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This paper introduces the Combined Drought Indicator dataset, a collection of raster maps generated by the Copernicus European Drought Observatory for monitoring agricultural drought in Europe. Computationally, the CDI involves three indicators: the Standardized Precipitation Index, the Soil Moisture Anomaly and the Fraction of the Photosyntetically Active Radiation anomaly. These are complemented by the use of crop and snow masks. The CDI dataset has a spatial resolution of 1/24 decimal degrees (∼5 km), a temporal resolution of 10 days and is available from 2012 onward. As drought effects are variegated both in space and time, the CDI provides an effective instrument for assessing the different stages of propagation of agricultural drought and their spatial extent. Furthermore, the CDI maps provide relevant information for those private and public actors (water resource agencies, farmers, land managers and so on) involved both in drought preparedness and planning to mitigate drought impacts. Users can access and download the dataset from the Copernicus European Drought Observatory web portal, where an online mapviewer and clickable maps facilitate its interactive exploration., Competing Interests: Competing interests: I declare that the authors have no competing interests as defined by Nature Research, or other interests that might be perceived to influence the results and/or discussion reported in this paper., (© 2025. The Author(s).)

Cartagena-La Union mining district (SE Spain) has unconnected dry riverbeds, which transport mining waste downstream under torrential rain events, polluting a coastal lagoon (Mar Menor). Additionally, in the cropland Campo de Cartagena, agricultural activities promote nitrate and phosphate accumulation in that lagoon. Therefore, this study aimed to evaluate the spatial-temporal trends of sediments and runoff water properties in El Albujón y La Carrasquilla riverbeds. The sampling campaign was carried out before (BR) and after (AR) rainy period. Georeferenced points were established from the headwaters to the mouth of two riverbeds, 12 sediment samples were collected in each riverbed. Meanwhile, runoff water in El Albujón consisted of 9 points covering the zone that continuously drained into Mar Menor lagoon. Also, water samples were collected in La Carrasquilla during the rainy period, from 18th to 28th of March, the samples were located in the headwater and the mouth of the dry riverbed. Sediments samples were analyzed for pH, electrical conductivity, organic/inorganic carbon, nutrients and heavy metals. To determine the pollution level by metal(loid)s in sediment and water, the reference background values established by World Health Organization (WHO) for water, and pollution indexes (contamination factor, pollution load index, potential ecological risk index) for sediments were used. The results of the runoff water of El Albujón exhibited no temporal variation, with a high concentration of NO 3 - along the discharge zone, which exceeds the standards established by WHO (102 mg L -1 BR and 101 mg L -1 AR). In the sediments of El Albujón, the pollution indexes showed no contamination of metal(loid). Oppositely, La Carrasquilla dry riverbed presented metal(loid)s contamination in the sediment in all the sampling points for both sampling periods (BR and AR). In the case of runoff water, in La Carrasquilla, during the rain event, the results exhibited concentrations over the limits for Cd, Mn, and Zn in the headwater. The temporal variability between a dry and rainy period represented a significant variance, especially for the metal(loid)s concentration on both sites. These results can support the design of mitigation plans for reducing environmental impacts associated with these riverbeds., Competing Interests: Declaration of competing interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Agroecological ecosystems produce significant carbon dioxide fluxes; however, the equilibrium of their carbon sequestration, as well as emission rates, faces considerable uncertainties. Therefore, sustainable cropping practices represent a unique opportunity for carbon sequestration, compensating greenhouse gas emissions. In this research, we evaluated the short-term effect of different management practices in alleys (tillage, no tillage, alley cropping with Rosmarinus officinalis and Thymus hyemalis on soil properties, carbon sequestration, and CO 2 emissions in a grapefruit orchard under semiarid climate). For two years every four months, soil sampling campaigns were performed, soil CO 2 emissions were measured, and rhizosphere soils were sampled at the end of the experimental period. The results show that alley cropping with Thymus and Rosmarinus contributed to improve soil fertility, increasing soil organic carbon (SOC), total nitrogen, cation exchange capacity, and nutrients. The CO 2 emission rates followed the soil temperature/moisture pattern. Tillage did not contribute to higher overall CO 2 emissions, and there were no decreased SOC contents. In contrast, alley crops increased CO 2 emission rates, especially Rosmarinus ; however, the bigger root system and biomass of Rosmarinus contributed to soil carbon sequestration at a greater rate than Thymus . Therefore, Rosmarinus is positioned as a better option than Thymus to be used as an alley crop, although long-term monitoring is required to evaluate if the reported short-term benefits are maintained over time.

Background: The 2014 expansion of Medicaid under the Affordable Care Act (ACA) reshaped healthcare delivery in the United States. This study assessed how Medicaid expansion affected in-hospital mortality in patients with extreme risk of mortality (EROM) from traumatic injuries., Methods: Data from inpatients aged 18-64 years, registered in the National Inpatient Sample between 2007 and 2020, and identified with trauma-related All-Patient Refined Diagnosis Related Groups (APRDRG) codes, were analyzed. Within this group, a subset of patients was selected based on the APRDRG classification identifying them as at EROM for the principal unit of analysis. The cohort was divided into high-implementation (HIR) and low-implementation (LIR) regions based on Medicaid expansion coverage. In-hospital mortality was assessed using interrupted time-series analysis. Sensitivity analyses considered seasonality, autocorrelation, and exogenous events., Results: Analysis encompassed 70 381 trauma inpatient stays, corresponding to 346 659 patients based on National Inpatient Sample weighting. There was a consistent monthly decline in in-hospital mortality of .08% (95% CI: -.103 to -.048; P < .001) prior to Medicaid expansion, a trend unaffected by expansion. This pattern persisted across both LIR and HIR Medicaid implementation regions. Although Medicaid enrollment increased in HIR, that in LIR remained unchanged., Discussion: Over the study period, the in-hospital mortality among severely injured patients consistently decreased, and this trend was not influenced by Medicaid expansion. The statistical models and results from this study can offer valuable guidance to policymakers and healthcare leaders as they formulate more efficient and effective policies., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Persistent disparities in trauma in-hospital mortality owing to insurance status and race remain a prominent issue within healthcare. This study explores the relationships among insurance status, race, length of stay (LOS) in-hospital mortality outcomes in trauma patients at extreme risk of mortality (EROM) trauma patients., Methods: Data was retrieved from the National Inpatient Sample, focusing on high-acuity trauma patients from 2007 to 2020, aged 18-64 years. Patients were identified using specific All Patient Refined Diagnosis Related Groups codes. Emphasis was placed on those with EROM owing to their resource-intensive nature and the potential influence of insurance on outcomes. Patients aged 65 years or older were excluded owing to distinct trauma patterns, as were those diagnosed with burns or non-trauma conditions., Results: The study encompassed 70,381 trauma inpatients with EROM, representing a national estimate of 346,659. Being insured was associated with a 34% decrease in the odds of in-hospital mortality compared to being uninsured. The in-hospital mortality risk associated with insurance status varied over time, with insurance having no impact on in-hospital mortality during hospitalizations of less than 2 days (short LOS). In the overall group, Black patients showed an 8% lower risk of in-hospital mortality compared to White patients, while they experienced a 33% higher risk of in-hospital mortality during short LOS., Conclusion: Insured trauma inpatients demonstrated a significant reduction in the odds of in-hospital mortality compared to their uninsured counterparts, although this advantage was not present in the short LOS group. Black patients experienced lower in-hospital mortality rates compared to White patients, but this trend reversed in the short LOS group. These findings underscore the intricate relationships between insurance status, race, and duration of hospitalization, highlighting the need for interventions to improve patient outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 José A. Acosta. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The objective of this study was to evaluate the level of pollution, sources and potential risk of heavy metals (Zn, Cu, Mn, Cd, Cr, Ni, Fe and Pb) and arsenic (As) in four dry riverbeds affected by mine tailing, which drain into one of the biggest coastal lagoon of Europe (Mar Menor). El Beal, La Carrasquilla, Las Matildes and Ponce dry riverbeds sediments were sampled along its course (20, 18, 13, 19 samples were collected, respectively), and total/soluble metal(loid)s, water soluble ions, nitrogen, and organic/inorganic carbon contents were analyzed. Spatial distribution, principal component analysis (PCA), hierarchical cluster analysis (HCA), contamination factor (Cf), pollution load index (PLI) and potential ecological risk index (RI) were used to identify the possible sources of metal(loid)s and to assess the sediment pollution status. The results showed that the mean total concentrations of As, Cu, Cd, Mn, Zn and Pb exceeded the natural background levels of the study area, with the highest values located close to the mining areas. Correlation and cluster analysis identified that Cd and Zn were associated mainly with anthropogenic activities for all riverbeds, while Cr and Ni come from parent. PLI graded the four riverbeds as contaminated by heavy metals, while RI manifested that 100% of samples located in El Beal, La Carrasquilla and Las Matildes had a significantly high ecological risk. Therefore, this study suggests that mine wastes are the main source of metal(loids) contamination in the dry riverbeds, which results can be used to design actions and measures to reduce the environmental impact of metal(loid)s in the Mar Menor coastal lagoon., (© 2023. The Author(s).)

The aim of this study was to evaluate the most abundant native plants that could be used as a bio-monitor of metal(loid) concentration in dry riverbeds affected by mining activities. Three plants species and their respective rhizospheric soils were sampled from the El Beal ( Piptatherum miliaceum , 15 samples), La Carrasquilla ( Foeniculum vulgare , 10 samples), and Ponce ( Dittrichia viscosa , 12 samples) dry riverbeds from the mining district of Cartegena-La Unión (SE Spain). There is scanty bibliography of the capacity of these species to be used as bio-monitors in the dry riverbeds. Plants categorized as a bio-monitor were established according to the bioaccumulation factor (BF), mobility ratio (MR), and linear correlations between metal(loid) concentrations in plants tissues (root or stem)-rhizospheric soils. The rhizospheric soils were highly contaminated for As, Cd, Pb, and Zn (Cf ≥ 6), and moderately contaminated for Mn (1 ≤ Cf < 3). Piptatherum miliaceum presented on Cd similar mean concentrations on rhizospheric soil and root, BF = 1.07, with a strong correlation soil-root (r = 0.61, p = 0.02). Therefore, of the three species with the capacity to grow in the area, Piptatherum miliaceum showed characteristics to be considered as a bio-monitor for Cd, with a BF > 1, and a positive-significant correlation between the rhizospheric soil and roots.

Mining activities accumulate large quantities of waste in tailing ponds, which results in several environmental impacts. In Cartagena-La Unión mining district (SE Spain), a field experiment was carried out in a tailing pond to evaluate the effect of aided phytostabilization on reducing the bioavailability of zinc (Zn), lead (Pb), copper (Cu) and cadmium (Cd) and enhancing soil quality. Nine native plant species were planted, and pig manure and slurry along with marble waste were used as amendments. After 3 years, the vegetation developed heterogeneously on the pond surface. In order to evaluate the factors affecting this inequality, four areas with different VC and an area without treatment (control area) were sampled. Soil physicochemical properties, total, bioavailable and soluble metals, and metal sequential extraction were determined. Results revealed that pH, organic carbon, calcium carbonate equivalent and total nitrogen increased after the aided phytostabilization, while electrical conductivity, total sulfur and bioavailable metals significantly decreased. In addition, results indicated that differences in VC among sampled areas were mainly owing to differences in pH, EC and concentration of soluble metals, which in turn were modified by the effect of non-restored areas on close restored areas after heavy rains due to a lower elevation of the restored areas compared to the unrestored ones. Therefore, to achieve the most favorable and sustainable long-term results of aided phytostabilization, along with plant species and amendments, micro-topography should be also taken into consideration, which causes different soil characteristics and thus different plant growth and survival., (© 2023. The Author(s).)

Mining activity has an adverse impact on the surrounding ecosystem, especially via the release of potentially toxic elements (PTEs); therefore, there is an urgent need to develop efficient technologies to remediate these ecosystems, especially soils. Phytoremediation can be potentially used to remediate contaminated areas by potentially toxic elements. However, in soils affected by polymetallic contamination, including metals, metalloids, and rare earth elements (REEs), it is necessary to evaluate the behavior of these toxic elements in the soil-plant system, which will allow the selection of the most appropriate native plants with phytoremediation potential to be used in phytoremediation programs. This study was conducted to evaluate the level of contamination of 29 metal(loid)s and REEs in two natural soils and four native plant species ( Salsola oppositifolia , Stipa tenacissima , Piptatherum miliaceum , and Artemisia herba-alba ) growing in the vicinity of a Pb-(Ag)-Zn mine and asses their phytoextraction and phytostabilization potential. The results indicated that very high soil contamination was found for Zn, Fe, Al, Pb, Cd, As, Se, and Th, considerable to moderate contamination for Cu, Sb, Cs, Ge Ni, Cr, and Co, and low contamination for Rb, V, Sr, Zr, Sn, Y, Bi and U in the study area, dependent of sampling place. Available fraction of PTEs and REEs in comparison to total concentration showed a wide range from 0% for Sn to more than 10% for Pb, Cd, and Mn. Soil properties such as pH, electrical conductivity, and clay content affect the total, available, and water-soluble concentrations of different PTEs and REEs. The results obtained from plant analysis showed that the concentration of PTEs in shoots could be at a toxicity level (Zn, Pb, and Cr), lower than toxic but more than sufficient or natural concentration accepted in plants (Cd, Ni, and Cu) or at an acceptable level (e.g., V, As, Co, and Mn). Accumulation of PTEs and REEs in plants and the translocation from root to shoot varied between plant species and sampling soils. A. herba-alba is the least efficient plant in the phytoremediation process; P. miliaceum was a good candidate for phytostabilization of Pb, Cd, Cu, V, and As, and S. oppositifolia for phytoextraction of Zn, Cd, Mn, and Mo. All plant species except A. herba-alba could be potential candidates for phytostabilization of REEs, while none of the plant species has the potential to be used in the phytoextraction of REEs.

Introduction: Enhanced recovery after lung surgery (ERALS) protocols have proven useful in reducing postoperative stay (POS) and postoperative complications (POC). We studied the performance of an ERALS program for lung cancer lobectomy in our institution, aiming to identify which factors are associated with a reduction of POC and POS., Methods: Analytic retrospective observational study conducted in a tertiary care teaching hospital involving patients submitted to lobectomy for lung cancer and included in an ERALS program. Univariable and multivariable analysis were employed to identify factors associated with increased risk of POC and prolonged POS., Results: A total 624 patients were enrolled in the ERALS program. The median POS was 4 days (range 1-63), with 2.9% of ICU postoperative admission. A videothoracoscopic approach was used in 66.6% of cases, and 174 patients (27.9%) experienced at least one POC. Perioperative mortality rate was 0.8% (5 cases). Mobilization to chair in the first 24h after surgery was achieved in 82.5% of cases, with 46.5% of patients achieving ambulation in the first 24h. Absence of mobilization to chair and preoperative FEV1% less than 60% predicted, were identified as independent risk factors for POC, while thoracotomy approach and the presence of POC predicted prolonged POS., Conclusions: We observed a reduction in ICU admissions and POS contemporaneous with the use of an ERALS program in our institution. We demonstrated that early mobilization and videothoracoscopic approach are modifiable independent predictors of reduced POC and POS, respectively., (Copyright © 2022 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF., Objective: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender., Methods: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender., Results: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women., Conclusions: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk., (Copyright: © 2023 Permanyer.)

The implementation of alley cropping in orchards can be a sustainable strategy to increase farm productivity by crop diversification and contribute to climate change mitigation. In this research, we evaluated the short-term effect of alley cropping with reduced tillage on soil CO 2 and N 2 O emissions and soil total organic carbon (TOC) in an almond orchard under Mediterranean rainfed conditions. We compared an almond monoculture with tillage in all plot surface (MC) with almond crop with reduced tillage and growth of Capparis spinosa (D1) and almond crop with reduced tillage and growth of Thymus hyemalis (D2). For two years, soil CO 2 and N 2 O were measured, with soil sampling at the start and end of the experimental period. Results showed that CO 2 emission rates followed the soil temperature pattern, while N 2 O emissions were not correlated with temperature nor moisture. Soil CO 2 emissions were significantly higher in MC (87 mg m -2 h -1 ), with no significant differences between D1 and D2 (69 mg m -2 h -1 ). Some peaks in CO 2 effluxes were observed after tillage operations during warm days. Soil N 2 O emission rates were not significantly different among treatments. Cumulative CO 2 and CO 2 equivalent (CO 2 e) emissions were significantly highest in MC. When CO 2 e emissions were expressed on a crop production basis, D2 showed the significantly lowest values (5080 g kg -1 ) compared to D1 (50,419 g kg -1 ) and MC (87,836 g kg -1 ), owing to the high thyme yield, additional to the almond yield. No production was obtained for C. spinosa, since at least two more years are required. TOC did not change with time in MC neither D1, but it significantly increased in D2 from 3.85 g kg -1 in 2019 to 4.62 g kg -1 in 2021. Thus, alley cropping can contribute to increase the agroecosystem productivity and reduce CO 2 emissions. However, it is necessary to grow evergreen alley crops such as thyme to obtain short-term increases in soil organic matter. Thus, to estimate increases in TOC with alley cropping, the plantation density and the period required by the crop to cover most of the surface are essential factors at planning the cropping strategy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Raul Zornoza reports financial support was provided by European Commission., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/aim: Although some mutations of KRAS proto-oncogene, GTPase (KRAS) have been associated with the prognosis and therapeutic management of colorectal cancer (CRC), the epigenetic mechanisms (DNA methylation and microRNA expression) that regulate wild-type KRAS expression in patients with CRC are poorly known. The aim of this study was to establish whether there is a relationship between the expression of the wild-type KRAS gene, the methylation status of its distal promoter, and miR-143 and miR-18a-3p levels in samples of sporadic CRC., Patients and Methods: A total of 51 cases of sporadic CRC with wild-type KRAS were analyzed. The expression levels of KRAS mRNA, miR-18a-3p, miR-143, and KRAS protein, as well as methylation in the distal promoter of the KRAS gene were evaluated., Results: In the analyzed cases, KRAS mRNA expression was detected in 51.1%; wild-type KRAS protein was found in the membrane in 31.4% and in the cytoplasm in 98% of cases. An inverse relationship of marginal significance was observed between miR-18a-3p and KRAS protein expression in the cytoplasm (odds ratio=0.14, 95% confidence interval=0.012-1.092; p=0.08). The methylation status of the distal promoter of KRAS at four CpG islands was analyzed in 30 cases (58.8%): partial methylation of the four CpG islands evaluated was observed in two cases (6.7%). In these cases, KRAS protein expression was not evidenced at the membrane level; miR-18a-3p expression was not detected either but high expression of miR-143 was observed., Conclusion: No association was found between the expression levels of KRAS mRNA, miR-18a-3p, miR-143 and methylation status. Methylation status was detected with low frequency, thus being the first report of methylation in wild-type KRAS., Competing Interests: The Authors declare that they have no competing interests., (Copyright 2022, International Institute of Anticancer Research.)

Water scarcity in arid and semiarid regions poses problems for agricultural systems, awakening special interest in the development of deficit irrigation strategies to improve water conservation. Toward this purpose, farmers and technicians must monitor soil water and soluble nutrient contents in real time using simple, rapid and economical techniques through time and space. Thus, this study aimed to achieve the following: (i) create a model that predicts water and soluble nutrient contents in soil profiles using electrical resistivity tomography (ERT); and (ii) apply the model to different woody crops under different irrigation regimes (full irrigation and regulated deficit irrigation (RDI)) to assess the efficiency of the model. Simple nonlinear regression analysis was carried out on water content and on different ion contents using electrical resistivity data as the dependent variable. A predictive model for soil water content was calibrated and validated with the datasets based on exponential decay of a three-parameter equation. Nonetheless, no accurate model was achieved to predict any soluble nutrient. Electrical resistivity images were replaced by soil water images after application of the predictive model for all studied crops. They showed that under RDI situations, soil profiles became drier at depth while plant roots seemed to uptake more water, contributing to reductions in soil water content by the creation of desiccation bulbs. Therefore, the use of ERT combined with application of the validated predictive model could be a sustainable strategy to monitor soil water evolution in soil profiles under irrigated fields, facilitating land irrigation management.

This study aimed to determine the transfer of metals (Cd, Pb and Zn) and As to a Mediterranean forest close to five tailings ponds in Cartagena-La Union mining district (SE Spain). In addition, the effect of the rhizosphere of two native plant species, Olea europaea (OE) and Pistacia lentiscus (PL), on soil properties and chemical speciation of metal(oid)s was evaluated. Results showed there was no influence of the rhizosphere in the total concentration of metal(loid)s in soil, decreasing as Pb > Zn > As > Cd. Chemical partitioning revealed that only Cd and As can be considered hazardous, with a high percentage of these elements in the soil-labile fractions (20-40%). The accumulation in vegetal tissues was only high for Pb in PL roots, which makes it a suitable species for phytostabilization. Additionally, translocation factors showed transfer of Pb and Zn in OE, and Zn in PL to aerial parts, although no toxicity evidences for plants or animals were found. Finally, soil properties affected metal(loid)s accumulation in plants. The OE species was related to soil-labile metal(loid) fractions and pH, total N, organic carbon and silt content. The PL species were associated with immobilized metal(loid) fractions, sand content, electrical conductivity and total concentrations of As, Cd and Pb. Hence, mining activity has affected native adjacent soils, with accumulation of metals in plant species, although translocation was low, likely due to physiological strategies of the studied species to protect themselves against hazardous elements, and to the high soil pH, which limits metals' mobility., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Abstract: In the future, United States Navy Role 1 and Role 2 shipboard medical departments will be caring for patients during Distributed Maritime Operations in both contested and noncontested austere environments; likely for prolonged periods of time. This literature review examines 25 modern naval mass casualty incidents over a 40-year period representative of naval warfare, routine naval operations, and ship-based health service support of air and land operations. Challenges, lessons learned, and injury patterns are identified to prepare afloat medical departments for the future fight., Level of Evidence: Literature Review, level V., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study objectives were to determine the effects of continuously infusing glucose (GLC) or casein (CAS) into the terminal ileum on biomarkers of metabolism, inflammation, and intestinal morphology in growing pigs. Crossbred gilts (n = 19; 81 ± 3 kg body weight [BW]) previously fitted with T-cannulas at terminal ileum were used in the current experiment. Following 4 d of acclimation, pigs were enrolled in 2 experimental 4-d periods (P). During P1, pigs were housed in individual pens and fed ad libitum for collection of baseline parameters. At the beginning of P2, pigs were assigned to 1 of 3 infusion treatments: 1) control (CON; water; 3 liters/d; n = 7), 2) GLC (dextrose 50%; 500 g/d; n = 6;), or 3) CAS (casein sodium salt; 300 g/d; n = 6). Water, GLC, and CAS solutions were continuously infused at a rate of 125 mL/h for the entirety of P2. Animals were euthanized at the end of P2, and intestinal tissue was collected. During P2, average daily feed intake differed across treatments and was reduced in GLC compared with CON pigs (14%), while CAS pigs consumed an intermediate amount (P = 0.05). Average daily gain and final BW were similar across treatments. A treatment by time interaction was observed for blood urea nitrogen (BUN; P < 0.01), as it decreased in GLC (21%) while it gradually increased in CAS (76%) pigs relative to CON pigs. Mild hyperthermia occurred with both GLC and CAS infusions relative to CON (+0.3 and 0.2 °C, respectively; P < 0.01). Blood neutrophils increased in CAS relative to CON pigs (26%) but remained similar between CON and GLC treatments (P < 0.01). Blood monocytes decreased in GLC relative to CON pigs (24%) while CAS pigs had an intermediate value (P = 0.03). Circulating lipopolysaccharide binding protein tended to decrease in GLC (29%) relative to CON pigs but remained similar between CON and CAS pigs (P = 0.10). Plasma tumor necrosis factor-alpha was similar across treatments. Ileum villus height:crypt depth was increased in CAS compared with CON pigs (33%; P = 0.05) while GLC pigs had an intermediate value. Colon myeloperoxidase-stained area increased in CAS compared with CON pigs (45%; P = 0.03) but remained similar between GLC and CON pigs. In summary, continuously infusing GLC or CAS into the terminal ileum appeared to stimulate a mild immune response and differently altered BUN patterns but had little or no effects on blood inflammatory markers, intestinal morphology, or key production parameters., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The approach of this experiment was to apply the regression method for the estimation of endogenous intestinal losses of ether extract (EEE) when pigs are fed complete diets ad libitum and using dietary levels of fat typical of those employed in commercial situations. A total of 40 gilts (PIC 337 sires × C22 or C29) were allotted to individual pens and randomly assigned to diets (8 pigs per treatment) with 5 different levels of acid hydrolyzed ether extract (AEE). The dietary treatments consisted of a corn-soybean meal diet with no added fat (L1); a corn-soy diet with 6% each of corn distiller's dried grains with solubles (DDGS), corn germ meal, and wheat middlings (L2); the L2 diet but with 12% each of corn DDGS, corn germ meal, and wheat middlings (L3); the L2 diet plus soybean oil to equalize the NE concentration of the L2 diet with L1 (L4); and the L3 diet plus soybean oil to equalize the NE concentration of the L3 diet with L1 (L5). Pigs received feed and water ad libitum for the growing period (initial BW = 38.5 ± 1.2 kg) and the finishing period (initial BW = 73.82 ± 2.9 kg). A quadratic broken-line model was employed to estimate the response of apparent total tract digestibility (ATTD) of AEE to dietary AEE level. The average true total tract digestibility (TTTD) of AEE and endogenous losses of AEE were estimated using regression analysis of dietary AEE intake (g/kg of DM) against apparent digested AEE (g/kg of DMI). The ATTD of AEE increased in curvilinear fashion as dietary AEE level increased in growing and in finishing pigs ( P < 0.001). This suggests an influence of EEE on the ATTD of AEE estimates. The linear regression of apparent digested AEE against dietary AEE intake (L1-L5; P < 0.001, R 2 = 0.99 for growing pigs and P < 0.001, R 2 = 0.99 for finishing pigs) estimated greater EEE ( P < 0.05) and TTTD of AEE ( P < 0.05) for growing than finishing pigs. Estimated EEE from growing pigs ranged between 18.1 and 20.2 g/kg of DMI, while TTTD of AEE ranged between 96.40% and 100.70%. In finishing pigs, EEE ranged between 21.6 and 23.8 g/kg of DMI and TTTD of AEE ranged between 91.30% and 95.25%. In conclusion, EEE under practical conditions is estimated to be 19.2 g/kg of DMI in growing and 22.7 g/kg of DMI in finishing pigs., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

The tobacco variant Nicotiana benthamiana has recently emerged as a versatile host for the manufacturing of protein therapeutics, but the fidelity of many recombinant proteins generated in this system is compromised by inadvertent proteolysis. Previous studies have revealed that the anti-HIV-1 antibodies 2F5 and PG9 as well as the protease inhibitor α 1 -antitrypsin (A1AT) are particularly susceptible to N. benthamiana proteases. Here, we identify two subtilisin-like serine proteases (NbSBT1 and NbSBT2) whose combined action is sufficient to account for all major cleavage events observed upon expression of 2F5, PG9 and A1AT in N. benthamiana. We propose that downregulation of NbSBT1 and NbSBT2 activities could constitute a powerful means to optimize the performance of this promising platform for the production of biopharmaceuticals. DATABASES: NbSBT sequence data are available in the DDBJ/EMBL/GenBank databases under the accession numbers MN534996 to MN535005., (© 2020 Federation of European Biochemical Societies.)

This study presents the results of a physical-chemical characterisation of phosphogypsum deposits generated with hydrochloric and sulphuric acid during the wet acid process. The paper aims to establish an efficient methodology based on electrical resistivity tomography (ERT), chemical analysis and multivariate analysis identifying the areas most contaminated by heavy metals in an abandoned factory where fertiliser was derived from phosphoric rock. This fertiliser has provided many benefits to agriculture; however, it generates a vast amount of waste (5 tonnes phosphoric rock/1 tonne fertiliser). The chemical composition of this by-product varies according to the industrial process performed. Hydrochloric acid (HCl) recovers more than 90% of phosphorus, while sulphuric acid (H 2 SO 4 ) recovers around 30%. Therefore, a chemical assessment of the remaining waste is a necessary step prior to initiating any remediation process. ERT provided the geometry of the deposits and the distribution of the phosphogypsum. The chemical analyses consistently validated the electrical contrast found within the deposits. We employed a correlation analysis combined with multivariate analysis to identify the relationships among the metal concentrations and resistivity. Principal component analysis (PCA) reduced the information contained in all the variables to a few principal components. The first three principal components accounted for 74% of the variability of all the studied variables. Partial least squares-discriminant analysis (PLS-DA) for classification allowed the discrimination of the two populations. Electrical resistivity was the most influential variable for separating HCl waste from that of H 2 SO 4 . The use of ERT saves time and reduces costs yielding a methodology which facilitates the environmental assessment of large areas., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Assessment of street dust is an invaluable approach for monitoring atmospheric pollution. Little information is available on the size distribution of contaminants in street dusts and urban soils, and it is not known how the population density would influence them. This research was carried out to assess the size distribution of trace metal(loid)s in street dust and urban soil, and to understand how population density might influence the size-resolved concentration of metal(loid)s. Three urban areas with a high, medium and low population density and a natural area were selected and urban soil and street dust sampled. They were fractionated into 8 size fractions: 2000-850, 850-180, 180-106, 106-50, 50-20, 20-10, 10-2, and < 2 µm. The concentration of Pb, Zn, Cu, Cd, Cr, Ni, As, and Fe was determined, and enrichment factor and grain size fraction loadings were computed. The results indicated that the concentration of Pb, Zn, Cu, Cd, and Cr was highly size dependent, particularly for particles < 100 µm, especially for street dust. Low concentrations of Ni and As in street dust and urban soil were size and population density independent. Higher size dependency of the metals concentration and the higher degree of elemental enrichment in the street dust fractions than the urban soils indicate higher contribution of human-induced pollution to the dust. Findings also confirm the inevitability of size fractionation when soils or dusts are environmentally assessed, particularly in moderately to highly polluted areas. Otherwise, higher concentrations of certain pollutants in fine-sized particles might be overlooked leading to inappropriate decisions for environmental remediation.

Anthropogenic activities such as industrial, mining, or agricultural are the main sources of environmental contamination. One of the most problematic contaminations concerns metals and metalloids from mining activities. This contamination raises the question of the environmental risk induced and the spread of this pollution (geographical and trophic) and the associated health risk. The integrated, multi-analytical approach of this study conducted on the mining district of Cartagena-La Union (Murcia, Spain) as part of the Interreg SUDOE European project "Soil Take Care" aims to (i) precisely define the speciation of contaminants of interest (Zn, Pb, Cd, As), (ii) predict the environmental risk related to storage stability, and (iii) establish the link between the speciation of the bearing phases and the associated health risk. To do this, a representative zone in the Cartagena-La Union mining district close to the populations was chosen. A physic-chemical characterization of the samples was performed (pH, electrical conductivity, CEC, and total metal(loid) concentrations), and the mineralogy was determined using XRD and SEM-EDS. The environmental risk was highlighted from sequential BCR-type extractions and EN-12457 leaching tests. Finally, the health risk was defined using the PSF inhalation bioaccessibility test and UBM bioaccessibility protocol (based on an operational chemical methodology mimicking soil ingestion and its residence in the gastrointestinal tract of the human body). These analyses revealed 2 groups of samples with distinct behavior. The first group of samples presents relatively stable bearing phases, mainly found in the residual fraction (As and Pb), presenting only a low health risk (very low bioaccessible). The second group consists of Cd and/or Zn-bearing phases, mainly labile (resulting from dissolution/precipitation phenomena), while gastric bioaccessibility reaches more than 85%. Note that Pb, Cd, and Zn have the potential to cause non-carcinogenic risks to children and As and Pb present a carcinogenic risk for children and adults even if only the bioaccessible fraction is considered. It has therefore been shown that the meteoric alteration of the tailing induces a change in speciation leads to an increase in environmental and health risks. These results are essential because they highlight the need for an integrated approach in order to clearly highlight the presence of risks but also that this approach will allow a better understanding of the potential rehabilitation path of this site.

Diabetes is constantly increasing at a rate that outpaces genetic variation and approaches to pandemic magnitude. Skin cells physiology and the cutaneous healing response are progressively undermined in diabetes which predisposes to lower limb ulceration, recidivism, and subsequent lower extremities amputation as a frightened complication. The molecular operators whereby diabetes reduces tissues resilience and hampers the repair mechanisms remain elusive. We have accrued the notion that diabetic environment embraces preconditioning factors that definitively propel premature cellular senescence, and that ulcer cells senescence impair the healing response. Hyperglycemia/oxidative stress/mitochondrial and DNA damage may act as major drivers sculpturing the senescent phenotype. We review here historical and recent evidences that substantiate the hypothesis that diabetic foot ulcers healing trajectory, is definitively impinged by a self-expanding and self-perpetuative senescent cells society that drives wound chronicity. This society may be fostered by a diabetic archetypal secretome that induces replicative senescence in dermal fibroblasts, endothelial cells, and keratinocytes. Mesenchymal stem cells are also susceptible to major diabetic senescence drivers, which accounts for the inability of these cells to appropriately assist in diabetics wound healing. Thus, the use of autologous stem cells has not translated in significant clinical outcomes. Novel and multifaceted therapeutic approaches are required to pharmacologically mitigate the diabetic cellular senescence operators and reduce the secondary multi-organs complications. The senescent cells society and its adjunctive secretome could be an ideal local target to manipulate diabetic ulcers and prevent wound chronification and acute recidivism. This futuristic goal demands harnessing the diabetic wound chronicity epigenomic signature., (Copyright © 2020 Berlanga-Acosta, Guillén-Nieto, Rodríguez-Rodríguez, Mendoza-Mari, Bringas-Vega, Berlanga-Saez, García del Barco Herrera, Martinez-Jimenez, Hernandez-Gutierrez and Valdés-Sosa.)

The objective of this study was to determine the impact of reducing the mean particle size (PS) of corn distillers dried grains with solubles (DDGS) with a hammermill (HM) or with a roller mill (RM) on the apparent total tract digestibility (ATTD) of dry matter (DM), gross energy (GE), N, acid hydrolyzed ether extract (AEE), and fiber components in growing and finishing pigs. Twenty-four growing barrows were housed in individual pens and were randomly assigned to a 3 × 2 factorial design ( n = 8): three grinding methods [either corn DDGS ground with an HM to a PS of 450 μm; corn DDGS ground with an RM to a PS of 450 μm; and corn DDGS with a PS of 670 μm (not further ground)] and two body weight (BW) periods (growing pigs with an average initial BW of 54.7 ± 0.9 kg, and finishing pigs with an average initial BW of 107.8 ± 1.5 kg BW). Fecal samples were collected for each BW period in the last 3 d of an 11-d feeding period. Titanium dioxide was used as an indigestible marker. Digestibility data were analyzed using the MIXED procedure of SAS. Results showed that finishing pigs tended to have better ATTD of DM than growing pigs ( P = 0.09) and had increased ATTD of GE and N than growing pigs ( P = 0.03 and P < 0.01, respectively). On the other hand, growing pigs had better ATTD of AEE than finishing pigs ( P = 0.01). Pig BW period did not affect the ATTD of neutral detergent fiber (NDF), acid detergent fiber (ADF), and hemicellulose. Reducing the mean PS of corn DDGS with either HM or RM (from 670 to 450 µm) improved the ATTD of DM and GE ( P < 0.01 and P < 0.01), tended to improve the ATTD of N ( P = 0.08), and improved the ATTD of AEE ( P < 0.01). No effect of reducing PS was observed for the ATTD of NDF, ADF, or hemicellulose. There were no differences between HM and RM in any of the ATTD variables tested. In conclusion, reducing PS of corn DDGS from 670 to 450 μm either with an HM or with an RM improved the digestibility of DM, GE, and AEE and modestly improved the digestibility of N in growing and finishing pigs. However, reducing the PS of corn DDGS did not affect the digestibility of fiber components., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science.)

The objective of this study was to determine the differences in response to distillers dried grains with solubles (DDGS) level under constant nutrient or floating nutrient concentrations. A total of 21 ileal-cannulated gilts (33.1 ± 0.4 kg body weight) were randomly allotted to one of seven dietary treatments in a 3-period incomplete Latin square design (n = 9). Treatments consisted of a 0% DDGS basal diet, plus diets containing 15%, 30%, or 45% DDGS. Diets were formulated using one of two different formulation methods: 1) constant nutrient (CNU) where nutrients were held equal to the basal diet or 2) constant ingredients (CIN) where DDGS were added at the expense of corn and all other ingredients remained constant, so nutrient levels were allowed to "float." Chromic oxide was added to the diets at 0.5% as an indigestible marker. Increasing the level of DDGS decreased the apparent ileal digestibility (AID) of dry matter (DM), gross energy (GE), starch, dispensable amino acids (AA), and fiber components (P < 0.050). The decrease in the AID of Lys, Met, Thr, and Trp was more pronounced under CNU compared with the CIN formulation method (P < 0.050). The decrease in the AID of hemicellulose was less pronounced under CNU compared with the CIN formulation method (P = 0.045). There was a DDGS level × formulation method interaction for the AID of acid hydrolyzed ether extract (AEE; P = 0.015); for the CNU formulation method, increasing level of DDGS decreased the AID of AEE from 0% to 30% and remained similar from 30% to 45% DDGS, whereas the CIN had no effect on the AID of AEE. Increasing the level of DDGS decreased the apparent total tract digestibility (ATTD) of DM, GE, and fiber components (P < 0.050), except for acid detergent fiber, which was not affected. The decrease in the ATTD of insoluble dietary fiber and total dietary fiber was less pronounced under CNU compared with CIN (P < 0.050). The ATTD of AEE decreased for CNU compared with CIN (P < 0.010). In conclusion, increasing the insoluble fiber level in the form of DDGS decreased the digestibility of most dietary components, including DM, GE, starch, insoluble fiber, and AA. The CNU and CIN formulation methods are equivalent when evaluating the digestibilities of DM, GE, starch, crude protein, and AA (when they were not added in purified synthetic forms). Differences between CNU and CIN formulation methods were detected for the digestibility of insoluble fiber, fat, and essential AA (when added as crystalline AA)., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Feed grains are processed to improve their value in pig diets by exposing kernel contents to enzymatic and microbial action. The objective of this study was to quantify the effect of reducing mean particle size (PS) of wheat grain ground with two different grinding methods (GMs) on the apparent total tract digestibility (ATTD) of nutrients and energy in growing and finishing pigs. Forty-eight barrows were housed in individual pens for 11 d for two periods. Pigs were randomly assigned to a 3 × 2 × 2 factorial experimental design: three target mean PS of wheat grain (300, 500, and 700 µm), two GMs (roller mill and hammermill), and two body weight (BW) periods (growing period; initial BW of 54.9 ± 0.6 kg and finishing period; initial BW of 110.7 ± 1.4 kg). Diets contained one of six hard red wheat grain samples, vitamins, minerals, and titanium dioxide as an indigestible marker. Feed allowance provided 2.5 (for the two lightest pigs in each treatment) or 2.7 (for the remaining six pigs in each treatment) times the estimated daily maintenance energy requirement for each growth stage. Fecal samples were collected for the last 3 d of each period. Data were analyzed as a linear mixed model with pig as a random effect and PS, GM, and BW period and their interactions as fixed effects utilizing the MIXED procedure of SAS. Growing pigs had greater ( P < 0.05) ATTD of dry matter (DM), gross energy (GE), N, acid hydrolyzed ether extract (AEE), and neutral detergent fiber (NDF) by lowering mean PS from 700 to 500 μm using either a roller mill or a hammermill. However, digestibility did not increase when PS was reduced from 500 to 300 μm, except for AEE ( P < 0.05). Finishing pigs had greater ATTD of DM, GE, N, AEE, and NDF by lowering mean PS with a hammermill from 700 to 500 μm ( P < 0.05), but it was greater for 500 μm than for 300 μm ( P < 0.05). Using a roller mill reduced the ATTD of DM and NDF by lowering PS from 700 to 300 μm ( P < 0.05). The ATTD of GE decreased by lowering PS from 700 to 500 μm with a roller mill ( P < 0.05) for finishing pigs. The ATTD of N and AEE for finishing pigs were similar from 700 to 300 μm when ground by a roller mill. These data suggest that the PS that maximized digestibility for a hammermill is 500 μm for both growing and finishing pigs. However, for the roller mill, the PS resulting in the best digestibility were 500 and 700 μm for growing and finishing pigs, respectively., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science.)

A study was conducted to investigate the effect of oregano essential oil (OEO) and monensin sodium on the oxidative stability, colour, texture, and the fatty acid profile of lamb meat (m. Longissimus lumborum ). Twenty Dorper x Pelibuey lambs were randomly divided into five treatments; control (CON), monensin sodium (SM, Rumensin 200 ® 33 mg/kg), a low level of OEO (LO, 0.2 g/kg dry matter (DM)), a medium level of OEO (MO, 0.3g/ kg DM), and a high level of OEO (HO, 0.4 g/kg DM). Dietary supplementation of OEO at any concentration lowered the compression strength in comparison with CON and SM. MO had the highest a* values (7.99) and fatty acid concentration (C16:1n7, C18:1n9c, C18:1n6c, C20:1n9, and C18:2n6c) during storage for 7 d at 3 °C. Lipid oxidation was not promoted ( p > 0.05) by the moderated supplementation of oregano essential oil; however, OEO at 0.3 g/kg DM showed a slight lipid pro-oxidant effect. Dietary supplementation of MO and SM had the same effect on colour, tenderness, and the fatty acid profile of lamb ( L. lumborum ). It was demonstrated that oregano essential oil was beneficial for lambs feeding, and it could be a natural alternative to replace monensin in lamb diets with improvements in the quality of the meat.

The objective of this study was to determine the effects of lactose (LA) and a prototype Lactobacillus acidophilus fermentation product (FP) on growth performance, diet digestibility, nitrogen (N) balance, and intestinal function of weaned pigs. Twenty-eight newly weaned pigs [approximately 21 d of age; initial body weight (BW) = 5.20 ± 0.15 kg] were housed in metabolism crates and assigned to one of four treatments ( n = seven pigs per treatment) corresponding to a 2 × 2 factorial design: with (LA + ; 15% inclusion) or without (LA-) LA and with (FP+) or without (FP-) the prototype FP (1 g of FP per kilogram of diet; Diamond V, Cedar Rapids, IA). Feed and water were provided ad libitum. At day 5, pigs were orally given lactulose and mannitol to assess small intestinal permeability. Fecal samples were collected on days 5-9 to determine the apparent total tract digestibility (ATTD) of dry matter (DM), gross energy (GE), and N. Total urine output and fecal samples were collected on days 10-13 to determine N retention. On day 15, all pigs were euthanized to collect intestinal lumen and tissue samples. Data were analyzed for the main effects of LA and FP and their interaction using the MIXED procedure of SAS. Lactose improved average daily feed intake (ADFI; P = 0.017), the ATTD of DM ( P = 0.014), the ATTD of GE ( P = 0.028), and N retention ( P = 0.043) and tended to increase the butyric acid concentration in the colon ( P = 0.062). The FP tended to increase the digestibility of N ( P = 0.090). Neither LA nor the FP affected intestinal barrier function or inflammation markers. The interaction between LA and FP affected intestinal morphology: in the jejunum, pigs fed LA+FP- had increased villus height compared with those fed LA+FP+ and LA-FP-, whereas LA+FP+ was intermediate (interaction P = 0.034). At the terminal ileum, pigs fed LA-FP+ and LA+FP- had increased villus height and villus: crypt compared with those fed LA-FP-, whereas LA+FP+ was intermediate (interaction P = 0.007 and P = 0.007, respectively). In conclusion, the addition of LA brings important nutritional attributes to nursery diets by improving feed intake, digestibility of DM and GE, and the N retention of weaned pigs; however, the functional capacity of LA to improve markers of intestinal function is limited. On the other hand, the FP showed only a mild increase in the digestibility of N but a limited capacity to improve markers of intestinal function., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Context: Despite being a validated source of biomarkers, liquid biopsy has not yet succeeded in becoming part of the standard clinical practice in prostate cancer patients. Few biomarkers undergo adequate validation, prospective and independent, of their predictive and/or prognostic value, which results in a lack of the different available tests in the clinical practice., Objective: To carry out a pragmatic synthesis of current scientific evidence on liquid biopsy for prostate cancer patients., Evidence Acquisition: Non-systematic literature review, narrowing the search to papers on liquid biopsy from blood samples in prostate cancer patients. We mainly selected works evaluating clinical endpoints in prostate cancer., Evidence Synthesis: The most clinically advanced forms of liquid biopsy are circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Both CTCs and ctDNA have demonstrated their prognostic value in metastatic disease. ARV7 determination is the first predictive biomarker of the disease. Its implementation into routine clinical practice requires methodological standardization and adequate clinical validation of the different available ways to detect it. The detection of CTCs in the early stages of the disease still depends on the optimization of the diagnostic methods and on the development of the biological characterization of these cells. The biological information provided by CTCs and ctDNA is different; therefore, the study of its adequate combination is the object of cutting-edge research., Conclusions: The absence of protocols and methodological standards is the limiting factor when aiming to reach conclusions that could have a potential impact on clinical practice. Therefore, the real short-term challenge for liquid biopsy is the establishment of consensus and common criteria., (Copyright © 2019 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Disseminated disease is present in ≈50% of colorectal cancer patients upon diagnosis, being responsible for most of cancer deaths. Addition of biological drugs, as Bevacizumab, to chemotherapy, has increased progression free survival and overall survival of metastatic colorectal cancer (mCRC) patients. However, these benefits have been only reported in a small proportion of patients. To date, there are not biomarkers that could explain the heterogeneity of this disease and would help in treatment selection. Recent findings demonstrated that microRNAs (miRNAs) play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles (EVs) that are released in biological fluids. EVs can act as cell-to-cell communicators, transferring genetic information, such as miRNAs. In this context, we aimed to investigate serum EV associated miRNAs (EV-miRNAs) as novel non-invasive biomarkers for the diagnosis and prognosis of Bevacizumab-treated mCRC patients. We observed that baseline miRNA-21 and 92a outperformed carcinoembryonic antigen levels in the diagnosis of our 44 mCRC patients, compared to 17 healthy volunteers. In addition, patients who died presented higher levels of miRNA-92a and 222 at 24 weeks. However, in the multivariate Cox analysis, higher levels of miRNA-222 at 24 weeks were associated with lower overall survival. Altogether, these data indicate that EV-miRNAs have a strong potential as liquid biopsy biomarkers for the identification and prognosis of mCRC.

Broadly neutralizing antibodies (bNAbs) to human immunodeficiency virus type 1 (HIV-1) hold great promise for immunoprophylaxis and the suppression of viremia in HIV-positive individuals. Several studies have demonstrated that plants as Nicotiana benthamiana are suitable hosts for the generation of protective anti-HIV-1 antibodies. However, the production of the anti-HIV-1 bNAbs 2F5 and PG9 in N. benthamiana is associated with their processing by apoplastic proteases in the complementarity-determining-region (CDR) H3 loops of the heavy chains. Here, it is shown that apoplastic proteases can also cleave the CDR H3 loop of the bNAb 2G12 when the unusual domain exchange between its heavy chains is prevented by the replacement of Ile 19 with Arg. It is demonstrated that CDR H3 proteolysis leads to a strong reduction of the antigen-binding potencies of 2F5, PG9, and 2G12-I19R. Inhibitor profiling experiments indicate that different subtilisin-like serine proteases account for bNAb fragmentation in the apoplast. Differential scanning calorimetry experiments corroborate that the antigen-binding domains of wild-type 2G12 and 4E10 are more compact than those of proteolysis-sensitive antibodies, thus shielding their CDR H3 regions from proteolytic attack. This suggests that the extent of proteolytic inactivation of bNAbs in plants is primarily dictated by the steric accessibility of their CDR H3 loops., (© 2019 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The increasing frequency and intensity of cyanobacterial blooms pose a serious threat to aquatic ecosystems. These blooms produce potent toxins that can contaminate drinking water and endanger the life of wild and domestic animals as well as humans. Consequently, the development of effective methods for their control is a matter of high priority. We have previously shown that some γ-benzylidenebutenolides, related to the rubrolide family of natural products, are capable of inhibiting the photosynthetic electron transport chain (Hill reaction), a target of commercial herbicides. Here we report the synthesis and biological properties of a new class of rubrolide-inspired molecules featuring a tetronamide motif., Results: A total of 47 N-aryl tetronamides, including 38 aldol adducts, were prepared bearing phenyl, biphenyl, naphthyl, aliphatic and heteroaromatic groups. Some of the aldol adducts were dehydrated to the corresponding γ-benzylidenetetronamides, although satisfactory yields were obtained in only three cases (52-97%). None of the synthesized compounds were capable of blocking the Hill reaction. This notwithstanding, several aldol adducts equipped with a biphenyl substituent displayed excellent inhibitory activity against Synechococcus elongatus and other cyanobacterial strains (IC 50  = 1-5 μM). Further, these tetronamides were found to be essentially inactive against eukaryotic microorganisms., Conclusion: Several newly synthesized biphenyl-containing tetronamides were shown to display potent and selective inhibitory activity against cyanobacteria. These compounds appear to exert their biological effects without interfering with the Hill reaction. As such, they represent novel leads in the search of environmentally benign agents for controlling cyanobacterial blooms. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Objectives: This paper describes some operational tactical procedures (OTP) and discusses the results of a 14-year-long study, spanning the period 2003-2016, conducted by the Municipal Police of Cádiz, Spain, which comprised 3 time periods: 2003-2006, when the officers were trained in traditional policing procedures; 2007-2013, when the officers were taught an innovative set of OTP in the form of a basic set of self-defense and arrest mechanisms, different from the traditional policing procedures that rely on martial arts and combat sports; and finally 2014-2016, when the OTP training was discontinued. The aim of this study was to improve policing and reduce officer injuries resulting from interventions in controversial or violent situations, such as problematic arrests., Material and Methods: The study involved 162 police officers and commanders of the Municipal Police of Cádiz, who were in street duty for their first time. There were 8 females and 154 males aged 24-55 years. Three OTP stages are shown as examples., Results: Based on the analysis of "training hours" and "physical interventions in problematic arrests," the results were: 1) the number of sick leaves in the police was identical according to the number of arrests, and 2) data on sick leaves show remarkable differences among the 3 periods under analysis., Conclusions: The OTP-based training substantially reduced officer sick leaves. The overall reduction in sick leaves in the period 2007-2013 was observed that cannot be ascribed to a decrease in criminal acts, and hence in police physical interventions. Int J Occup Med Environ Health. 2020;33(1):35-43., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Soil contamination by petroleum compounds threatens the health of soil and water resources. This research was conducted with the objective of reaching an efficient technique for the removal or reduction of harmful effects caused by total petroleum hydrocarbons (TPH) in soils. In a greenhouse experiment, the effect of biochar (B), mycorrhizae (M) and combination of mycorrhizae and biochar (M + B) on the growth of two native species; clover (Trifolium arvense) and mallow (Malva sylvestris L.), and removal efficiency of TPH (16.79 mg kg-1) from an oil-contaminated soil were studied. The plant analyses after 50 days of growth period showed a significant (p ≤ 0.05) increase in shoot dry weight of mallow in B and M + B treatments but no significant effect was observed for clover compared to the control (C). The initial TPH concentration, determined by gas chromatography technique was reduced from 9.4% in unplanted soil until 56.4% (clover) and 55.9% (mallow) in M + B treatment. The relative concentration of long chain alkanes (LCAs) were also reduced when treatments were applied, in which the highest and lowest reductions was found in C21-C25 and C11-C15, respectively, though octacosane (C28) was increased or unchanged in soil. This result suggests that likely the occurrence of C 28 in the mycorrhizal hyphae or the higher removal of the other alkanes increase octacosane relative concentration in soil, which more research is necessary., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Soil under an intensive agriculture production could result in metal pollution if bad management practices are carried out. The aims of this study were to evaluate the influence of cropping systems on soil metal(loid)s accumulation and speciation and to identify metal sources for each cropping system. To achieve these objectives, 40 soil samples from cereal, fruit, citrus and horticultural cropping areas and 15 samples from non-disturbed areas were collected. pH, salinity, particle size distribution, organic carbon and carbonate contents were analysed. In addition, total, DTPA-extractable and water-soluble Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Zn and As concentrations and their chemical speciation were determined. Results showed an enrichment of Pb in cereal and horticultural soils, of Zn in fruit and horticultural soils and of Cu and Cd in citrus soils. The most available metals were Pb and Cd which was due to their ability to bind to carbonate and reducible phases of soils. The PCA suggested an anthropogenic origin of Pb, Cd, Cu and Zn in most of the cropping systems; this origin was related to both agriculture management practices and other anthropic actions, such as traffic. Therefore, changes in crop managements are necessary for a sustainable agriculture in the studied crop systems.

Nowadays, air pollution has a major impact on the environment and human health. Owen gauges allow the sampling of atmospheric depositions in polluted sites for further characterisation. This paper shows the study of the air particles of an old mining zone in Cartagena-La Unión (South-east of Spain) in order to quantify their potential risk on human health. There were 4 strategic sites monitored: the main mining tailing (Avenque), the urban area (La Unión), an agricultural zone (formerly mining) and a site in the Mediterranean coast. Physico-chemical and mineralogical characterisation was applied to atmospheric fallouts. The granulometry revealed a dust particle size around 15 μm, with the coarsest particles in the urban area and the thinnest at the tailing site. XRD analyses showed the presence of quartz, carbonates, sulphides and sulphates. Observations with SEM-EDX confirmed chemical spectra and allowed us to classify the particles into well-crystallised minerals and heterogeneous dusts. Total metal content determination was carried out by ICP-MS analyses and results showed Zn, Pb, As and Cd fluxes (respectively 2549, 1275, 68 and 7 μg·m -2 ·d -1 ) exceeding the limit values set by European legislations in the mining area. The fluxes of Zn, Pb and As also exceed these standards in the urban area whereas the coastal zone only exceeds the thresholds in the case of As. Inhalation health risk (defined by US EPA, 2009) was quantified in the sites using total and bioaccessible metal contents of the dusts. Risk calculations using total metal content considering a residential scenario showed acceptable risk for all sites except for the mining tailing which presented non-acceptable cancer and hazard risk mainly due to the total As and Pb contents. When considering the bioaccessible fraction of As and Pb, the risk diminished to acceptable values, demonstrating the overestimation produced when using total metal contents., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To determine whether elevated intra-abdominal pressure (IAP) is associated with a higher rate of enteral nutrition-related gastrointestinal (GI) complications; to assess the value of IAP as a predictor of enteral nutrition (EN) intolerance. Intensive Care Unit (ICU) patients on mechanical ventilation requiring at least 5 days of EN were recruited for a prospective, observational, non-interventional, multicenter study. EN was performed and GI complications were managed with an established protocol. IAP was determined via a urinary catheter. Patients who developed any GI complications were considered as presenting EN intolerance. Variables related to EN, IAP and GI complications were monitored daily. Statistical analysis compared patients without GI complications (group A) vs. GI complications (group B). 247 patients were recruited from 28 participating ICUs (group A: 119, group B: 128). No differences between groups were recorded. Patients in group B ( p < 0.001) spent more days on EN (8.1 ± 8.4 vs. 18.1 ± 13.7), on mechanical ventilation (8.0 ± 7.7 vs. 19.3 ± 14.9) and in the ICU (12.3 ± 11.4 vs. 24.8 ± 17.5). IAP prior to the GI complication was (14.3 ± 3.1 vs. 15.8 ± 4.8) ( p < 0.003). The best IAP value identified for EN intolerance was 14 mmHg but it had low sensitivity and specificity. Although a higher IAP was associated with EN intolerance, IAP alone did not emerge as a good predictor of EN intolerance in critically ill patients.