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This study explores how reducing lubricant viscosity affects fuel economy in passenger cars through experimental characterization and semi-predictive modelling. Thus, three engine oils (0W-20, 5W-30, and 5W-40) were tested for their rheological and tribological properties. Data were introduced into a detailed GT-Suite model of a turbocharged gasoline SUV. Simulations over six different driving cycles, including European homologation and real-driving conditions, used a fast-running model (FRM) to assess engine friction and wear protection. Results showed that lower viscosity oils, especially 0W-20, significantly reduced frictional losses, enhancing fuel economy. However, lower viscosity also increased contact friction under high power demand, raising durability concerns. A comprehensive evaluation of lubricants performance, offering insights into the trade-offs between fuel economy improvements and potential durability risks.

Abstract Mangrove forests are recognized as one of the most effective ecosystems for storing carbon. In drylands, mangroves operate at the extremes of environmental gradients and, in many instances, offer one of the few opportunities for vegetation-based sequestering of carbon. Developing accurate and reproducible methods to map carbon assimilation in mangroves not only serves to inform efforts related to natural capital accounting, but can help to motivate their protection and preservation. Remote sensing offers a means to retrieve numerous vegetation traits, many of which can be related to plant biophysical or biochemical responses. The leaf area index (LAI) is routinely employed as a biophysical indicator of health and condition. Here, we apply a linear regression model to UAV-derived multispectral data to retrieve LAI across three mangrove sites located along the coastline of the Red Sea, with estimates producing an R2 of 0.72 when compared against ground-sampled LiCOR LAI-2200C LAI data. To explore the potential of monitoring carbon assimilation within these mangrove stands, the UAV-derived LAI estimates were combined with field-measured net photosynthesis rates from a LiCOR 6400/XT, providing a first estimate of carbon assimilation in dryland mangrove systems of approximately 3000 ton C km−2 yr−1. Overall, these results advance our understanding of carbon assimilation in dryland mangroves and provide a mechanism to quantify the carbon mitigation potential of mangrove reforestation efforts.

Hydrokinetic energy constitutes a source of renewable energy. However, many regions have flow velocities that are too low for effective energy extraction, and conventional turbines are not suitable for these sites. In order to address this challenge, the present work proposes a novel vertical axis hydrokinetic turbine designed for environments where conventional turbines are not feasible due to a low water velocity. The turbine’s design is inspired by biological principles, enhancing the traditional Savonius turbine by incorporating a Fibonacci spiral-inspired blade configuration. The turbine’s performance was subjected to a rigorous analysis through Computational Fluid Dynamics (CFD). The results demonstrate a notable improvement, with a 15.1% increase in the power coefficient compared to the traditional Savonius turbine. This innovative approach not only extends the applicability of hydrokinetic turbines to low-flow regions but also underscores the potential of biomimicry in optimizing renewable energy technologies. The findings of this study indicate that integrating natural design principles can result in more efficient and sustainable energy solutions, thereby paving the way for the broader adoption of hydrokinetic power in diverse geographical settings.

Abstract The microbiota in humans and animals play crucial roles in defense against pathogens and offer a promising natural source for immunomodulatory products. However, the development of physiologically relevant model systems and protocols for testing such products remains challenging. In this study, we present an experimental condition where various natural products derived from the registered lactic acid bacteria Ligilactobacillus salivarius CECT 9609, known for their immunomodulatory activity, were tested. These products included live and inactivated bacteria, as well as fermentation products at different concentrations and culture times. Using our established model system, we observed no morphological changes in the airway epithelium upon exposure to Pasteurella multocida, a common respiratory pathogen. However, early molecular changes associated with the innate immune response were detected through transcript analysis. By employing diverse methodologies ranging from microscopy to next-generation sequencing (NGS), we characterized the interaction of these natural products with the airway epithelium and their potential beneficial effects in the presence of P. multocida infection. In particular, our discovery highlights that among all Ligilactobacillus salivarius CECT 9609 products tested, only inactivated cells preserve the conformation and morphology of respiratory epithelial cells, while also reversing or altering the natural immune responses triggered by Pasteurella multocida. These findings lay the groundwork for further exploration into the protective role of these bacteria and their derivatives.

With its linguistic and cultural diversity, Austronesia is important in the study of evolutionary forces that generate and maintain cultural variation. By analysing publicly available datasets, we have identified four classes of cultural features in Austronesia and distinct clusters within each class. We hypothesized that there are differing modes of transmission and patterns of variation in these cultural classes and that geography alone would be insufficient to explain some of these patterns of variation. We detected relative differences in the verticality of transmission and distinct patterns of cultural variation in each cultural class. There is support for pulses and pauses in the Austronesian expansion, a west-to-east increase in isolation with explicable exceptions, and correspondence between linguistic and cultural outliers. Our results demonstrate how cultural transmission and patterns of variation can be analysed using methods inspired by population genetics.

Binge Drinking (BD) is characterized by consuming large amounts of alcohol on one occasion, posing risks to brain function. Nonetheless, it remains the most prevalent consumption pattern among students. Cross-sectional studies have explored the relationship between BD and anomalies in resting-state functional connectivity (RS-FC), but the medium/long-term consequences of BD on RS-FC during developmental periods remain relatively unexplored. In this two-year follow-up study, the impact of sustained BD on RS-FC was investigated in 44 college students (16 binge-drinkers) via two fMRI sessions at ages 18–19 and 20–21. Using a seed-to-voxel approach, RS-FC differences were examined in nodes of the main brain functional networks vulnerable to alcohol misuse, according to previous studies. Group differences in RS-FC were observed in four of the explored brain regions. Binge drinkers, compared to the control group, exhibited, at the second assessment, decreased connectivity between the right SFG (executive control network) and right precentral gyrus, the ACC (salience network) and right postcentral gyrus, and the left amygdala (emotional network) and medial frontal gyrus/dorsal ACC. Conversely, binge drinkers showed increased connectivity between the right Nacc (reward network) and four clusters comprising bilateral middle frontal gyrus (MFG), right middle cingulate cortex, and right MFG extending to SFG. Maintaining a BD pattern during critical neurodevelopmental years impacts RS-FC, indicating mid-to-long-term alterations in functional brain organization. This study provides new insights into the neurotoxic effects of adolescent alcohol misuse, emphasizing the need for longitudinal studies addressing the lasting consequences on brain functional connectivity.

Abstract Background Tumor deposits (TDs) are an infrequently mentioned feature of head and neck squamous cell carcinoma (HNSCC) that are currently grouped under extranodal extension (ENE) in the AJCC 8th edition of HNSCC TNM staging. The prognostic implication of TDs in comparison to ENE remains uncertain. Methods This observational, retrospective, non‐randomized study evaluated patients with HNSCC who underwent initial surgical resection, with neck dissection and adjuvant radiotherapy ± chemotherapy. Clinical variables were considered, and statistical analyses were conducted to compare time progression and overall survival (OS) in patients with TDs against those with ENE. Results Of the 71 patients included in the study, 50 were diagnosed with ENE (pN2a‐ENE in 38 patients and pN3b‐ENE in 12), while 21 had TDs ± ENE. The median time to progression was significantly different based on the presence of ENE or TDs (p = .002) and pN2a‐ENE/pN3b‐ENE or TDs (p = .007). The three‐year OS was 55.7% for the entire group, 60.4% in ENE and 38.4% in TDs (p = .021). The OS difference between the pN2a‐ENE, pN3b‐ENE, and the TDs group was also significant (p = .05). The hazard ratio between ENE and TDs was Exp (B) 4.341 (p = .044). Conclusions TDs in HNSCC are associated with a lower OS than ENE, despite intensified adjuvant therapy. Our results confirm a better prognosis for pN2a‐ENE vs. pN3b‐ENE, and pN3b‐ENE vs. TDs. TDs may serve as an indicator of poor prognosis and require separate TNM classification in HNSCC staging. Larger studies are needed to evaluate TDs impact on treatment strategies and outcomes.

Antimicrobial resistance is a critical challenge due to the overuse of conventional antimicrobials, and alternative solutions are urgently needed. This study investigates the efficacy of compounds derived from lactic acid bacteria (LAB) fermentation combined with antibiotics against multidrug-resistant pathogens isolated from clinical cases in a hospital setting. Strains of Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium and faecalis were isolated and selected from blood, respiratory, and urine samples. They were tested against the fermentation products from the Ingulados LAB collection (BAL5, BAL6, BAL8, BAL13, and BAL16), recognized for their antimicrobial efficacy against veterinary pathogens. The activity against multidrug-resistant (MDR) pathogens was evaluated initially, followed by synergy tests using checkerboard assays and subsequent analysis. Bioinformatic assessments and supernatant treatments were performed to characterize the nature of the compounds responsible for the antimicrobial activity. Notably, BAL16 exhibited significant growth inhibition against multidrug-resistant E. faecium. Synergy tests highlighted its combined activity with tetracycline through FICI and surface analysis and bioinformatic analysis unveiled the protein fraction containing bacteriocins as the underlying mechanism. This study highlights BAL16 fermentation products potential as valuable antimicrobial agents against MDR E. faecium infections, attributed to bacteriocins. Further in-depth studies are necessary for complete bacteriocin characterization.

Introducción: Ante el aumento de las artroplastias de cadera en el último siglo, los defectos acetabulares graves son eventos cada vez más frecuentes. Su tratamiento representa un verdadero desafío, debido al déficit y la pobre calidad ósea, habitual en estos pacientes. Materiales y Métodos: Se presentan 6 pacientes tratados entre 2016 y 2021. Cinco casos de disrupción pélvica por revisiones fallidas, clasificadas como tipo IIIB de Paprosky y una fractura transversal de acetábulo, posible opción de tratamiento en casos de pacientes osteoporóticos. Resultados: Los pacientes tratados con esta técnica multidisciplinaria fueron controlados durante un promedio de 20 meses, ninguno presentó complicaciones posoperatorias. Los resultados valorados con escalas analógicas son prometedores e invitan a establecer este procedimiento como el patrón de referencia. Conclusiones: La evaluación estricta es necesaria en los defectos acetabulares. La inclusión de ingeniería informática médica permite estudiar la necesidad de usar injerto de banco, fabricar implantes a medida de titanio/tantalio trabecular multiporos, lo que es ideal para lograr la osteointegración, sumado a la posibilidad de planificar la dirección y la longitud de los tornillos al hueso remanente, según su calidad. La cementación de un cotilo de doble movilidad dentro del implante a medida disminuye el riesgo de luxación y de sobrecarga de este último, al eliminar la fricción metal-metal.

Abstract Mimicking angiogenetic processes in vascular territories acquires importance in the analysis of the multi-scale circulatory cascade and the coupling between blood flow and cell function. The present work extends, in several aspects, the Constrained Constructive Optimisation (CCO) algorithm to tackle complex automatic vascularisation tasks. The main extensions are based on the integration of adaptive optimisation criteria and multi-staged space-filling strategies which enhance the modelling capabilities of CCO for specific vascular architectures. Moreover, this vascular outgrowth can be performed either from scratch or from an existing network of vessels. Hence, the vascular territory is defined as a partition of vascular, avascular and carriage domains (the last one contains vessels but not terminals) allowing one to model complex vascular domains. In turn, the multi-staged space-filling approach allows one to delineate a sequence of biologically-inspired stages during the vascularisation process by exploiting different constraints, optimisation strategies and domain partitions stage by stage, improving the consistency with the architectural hierarchy observed in anatomical structures. With these features, the aDaptive CCO (DCCO) algorithm proposed here aims at improving the modelled network anatomy. The capabilities of the DCCO algorithm are assessed with a number of anatomically realistic scenarios.

Previous cross-sectional research has largely associated binge drinking (BD) with changes in volume and thickness during adolescence and early adulthood. Nevertheless, the long-term alcohol-related effects on gray matter features in youths who had maintained a BD pattern over time have not yet been sufficiently explored. The present study aimed to assess group differences both cross-sectionally and longitudinally [using symmetric percent change (SPC)] on several structural measures (i.e., thickness, surface area, volume). For this purpose, magnetic resonance imaging was recorded twice within a 2-year interval; at baseline (18–19 years) and a follow-up (20–21 years). The sample included 44 university students who were classified as 16 stable binge drinkers (8 females) and 28 stable controls (13 females). Whole-brain analysis showed larger insular surface area in binge drinkers relative to controls at follow-up (cluster-wise p = 0.045). On the other hand, region of interest (ROI) analyses on thickness also revealed a group by sex interaction at follow-up (p = 0.005), indicating that BD males had smaller right rostral middle frontal gyrus thickness than both control males (p = 0.011) and BD females (p = 0.029). Similarly, ROI-based analysis on longitudinal data showed a group by sex interaction in the right nucleus accumbens (p = 0.009) which revealed a decreased volume across time in BD males than in control males (p = 0.007). Overall, continued BD pattern during emerging adulthood appears to lead to gray matter abnormalities in regions intimately involved in reward processing, emotional regulation and executive functions. Notably, some anomalies varied significantly depending on sex, suggesting a sex-specific impact of BD on typical neurodevelopment processes.

A fin de profundizar la comprensión de las múltiples y crecientemente aceleradas transformaciones de la experiencia humana en el mundo moldeadas por desarrollos técnicos algorítmicamente articulados, entendemos que la distinción entre sistema y entorno—base de la teoría de modelos sociales desde la década de 1970—debe ser puesta en cuestión: no sólo la construcción de los modelos se ha transformado técnica y conceptualmente, sino que los mismos sistemas que se modelan, incluido el sistema-mundo, se hallan en un proceso de transformación radical. En efecto: los mismos objetos técnicos tienden a la deslocalización, adquiriendo un carácter ambiental y un modo de existencia procesual capaz de condicionar de maneras específicas la constitución del mundo y la experiencia humana, lo cual impele a la adopción de perspectivas novedosas sobre el poder. En este marco, será un enfoque ecológico el que permita avanzar en la aprehensión de la relación entre sistema y proceso—ambiental—asumiendo la pregnancia ontológica de la segunda dimensión y, además, abordar de manera más adecuada las urgentes preguntas en torno a las relaciones de poder, las formas contemporáneas de subjetivación y las posibilidades de emergencia de procesos críticos y de transformación. A este respecto, en principio, desarrollamos algunas consideraciones relevantes para tematizar “lo digital” en la contemporaneidad, marcando dimensiones ineludibles para reflexionar en torno al ubicuo fenómeno de digitalización de la vida En segundo lugar, reconstruimos algunos elementos clave del pensamiento cibernético como paradigma interpretativo. Finalmente, enfatizando en la dimensión política, presentamos una serie de reflexiones en torno al concomitante carácter ambiental de los objetos técnicos y del poder, junto con la explicitación del potencial que, a nuestro entender, anida en la noción del entramado localizado de gubernamentalidades múltiples para el pensamiento político y la evaluación crítica de experiencias de articulación específica entre técnica y política.

Wildfires affect the structure, functioning, and composition of ecosystems. Long-term monitoring of the occurrence, abundance, and growth of plant species is key to assessing the responses of the dynamics of plant populations with regard to environmental disturbances, such as wildfires. In this work, we evaluated the changes in the number of individuals and the canopy cover extent of a population of Juniperus communis L. during a four-decade period following a wildfire in a Mediterranean high-mountain ecosystem (Sierra Nevada, Spain). To do this, we used object-based image analysis (OBIA) applied to very high-resolution aerial images. Our study also provides a new approach to optimize the shrub identification process and to semi-automatically evaluate the accuracy of the number of shrubs and their canopy cover. From the 752 individuals present in 1977, only 433 remained immediately after a fire (1984), a few more disappeared one decade later (420 shrubs in 1997), while by 2008, the population had partially recovered to 578 shrubs. The wildfire decreased juniper canopy cover from 55,000 m2 to 40,000 m2, but two decades later it had already recovered to 57,000 m2. The largest shrubs were more resistant to fire than the smallest ones and recovered in a shorter time period. The protection measures introduced with the park declaration seemed to have contributed to the post-fire recovery. The potential of this methodology in the management and conservation of biodiversity in the future is also discussed.

Humans evolved by losing the capacity to synthesize the glycan Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal), which resulted in the development of a protective response mediated by anti-α-Gal IgM/IgG/IgA antibodies against pathogens containing this modification on membrane proteins. As an evolutionary trade-off, humans can develop the alpha-Gal syndrome (AGS), a recently diagnosed disease mediated by anti-α-Gal IgE antibodies and associated with allergic reactions to mammalian meat consumption and tick bites. However, the anti-α-Gal antibody response may be associated with other immune-mediated disorders such as those occurring in patients with COVID-19 and Guillain-Barré syndrome (GBS). Here, we provide a dataset (209 entries) on the IgE/IgM/IgG/IgA anti-α-Gal antibody response in healthy individuals and patients diagnosed with AGS, tick-borne allergies, GBS and COVID-19. The data allows correlative analyses of the anti-α-Gal antibody response with factors such as patient and clinical characteristics, record of tick bites, blood group, age and sex. These analyses could provide insights into the role of anti-α-Gal antibody response in disease symptomatology and possible protective mechanisms.

Abstract Early Neospora caninum infection dynamics were investigated in pregnant heifers intravenously inoculated with PBS (G-Control) or 107 tachyzoites of high (G-NcSpain7)- or low (G-NcSpain1H)-virulence isolates at 110 days of gestation. Serial culling at 10 and 20 days post-infection (dpi) was performed. Fever was detected at 1 dpi in both infected groups (P

Carob, the fruit of Ceratonia siliqua L. exerts antidiabetic, anti-inflammatory, and antioxidant effects and could be a useful strategy for the treatment and/or prevention of metabolic syndrome (MetS). The aim of this study was to analyze whether supplementation with a carob fruit extract (CSAT+®), alone or in combination with aerobic training, accelerates the recovery of cardiometabolic health in mice with MetS subjected to a caloric restriction. For this purpose, mice were fed with a high fat (58% kcal from fat)/high sugar diet for 23 weeks to induce MetS. During the next two weeks, mice with MetS were switched to a diet with a lower caloric content (25% kcal from fat) supplemented or not with CSAT+® (4.8%) and/or subjected to aerobic training. Both caloric reduction and aerobic training improved the lipid profile and attenuated MetS-induced insulin resistance measured as HOMA-IR. However, only supplementation with CSAT+® enhanced body weight loss, increased the circulating levels of adiponectin, and lowered the plasma levels of IL-6. Moreover, CSAT+® supplementation was the only effective strategy to reduce the weight of epidydimal adipose tissue and to improve insulin sensitivity in the liver and in skeletal muscle. Although all interventions improved endothelial function in aorta segments, only supplementation with CSAT+® reduced obesity-induced hypertension, prevented endothelial dysfunction in mesenteric arteries, and decreased the vascular response of aorta segments to the vasoconstrictor AngII. The beneficial cardiometabolic effects of CSAT+® supplementation, alone or in combination with aerobic training, were associated with decreased mRNA levels of pro-inflammatory markers such as MCP-1, TNFα, IL-1β, and IL-6 and with increased gene expression of antioxidant enzymes, such as GSR, GPX-3, and SOD-1 in the liver, gastrocnemius, retroperitoneal adipose tissue, and aorta. In conclusion, supplementation with CSAT+®, alone or in combination with aerobic training, to mice with MetS subjected to caloric restriction for two weeks enhances body weight loss, improves the lipid profile and insulin sensitivity, and exerts antihypertensive effects through its anti-inflammatory and antioxidant properties.

The present work proposes an artificial neural network (ANN) to analyze vertical axis wind turbines of the Savonius type. These turbines are appropriate for low wind velocities due to their low starting torque. Nevertheless, their efficiency is too low. In order to improve the efficiency, several modifications are analyzed. First of all, an innovative blade profile biologically inspired is proposed. After that, the influence of several parameters such as the aspect ratio, overlap, and twist angle was analyzed through a CFD (computational fluid dynamics) model. In order to characterize the most appropriate combination of aspect ratio, overlap, and twist angle, an artificial neural network is proposed. A data set containing 125 data points was obtained through CFD. This data set was used to develop the artificial neural network. Once established, the artificial neural network was employed to analyze 793,881 combinations of different aspect ratios, overlaps, and twist angles. It was found that the maximum power coefficient, 0.3263, corresponds to aspect ratio 7.5, overlap/chord length ratio 0.1125, and twist angle 112°. This corresponds to a 32.4% increment in comparison to the original case analyzed with aspect ratio 1, overlap 0, and twist angle 0.

Humans evolved by losing the capacity to synthesize the glycan Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal), which resulted in the development of a protective response mediated by anti-α-Gal IgM/IgG/IgA antibodies against pathogens containing this modification on membrane proteins. As an evolutionary trade-off, humans can develop the alpha-Gal syndrome (AGS), a recently diagnosed disease mediated by anti-α-Gal IgE antibodies and associated with allergic reactions to mammalian meat consumption and tick bites. However, the anti-α-Gal antibody response may be associated with other immune-mediated disorders such as those occurring in patients with COVID-19 and Guillain-Barré syndrome (GBS). Here, we provide a dataset (209 entries) on the IgE/IgM/IgG/IgA anti-α-Gal antibody response in healthy individuals and patients diagnosed with AGS, tick-borne allergies, GBS and COVID-19. The data allows correlative analyses of the anti-α-Gal antibody response with factors such as patient and clinical characteristics, record of tick bites, blood group, age and sex. These analyses could provide insights into the role of anti-α-Gal antibody response in disease symptomatology and possible protective mechanisms.

Wind energy is gaining special interest worldwide due to the necessity of reducing pollutant emissions and employ renewable resources. Traditionally, horizontal axis wind turbines have been employed but certain situations require vertical axis wind turbines. With a view to improve the efficiency of a vertical axis wind turbine Savonius type, the present work proposes a bioinspired design blade profile relying on the Fibonacci spiral. This shape is repeatedly presented in nature and thus it leads to a bio-inspired blade profile. A numerical model was carried out and it was found that the Fibonacci shape improves the performance of the original Savonius shape, based on semicircular blade profiles. Particularly, the Fibonacci blade profile increases around 14% the power in comparison with the Savonius blade profile. Besides this comparison between Savonius and Fibonacci, a research study was carried out to improve the efficiency of the Fibonacci turbine. To this end, the effect of several parameters was analyzed: number of blades, aspect ratio, overlap, separation gap, and twist angle. Improvements on the average power greater than 30% were obtained.

Control of excessive mitochondrial oxidative stress could provide new targets for both preventive and therapeutic interventions in the treatment of chronic inflammation or any pathology that develops under an inflammatory scenario, such as rheumatoid arthritis (RA). Increasing evidence has demonstrated the role of mitochondrial alterations in autoimmune diseases mainly due to the interplay between metabolism and innate immunity, but also in the modulation of inflammatory response of resident cells, such as synoviocytes. Thus, mitochondrial dysfunction derived from several danger signals could activate tricarboxylic acid (TCA) disruption, thereby favoring a vicious cycle of oxidative/mitochondrial stress. Mitochondrial dysfunction can act through modulating innate immunity via redox-sensitive inflammatory pathways or direct activation of the inflammasome. Besides, mitochondria also have a central role in regulating cell death, which is deeply altered in RA. Additionally, multiple evidence suggests that pathological processes in RA can be shaped by epigenetic mechanisms and that in turn, mitochondria are involved in epigenetic regulation. Finally, we will discuss about the involvement of some dietary components in the onset and progression of RA.

Modern society has plunged us into a maelstrom of telematics information with little control. Teachers from any field must be trained in order to pass on the confidence and values to withstand this media pressure to their students. To this end, one of the areas of knowledge on which greater emphasis should be placed is that related to emotional intelligence. The study reported on here focused on this type of knowledge among professional music studies teachers in conservatories, asking what the perception of this group on the aforementioned area of knowledge is and to what extent it has been received during their initial training. For this investigation we used a quantitative methodological approach, and via descriptive analysis, a non-parametric Wilcoxon signed-rank test, and inferential analysis, we found significant differences regarding the two scales considered: level of agreement and emotional intelligence training received. Furthermore, regarding the descriptive variables, significant differences were also found through the application of the Mann-Whitney U and Kruskal-Wallis test.

The acute-on-chronic liver failure (ACLF) is a syndrome characterized by liver decompensation, hepatic encephalopathy (HE) and high mortality. We aimed to determine the mechanisms implicated in the development of HE-associated cerebral vasculopathy in a microsurgical liver cholestasis (MHC) model of ACLF. Microsurgical liver cholestasis was induced by ligating and extracting the common bile duct and four bile ducts. Sham-operated and MHC rats were maintained for eight postoperative weeks Bradykinin-induced vasodilation was greater in middle cerebral arteries from MHC rats. Both Nω-Nitro-L-arginine methyl ester and indomethacin diminished bradykinin-induced vasodilation largely in arteries from MHC rats. Nitrite and prostaglandin (PG) F1α releases were increased, whereas thromboxane (TX) B2 was not modified in arteries from MHC. Expressions of endothelial nitric oxide synthase (eNOS), inducible NOS, and cyclooxygenase (COX) 2 were augmented, and neuronal NOS (nNOS), COX-1, PGI2 synthase, and TXA2S were unmodified. Phosphorylation was augmented for eNOS and unmodified for nNOS. Altogether, these endothelial alterations might collaborate to increase brain blood flow in HE.

Introduction The evidence currently available from enhanced recovery after surgery (ERAS) programmes concerns their benefits in the immediate postoperative period, but there is still very little evidence as to whether their correct implementation benefits patients in the long term. The working hypothesis here is that, due to the lower response to surgical aggression and lower rates of postoperative complications, ERAS protocols can reduce colorectal cancer-related mortality. The main objective of this study is to analyse the impact of an ERAS programme for colorectal cancer on 5-year survival. As secondary objectives, we propose to analyse the weight of each of the predefined items in the oncological results as well as the quality of life.Methods and analysis A multicentre prospective cohort study was conducted in patients older than 18 years of age who are scheduled to undergo surgery for colorectal cancer. The study involved 12 hospitals with an implemented enhanced recovery protocol according to the guidelines published by the Spanish National Health Service. The intervention group includes patients with a minimum implementation level of 70%, and the control group includes those who fail to reach this level. Compliance will be studied using 18 key performance indicators, and the results will be analysed using cancer survival indicators, including overall survival, cancer-specific survival and relapse-free survival. The time to recurrence, perioperative morbidity and mortality, hospital stay and quality of life will also be studied, the latter using the validated EuroQol Five questionnaire. The propensity index method will be used to create comparable treatment and control groups, and a multivariate regression will be used to study each variable. The Kaplan-Meier estimator will be used to estimate survival and the log-rank test to make comparisons. A p value of less than 0.05 (two-tailed) will be considered to be significant.Ethics and dissemination Ethical approval for this study was obtained from the Aragon Ethical Committee (C.P.-C.I. PI20/086) on 4 March 2020. The findings of this study will be submitted to peer-reviewed journals (BMJ Open, JAMA Surgery, Annals of Surgery, British Journal of Surgery). Abstracts will be submitted to relevant national and international meetings.Trial registration number NCT04305314.

In recent years, gut dysbiosis has been related to some peripheral vascular alterations linked to hypertension. In this work, we explore whether gut dysbiosis is related to vascular innervation dysfunction and altered nitric oxide (NO) production in the superior mesenteric artery, one of the main vascular beds involved in peripheral vascular resistance. For this purpose, we used spontaneously hypertensive rats, either treated or not with the commercial synbiotic formulation Prodefen® (108 colony forming units/day, 4 weeks). Prodefen® diminished systolic blood pressure and serum endotoxin, as well as the vasoconstriction elicited by electrical field stimulation (EFS), and enhanced acetic and butyric acid in fecal samples, and the vasodilation induced by the exogenous NO donor DEA-NO. Unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in rats supplemented with Prodefen®. Both neuronal NO release and neuronal NOS activity were enhanced by Prodefen®, through a hyperactivation of protein kinase (PK)A, PKC and phosphatidylinositol 3 kinase-AKT signaling pathways. The superoxide anion scavenger tempol increased both NO release and DEA-NO vasodilation only in control animals. Prodefen® caused an increase in both nuclear erythroid related factor 2 and superoxide dismutase activities, consequently reducing both superoxide anion and peroxynitrite releases. In summary, Prodefen® could be an interesting non-pharmacological approach to ameliorate hypertension.

Abstract Experimental infections in pregnant sheep have been focused on studying the effect of the time of challenge on the outcome of N. caninum infection, whereas the impact of the dose and route of challenge has not been studied in depth. Therefore, clinical outcome, immune responses, parasite detection and burden, and lesion severity in placental tissues and foetal brains were investigated in 90-day-pregnant sheep inoculated intravenously with 105 (G1), 104 (G2), 103 (G3), or 102 (G4) tachyzoites or subcutaneously with 104 (G5) tachyzoites of the virulent Nc-Spain7 isolate and an uninfected group (G6). Comparing challenge doses, G1 was the only group that had 100% abortion. Likewise, IFNγ levels in G1 increased earlier than those in other intravenously infected groups, and IgG levels on day 21 post-infection (pi) were higher in G1 than those in other intravenously infected groups. Concerning vertical transmission, G1 shows a higher parasite burden in the foetal brain than did G2 and G3. Comparing routes of administration, no differences in foetal survival rate or parasite load in the foetal brain were found. Although G2 had higher IFNγ levels than G5 on day 10 pi, no differences were found in humoral immune responses. Because the outcome after intravenous infection with 105 tachyzoites was similar to that observed after intravenous infection with 106 tachyzoites used in a previous work (100% abortion and vertical transmission), we conclude that it may be reasonable to use 105 tachyzoites administered by the intravenous route in further experiments when assessing drugs or vaccine candidates.

Neospora caninum is one of the main causes of abortion in cattle, and recent studies have highlighted its relevance as an abortifacient in small ruminants. Vaccines or drugs for the control of neosporosis are lacking. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites in vitro and in laboratory animal models. We here present the pharmacokinetics, safety and efficacy of BKI-1553 in pregnant ewes and foetuses using a pregnant sheep model of N. caninum infection. BKI-1553 showed exposure in pregnant ewes with trough concentrations of approximately 4 μM, and of 1 μM in foetuses. Subcutaneous BKI-1553 administration increased rectal temperatures shortly after treatment, and resulted in dermal nodules triggering a slight monocytosis after repeated doses at short intervals. BKI-1553 treatment decreased fever in infected pregnant ewes already after two applications, resulted in a 37–50% reduction in foetal mortality, and modulated immune responses; IFNγ levels were increased early after infection and IgG levels were reduced subsequently. N. caninum was abundantly found in placental tissues; however, parasite detection in foetal brain tissue decreased from 94% in the infected/untreated group to 69–71% in the treated groups. In summary, BKI-1553 confers partial protection against abortion in a ruminant experimental model of N. caninum infection during pregnancy. In addition, reduced parasite detection, parasite load and lesions in foetal brains were observed. Keywords: Neospora caninum, Sheep, Pregnancy, Treatment, Protein kinase inhibitor, BKI-1553

Microangiopathy may worsen the clinical outcome of Chagas disease. Given the obstacles to investigating the dynamics of inflammation and angiogenesis in heart tissues parasitized by Trypanosoma cruzi, here we used intravital microscopy (IVM) to investigate microcirculatory alterations in the hamster cheek pouch (HCP) infected by green fluorescent protein-expressing T. cruzi (GFP-T. cruzi). IVM performed 3 days post-infection (3 dpi) consistently showed increased baseline levels of plasma extravasation. Illustrating the reciprocal benefits that microvascular leakage brings to the host-parasite relationship, these findings suggest that intracellular amastigotes, acting from inside out, stimulate angiogenesis while enhancing the delivery of plasma-borne nutrients and prosurvival factors to the infection foci. Using a computer-based analysis of images (3 dpi), we found that proangiogenic indexes were positively correlated with transcriptional levels of proinflammatory cytokines (pro-IL1β and IFN-γ). Intracellular GFP-parasites were targeted by delaying for 24 h the oral administration of the trypanocidal drug benznidazole. A classification algorithm showed that benznidazole (>24 h) blunted angiogenesis (7 dpi) in the HCP. Unbiased proteomics (3 dpi) combined to pharmacological targeting of chymase with two inhibitors (chymostatin and TY-51469) linked T. cruzi-induced neovascularization (7 dpi) to the proangiogenic activity of chymase, a serine protease stored in secretory granules from mast cells.

This paper examines how consumers develop their attitude toward a destination website and are influenced by its usability, perceived risk and perceived usefulness – all of which can enhance their purchase intention. To create an authentic browsing scenario for the study, a website was specially designed for a fictitious tourist destination. Participants were invited to browse the site freely while carrying out the task assigned to them. This approach contributed added value to the research by simulating the real behavior of consumers who are faced with a range of options when selecting their purchase. The findings confirm that perceived usability and usefulness exert a positive influence on attitude toward the website, while the effect of the perceived risk is negative. The key implication is that if tourism business managers can better understand how attitude toward a website is developed this will enable them to market their products and services more effectively.

Nuestro objetivo es formular una propuesta teórico-metodológica para el estudio de la historia intelectual, capaz de explicar las interrelaciones entre cambio social y cambio lingüístico, traduciendo tales reflexiones en herramientas para la investigación histórica. Para tal fin, tomamos la distinción semántica/estructura social, elaborada por la sociología del conocimiento de Niklas Luhmann y la redescribimos introduciendo la distinción entre información y significado. El mencionado marco teórico es puesto a prueba realizando un bosquejo de la historia conceptual y social del totalitarismo. Llegamos a la conclusión de que el concepto de totalitarismo nos permite dar cuenta de cómo los significados se autoorganizan siguiendo una dinámica histórica propia, aunque ninguna producción de significado puede tener lugar fuera de los sistemas sociales y de los códigos que éstos emplean para procesar información. La historia intelectual se escribe simultáneamente sobre los dos registros de la información y el significado.