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IntroductionPancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a poor survival outcome. Predicting patient survival allows physicians to tailor treatments to specific individuals. Thus, a simple and cost-effective prognosis model is sorely needed.MethodsThis retrospective study assesses the prognostic value of blood biomarkers in advanced and metastatic PDAC patients (n=96) from Spain. Cut-off points for hematological parameters were calculated and correlated with overall survival (OS) using Kaplan-Meier, log-rank test, robust Cox proportional hazards and logistic regressions.ResultsIn univariate analysis, individuals with low levels of GGT, LDH, ALP, leukocyte-, neutrophil- and monocyte counts showed significantly longer survival than patients with higher levels. In multivariate analysis, lower levels of GGT (HR (95%CI), 2.734 (1.223-6.111); p=0.014), LDH (HR (95%CI), 1.876 (1.035-3.400); p=0.038) and monocyte count (HR (95%CI), 1.657 (1.095-2.506); p = 0.017) remained significantly beneficial. In consequence, we propose a prognostic model based on logistic regression (AUC=0.741) of these three biomarkers as a pioneer tool to estimate OS in PDAC.ConclusionThis study has demonstrated that the joint use of GGT (

Tumor related angiogenesis is an attractive target in cancer therapeutic research due to its crucial role in tumor growth, invasion, and metastasis. Different agents were developed aiming to inhibit this process; however they had limited success. Cancer vaccines could be a promising tool in anti-cancer/anti-angiogenic therapy. Cancer vaccines aim to initiate an immune response against cancer cells upon presentation of tumor antigens which hopefully will result in the eradication of disease and prevention of its recurrence by inducing an efficient and long-lasting immune response. Different vaccine constructs have been developed to achieve this and they could include either protein-based or nucleic acid-based vaccines. Nucleic acid vaccines are simple and relatively easy to produce, with high efficiency and safety, thus prompting a high interest in the field. Different DNA vaccines have been developed to target crucial regulators of tumor angiogenesis. Most of them were successful in pre-clinical studies, mostly when used in combination with other therapeutics, but had limited success in the clinic. Apparently, different tumor evasion mechanisms and reduced immunogenicity still limit the potential of these vaccines and there is plenty of room for improvement. Nowadays, mRNA cancer vaccines are making remarkable progress due to improvements in the manufacturing technology and represent a powerful potential alternative. Apart from their efficiency, mRNA vaccines are simple and cheap to produce, can encompass multiple targets simultaneously, and can be quickly transferred from bench to bedside. mRNA vaccines have already accomplished amazing results in cancer clinical trials, thus ensuring a bright future in the field, although no anti-angiogenic mRNA vaccines have been described yet. This review aims to describe recent advances in anti-angiogenic DNA vaccine therapy and to provide perspectives for use of revolutionary approaches such are mRNA vaccines for anti-angiogenic treatments.

Abstract Previous studies suggest that meridional migrations of the Antarctic Circumpolar Current may have altered wind-driven upwelling and carbon dioxide degassing in the Southern Ocean during past climate transitions. Here, we report a quantitative and continuous record of the Antarctic Circumpolar Current latitude over the last glacial-interglacial cycle, using biomarker-based reconstructions of surface layer temperature gradient in the southern Indian Ocean. The results show that the Antarctic Circumpolar Current was more equatorward during the ice ages and shifted ~6° poleward at the end of glacial terminations, consistent with Antarctic Circumpolar Current migration playing a role in glacial-interglacial atmospheric carbon dioxide change. Comparing the temporal evolution of the Antarctic Circumpolar Current mean latitude with other observations provides evidence that Earth’s axial tilt affects the strength and latitude range of Southern Ocean wind-driven upwelling, which may explain previously noted deviations in atmospheric carbon dioxide concentration from a simple correlation with Antarctic climate.

Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.

Abstract Studies have suggested that cancerous tissue has a lower 15N/14N ratio than benign tissue. However, human data have been inconclusive, possibly due to constraints on experimental design. Here, we used high-sensitivity nitrogen isotope methods to assess the 15N/14N ratio of human breast, lung, and kidney cancer tissue at unprecedented spatial resolution. In lung, breast, and urothelial carcinoma, 15N/14N was negatively correlated with tumor cell density. The magnitude of 15N depletion for a given tumor cell density was consistent across different types of lung cancer, ductal in situ and invasive breast carcinoma, and urothelial carcinoma, suggesting similar elevations in the anabolism-to-catabolism ratio. However, tumor 15N depletion was higher in a more aggressive metaplastic breast carcinoma. These findings may indicate the ability of certain cancers to more effectively channel N towards growth. Our results support 15N/14N analysis as a potential tool for screening biopsies and assessing N metabolism in tumor cells.

The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55–75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [β-coefficient (95% confidence interval) p = 0.002. >9 h vs. 7–9 h: −1.1 (−2.0 to −0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [β-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night.

Melasma is a pathology with multifactorial causes that results in hyperpigmentation of sun-exposed areas, particularly facial skin. New treatments targeting the different factors regulating this condition need to be effective with and have limited adverse effects. Here, we describe a novel combination of two natural compounds (apigenin and phloretin) that has synergistic effects regulating melanogenesis in vitro. Both compounds inhibit Wnt-stimulated melanogenesis and induce autophagy in melanocytes. Apigenin induces DKK1, a Wnt pathway inhibitor, and reduces VEGF, a melanogenesis and proangiogenic factor, in fibroblasts. Moreover, apigenin induces miR-675, a melanogenesis inhibitor miRNA that is reduced in melasma skin in melanocytes. Both compounds showed senomorphic effects by regulating extracellular-matrix-related genes in senescent fibroblasts. Topical application of the compounds also showed significant melanin reduction in a reconstructed human epidermis after 7 days. Thus, the combination of apigenin and phloretin shows promising results as an effective topical treatment of skin hyperpigmentation conditions.

Background: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. Methods: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. Results: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). Conclusions: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

Abstract There is limited understanding of temperature and atmospheric circulation changes that accompany an Atlantic Meridional Overturning Circulation (AMOC) slowdown beyond the North Atlantic realm. A Peqi’in Cave (Israel) speleothem dated to the last interglacial period (LIG), 129–116 thousand years ago (ka), together with a large modern rainfall monitoring dataset, serve as the base for investigating past AMOC slowdown effects on the Eastern Mediterranean. Here, we reconstruct LIG temperatures and rainfall source using organic proxies (TEX86) and fluid inclusion water d-excess. The TEX86 data show a stepwise cooling from 19.8 ± 0.2° (ca. 128–126 ka) to 16.5 ± 0.6 °C (ca. 124–123 ka), while d-excess values decrease abruptly (ca. 126 ka). The d-excess shift suggests that rainfall was derived from more zonal Mediterranean air flow during the weakened AMOC interval. Decreasing rainfall d-excess trends over the last 25 years raise the question whether similar atmospheric circulation changes are also occurring today.

La represión de la diversidad sexual anterior al Orgullo es el tema de un creciente número de películas documentales estrenadas en la segunda década del siglo XXI, entre las que se encuentra La memoria homosexual (2019) de Espino Diéguez. Un análisis de este documental como caso de estudio revela que las estrategias enunciativas del género documental, tales como los modos expositivo y participativo, resultan aptas para la recuperación de una memoria audiovisual queer capaz de rescatar las experiencias de la vergüenza y el oprobio desde perspectivas más claramente alineadas con el Orgullo. Este tipo de recuperación de la memoria establece una doble temporalidad, ya que el relato de las experiencias memorializadas participa de las premisas discursivas de la coyuntura histórica desde la que se enuncia, caracterizada tanto por la hegemonía de la memoria democrática como por procesos de hipernormalización de la diversidad sexual.

Enamel-bound nitrogen isotopes in modern and fossil mammal teeth preserve dietary and trophic level information. This novel geochemical archive can be used to reconstruct trophic niche in ancient ecosystems.

Background: There is a strong interest in designing new scaffolds for their potential application in tissue engineering and regenerative medicine. The incorporation of functionalization molecules can lead to the enhancement of scaffold properties, resulting in variations in scaffold compatibility. Therefore, the efficacy of the therapy could be compromised by the foreign body reaction triggered after implantation.Methods: In this study, the biocompatibilities of three scaffolds made from an alginate–chitosan combination and functionalized with gold nanoparticles (AuNp) and alginate-coated gold nanoparticles (AuNp + Alg) were evaluated in a subcutaneous implantation model in Wistar rats. Scaffolds and surrounding tissue were collected at 4-, 7- and 25-day postimplantation and processed for histological analysis and quantification of the expression of genes involved in angiogenesis, macrophage profile, and proinflammatory (IL-1β and TNFα) and anti-inflammatory (IL-4 and IL-10) cytokines.Results: Histological analysis showed a characteristic foreign body response that resolved 25 days postimplantation. The intensity of the reaction assessed through capsule thickness was similar among groups. Functionalizing the device with AuNp and AuNp + Alg decreased the expression of markers associated with cell death by apoptosis and polymorphonuclear leukocyte recruitment, suggesting increased compatibility with the host tissue. Similarly, the formation of many foreign body giant cells was prevented. Finally, an increased detection of alpha smooth muscle actin was observed, showing the angiogenic properties of the elaborated scaffolds.Conclusion: Our results show that the proposed scaffolds have improved biocompatibility and exhibit promising potential as biomaterials for elaborating tissue engineering constructs.

Introduction: Perinatal asphyxia (PA) represents a major problem in perinatology and may cause visual losses, including blindness. We, and others, have shown that hypothermia prevents retinal symptoms associated to PA. In the present work, we evaluate whether a hypothermia mimetic small molecule, zr17-2, has similar effects in the context of PA.Methods: Four experimental groups were studied in male rats: Naturally born rats as controls (CTL), naturally born rats injected s.c. with 50 µL of 330 nmols/L zr17-2 (ZR), animals that were exposed to PA for 20 min at 37°C (PA), and rats that were exposed to PA and injected with zr17-2 (PA-ZR). Forty-five days after treatment, animals were subjected to electroretinography. In addition, morphological techniques (TUNEL, H&E, multiple immunofluorescence) were applied to the retinas.Results: A reduction in the amplitude of the a- and b-wave and oscillatory potentials (OP) of the electroretinogram (ERG) was detected in PA animals. Treatment with zr17-2 resulted in a significant amelioration of these parameters (p < 0.01). In PA animals, a large number of apoptotic cells was found in the GCL. This number was significantly reduced by treatment with the small molecule (p < 0.0001). In a similar way, the thickness of the inner retina and the intensity of GFAP immunoreactivity (gliosis) increased in PA retinas (p < 0.0001). These parameters were corrected by the administration of zr17-2 (p < 0.0001). Furthermore, injection of the small molecule in the absence of PA did not modify the ERG nor the morphological parameters studied, suggesting a lack of toxicity.Discussion: In conclusion, our results indicate that a single s.c. injection of zr17-2 in asphyctic neonates may provide a novel and efficacious method to prevent the visual sequelae of PA.

Abstract Lake sediment records from Holzmaar and the infilled maar of Auel (Eifel, Germany) are used to reconstruct landscape changes and megafauna abundances. Our data document a forested landscape from 60,000 to 48,000 yr b2k and a stepwise vegetation change towards a glacial desert after 26,000 yr b2k. The Eifel landscape was continuously inhabited from 48,000 to 9000 yr b2k by large mammals, documented by the presence of spores of coprophilous fungi from Sordaria and Sporormiella fungi that grow on fecal remains of the megafauna. Megafauna reached higher numbers during cold stadial climates but was present also during the warmer interstadials. Highest abundance was at 56,500/48,500/38,500/33,000/27,000/21,000/16,200/14,000 yr b2k, i.e. under different climate regimes. Some of these dates were associated with clear human presence, which indicates that megafauna was not overkilled by humans. In contrast, human presence could quite likely have been stimulated by the abundant food supply. Megafauna presence decreased significantly when tree abundance increased during interstadials. The Megafauna disappeared finally at 11,400 yr b2k with the development of the early Holocene forest cover, which appears to be the most important threshold for megafauna presence.

The treatment of stabilized leachates with high refractory organic matter content, which are over 10 years old, presents a challenge. This study explored the potential of electro-coagulation (EC) and electro-oxidation (EO) treatment systems to address this issue. The objective of this study was to investigate the phytotoxicity of the proposed treatment system on seed growth and examine possible relationships between phytotoxicity results and the characterization of leachates, effluents, soil, and radicles. Phytotoxicity tests were conducted on seeds of Lactuca sativa, Cucumis sativus, and Phaseolus vulgaris, using Inductively Coupled Plasma-Optical analysis. The evolution of organic matter was monitored by fractionating the chemical oxygen demand (COD) and humic substances. The biodegradability index increased from 0.094 in raw leachate to 0.26 and 0.48 with EC and EO, respectively. Removal rates of 82%, 86%, 99%, and 81% were achieved for COD, dissolved organic carbon, color, and ammoniacal nitrogen, respectively. The biodegradable COD increased from 26% in raw leachate to 39% in the EC process and 58% in the EO process effluent. The proposed treatment system successfully broke the aromatic structures of the humic substances present in the raw leachate, thereby increasing the content of biodegradable material. Phytotoxicity tests revealed that the proposed treatment system significantly reduced the phytotoxicity of the generated effluents.

Introducción: La lesión traumática de la médula espinal es la principal causa de discapacidad motora en el mundo, y representa una prioridad para la Organización Mundial de la Salud. Se estudió, a nivel estructural y bioquímico, el efecto de la hipotermia sobre la expresión de la CIRBP (proteína activada por frío) en el asta anterior de la médula de ratas Sprague-Dawley albinas macho de 60 días, planteándola como terapéutica posible. Materiales y Métodos: Se dividió a 24 ratas en dos grupos: normotermia a 24 °C (n = 6) e hipotermia a 8 °C (n = 18), durante 180 min, sacrificadas a las 12, 24 y 48 h después del tratamiento. Se utilizó Western blot e inmunohistoquímica para la CIRBP. Resultados: Se observó un aumento progresivo de la expresión de la CIRBP de 12 a 48 h en las motoneuronas del asta anterior. Los valores fueron estadísticamente significativos entre los grupos de 24 h y 48 h comparados con los de los controles. Conclusiones: Este modelo experimental resultó eficaz, accesible y económico para generar hipotermia sistémica y abre un abanico de estrategias terapéuticas. El aumento en la expresión de las proteínas inducibles por frío en la médula espinal de ratas permite, por primera vez, estudiar el beneficio que aporta la hipotermia a nivel molecular, lo que resulta de suma importancia para estudios de terapéuticas en las lesiones medulares.

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55–75 years (men) and 60–75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality.

Introducción: Los ensayos de hipotermia sistémica en murinos son costosos, debido a la complejidad de los sistemas. El objetivo de este estudio fue evaluar si el modelo de hipotermia sistémica exógena utilizado en nuestro laboratorio para la hipotermia ocular es útil para reducir significativamente la temperatura de la médula espinal en ratas adultas. Materiales y Métodos: Se utilizaron 36 ratas Sprague-Dawley albinas macho de 60 días, distribuidas en dos grupos: grupo normotermia a 24 °C (n = 18) y grupo hipotermia (n = 18) en cámara fría a 8 °C durante 180 minutos. Resultados: La temperatura rectal promedio fue de 37,71 ± 0,572 °C en el grupo normotermia y 34,03 ± 0,250 °C en el grupo hipotermia (p

Introduction: Ocular and periocular traumatisms may result in loss of vision. Our previous work showed that therapeutic hypothermia prevents retinal damage caused by traumatic neuropathy. We also generated and characterized small molecules that elicit the beneficial effects of hypothermia at normal body temperature. Here we investigate whether one of these mimetic molecules, zr17-2, is able to preserve the function of eyes exposed to trauma.Methods: Intraorbital optic nerve crush (IONC) or sham manipulation was applied to Sprague-Dawley rats. One hour after surgery, 5.0 µl of 330 nmol/L zr17-2 or PBS, as vehicle, were injected in the vitreum of treated animals. Electroretinograms were performed 21 days after surgery and a- and b-wave amplitude, as well as oscillatory potentials (OP), were calculated. Some animals were sacrificed 6 days after surgery for TUNEL analysis. All animal experiments were approved by the local ethics board.Results: Our previous studies showed that zr17-2 does not cross the blood-ocular barrier, thus preventing systemic treatment. Here we show that intravitreal injection of zr17-2 results in a very significant prevention of retinal damage, providing preclinical support for its pharmacological use in ocular conditions. As previously reported, IONC resulted in a drastic reduction in the amplitude of the b-wave (p < 0.0001) and OPs (p < 0.05), a large decrease in the number of RGCs (p < 0.0001), and a large increase in the number of apoptotic cells in the GCL and the INL (p < 0.0001). Interestingly, injection of zr17-2 largely prevented all these parameters, in a very similar pattern to that elicited by therapeutic hypothermia. The small molecule was also able to reduce oxidative stress-induced retinal cell death in vitro.Discussion: In summary, we have shown that intravitreal injection of the hypothermia mimetic, zr17-2, significantly reduces the morphological and electrophysiological consequences of ocular traumatism and may represent a new treatment option for this cause of visual loss.

The analyses of the stable isotope ratios of carbon (δ13C), nitrogen (δ15N), and oxygen (δ18O) in animal tissues are powerful tools for reconstructing the feeding behavior of individual animals and characterizing trophic interactions in food webs. Of these biomaterials, tooth enamel is the hardest, most mineralized vertebrate tissue and therefore least likely to be affected by chemical alteration (i.e., its isotopic composition can be preserved over millions of years), making it an important and widely available archive for biologists and paleontologists. Here, we present the first combined measurements of δ13C, δ15N, and δ18O in enamel from the teeth of modern fauna (herbivores, carnivores, and omnivores) from the well-studied ecosystem of Gorongosa National Park (GNP) in central Mozambique. We use two novel methods to produce high-precision stable isotope enamel data: (i) the “oxidation-denitrification method,” which permits the measurement of mineral-bound organic nitrogen in tooth enamel (δ15Nenamel), which until now, has not been possible due to enamel’s low organic content, and (ii) the “cold trap method,” which greatly reduces the sample size required for traditional measurements of inorganic δ13Cenamel and δ18Oenamel (from ≥0.5 to ≤0.1 mg), permitting analysis of small or valuable teeth and high-resolution serial sampling of enamel. The stable isotope results for GNP fauna reveal important ecological information about the trophic level, dietary niche, and resource consumption. δ15Nenamel values clearly differentiate trophic level (i.e., carnivore δ15Nenamel values are 4.0‰ higher, on average, than herbivores), δ13Cenamel values distinguish C3 and/or C4 biomass consumption, and δ18Oenamel values reflect local meteoric water (δ18Owater) in the park. Analysis of combined carbon, nitrogen, and oxygen stable isotope data permits geochemical separation of grazers, browsers, omnivores, and carnivores according to their isotopic niche, while mixed-feeding herbivores cannot be clearly distinguished from other dietary groups. These results confirm that combined C, N, and O isotope analyses of a single aliquot of tooth enamel can be used to reconstruct diet and trophic niches. Given its resistance to chemical alteration, the analysis of these three isotopes in tooth enamel has a high potential to open new avenues of research in (paleo)ecology and paleontology.

Hemorrhagic stroke remains an important health challenge. Adrenomedullin (AM) is a vasoactive peptide with an important role in cardiovascular diseases, including stroke. Serum AM and nitrate–nitrite and S-nitroso compounds (NOx) levels were measured and compared between healthy volunteers (n = 50) and acute hemorrhagic stroke patients (n = 64). Blood samples were taken at admission (d0), 24 h later (d1), and after 7 days or at the time of hospital discharge (d7). Neurological severity (NIHSS) and functional prognosis (mRankin) were measured as clinical outcomes. AM levels were higher in stroke patients at all times when compared with healthy controls (p < 0.0001). A receiving operating characteristic curve analysis identified that AM levels at admission > 69.0 pg/mL had a great value as a diagnostic biomarker (area under the curve = 0.89, sensitivity = 80.0%, specificity = 100%). Furthermore, patients with a favorable outcome (NIHSS ≤ 3; mRankin ≤ 2) experienced an increase in AM levels from d0 to d1, and a decrease from d1 to d7, whereas patients with unfavorable outcome had no significant changes over time. NOx levels were lower in patients at d0 (p = 0.04) and d1 (p < 0.001) than in healthy controls. In conclusion, AM levels may constitute a new diagnostic and prognostic biomarker for this disease, and identify AM as a positive mediator for hemorrhagic stroke resolution.

Abstract Fossil‐bound organic material holds great potential for the reconstruction of past changes in nitrogen (N) cycling. Here, with a series of laboratory experiments, we assess the potential effect of oxidative degradation, fossil dissolution, and thermal alteration on the fossil‐bound N isotopic composition of different fossil types, including deep and shallow water scleractinian corals, foraminifera, diatoms and tooth enamel. Our experiments show that exposure to different oxidizing reagents does not significantly affect the N isotopic composition or N content of any of the fossil types analyzed, demonstrating that organic matter is well protected from changes in the surrounding environment by the mineral matrix. In addition, we show that partial dissolution (of up to 70%–90%) of fossil aragonite, calcite, opal, or enamel matrixes has a negligible effect on the N isotopic composition and N content of the fossils. These results suggest that the isotopic composition of fossil‐bound organic material is relatively uniform, and also that N exposed during dissolution is lost without significant isotopic discrimination. Finally, our heating experiments show negligible changes in the N isotopic composition and N content of all fossil types at 100°C. At 200°C and hotter, any N loss and associated nitrogen isotope changes appear to be directly linked to the sensitivity of the mineral matrix to thermal stress, which depends on the biomineral type. These results suggest that, so long as high temperature does not compromise the mineral structure, the biomineral matrix acts as a closed system with respect to N, and the N isotopic composition of the fossil remains unchanged.

This paper aims to identify potential explanatory variables of the entrepreneurial orientation and innovation capacity (EO-IC) of family enterprises (FEs) through a comparative study of family businesses in Spain and Latin America. The innovation literature reports a paradigm shift whereby the dynamic boost provided by corporate governance and productivity is playing an increasing role as a driver of EO-IC and sustainable competitive advantage. This issue acquires particular relevance in the ase of family firms, where entrepreneurial and innovation capacities are characteristically hampered by socio-emotional and risk-aversion factors. We construct a panel of data on 182 large family enterprises (1,820 observations) domiciled in Argentina, Brazil, Chile, Colombia, Mexico, Peru, Uruguay and Spain, drawing on the Thomson Onebanker and ORBIS databases for the period 2008-2018. The results reveal the emergence of new explanatory variables for the structure of the family-firm EO-IC framework, some related to productivity; others more basically to corporate governance. They also show that, in Latin America, the use of business efficiency (productivity) factors in the planning and potentiation of EO-IC by family firms is hampered by the institutional (legal, regulatory, labour and educational) environment, where traditional factors such as firm size and ownership concentration are more relevant. In the Spanish case, however, the evidence points to a transition from traditional inputs towards business efficiency and productivity-related factors.

Sanitary landfill leachate was treated by chemical precipitation and the potential use of mixtures of the chemical precipitation sludge (CPS) generated and natural soil to cover the solid waste at sanitary landfills was evaluated. Tests were performed with soils having 0, 5 and 10% CPS, and the organic matter, pH, compaction, hydraulic conductivity, particle-size, liquid limit, plastic limit, and plasticity index were determined. It was found that leaching increased with CPS concentration, as well as the fine particles content in the soil, which reduced the hydraulic conductivity. pH was the most affected parameter, with values of 7.03, 7.12, and 11.46 for 0, 5 and 10% CPS, respectively. However, at 5% CPS, biodegradability was favored without a significant increase in the leaching process, showing that CPS can be used as temporary cover material, without adversely affecting the landfill system, being an eco-innovative solution for the final disposal of the sludge.

The presence of refractory compounds in stabilized leachates makes treatment complex. In leachate treatment systems, the lack of data on the characterization of leachates and effluents makes it difficult to track and explain the evolution of organic matter. In this study, the fractionation of chemical oxygen demand (COD) and humic substances, including humic acids (HA) and fulvic acids (FA), in addition to the application of spectroscopic techniques (Fourier transform infrared and ultraviolet–visible spectroscopy), were used to solve this data gap. A treatment system was proposed: electro-coagulation (EC) and electro-oxidation (EO). Optimal conditions (maximum COD removal) were EC, I: 4.3 A, stirring: 120 revolutions per minute, and pH: 7; EO, added NaCl: 1.0 g L−1, distance between electrodes: 0.75 cm, I: 2 A, and pH: 7. Under optimal conditions COD, HA, and FA % removals were achieved: EC: 64, 69, and 63; EO: 83, 40, and 55; respectively. In EC, the % of biodegradable COD increased from 26 to 39 and in EO it increased from 39 to 58. The biodegradability index increased from 0.094 to 0.26 with EC and reached 0.46 with EO. The generated data allowed us to establish the transformations of organic matter in the process, which was useful for understanding the processes and functioning as a tool for improving treatment systems.

A Southern Ocean influences on the carbon cycle is considered a key component of deglacial changes. Here, the authors show spatial differences in glacial Southern Ocean carbon storage that dissipated rapidly 14.6 kyr ago, revealing a South Indian Ocean contribution to rapid deglacial atmospheric CO2 increases.

Continuous illumination induces the degeneration of photoreceptors. This animal model of light-induced retinal degeneration resembles many characteristics of human degenerative diseases of the outer retina, such as age-related macular degeneration. This work aimed to evaluate the potential neuroprotective effect of the modulation of adenosine A2A receptor in the model of light-induced retinal degeneration. Sprague-Dawley rats were intravitreally injected in the right eye with either CGS 21680, an adenosine A2A receptor agonist, or SCH 58261, an adenosine A2A receptor antagonist. Contralateral eyes were injected with respective vehicles as control. Then, rats were subjected to continuous illumination (12,000 lux) for 24 h. Retinas were processed by glial fibrillary acidic protein (GFAP) immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) technique, Western blotting (WB), and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Another group of rats was subjected to functional studies by electroretinography. Animals treated with CGS21680 showed a significant increase of apoptotic nuclei in the outer nuclear layer and a significant increase of GFAP immunoreactive area of the retinas but did not alter WB nor electroretinography results. qRT-PCR showed that CGS 21680 significantly increased the expression of interleukin-1β. On the opposite, SCH 58261 significantly decreased apoptotic nuclei in the outer nuclear layer and GFAP immunoreactive area of the retinas. It also significantly decreased GFAP and activated caspase-3 levels as measured by WB and preserved retinal function, as treated eyes showed significantly greater amplitudes of a- and b-waves and oscillatory potentials. qRT-PCR revealed that SCH 58261 significantly decreased the expression of tumor necrosis factor-α. These results show that the blockade of the A2A receptor before the start of the pathogenic process is neuroprotective, as it prevents light-induced retinal damage. The use of A2A receptor antagonists deserves to be evaluated in retinal degenerative diseases.

The production of biofuels, such as bioethanol from lignocellulosic biomass, is an important task within the sustainable energy concept. Understanding the metabolism of ethanologenic microorganisms for the consumption of sugar mixtures contained in lignocellulosic hydrolysates could allow the improvement of the fermentation process. In this study, the ethanologenic strain Escherichia coli MS04 was used to ferment hydrolysates from five different lignocellulosic agroindustrial wastes, which contained different glucose and xylose concentrations. The volumetric rates of glucose and xylose consumption and ethanol production depend on the initial concentration of glucose and xylose, concentrations of inhibitors, and the positive effect of acetate in the fermentation to ethanol. Ethanol yields above 80% and productivities up to 1.85 gEtOH/Lh were obtained. Furthermore, in all evaluations, a simultaneous co-consumption of glucose and xylose was observed. The effect of deleting the xyIR regulator was studied, concluding that it plays an important role in the metabolism of monosaccharides and in xylose consumption. Moreover, the importance of acetate was confirmed for the ethanologenic strain, showing the positive effect of acetate on the co-consumption rates of glucose and xylose in cultivation media and hydrolysates containing sugar mixtures.

Non-specific low back pain (NSLBP) affects many people and represents a high cost for health care. Manual pressure release of myofascial trigger points is used to treat NSLBP and is very effective but difficult to standardize since it is provided by different therapists, which also suffer musculoskeletal complications from this highly repetitive activity. A robot designed for this purpose may help in reducing these problems. Here, we present data from a two-arm, single-blinded, randomized controlled clinical trial evaluating the efficiency of a therapeutic massage robot (ADAMO) in reducing NSLBP (clinicaltrials.gov, registration number: NCT04882748). Forty-four patients were randomly distributed into the two arms of the study (robot vs. control). A physician filled the Oswestry disability index (ODI) before starting the treatment and at the end of it, in a blind fashion. In addition, patients filled a visual analogue scale (VAS) after each of the 10 treatment sessions. The ODI and the VAS were analyzed as the primary and secondary outcome measures. Both treatments (robot and control) resulted in a significantly lower ODI (p < 0.05). On the other hand, robot-treated patients significantly reduced their VAS levels (p = 0.0001) whereas control treatment did not reach statistical significance. Patients of both sexes obtained similar benefits from either treatment. Overweight patients (body mass index ≥ 25kg/m2) in the robot arm benefited more from the treatment (p = 0.008) than patients with normal weight. In conclusion, the ADAMO robot is, at least, as efficient as regular treatment in reducing low back pain, and may be more beneficial for specific patients, such as those with excessive weight.

Stroke remains an important health challenge. Here, we study whether circulating chemokine (C-C motif) ligand 5 (CCL5) levels may predict clinical outcomes for stroke patients. A total of 100 consecutive stroke patients (36 acute ischemic and 64 hemorrhagic) were admitted to the stroke unit. Clinical history data and monitoring parameters were recorded. Blood serum was collected at days 0, 1, and hospital discharge to measure CCL5 levels by ELISA. Infarct or hemorrhagic volume, neurological severity (NIHSS), and functional prognosis (mRankin scale) were measured as clinical outcomes. CCL5 levels were lower in patients with hemorrhagic stroke than in patients with acute ischemic stroke. No differences were found between females and males in both types of stroke. Ischemic stroke patients whose infarct volume grew had lower CCL5 levels at day 0. Levels of CCL5 in ischemic and hemorrhagic patients were not associated with more severe symptoms/worse prognosis (NIHSS > 3; mRankin > 2) at admission or at 3 months. CCL5 could be used as a diagnostic marker to distinguish between ischemic and hemorrhagic strokes. Furthermore, CCL5 levels could predict the infarct volume outcomes in ischemic patients.

The main aim of this research was to compare a bio-coagulant, organic coagulant, and a conventional coagulant applied to the treatment of leachates. Coagulant options were Stage 1 FeCl3, Stage 2 Polyamine, and Stage 3 Opuntia ficus mucilage (OFM). Optimal conditions for maximum chemical oxygen demand (COD) removal were determined by experimental data and Response Surface Methodology. The application of Multiple Criteria Decision Analysis using Multi-Criteria Matrix (MCM) was explored by evaluating the Coagulation–Flocculation processes. Maximum COD removal (%) and the best MCM scores (on a scale from 0 to 100) were: Stage 1: 69.2±0.9 and 48.50, Stage 2: 37.8±1.1 and 79.0, and Stage 3: 71.1±1.7, and 81.5. Maximum COD removal using FeCl3 and OFM was not statistically different (p 0.15 < 0.05). OFM extraction process was evaluated (yield 0.70 ± 1.17%, carbohydrate content 32.6 ± 1.18%). MCM allows the evaluation of additional technical aspects, besides oxygen COD removal, as well as economic aspects, permitting a more comprehensive analysis. Significant COD removals indicate that the use of OFM as a coagulant in the treatment of stabilized leachate was effective. Opuntia ficus cladodes, a residue, were used to treat another residue (leachates).

The fact that not all individuals exposed to the same environmental risk factors develop obesity supports the hypothesis of the existence of underlying genetic and epigenetic elements. There is suggestive evidence that environmental stimuli, such as dietary pattern, particularly during pregnancy and early life, but also in adult life, can induce changes in DNA methylation predisposing to obesity and related comorbidities. In this context, the DNA methylation marks of each individual have emerged not only as a promising tool for the prediction, screening, diagnosis, and prognosis of obesity and metabolic syndrome features, but also for the improvement of weight loss therapies in the context of precision nutrition. The main objectives in this field are to understand the mechanisms involved in transgenerational epigenetic inheritance, and featuring the nutritional and lifestyle factors implicated in the epigenetic modifications. Likewise, DNA methylation modulation caused by diet and environment may be a target for newer therapeutic strategies concerning the prevention and treatment of metabolic diseases.

Perinatal asphyxia (PA) can cause retinopathy and different degrees of visual loss, including total blindness. In a rat model of PA, we have previously shown a protective effect of hypothermia on the retina when applied simultaneously with the hypoxic insult. In the present work, we evaluated the possible protective effect of hypothermia on the retina of PA rats when applied immediately after delivery. Four experimental groups were studied: Rats born naturally as controls (CTL), animals that were exposed to PA for 20 min at 37°C (PA), animals exposed to PA for 20 min at 15°C (HYP), and animals that were exposed to PA for 20 min at 37°C and, immediately after birth, kept for 15 min at 8°C (HYP-PA). To evaluate the integrity of the visual pathway, animals were subjected to electroretinography at 45 days of age. Molecular (real time PCR) and histological (immunohistochemistry, immunofluorescence, TUNEL assay) techniques were applied to the eyes of all experimental groups collected at 6, 12, 24, and 48 h, and 6 days after birth. PA resulted in a significant reduction in the amplitude of the a- and b-wave and oscillatory potentials (OP) of the electroretinogram. All animals treated with hypothermia had a significant correction of the a-wave and OP, but the b-wave was fully corrected in the HYP group but only partially in the HYP-PA group. The number of TUNEL-positive cells increased sharply in the ganglion cell layer of the PA animals and this increase was significantly prevented by both hypothermia treatments. Expression of the cold-shock proteins, cold-inducible RNA binding protein (CIRP) and RNA binding motif protein 3 (RBM3), was undetectable in retinas of the CTL and PA groups, but they were highly expressed in ganglion neurons and cells of the inner nuclear layer of the HYP and HYP-PA groups. In conclusion, our results suggest that a post-partum hypothermic shock could represent a useful and affordable method to prevent asphyxia-related vision disabling sequelae.

Neurodegenerative diseases pose a major problem for developed countries, and stress has been identified as one of the main risk factors in the development of these disorders. Here, we have examined the protective properties against brain oxidative stress of two diets supplemented with 5% (w/w) of Agaricus bisporus (white button mushroom) or Agaricus bisporus brunnescens (Portobello mushroom) in mice. These diets did not modify the weight gain of the animals when compared to those fed with a regular diet, even after feeding on them for 15 weeks. The long-term modification of the microbiota after 12 weeks on the diets was investigated. At the phylum level, there was a large increase of Verrucomicrobia and a reduction of Cyanobacteria associated with the mushroom diets. No changes were observed in the Firmicutes/Bacteroidetes ratio, whose stability is a marker for a healthy diet. At the family level, three groups presented significant variations. These included Akkermansiaceae and Tannerellaceae, which significantly increased with both diets; and Prevotellaceae, which significantly decreased with both diets. These bacteria participate in the generation of microbiota-derived short-chain fatty acids (SCFAs) and provide a link between the microbiota and the brain. Mice subjected to restraint stress showed an upregulation of Il-6, Nox-2, and Hmox-1 expression; a reduction in the enzymatic activities of catalase and superoxide dismutase; and an increase in lipid peroxidation in their brains. All these parameters were significantly prevented by feeding for 3 weeks on the Agaricus-supplemented diets. In summary, the supplementation of a healthy diet with Agaricus mushrooms may significantly contribute to prevent neurodegenerative diseases in the general population.

Perinatal asphyxia (PA) is responsible for a large proportion of neonatal deaths and numerous neurological sequelae, including visual dysfunction and blindness. In PA, the retina is exposed to ischemia/reoxygenation, which results in nitric oxide (NO) overproduction and neurotoxicity. We hypothesized that methylene blue (MB), a guanylyl cyclase inhibitor, and free-radical scavenger currently used in the clinic, may block this pathway and prevent PA-induced retinal degeneration. Male rat pups were subjected to an experimental model of PA. Four groups were studied: normally delivered (CTL), normally delivered treated with 2 mg Kg-1 MB (MB), exposed to PA for 20 min at 37°C (PA), and exposed to PA and, then, treated with MB (PA-MB). Scotopic electroretinography performed 45 days after birth showed that PA animals had significant defects in the a- and b-waves and oscillatory potentials (OP). The same animals presented a significant increase in the thickness of the inner retina and a large number of TUNEL-positive cells. All these physiological and morphological parameters were significantly prevented by the treatment with MB. Gene expression analysis demonstrated significant increases in iNOS, MMP9, and VEGF in the eyes of PA animals, which were prevented by MB treatment. In conclusion, MB regulates key players of inflammation, matrix remodeling, gliosis, and angiogenesis in the eye and could be used as a treatment to prevent the deleterious visual consequences of PA. Given its safety profile and low cost, MB may be used clinically in places where alternative treatments may be unavailable.

Abstract We present the first nitrogen isotope (δ15N) measurements of planktic foraminifera, paleoceanographically important zooplankton, from the nutrient‐rich waters of the modern Southern Ocean. Foraminifera were collected from net tows in the Subantarctic and Polar Frontal Zones (SAZ and PFZ, respectively) south of Africa during winter 2015 and late summer 2016. In late summer, consistent with preferential uptake of 14N‐nitrate and the progressive, northward depletion of nitrate by phytoplankton across the Southern Ocean, foraminifer tissue and shell‐bound δ15N rise equatorward along with nitrate δ15N. However, foraminifer δ15N is ~3‰ lower than expected for heterotrophs relying on photosynthetic biomass generated directly from nitrate. This discrepancy appears to originate with the particulate organic N (PON) in late‐summer surface waters, the δ15N of which is lowered by ammonium recycling. In winter, when overall productivity and foraminifer production are reduced, foraminifer δ15N is higher (by 4.6 ± 0.8‰ for tissue and by 4.0 ± 1.5‰ for shell‐bound N compared to late summer) and exhibits no clear north‐south trend. These characteristics can also be explained by the feeding‐driven connection of foraminifera to PON, which is elevated in δ15N by net degradation in winter. Therefore, foraminifer δ15N is more closely tied to PON δ15N than to nitrate δ15N in the Southern Ocean mixed layer. Combining our isotope data with previously reported sediment trap fluxes from the western Pacific SAZ/PFZ suggests that, under modern conditions, the late‐summer ammonium recycling signal outweighs that of wintertime decomposition on the annually integrated δ15N of sinking foraminifera.

Hereditary hemorrhagic telangiectasia (HHT) is a rare disease characterized by vascular malformations and profuse bleeding. The disease is caused by mutations in the components of the BMP-9 receptor: endoglin (ENG) and activin receptor-like kinase 1 (ACVRL1) genes. Recently, we reported that HHT patients expressed higher serum levels of adrenomedullin (AM) than healthy volunteers; thus, we studied the expression of AM (by enzyme immunoassay, qRT-PCR, immunohistochemistry, and Western blotting) in mice deficient in either one of the receptor components to investigate whether these defects may be the cause of that elevated AM in patients. We found that AM expression is not affected by these mutations in a consistent pattern. On the contrary, in some organs (blood, lungs, stomach, pancreas, heart, kidneys, ovaries, brain cortex, hippocampus, foot skin, and microvessels), there were no significant changes, whereas in others we found either a reduced expression (fat, skin, and adrenals) or an enhanced production of AM (cerebellum and colon). These results contradict our initial hypothesis that the increased AM expression found in HHT patients may be due directly to the mutations, but open intriguing questions about the potential phenotypic manifestations of Eng and Acvrl1 mutants that have not yet been studied and that may offer, in the future, a new focus for research on HHT.

Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two bioactive peptides derived from the same precursor with several biological functions including vasodilation, angiogenesis, or anti-inflammation, among others. AM and PAMP are widely expressed throughout the gastrointestinal (GI) tract where they behave as GI hormones, regulating numerous physiological processes such as gastric emptying, gastric acid release, insulin secretion, bowel movements, or intestinal barrier function. Furthermore, it has been recently demonstrated that AM/PAMP have an impact on gut microbiome composition, inhibiting the growth of bacteria related with disease and increasing the number of beneficial bacteria such as Lactobacillus or Bifidobacterium. Due to their wide functions in the GI tract, AM and PAMP are involved in several digestive pathologies such as peptic ulcer, diabetes, colon cancer, or inflammatory bowel disease (IBD). AM is a key protective factor in IBD onset and development, as it regulates cytokine production in the intestinal mucosa, improves vascular and lymphatic regeneration and function and mucosal epithelial repair, and promotes a beneficial gut microbiome composition. AM and PAMP are relevant GI hormones that can be targeted to develop novel therapeutic agents for IBD, other GI disorders, or microbiome-related pathologies.

Marine sedimentary records and the proxies within play a central role in unlocking our understanding of past climates, yet interpreting the signals they contain can be complex. Here, the authors reveal and discuss the complex effects of hydrodynamics on carbon accumulation in the sediments off the Iberian margin.

El objetivo del trabajo fue programar el mantenimiento preventivo de las unidades generadoras de un sistema de potencia con un modelo de optimización que minimiza el costo de operación y mantenimiento. Para modelar el costo de operación de las unidades se utiliza una función cuadrática y para el mantenimiento una función lineal, ambas dependen de la demanda del sistema. Las propuestas de programación y la combinatoria que garantiza el menor costo de operación en el predespacho económico de las unidades son generadas con un algoritmo de optimización por enjambre de partículas. La función multi-variable no-lineal con restricciones que resulta como objetivo se optimiza mediante un método de programación cuadrática secuencial Cuasi-Newton que aproxima la Hessiana en cada iteración por diferencias finitas. El trabajo muestra como el margen de reserva del sistema afecta la programación del mantenimiento preventivo de un sistema de potencia con presencia de fuentes no convencionales de energía.

Introducción: las raciones de consumo son cantidades estándares de alimentos o bebidas sugeridas para asesorar sobre la cantidad de alimento a consumir para preservar un estado de salud adecuado. El objetivo principal de este trabajo es establecer los tamaños de ración de consumo de frutas y hortalizas (FH) para uso en guías alimentarias. Material y métodos: Se adaptó la metodología de la United States Department of Agriculture (USDA) para el establecimiento de los tamaños de ración de consumo para guías, y la del sistema de Intercambios. Se recopilaron datos de porción reportados en encuestas y calibres comunes en el mercado, se ajustó a cantidades de alimento fácilmente reconocibles y con equivalencia de nutrientes clave y se evaluó el grado de cumplimiento de los objetivos de salud pública para el consumo de FH. Resultados: Los tamaños de porción típicamente reportados en encuestas españolas son escasos y poco homogéneos, y no se encontraron datos publicados en revistas científicas sobre los calibres. Las guías alimentarias españolas, a pesar de mostrar un rango de tamaño de ración para FH no aseguran que sean intercambiables ni especifican el método para llegar a las mismas. La ración de hortalizas obtenida ha sido de 139,44 g (DS:±21,98; CV:0,16), de 137,68 g (DS:±49,61; CV:0,36) para frutas y 28,00g (DS:±7,53; CV:0,27) para frutas desecadas. Conclusiones: Con las raciones establecidas, el mensaje “consume al menos 5 raciones entre FH al día” permitiría alcanzar los objetivo de Salud Pública para FH establecidos en 600 g (peso neto)/persona/día. Se recomienda a la Agencia Española de Consumo, Seguridad Alimentaria y Nutrición (AECOSAN) que use esta misma metodología para el establecimiento de raciones en el resto de grupos de alimentos que configuran la Guía Dietética Basada en Alimentos para la población española.

Sabkhas are important settings for understanding early earth biological environments, and the algal mats associated with them are thought to be potential source rocks for hydrocarbon production. In this study we compare the sedimentological facies and distribution of branched, and isoprenoid glycerol dialkyl glycerol tetraethers (GDGTs) in modern and mid-Holocene sabkha sediments from Abu Dhabi with well-preserved Miocene (12–13 Ma) sabkha sediments recently recovered at IODP site U1464 off the north coast of Australia. We show that the facies of the Miocene sediments is very similar to Holocene and modern sabkhas. Furthermore, we show that there are distinct patterns of isoprenoid GDGT distributions in the modern sabkha and that these patterns are well preserved in both the buried Holocene and the Miocene algal mats. The sabkha sediments analyzed are characterized by high %GDGT-0 and methane index, dominance of branched GDGTs over crenarchaeol (high BIT index), an unusual distribution of isoprenoid GDGTs 1–3, and also low abundance of archeol. The distribution of branched GDGT differs between modern and Miocene sabkhas and is similar in Miocene sabkha and non-sabkha sediments suggesting that they may be of limited use to distinguish paleo-sabkha sediments. Overall, isoprenoid GDGT distributions appear to be different from those found in modern soils, lakes and marine sediments, as well as from those found in Miocene shallow water sediments right below the sabkha, therefore they could be used in combination with facies analysis to identify paleo-sabkha environments in sedimentary sequences.

Introducción: el Índice de Western Ontario para Manguito Rotador (WORC) evalúa la calidad de vida en pacientes con patología del manguito rotador. El objetivo de este estudio fue traducir la escala al español y evaluar su consistencia interna y reproducibilidad en pacientes con esta enfermedad. Métodos: siguiendo las guías de la literatura, se tradujo la escala de WORC y se aplicó a sesenta pacientes con patología del manguito rotador. Para evaluar la confiabilidad, los pacientes debían responder la escala por segunda vez, en un período no mayor a 14 días. Se calcularon el alfa de Cronbach y el coeficiente de correlación intraclase (ICC) para determinar la confiabilidad test-retest y la consistencia interna. El gráfico de Bland-Altman y el índice de cambio confiable (RCI) se usaron para calcular el error de medición. Resultados: el alfa de Cronbach fue 0,96 para el valor total del WORC (rango de 0,85-0,94 para los cinco dominios). La confiabilidad test-retest fue excelente con un ICC de 0,98 (rango de 0,91-0,97 para los dominios). El gráfico de Bland-Altman no demostró diferencias sistemáticas y el RCI fue 7,6 %. Conclusión: la versión en español de la escala de WORC es una herramienta válida y confiable para evaluar calidad de vida en pacientes con patología del manguito rotador y puede utilizarse en países de habla hispana como Colombia. Nivel de evidencia: estudio de ciencias básicas, desarrollo o validación de instrumentos para medición de desenlaces.

A raíz de la inclusión de elementos seculares en las estructuras administrativas de las instituciones de beneficencia y los primeros pasos en la unificación y racionalización de los establecimientos asistenciales por mandato real a finales del siglo XV, se produce un punto de inflexión en la evolución del sistema hospitalario a nivel nacional que en el caso de La Rioja supone una rápida municipalización de la asistencia hospitalaria centrada en los núcleos urbanos gracias a la existencia previa de un elevado número de hospitales en relación al Camino de Santiago y las características político-económicas de la región.

El propòsit d'aquest article és promoure la comprensió del to com a qualitat del so i dels conceptes matemàtics associats a la seva modelització, mitjançant el disseny i l'aplicació d'activitats didàctiques. El concepte de so i les seves qualitats formen part del programa d'estudis de segon grau de l'educació bàsica de física a Mèxic i del quart grau de secundària a Colòmbia (edats entre 13 i 15 anys). Per al disseny de les activitats es va requerir l'ocupació d'aplicacions informàtiques (apps) disposades en dispositius mòbils com a laboratori portable, un marc didàctic i el desenvolupament d'una proposta de modelització. L'experiència es va implementar en dos països i es va desenvolupar en quatre fases. Es mostraran evidències del canvi conceptual en els estudiants.

Abstract Ocular and periocular traumatisms may result in loss of vision. Hypothermia provides a beneficial intervention for brain and heart conditions and, here, we study whether hypothermia can prevent retinal damage caused by traumatic neuropathy. Intraorbital optic nerve crush (IONC) or sham manipulation was applied to male rats. Some animals were subjected to hypothermia (8 °C) for 3 h following surgery. Thirty days later, animals were subjected to electroretinography and behavioral tests. IONC treatment resulted in amplitude reduction of the b-wave and oscillatory potentials of the electroretinogram, whereas the hypothermic treatment significantly (p