The expression of mesenchymal markers and migratory capacity was greater in HNSCC lines compared to CSCC, but no correlation with PDT response was observed. The translocation to the nucleus of β-catenin and GSK3β and the activation of NF-κβ is related to the poor response to PDT in the HNSCC lines. Therefore, we propose that intracellular localization of GSK3β could be a good marker of response to PDT in HNSCC. Although the molecular mechanism of response to PDT needs further elucidation, this work shows that the most MAL-resistant line of CSCC is more sensitive to Temoporfin.

Resumen: Objetivo: Descripción y análisis de la relación entre las fracturas de húmero proximal y la lesión traumática del nervio axilar circunflejo. Material y método: Estudio prospectivo, observacional, de una serie de casos consecutivos de fracturas de extremo proximal de húmero. Se realizó valoración radiográfica, clasificando las fracturas según el sistema AO (Arbeitsgemeinshaft für Osteosynsthesefragen, Asociación de Grupo de Trabajo para el Estudio de la Fijación Interna de las Fracturas), y electromiografía (EMG) para la evaluación de la lesión del nervio axilar. Resultados: De 105 casos consecutivos de fracturas de húmero proximal, 31 pacientes cumplían los criterios de inclusión. Muestra: 86% mujeres y 14% hombres con edad media de 71,8 años (30-96 años). De los pacientes incluidos en el estudio, 58% presentó una EMG normal o leve axonotmesis, 23% presentó neuropatía del nervio axilar sin denervación muscular y 19%, lesión con denervación del nervio axilar. Los pacientes que sufrieron fracturas complejas de húmero proximal (AO11B y AO11C) tuvieron más riesgo de presentar lesiones tipo neuropatía axilar con denervación muscular en la EMG, siendo esta relación estadísticamente significativa (p < 0,001). Conclusiones: Los pacientes que sufren fracturas complejas de húmero proximal (AO11B y AO11C) tienen más riesgo de presentar lesiones tipo neuropatía axilar con denervación muscular en la EMG (p < 0,001). Abstract: Objective: Description and analysis of the relation between the proximal humerus fracture patterns and the traumatic injury of the axillary nerve. Material and method: Prospective, observational study of a consecutive case series that analyzed proximal humerus fractures. Radiographic evaluation was performed, and AO (Arbeitsgemeinshaft für Osteosynsthesefragen) system was used to classify the fractures. Electromyography was used to diagnose the axillary nerve injury. Results: Thirty-one patients on 105 who had a proximal humerus fracture met inclusion criteria. Eighty-six percent of the patients included were women and 14% men. The mean age was 71.8 years (30–96 years). Of the patients included in the study, 58% had normal or mild axonotmesis EMG, 23% had axillary nerve neuropathy without muscle denervation and 19% had injury with axillary nerve denervation. Patients who suffered complex fractures of the proximal humerus (AO11B and AO11C) had a higher risk of presenting axillary neuropathy type lesions with muscle denervation in the EMG, this relationship being statistically significant (p

Objective: Description and analysis of the relation between the proximal humerus fracture patterns and the traumatic injury of the axillary nerve. Material and method: Prospective, observational study of a consecutive case series that analysed proximal humerus fractures. Radiographic evaluation was performed, and AO (Arbeitsgemeinshaft für Osteosynsthesefragen) system was used to classify the fractures. Electromyography was used to diagnose the axillary nerve injury. Results: Thirty-one patients on 105 who had a proximal humerus fracture met inclusion criteria. Eighty-six percent of the patients included were women and 14% men. The mean age was 71.8 years (30–96 years). Of the patients included in the study, 58% had normal or mild axonotmesis EMG, 23% had axillary nerve neuropathy without muscle denervation and 19% had injury with axillary nerve denervation. Patients who suffered complex fractures of the proximal humerus (AO11B and AO11C) had a higher risk of presenting axillary neuropathy type lesions with muscle denervation in the EMG, this relationship being statistically significant (p

Issues of chronology are central to inferences pertaining to relationships between both contemporaneous and successive prehistoric typo-technological entities (i.e., archaeological cultures), culture–environment relationships, and ultimately the mechanisms at play behind cultural changes observed through time in the archaeological record. We refine the chronology of Upper Paleolithic archaeological cultures between 35–18 calibrated kiloanni before the present in present-day France by incorporating recently published radiocarbon data along with new 14C ages that we obtained from several Gravettian archaeological contexts. We present the results of a Bayesian age model that includes these new radiometric data and that, more importantly, separates Gravettian contexts in regions north of the Garonne River into two successive cultural phases: The Northern Noaillian and the Rayssian, respectively. This new age model places the beginning of the Noaillian during Greenland Stadial 5.2. The appearance of contexts containing assemblages associated with the Rayssian lithic technical system occurs immediately prior to the termination of Greenland Interstadial 5.1, and it is present throughout Heinrich Event 3 (GS-5.1) and into the following GI-4 climatic amelioration. Despite the Rayssian’s initial appearance during the brief and relatively weakly expressed Greenland Interstadial 5.1, its duration suggests that Rayssian lithic technology was well-suited to the environmental conditions of Greenland Stadial 5.1.

La reflexión en torno a la ontología del cine ha sido una preocupación básica en las teorías fílmicas desde sus orígenes (Casetti, 1994). Sin embargo, las relaciones entre cine y verdad solo pueden abordarse desde un sistema filosófico que analice la estructura tecnológica del dispositivo cinematográfico. En el presente artículo asumimos las coordenadas del materialismo filosófico de Gustavo Bueno (2018) para criticar la consideración del cine como simulación falaz. Confrontando posiciones realistas e idealistas, definimos el cine como una representación indeterminada cuya verdad puede constituirse dialógicamente.

Non-melanoma skin cancer has recently seen an increase in prevalence, and it is estimated that this grow will continue in the coming years. In this sense, the importance of therapy effectiveness has increased, especially photodynamic therapy. Photodynamic therapy has attracted much attention as a minimally invasive, selective and repeatable approach for skin cancer treatment and prevention. Although its high efficiency, this strategy has also faced problems related to tumor resistance, where the tumor microenvironment has gained a well-deserved role in recent years. Tumor microenvironment denotes a wide variety of elements, such as cancer-associated fibroblasts, immune cells, endothelial cells or the extracellular matrix, where their interaction and the secretion of a wide diversity of cytokines. Therefore, the need of designing new strategies targeting elements of the tumor microenvironment to overcome the observed resistance has become evident. To this end, in this review we focus on the role of cancer-associated fibroblasts and tumor-associated macrophages in the resistance to photodynamic therapy. We are also exploring new approaches consisting in the combination of new and old drugs targeting these cells with photodynamic therapy to enhance treatment outcomes of non-melanoma skin cancer.

El objetivo del trabajo es revisar la terminología de un campo muy específico del léxico agrícola en el siglo XVII: las herramientas de corte. Es decir, las que podríamos englobar bajo hiperónimos como hoz, hacha, rozón o guadaña. Para ello se utiliza un corpus, el CorLexIn, que se nutre de documentación notarial sobre registros de bienes. El estudio es, por tanto, histórico pero también diatópico, por lo que los datos obtenidos se cruzan con los atlas lingüísticos modernos, en los que esos mismos conceptos suelen aparecer regularmente.

Objective: Cancer metabolic reprogramming promotes resistance to therapies. In this study, we addressed the role of the Warburg effect in the resistance to photodynamic therapy (PDT) in skin squamous cell carcinoma (sSCC). Furthermore, we assessed the effect of metformin treatment, an antidiabetic type II drug that modulates metabolism, as adjuvant to PDT. Methods: For that, we have used two human SCC cell lines: SCC13 and A431, called parental (P) and from these cell lines we have generated the corresponding PDT resistant cells (10GT). Results: Here, we show that 10GT cells induced metabolic reprogramming to an enhanced aerobic glycolysis and reduced activity of oxidative phosphorylation, which could influence the response to PDT. This result was also confirmed in P and 10GT SCC13 tumors developed in mice. The treatment with metformin caused a reduction in aerobic glycolysis and an increase in oxidative phosphorylation in 10GT sSCC cells. Finally, the combination of metformin with PDT improved the cytotoxic effects on P and 10GT cells. The combined treatment induced an increase in the protoporphyrin IX production, in the reactive oxygen species generation and in the AMPK expression and produced the inhibition of AKT/mTOR pathway. The greater efficacy of combined treatments was also seen in vivo, in xenografts of P and 10GT SCC13 cells. Conclusions: Altogether, our results reveal that PDT resistance implies, at least partially, a metabolic reprogramming towards aerobic glycolysis that is prevented by metformin treatment. Therefore, metformin may constitute an excellent adjuvant for PDT in sSCC.

Alterations of cholesterol metabolism have been described for many neurodegenerative pathologies, such as Alzheimer’s disease in the brain and age-related macular degeneration in the retina. Recent evidence suggests that glaucoma, which is characterized by the progressive death of retinal ganglion cells, could also be associated with disruption of cholesterol homeostasis. In the present study we characterized cholesterol metabolism in a rat model of laser-induced intraocular hypertension, the main risk factor for glaucoma. Sterol levels were measured using gas-chromatography and cholesterol-related gene expression using quantitative RT-PCR at various time-points. As early as 18 hours after the laser procedure, genes implicated in cholesterol biosynthesis and uptake were upregulated (+49% and +100% for HMG-CoA reductase and LDLR genes respectively, vs. naive eyes) while genes involved in efflux were downregulated (-26% and -37% for ApoE and CYP27A1 genes, respectively). Cholesterol and precursor levels were consecutively elevated 3 days post-laser (+14%, +40% and +194% for cholesterol, desmosterol and lathosterol, respectively). Interestingly, counter-regulatory mechanisms were transcriptionally activated following these initial dysregulations, which were associated with the restoration of retinal cholesterol homeostasis, favorable to ganglion cell viability, one month after the laser-induced ocular hypertension. In conclusion, we report here for the first time that ocular hypertension is associated with transient major dynamic changes in retinal cholesterol metabolism.

Alterations of cholesterol metabolism have been described for many neurodegenerative pathologies, such as Alzheimer's disease in the brain and age-related macular degeneration in the retina. Recent evidence suggests that glaucoma, which is characterized by the progressive death of retinal ganglion cells, could also be associated with disruption of cholesterol homeostasis. In the present study we characterized cholesterol metabolism in a rat model of laser-induced intraocular hypertension, the main risk factor for glaucoma. Sterol levels were measured using gas-chromatography and cholesterol-related gene expression using quantitative RT-PCR at various time-points. As early as 18 hours after the laser procedure, genes implicated in cholesterol biosynthesis and uptake were upregulated (+49% and +100% for HMG-CoA reductase and LDLR genes respectively, vs. naive eyes) while genes involved in efflux were downregulated (-26% and -37% for ApoE and CYP27A1 genes, respectively). Cholesterol and precursor levels were consecutively elevated 3 days post-laser (+14%, +40% and +194% for cholesterol, desmosterol and lathosterol, respectively). Interestingly, counter-regulatory mechanisms were transcriptionally activated following these initial dysregulations, which were associated with the restoration of retinal cholesterol homeostasis, favorable to ganglion cell viability, one month after the laser-induced ocular hypertension. In conclusion, we report here for the first time that ocular hypertension is associated with transient major dynamic changes in retinal cholesterol metabolism.

Oxidative stress is a harmful effect induced on the skin by polycyclic aromatic hydrocarbons (PAH), including benzo[a]pyrene (BaP) air pollutants. This effect is amplified by the additive damaging effect of the sun, especially through the UVA light component. Besides being one of the main compounds that make up air pollution, BaP can also be found in tar, tobacco smoke, and various foods. In addition to its direct carcinogenic potential, BaP can act as a photosensitizer absorbing sunlight in the UVA range and thus generating ROS and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Fernblock® (FB) is an aqueous extract from the leaves of Polypodium leucotomos that has been proven to exert photoprotective and antioxidant effects on skin cells. In this study, we evaluate the potential of FB to prevent the damage induced by a combination of BaP and UVA light on human keratinocyte and mouse melanocyte cell lines (HaCaT and B16-F10, respectively). In particular, we have analyzed the capacity of FB to counteract the alterations caused on cellular morphology, viability, oxidative stress and melanogenic signaling pathway activation. Our data indicate that FB prevented cell damage and reduced oxidative stress and melanogenic signaling pathway activation caused by a combination of BaP and UVA light irradiation. Altogether, our findings support the fact that FB is able to prevent skin damage caused by the exposure to a combination of UVA and the air pollutant BaP.

Review of the book: El léxico de los documentos del monasterio de San Salvador de Oña (siglos X-XIII).

Exposure to sun and especially to ultraviolet radiation (UVR) exerts well known detrimental effects on skin which are implicated in malignancy. UVR induces production of cyclobutane pyrimidine dimers (CPDs), immediately during exposure and even hours after the exposure, these latter being called dark-CPDs, as consequence of the effects of different reactive species that are formed. Fernblock® (FB), an aqueous extract of Polypodium leucotomos, has proven to have photoprotective and antioxidant effects on skin. The aim of our work was to investigate the potential photoprotective effect of FB against dark-CPD formation. Murine melanocytes (B16-F10) were exposed to UVA radiation and the production of dark-CPDs and different reactive oxygen and nitrogen species (ROS and RNS) was measured. Significant dark-CPD formation could be seen at 3 h after UVA irradiation, which was inhibited by the pre-treatment of cells with FB. Formation of nitric oxide, superoxide and peroxynitrite was increased after irradiation, consistent with the increased CPD formation. FB successfully reduced the production of these reactive species. Hence, these results show how dark-CPDs are formed in UVA irradiated melanocytes, and that FB acts as a potential antioxidant and ROS scavenger, preventing the DNA damage induced by sun exposure.

El trabajo aborda el asunto del neutro de materia en el castellano desde una perspectiva diacrónica. La distinción continuo / discontinuo en el género de los sustantivos implica concordancias aparentemente anómalas, bien con el adjetivo (lana blanco), bien con otros elementos del decurso (la lana lo vendieron). El fenómeno, extendido por buena parte de ambas mesetas, se ha estudiado principalmente desde un punto de vista sincrónico. En este trabajo se aborda su estudio a partir de los materiales de un corpus de documentos notariales inéditos del Siglo de Oro, el CorLexIn, que nos proporciona abundantes casos así como la posibilidad de localizarlos geográficamente en el pasado.

A spectral analysis of the time series corresponding to the main monthly precipitation regimes of the Iberian Peninsula was performed using two methods, the Multi-Taper Method and Monte Carlo Singular Spectrum Analysis. The Multi-Taper Method gave a preliminary view of the presence of signals in some of the time series. Monte Carlo Singular Spectrum Analysis discriminated between potential oscillations and noise. From the results of the two methods it is concluded that there exist three significant quasi-oscillations at the 95% level of confidence: a 5.0 year quasi-oscillation and a long-term trend in the Atlantic pattern of March, a 3.2 year quasi-oscillation in the Cantabrian pattern of January, and a 4.0 year quasi-oscillation in the Catalonian pattern of February. These quasi-oscillations might be related to climatic variations with similar periodicities over the North Atlantic Ocean. The possible simultaneity of high values of precipitation generated by the significant quasi-oscillations and high sea–level pressures was studied by means of composite maps. It was found that high values of precipitation generated by the oscillations of the Atlantic patterns of January and March exist simultaneously with a specific high pressure structure over the North Atlantic Ocean, that allow cyclonic perturbations to cross the Iberian Peninsula. During the non-wet years, this high pressure structure moves northwards, keeping the track of the low pressure centers to the north, far from the Iberian Peninsula. On the other hand, high values of precipitation generated by the oscillation of the Cantabrian pattern of January exist simultaneously with a high pressure structure over the Galicia region and the Cantabrian Sea, that allow a northerly flow over the region. Also, a positive trend in the NAO index for March has been found, starting in the sixties, which is not evident for other winter months. This trend agrees with the decreasing trend found in the March Atlantic pattern.Key words. Meteorology and atmospheric dynamics (climatology; precipitation) Oceanography: general (climate and interannual variability)

En este artículo presentamos un estado actual de la cuestión en relación a la posicióncronocultural de las denominadas industrias con piezas de Bertonne en el seno delPaleolítico superior de Europa occidental. Atribuidas en un primer momento alAuriñaciense (Leyssalles y Noone 1949), más tarde al Protosolutrense (Arambourou1970), estas industrias han sido recientemente adscritas al Badeguliense basándose en laasociación de las piezas de Bertonne a uno de los útiles más evocadores de esta culturamaterial, la raclette (Lenoir 2000a y b). Esta asociación ha sido en efecto señalada endiferentes niveles del yacimiento de Laugerie-Haute Est (Dordoña. Francia) uno de loscuales arroja una datación de 17 040 ± 440 BP (Ly-973 ; Évin et al. 1976: 80). Esta esla única datación radiocarbónica disponible actualmente para estas industrias. Por otrolado, el empleo de la presión, recientemente reconocido para la obtención de hojitas apartir de piezas de Bertonne y el retoque de útiles sobre lascas delgadas, junto a lapresencia anecdótica de piezas foliáceas son, a nuestro entender, otros tantos elementosque estas industrias comparten con las del Solutrense y que parecen evidenciar laaparición de industrias con piezas de Bertonne antes del 17 000 BP, a caballo entre elSolutrense y el Badeguliense.In this article we present a overview of current knowledge regarding the chronocultural position of industries with La Bertonne pieces within the Western European Upper Paleolithic. Initially attributed to the Aurignacian (Leyssalles and Noone 1949) and then to the Proto-Solutrean (Arambourou 1970), these industries are now attributed to the Badegoulian due to the association of La Bertonne pieces with one of the most typical tools of this material culture, the raclette (Lenoir 2000a and b). This association has indeed been pointed out in several levels at the site of Laugerie-Haute Est (France, Dordogne), one of which has been dated to 17040 ± 440 BP (Ly-973; Évin et al. 1976: 80). This is the only available radiocarbon date for these industries. In addition, the use of pressure flaking, recently identified for the detachment of bladelets from La Bertonne pieces and to create retouched tools on thin flakes, and the sporadic presence of foliate pieces, are, in our view, elements that these industries share with the Solutrean. They suggest the appearance of La Bertonne industries somewhat earlier than 17000 BP at the transition between the Solutrean and the Badegoulian.

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