Considerations Relevant to the Stability of Granite Boulders

Granite boulders are characteristic geomorphological structures formed in granitic terrains. Due to their formation process associated with typical spheroidal weathering phenomena, they tend to show more or less ellipsoidal shapes prone to instability, and they often lie on small contact surfaces. Analyzing the stability of these boulders is not a straightforward task. First, these boulders may topple or slide. Additionally, their typically irregular geometry and uneven contact with the surface where they lie makes the analysis more complex. The authors have identified some critical issues that are relevant to characterize these boulders from a rock mechanics point of view, with the aim of estimating the stability of boulders. In particular, an accurate description of the geometry of the boulder is necessary to perform accurate toppling calculations. Additionally, the contact area and the features of the contact plane need to be known in detail. The study is intended to serve as a guideline to address the stability of these granite boulders in a rigorous way, since standard rock mechanics approaches (planar failure, toppling stability, standard rock joint strength criteria, etc.) may not be directly applicable to these particular cases.The first author acknowledges the Spanish Ministry of Science, Innovation and Universities for financial support of a related project awarded under Contract Reference No. RTI2018-093563-B-I00, partially financed by means of ERDF funds from the EU. The first author also gratefully thanks the Commission for Cultural, Educational, Scientific Exchange between the USA and Spain of the Fulbright Program for financing a Scholar Visit to Colorado School of Mines, where part of this study was completed. The fourth author acknowledges funding of part of his research in association boulder geometry acquisition from EU FEDER under Project TEC2017-85244-C2-1-P and by the University of Alicante (vigrob-157 and GRE18-05)

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Actividad biológica e inmunogénica de Synsepalum dulcificum para el desarrollo de alimentos funcionales

El azúcar es el edulcorante más utilizado a lo largo de todos los tiempos, sin embargo, son muchos los estudios que señalan a su consumo excesivo como la causa de un gran número de patologías. Por otro lado, hay grupos de la población que no pueden consumir el azúcar, como las personas que padecen diabetes, u otros que son incapaces de percibir de forma normal el sabor de la comida, como es el caso de las personas con disgeusia. El objetivo de reducir el consumo de azúcar junto con el de mejorar la calidad de vida de estos sectores de la población conducen a la baya milagrosa de la planta Synsepalum dulcificum, en cuya pulpa se encuentra una glicoproteína, que recibe el nombre de miraculina, capaz de transformar el sabor ácido en dulce. Gracias a esta propiedad, se puede experimentar la percepción del sabor dulce sin incrementar el índice glucémico además de mejorar la palatabilidad de las personas con disgeusia. Esto hace que la proteína miraculina se convierta en el sustituto y gran competidor del azúcar. Para llevar al mercado esta estrategia nutricional, la empresa Medicinal Gardens S.L. se ha encargado de elaborar un dossier para asegurar la seguridad alimentaria de este Nuevo Alimento, que consiste en el polvo liofilizado de la pulpa y piel de la baya, con el nombre de DMB®, y de esta forma obtener la aprobación por parte de la Autoridad Europea de Seguridad Alimentaria. El objetivo del presente trabajo consistió en la realización de una serie de experimentos que fueron incluidos en el dossier con el fin de conseguir dicha autorización. Entre los experimentos realizados destacan el análisis fisicoquímico de la fruta (humedad y estabilidad), el establecimiento de un método de extracción y purificación de la proteína miraculina, el diseño de un método de producción recombinante de miraculina, la elaboración de un método de cuantificación de este principio activo, la determinación de su contenido en lectinas y el análisis de la posible alergenicidad y poder inmunogénico. Finalmente, tras varios meses de evaluación y gracias a todo el esfuerzo dedicado en la realización de todos estos experimentos, en junio de 2021, la empresa ha obtenido una respuesta favorable de la Autoridad Europea de Seguridad Alimentaria consiguiendo automáticamente la exclusividad comercial del producto durante 5 años en toda Europa. ----------ABSTRACT---------- Sugar is the most widely used sweetener throughout all time, however, many studies point to its excessive consumption as the cause of a large number of pathologies. On the other hand, there are groups of the population that cannot consume sugar, such as people with diabetes, or others who are unable to perceive the taste of food in a normal way, as is the case of people with dysgeusia. The objective of reducing sugar consumption together with that of improving the quality of life of these sectors of the population leads to the miracle berry from Synsepalum dulcificum plant, in whose pulp there is a glycoprotein, which is called miraculin, capable of transforming the sour taste into sweet. Thanks to this property, the perception of sweet taste can be experienced without increasing the glycemic index in addition to improving the palatability of people with dysgeusia. This makes the miraculin protein the substitute and great competitor for sugar. To bring this nutritional strategy to the market, the company Medicinal Gardens S.L. has been in charge of preparing a dossier to ensure the food safety of this Novel Food, which consists of the lyophilized powder of the pulp and skin of the berry, with the name of DMB®, and in this way obtain approval from the European Food Safety Authority. The objective of this work consisted in carrying out a series of experiments that were included in the dossier to obtain said authorization. Among the experiments carried out, the physicochemical analysis of the fruit (humidity and miraculin stability), the establishment of a method for the extraction and purification of the miraculin protein, the design of a method for the recombinant production of miraculin, the development of a method for the quantification of this active principle, the determination of its lectin content and the analysis of possible allergenicity and immunogenicity. Finally, after several months of evaluation and thanks to all the effort dedicated to carrying out all these experiments, in June 2021, the company obtained a favorable response from the European Food Safety Authority, automatically achieving the commercial exclusivity of the product for 5 years across Europe

Miracle Berry as a Potential Supplement in the Control of Metabolic Risk Factors in Cancer

The increased incidence of chronic diseases related to altered metabolism has become a social and medical concern worldwide. Cancer is a chronic and multifactorial disease for which, together with genetic factors, environmental factors are crucial. According to the World Health Organization (WHO), up to one third of cancer-related deaths could be prevented by modifying risk factors associated with lifestyle, including diet and exercise. Obesity increases the risk of cancer due to the promotion of low-grade chronic inflammation and systemic metabolic oxidative stress. The effective control of metabolic parameters, for example, controlling glucose, lipid levels, and blood pressure, and maintaining a low grade of chronic inflammation and oxidative stress might represent a specific and mechanistic approach against cancer initiation and progression. Miracle berry (MB) (Synsepalum dulcificum) is an indigenous fruit whose small, ellipsoid, and bright red berries have been described to transform a sour taste into a sweet one. MB is rich in terpenoids, phenolic compounds, and flavonoids, which are responsible for their described antioxidant activities. Moreover, MB has been reported to ameliorate insulin resistance and inhibit cancer cell proliferation and malignant transformation in vitro. Herein, we briefly summarize the current knowledge of MB to provide a scientific basis for its potential use as a supplement in the management of chronic diseases related to altered metabolism, including obesity and insulin resistance, which are well-known risk factors in cancer. First, we introduce cancer as a metabolic disease, highlighting the impact of systemic metabolic alterations, such as obesity and insulin resistance, in cancer initiation and progression. Next, as oxidative stress is closely associated with metabolic stress, we also evaluate the effect of phytochemicals in managing oxidative stress and its relationship with cancer. Finally, we summarize the main biological activities described for MB-derived extracts with a special focus on the ability of miraculin to transform a sour taste into a sweet one through its interaction with the sweet taste receptors. The identification of sweet taste receptors at the gastrointestinal level, with effects on the secretion of enterohormones, may provide an additional tool for managing chronic diseases, including cancer

Effect of Regular Consumption of a Miraculin-Based Food Supplement on Taste Perception and Nutritional Status in Malnourished Cancer Patients: A Triple-Blind, Randomized, Placebo-Controlled Clinical Trial-CLINMIR Pilot Protocol

Taste disorders are common among cancer patients undergoing chemotherapy, with a prevalence ranging from 20% to 86%, persisting throughout treatment. This condition leads to reduced food consumption, increasing the risk of malnutrition. Malnutrition is associated not only with worse treatment efficacy and poor disease prognosis but also with reduced functional status and quality of life. The fruit of Synsepalum dulcificum (Daniell), commonly known as miracle berry or miracle fruit, contains miraculin, a taste-modifying protein with profound effects on taste perception. The CLINMIR Protocol is a triple-blind, randomized, placebo-controlled clinical trial designed to evaluate the regular consumption of a food supplement containing a miraculin-based novel food, dried miracle berry (DMB), on the taste perception (measured through electrogustometry) and nutritional status (evaluated through the GLIM Criteria) of malnourished cancer patients under active antineoplastic treatment. To this end, a pilot study was designed with 30 randomized patients divided into three study arms (150 mg DMB + 150 mg freeze-dried strawberries, 300 mg DMB, or placebo) for three months. Throughout the five main visits, an exhaustive assessment of different parameters susceptible to improvement through regular consumption of the miraculin-based food supplement will be conducted, including electrical and chemical taste perception, smell perception, nutritional and morphofunctional assessment, diet, quality of life, the fatty acid profile of erythrocytes, levels of inflammatory and cancer-associated cytokines, oxidative stress, antioxidant defense system, plasma metabolomics, and saliva and stool microbiota. The primary anticipated result is that malnourished cancer patients with taste distortion who consume the miraculin-based food supplement will report an improvement in food taste perception. This improvement translates into increased food intake, thereby ameliorating their nutritional status and mitigating associated risks. Additionally, the study aims to pinpoint the optimal dosage that provides maximal benefits. The protocol adheres to the SPIRIT 2013 Statement, which provides evidence-based recommendations and is widely endorsed as an international standard for trial protocols. The clinical trial protocol has been registered at the platform for Clinical Trials (NCT05486260)Ministerio de Ciencia, Innovación y Universidades (España)Depto. de MedicinaFac. de MedicinaTRUEpubDescuento UC

Implication of Different Tumor Biomarkers in Drug Resistance and Invasiveness in Primary and Metastatic Colorectal Cancer Cell Lines

Protein expression profiles are directly related to the different properties of cells and are conditioned by the cellular niche. As an example, they are the cause of the characteristic cell plasticity, epithelium–mesenchymal transition (EMT), and drug resistance of cancer cells. This article characterizes ten biomarkers related to these features in three human colorectal cancer cell lines: SW-480, SW-620, and DLD-1, evaluated by flow cytometry; and in turn, resistance to oxaliplatin is studied through dose–response trials. The main biomarkers present in the three studied lines correspond to EpCAM, CD-133, and AC-133, with the latter two in low proportions in the DLD-1 line. The biomarker CD166 is present in greater amounts in SW-620 and DLD-1 compared to SW-480. Finally, DLD-1 shows high values of Trop2, which may explain the aggressiveness and resistance of these cells to oxaliplatin treatments, as EpCAM is also highly expressed. Exposure to oxaliplatin slows cell growth but also helps generate resistance to the treatment. In conclusion, the response of the cell lines is variable, due to their genetic variability, which will condition protein expression and cell growth. Further analyses in this area will provide important information for better understanding of patients’ cellular response and how to prevent resistance

Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis—The ESCAPE Study

International audienceBackground: Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment.Methods: We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome.Results: Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59-29.13] and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03-838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2-84 months), led to minor adverse effects.Conclusion: L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients

Role of age and comorbidities in mortality of patients with infective endocarditis.

The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups: A total of 3120 patients with IE (1327  There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in th