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In the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads in tissues determined by RT-qPCR, histopathology in brain and lungs, immunohistochemical study in brain (IHC) as well as mortality rates, clinical signs and plasma inflammatory and coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 challenged mice presented higher viral loads in the brain and an increased frequency of neuroinvasion, with the greatest differences observed between groups at 3-4 days post-infection (dpi). Histopathological examination showed a higher severity of brain lesions in BCG-SARS-CoV-2 challenged mice, mainly consisting of neuroinflammation, increased glial cell population and neuronal degeneration, from 5 dpi onwards. This group also presented higher interstitial pneumonia and vascular thrombosis in lungs (3-4 dpi), BCG-SARS-CoV-2 mice showed higher values for TNF-α and D-dimer values, while iNOS values were higher in SARS-CoV-2 mice at 3-4 dpi. Results presented in this study indicate that BCG stimulation could have intensified the inflammatory and neurodegenerative lesions promoting virus neuroinvasion and dissemination in this experimental model. Although k18-hACE2 mice show higher hACE2 expression and neurodissemination, this study suggests that, although the benefits of BCG on enhancing heterologous protection against pathogens and tumour cells have been broadly demonstrated, potential adverse outcomes due to the non-specific effects of BCG should be considered., (© 2024. The Author(s).)

Purpose: The paper aims to evaluate the efficacy and safety of 223 Ra in patients who progressed after first-line androgen deprivation therapy., Patients and Methods: EXCAAPE (NCT03002220) was a multicentre, single-arm, open-label, non-controlled phase IIa trial in 52 patients with metastatic castration-resistant prostate cancer and asymptomatic bone metastases who have progressed on abiraterone acetate or enzalutamide, up to six doses of 223 Ra (55 kBq/kg of body weight per month). The primary end-point was radiographic progression-free survival (rPFS). Secondary end-points included rPFS based on androgen receptor splice variant 7 (AR-V7) expression in circulating tumour cells (CTCs), overall survival, and safety., Results: Median rPFS was 5.5 months (95% CI 5.3-5.5). Median rPFS of patients with AR-V7(-) CTCs was longer than that of patients with AR-V7(+) CTCs (5.5 versus 2.2 months, respectively; P = 0.056). Median overall survival was 14.8 months (95% CI 11.2-not reached) and was significantly greater for AR-V7(-) patients than for AR-V7(+) patients (14.8 months versus 3.5 months, respectively; P < 0.01). 223 Ra was well tolerated; anaemia and thrombocytopenia were the most common grade 3/4 adverse events (5.8% and 11.5%, respectively)., Conclusions: 223 Ra seems to be a reasonable treatment for patients with metastatic castration-resistant prostate cancer and asymptomatic bone metastases progressing on novel hormonal therapy and had an acceptable safety profile., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bayer, Johnson & Johnson, Bristol-Myers Squibb, Astellas Pharma, Pfizer, Sanofi, MSD, Roche, AstraZeneca, Asofarma, Ipsen, AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, Aveo Pharmaceuticals INC, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim España, S.A., , Clovis Oncology INC, Cougar Biotechnology INC, Deciphera Pharmaceuticals LLC, Exelixis INC, F. Hoffmann-La Roche LTD, Genentech INC, GlaxoSmithKline, Incyte Corporation, -Cilag, International NV, Karyopharm Therapeutics INC., EISAI, Merck Serono, Lilly, Novartis Pharmaceutical, S.A, Janssen, Eusa Pharma, Sanofi-Genzyme, Beigene, VCN biotech, and VCN biotech; Leurquin Mediolanum SAS, Pierre Fabre, Rovi, Daiichi Sankyo, Techdow, Leo Pharma, Menarini, Ferrer, Millennium Pharmaceuticals, INC, Medimmune, Nanobiotix SA, S.L.U, Puma Biotechnology, FJ Pharma LTD. II, Teva Pharma S.L.U., MEDSIR., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The aim of this study was to assess general anxiety levels in endodontists and dental assistants related to different conditions during the pandemic and lockdown and to evaluate hemodynamic changes in endodontists' heart rate (HR), blood pressure, and blood oxygenation during their workday., Methods: Anxiety levels in endodontists and dental assistants were recorded weekly during the state of alarm declared because of the coronavirus disease 2019 pandemic. Hemodynamic parameters were monitored using a sphygmomanometer for HR and blood pressure and a pulse oximeter for oxygen saturation. Measurements were taken before and after each root canal treatment as well as on arrival at the clinic and at the end of the working day. Rest data, recorded every Saturday, served as a control. Data analysis was performed using chi-square, paired t, Mann-Whitney, and analysis of variance tests (P < .05)., Results: General anxiety decreased over the weeks, with significant differences between weeks 1 and 4 (P < .05). Endodontists perceived higher anxiety levels of anxiety during anesthesia inoculation and dental assistants during the dental unit's disinfection and equipment material (P < .05). There was a significant increase in the cardiovascular response in all endodontists in the clinic registrations compared with rest data (P < .05). Values were higher in the strict confinement period and significant for HR when arriving at the clinic (P < .05)., Conclusions: Levels of general anxiety were higher during the first weeks. The chief perceived factors related to anxiety in endodontists and dental assistants were the risk of contagion and protection measures. Higher HR and blood pressure levels were registered during the workday, especially when arriving at the clinic., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: The present study aimed to evaluate anxiety in patients and to monitor their heart rate (HR) and blood oxygenation (SpO 2 ) before, during, and after a root canal treatment (RCT) during the state of alarm in 2 different periods of strict and partial confinement., Methods: The patients who required a primary RCT were selected. Demographic, preoperative, and postoperative variables were registered, including perceived dental anxiety, fear, HR, and SpO 2 . Spearman correlation, chi-square, Mann-Whitney, and Kruskal-Wallis tests were used for frequency distribution and variable interaction, and Wilcoxon and Mann-Whitney tests were used to compare HR and SpO 2 between groups and different treatment points., Results: Ninety-six patients were included. The median Modified Dental Anxiety Scale scores were 8 (interquartile range [IQR], 6-9.25) and 6 (IQR, 5.5-8) in patients treated during the strict and partial confinement periods. The median fear scores were 2 (IQR, 0-5) and 3 (IQR, 1-5), respectively. Having a previous dental bad experience resulted in higher dental anxiety and fear (P < .05). HR was increased in patients with higher MDAS and fear scores and in those treated during the strict confinement (P < .05). In treatment time points T6 (x-ray taking), and T7 (post-treatment), HR decreased compared with the other evaluated treatment time points (P < .05). No clinical differences were found regarding SpO 2 ., Conclusions: Self-perception on dental anxiety and fear was similar to other studies in a nonpandemic context. Patients with higher levels of dental anxiety and those treated in the strict confinement period presented an elevated HR. However, it can be stated that RCT performed by endodontists does not result in a significant alteration in patients., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

A complete analytical protocol for the determination of 25 doping-related peptidic drugs and 3 metabolites in urine was developed by means of accurate-mass quadrupole time-of-flight (Q-TOF) LC-MS analysis following solid-phase extraction (SPE) on microplates and conventional SPE pre-treatment for initial testing and confirmation, respectively. These substances included growth hormone releasing factors, gonadotropin releasing factors and anti-diuretic hormones, with molecular weights ranging from 540 to 1320Da. Optimal experimental conditions were stablished after investigation of different parameters concerning sample preparation and instrumental analysis. Weak cation exchange SPE followed by C18 HPLC chromatography and accurate mass detection provided the required sensitivity and selectivity for all the target peptides under study. 2mg SPE on 96-well microplates can be used in combination with full scan MS detection for the initial testing, thus providing a fast, cost-effective and high-throughput protocol for the processing of a large batch of samples simultaneously. On the other hand, extraction on 30mg SPE cartridges and subsequent target MS/MS determination was the protocol of choice for confirmatory purposes. The methodology was validated in terms of selectivity, recovery, matrix effect, precision, sensitivity (limit of detection, LOD), cross contamination, carryover, robustness and stability. Recoveries ranged from 6 to 70% (microplates) and 17-95% (cartridges), with LODs from 0.1 to 1ng/mL. The suitability of the method was assessed by analyzing different spiked or excreted urines containing some of the target substances., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The Fuente de Piedra lake is a hypersaline wetland of great extension (13.5km 2 ) and rich in aquatic birds and other species. It became therefore the third Spanish wetland to be included in the Ramsar convention and has been a "nature reserve" since 1984. The lake has an endorheic basin (150km 2 ) with variable-density flows dominated by complex hydrogeological conditions. The traditional conceptualization of endorheic basins in semiarid climates considered that the brine in this hydric system was exclusively of evaporative origin and was placed only in the lake and its surrounding discharge area in the basin. Previous geophysical and hydrochemical studies identified different types of waters and brines. In this work, natural tracers (Cl - , Br - , Na + , Mg 2+ ) and environmental isotopes ( 18 O, 2 H, 14 C, 13 C and 3 H) were employed to a) discriminate different types of brines according to their degree of evaporation and genesis, and b) to estimate residence times of brine waters and identify recharge areas of the different flow subsystems. A conceptual model of the hydrogeological system of the lake basin and its links to a regional karst system is proposed., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Evidence of original coloration in fossils provides insights into the visual communication strategies used by ancient animals and the functional evolution of coloration over time [1-7]. Hitherto, all reconstructions of the colors of reptile integument and the plumage of fossil birds and feathered dinosaurs have been of melanin-based coloration [1-6]. Extant animals also use other mechanisms for producing color [8], but these have not been identified in fossils. Here we report the first examples of carotenoid-based coloration in the fossil record, and of structural coloration in fossil integument. The fossil skin, from a 10 million-year-old colubrid snake from the Late Miocene Libros Lagerstätte (Teruel, Spain) [9, 10], preserves dermal pigment cells (chromatophores)-xanthophores, iridophores, and melanophores-in calcium phosphate. Comparison with chromatophore abundance and position in extant reptiles [11-15] indicates that the fossil snake was pale-colored in ventral regions; dorsal and lateral regions were green with brown-black and yellow-green transverse blotches. Such coloration most likely functioned in substrate matching and intraspecific signaling. Skin replicated in authigenic minerals is not uncommon in exceptionally preserved fossils [16, 17], and dermal pigment cells generate coloration in numerous reptile, amphibian, and fish taxa today [18]. Our discovery thus represents a new means by which to reconstruct the original coloration of exceptionally preserved fossil vertebrates., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Reconstructing the feeding mode of the latest common ancestor of deuterostomes is key to elucidating the early evolution of feeding in chordates and allied phyla; however, it is debated whether the ancestral deuterostome was a tentaculate feeder or a pharyngeal filter feeder. To address this, we evaluated the hydrodynamics of feeding in a group of fossil stem-group echinoderms (cinctans) using computational fluid dynamics. We simulated water flow past three-dimensional digital models of a Cambrian fossil cinctan in a range of possible life positions, adopting both passive tentacular feeding and active pharyngeal filter feeding. The results demonstrate that an orientation with the mouth facing downstream of the current was optimal for drag and lift reduction. Moreover, they show that there was almost no flow to the mouth and associated marginal groove under simulations of passive feeding, whereas considerable flow towards the animal was observed for active feeding, which would have enhanced the transport of suspended particles to the mouth. This strongly suggests that cinctans were active pharyngeal filter feeders, like modern enteropneust hemichordates and urochordates, indicating that the ancestral deuterostome employed a similar feeding strategy., (© 2015 The Author(s).)

Automation of sample preparation procedures in a doping control laboratory is of great interest due to the large number of samples that have to be analyzed, especially in large events where a high throughput protocol is required to process samples over 24 h. The automation of such protocols requires specific equipment capable of carrying out the diverse mechanical tasks required for accomplishing these analytical methodologies, which include pipetting, shaking, heating, or crimping. An automated sample preparation procedure for the determination of doping-related substances by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis, including enzymatic hydrolysis, liquid-phase extraction and derivatization steps, was developed by using an automated liquid handling system. This paper presents a description of the equipment, together with the validation data for 72 doping-related compounds including extraction efficiency, evaluation of carry-over, interferences, and robustness. Validation was approached as a comparison between the results obtained using the manual protocol and the transferred automated one. The described methodology can be applied for sample preparation in routine anti-doping analysis with high sample throughput and suitable performance., (Copyright © 2013 John Wiley & Sons, Ltd.)

This work aimed to determine the cause of the presence of high concentrations of mercury in several springs that exhibit a low concentration of metals in the bedrocks of their recharge areas in Gijón, NW Spain and the extent of this contamination. On the basis of geological mapping, different lithological substrata were analysed at the regional scale with the objective of establishing the base level of mercury in natural soils. The mercury content was simultaneously analysed in several water samples, and the following parameters were also determined: major anions and cations, As, Pb, δ(34)S, and δ(18)OSO4. The soils of the recharge area of the springs exhibited Hg concentrations that were higher than the base level established for sandstone at the regional level, and four of the total number of springs analysed exhibited Hg concentrations higher than 1 μg/l. In addition, the sulphate concentration exceeded the values that this type of aquifer shows in other parts of the region. A comparison between the regionally geochemical background of soils and mercury concentration in springs and soils of the study area did not exhibit a direct relationship, suggesting an anthropogenic and timely origin (most likely from industrial emissions) for this metal. The δ(34)S and δ(18)OSO4 values of dissolved sulphate from the springs with a higher Hg concentration also indicate an anthropogenic origin., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Since its 1995 closure and the subsequent 1998 accident, the Aznalcóllar mine pit has been used as a disposal site for diverse metal-rich materials, such as the polluted soils removed during the cleaning of areas along the Guadiamar River, waste rock, pyrite sludge, and ashes deriving from pyrite roasting. At present, the mining pit is partly flooded and contains a highly acidic (pH 2.7) pit lake with approximately 6 Mm3 of metal and sulphate-rich water. Recent detailed research performed in the area has proven that the reaction of the lake water with both the dumping mining wastes and the inflow of acid mine waters are strongly modifying the water quality of the pit lake. A major change was identified in the water quality that resulted from the dumping of 1.4 Mm3 of pyritic wastes during 2005 and 2006. The oxidative dissolution of this mineral has resulted in: (1) a total consumption of dissolved oxygen, (2) a notable increase of electric conductivity (from 8.6 to 12 mS/cm) and (3) a strong acidification (pH from 4.2 to 2.7) and an important heating that was observed as a result of the exothermic character of pyrite oxidation. Despite the total lack of oxidizing agents-such as 02 and Fe(III) (Fe[III] < 5% total Fe)-in the pit lake, pyrite is being oxidized with a continuous increase of the SO(4)2- and Fe concentrations.

The Campo de Dalias is an area with relevant seismicity associated to the active tectonic deformations of the southern boundary of the Betic Cordillera. A non-permanent GPS network was installed to monitor, for the first time, the fault- and fold-related activity. In addition, two high precision levelling profiles were measured twice over a one-year period across the Balanegra Fault, one of the most active faults recognized in the area. The absence of significant movement of the main fault surface suggests seismogenic behaviour. The possible recurrence interval may be between 100 and 300 y. The repetitive GPS and high precision levelling monitoring of the fault surface during a long time period may help us to determine future fault behaviour with regard to the existence (or not) of a creep component, the accumulation of elastic deformation before faulting, and implications of the fold-fault relationship.

Red soils are widely distributed in Mediterranean regions. They constitute one of the most important soil resources for crop production and other uses. The main objective of this paper is to estimate the inherent chemical susceptibility of red soils of La Mancha to chemical degradation. Selected 47 soil profiles, were analyzed in the area by means of multivariate analysis; we identified five soil attributes that are well represented in the local soils database, which are most likely to control the chemical vulnerability. These attributes are the calcium carbonate, organic matter and clays together with soil depth and drainage. The attributes were transformed and a simple vulnerability index (VI) was deviced. We concluded that the index may be used as a first approximation rating of La Mancha's red soils vulnerability against an eventual chemical degradation, or to aid resource management and prevent anthropogenic potential impacts.