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Glucagon-like peptide 1 receptor (GLP-1R) agonists decrease body weight and improve glycemic control in obesity and diabetes. Patient compliance and maximal efficacy of GLP-1 therapeutics are limited by adverse side effects, including nausea and emesis. In three different species (i.e., mice, rats, and musk shrews), we show that glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling blocks emesis and attenuates illness behaviors elicited by GLP-1R activation, while maintaining reduced food intake, body weight loss, and improved glucose tolerance. The area postrema and nucleus tractus solitarius (AP/NTS) of the hindbrain are required for food intake and body weight suppression by GLP-1R ligands and processing of emetic stimuli. Using single-nuclei RNA sequencing, we identified the cellular phenotypes of AP/NTS cells expressing GIPR and GLP-1R on distinct populations of inhibitory and excitatory neurons, with the greatest expression of GIPR in γ-aminobutyric acid-ergic neurons. This work suggests that combinatorial pharmaceutical targeting of GLP-1R and GIPR will increase efficacy in treating obesity and diabetes by reducing nausea and vomiting.

Summary Well-control management is nowadays frequently approached by means of mathematical optimization. However, in many practical situations the optimization algorithms used are still computationally expensive. In this paper, we present progressive optimization (PO), a simulator-nonintrusive four-stage methodology to accelerate optimal search substantially in well-control applications. The first stage of PO comprises a global exploration of the search space using design of experiments (DOEs). Thereafter, in the second stage, a fast-to-evaluate proxy model is constructed with the points considered in the experimental design. This proxy is based on generalized barycentric coordinates (GBCs), a generalization of the concept of barycentric coordinates used within a triangle. GBCs can be especially suited to problems in which nonlinearities are not strong, as is the case often for well-control optimization. This fact is supported by the good performance in these types of optimization problems of techniques that rely strongly on linearity assumptions, such as trajectory piecewise linearization, a procedure that is not always applicable due to its simulator-intrusive nature. In the third stage, the precision of the proxy model is iteratively improved and the enhanced surrogate model is reoptimized by means of manifold mapping (MM), a method that combines models with different levels of accuracy. MM has solid theoretical foundations and leads to efficient optimization schemes in multiple engineering disciplines. The final and fourth stage aims at additional improvement, resorting to direct optimization of the best solution from the previous stages. Nonlinear (operational) constraints are handled in PO with the filter method. The optimal search may be finalized earlier than at the fourth stage whenever the solution obtained is of satisfactory quality. PO is tested on two waterflooding problems built upon a synthetic model previously studied in well-control optimization literature. In these problems, which have 120 and 40 well controls and include nonlinear constraints, we observe for PO reductions in computational cost, for solutions of comparable quality, of approximately 30% and 50% with respect to Hooke-Jeeves direct search (HJDS), which, in turn, outperforms particle swarm optimization (PSO). HJDS and PSO are simulator-nonintrusive algorithms that usually perform well in optimization for oilfield operations. The novel concepts of GBC and MM within the framework of the PO paradigm can be extremely helpful for practitioners to efficiently deal with optimized well-control management. Savings of 50% in computing cost may be translated in practice into days of computations for just a single field and optimization run.

The aim of this study was to analyze and classify the soils of the municipality of Alcubillas (La Mancha, Central Spain) and establish their suitability for vine cultivation. Alcubillas is a traditional location dedicated to vineyards and the production of wine. The pedological fingerprint of this location is the iconic red Mediterranean soil, and a plausible process for the soil formation is discussed. Considering the nature of the soils and the extent and types of natural limitations, as defined by the eight classes of land capability established by the US Soil Conservation Service, the majority of the soils in Alcubillas are suitable for vineyards (i.e., classes 1, 2 and 3) while moderately suitable sites only occupy a small area. The marginally suitable land class is located around a single hill, which occupies only a few hectares of terrain. Given that soil is a major factor in terroir expression, the findings reported here highlight the importance of soil suitability in determining vine performance in vine-growing zones with a Mediterranean environment.

Brachial plexus injury is a lesion that results in loss of function of the arm, and there are multiple ways of surgically approaching its treatment. Controlled trials that compare all surgical repair strategies and their clinical outcomes have not been performed. A systematic review was conducted to identify all articles that reported clinical outcomes in different surgeries (nerve transfer, nerve graft, neurolysis, end-to-end, multiple interventions, and others). Advanced search in PubMed was performed using the Mesh terms “brachial plexus injury” as the main topic and “surgery” as a subtopic, obtaining a total of 2153 articles. The clinical data for eligibility extraction was focused on collecting motor, sensory, pain, and functional recovery. A statistical analysis was performed to find the superior surgical techniques in terms of motor recovery, through the assessment of heterogeneity between groups, and of relationships between surgery and motor recovery. The frequency and the manner in which clinical outcomes are recording were described. The differences that correspond to the demographics and procedural factors were not statistically significant among groups (p > 0.05). Neurolysis showed the highest proportion of motor recovery (85.18%), with significant results between preoperative and post-operative motor assessment (p = 0.028). The proportion of motor recovery in each group according to the surgical approach differed significantly (X2 = 82.495, p = 0.0001). The motor outcome was the most reported clinical outcome (97.56%), whereas the other clinical outcomes were reported in less than 15% of the included articles. Unexpectedly, neurolysis, a technique displaced by new surgical alternatives such as nerve transfer/graft, demonstrated the highest proportion of motor recovery. Clinical outcomes such as pain, sensory, and functional recovery were infrequently reported. These results introduce the need to re-evaluate neurolysis through comparative clinical trials, as well as to standardize the way in which clinical outcomes are reported.

Los alucinógenos incluyen a un grupo heterogéneo de sustancias que provocan cambios en la percepción sensorial, el pensamiento y la consciencia. El potencial terapéutico de diversas drogas alucinógenas está recibiendo un interés creciente en los últimos años. En este trabajo presentamos una revisión bibliográfica centrada en el posible uso de los alucinógenos (LSD, psilocibina y ketamina) en el tratamiento y prevención de las cefaleas. Para ello, se ha realizado unabúsqueda (sin límite temporal) en las bases de datos de Web of Sciences, Scopus y Pubmed, además de una búsqueda manual en las referencias de los artículos. Los resultados constatan la eficacia del LSD, especialmente a nivel profiláctico, mientras que la ketamina podría ser de utilidad para abortar los ataques agudos y la psilocibina ha demostrado ser efectiva en ambos aspectos. Los estudios existentes se han llevado a cabo principalmente en pacientes con migraña y con cefalea en racimos, entre otros tipos de cefaleas. Asimismo, se señalan diversas limitaciones metodológicas que pueden dificultar la generalización de los resultados, y se sugiere la necesidad de realizar futuras investigaciones en este campo emergente.

Purpose The main objective of the study was to evaluate the application of different doses of onion residue compost as mixtures with bovine manure as organic fertilizers for a round tomato crop planted in the field. Method The data were obtained experimentally in pilot fields. The experimental design was completely randomized, with 4 m2 plots with ten plants each as an experimental unit and with three replications per treatment (2 years). Five treatments were tested, namely one unfertilized control, three with organic fertilization and one mineral treatment. The variables measured were plant height (cm), stem base diameter (cm), fresh plant weight (g) and total dry matter (%). The parameters measured for the fruit were fresh fruit weight (g), fruit length (mm), fruit width (mm) and total soluble solids. Results The application of compost from the degradation of onion residues as mixtures with cow manure had positive effects on the growth of the plant and on the development of tomato fruit. Compost doses of 60 Mg ha–1 and 80 Mg ha–1 gave similar values ​​to chemical treatment and the control without fertilization was significantly lower than those with doses of organic and chemical fertilizer. These results indicate that this compost contains the nutrients required by the tomato crop for growth and development. Conclusion It was concluded that the agricultural use of quality compost is an effective strategy to obtain high quality products in an economically viable and environmentally sustainable way.

Ultra-short race-pace training (USRPT) is a high-intensity training modality used in swimming for the development of the specific race-technique. However, there is little information about the fatigue associated to this modality. In a crossover design, acute responses of two volume-equated sessions (1000-m) were compared on 14 national swimmers: i) USRPT: 20×50-m; ii) RPT: 10×100-m. Both protocols followed an equivalent work recovery ratio (1:1) based on individual 200-m race-pace. The swimming times and the arm-strokes count were monitored on each set and compared by mixed-models. Blood lactate [La-] and countermovement jump-height (CMJ) were compared within and between conditions 2 and 5 min after the protocols. The last bouts in RPT were 1.5–3% slower than the target pace, entailing an arm-strokes increase value of ~0.22 for every second increase in swimming time. USRPT produced lower [La-] ([Mean ± standard deviation], 2 min: 8.2±2.4 [p = 0.021]; 5 min: 6.9±2.8 mM/L [p = 0.008]), than RPT (2 min: 10.9±2.3; 5 min: 9.9±2.4 mM/L). CMJ was lowered at min 2 after RPT (-11.09%) and USRPT (-5.89%), but returned to the baseline in USRPT at min 5 of recovery (4.07%). In conclusion, lower fatigue and better recovery were achieved during USRPT compared to traditional high-volume set., CTS-527

The endothelium is a single cell layer of the vessel wall and a key regulator of blood flow in vascular beds. Local and systemic pathologies have been associated with alterations in endothelial function. However, targeting the endothelium with vasoconstrictor or vasodilator drugs is often accompanied by systemic effects. Here, we evaluated a liposome-microbubble delivery system as a vascular hydrophilic agonist carrier. Phenylephrine (Phe) or acetylcholine (Ach)-loaded liposomes were conjugated to microbubbles. The drug release was triggered by ultrasound (US), and the vascular response was assessed in rat aortic rings using an isolated organ chamber. Aortic rings incubated with Phe-liposome-microbubble conjugate, exposed to US showed a marked contractile response (0.79 ± 0.04 g) compared to empty liposomes conjugated to microbubbles, aortic rings exposed only to US, and Phe-liposome-microbubble conjugate without US exposure that elicited a minimal or no response. Expressed as %, contractile responses were 85.24 ± 4.31% and 12.62 ± 3.23% for Phe-Chol-liposome-microbubble conjugate and empty Chol-liposome-microbubble conjugate exposed to US, respectively. Addition of 1 × 10–5 M Ach to pre-contracted aortic rings decreased the contraction response from 1 to 0.21 g. The addition of Ach-liposome conjugate and exposure to US decreased the contraction response to 0.32 g. Additionally, the ED50 values for Phe and Ach released by US from liposome-microbubble conjugates were 3.6 × 10–8 M ± 2.8 × 10–9 M for Phe and 2.0 × 10−8 M ± 1.8 × 10–9 M. In conclusion, we evaluated a hybrid delivery system that consisted of loaded liposomes conjugated to microbubbles to deliver and release vascular agonists using UMMD.

This study ascertains how the proposed subtypes and specifiers of oppositional defiant disorder (ODD) based on irritability and prosocial emotions co-develop and describes the clinical characteristics of the resultant classes. A sample of 488 community children was followed up from ages 3 to 12 years and assessed with categorical and dimensional measures answered by parents and teachers. Latent class growth analysis for three parallel processes [defiant/headstrong, irritability, and limited prosocial emotions (LPE)] identified a 4-class model with adequate entropy (.912) and posterior probabilities of class membership (≥ .921). Class 1 (n = 38, 7.9%) was made up of children with defiant/headstrong with chronic irritability and LPE. Class 2 (n = 128, 26.3%) was comprised of children with defiant/headstrong with chronic irritability and typical prosocial emotions. Class 3 (n = 101, 20.7%) clustered children with LPE without defiant/headstrong and without irritability. Class 4 (n = 220, 45.1%) included children with the lowest scores in all the processes. The classes were distinguishable and showed different clinical characteristics through development. These findings support the validity of ICD-11 ODD subtypes based on chronic irritability and may help to guide clinicians' decision-making regarding treating oppositionality in children.

Purpose: Nowadays preserve fresh-cut fruits' quality is a challenge for their short shelf life and sooner undesired sensorial changes that cause unacceptability by consumers. This study aims to apply individual and combined citric acid and calcium chloride treatments in fresh-cut kiwifruit to improve its physicochemical properties, antioxidant content, and sensory acceptance. Research method: Kiwifruit cv. Hayward was disinfected and cut into slices of 10 mm thickness. Samples g were immersed for one minute in sterile distilled water (control), CaCl2 0.5%, Citric acid 1%, the citric acid and CaCl2 combination 1.0:0.5 (citric acid: CaCl2, %) and stored for 12 days at 5 °C. The physicochemical parameters, total antioxidant capacity, microbial quality, and consumer acceptability were measured during the storage. Findings: Individual treatments of CaCl2 conserve color parameters increasing luminosity,and citric acid treatment kept the titratable acidity under storage conditions. However, the combination treatments delayed kiwifruit's maturation process, avoiding weight loss under storage conditions for 12 days at 5 °C. Besides, other parameters like color, pH, and titratable acidity presented significant differences compared with citric acid, CaCl2 individual treatments and untreated fruits. Moreover, the citric acid and CaCl2 combination maintained phenolic content and antioxidant capacity by inhibiting DPPH and ABTS radicals. Meanwhile, the untreated control kiwifruits presented the lowest antioxidant activity at the end of storage. Finally, the kiwifruit-combined treatment did not show microbial growth and gave higher consumers acceptability than the untreated fruit. Limitations: No limitations were encountered. Originality/Value: This study showed that citric acid, calcium chloride, and their combination are useful to extend fresh-cut kiwifruit shelf life while maintaining antioxidant capacity and sensorial acceptability.

The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral administration of insulin. These nanocarriers, based on the coating of zein nanoparticles with a polymer conjugate containing PEG, displayed a size of 260 nm with a negative surface charge and an insulin payload of 77 μg/mg. In intestinal pig mucus, the diffusivity of these nanoparticles (PPA-NPs) was found to be 20-fold higher than bare nanoparticles (NPs). These results were in line with the biodistribution study in rats, in which NPs remained trapped in the mucus, whereas PPA-NPs were able to cross this layer and reach the epithelium surface. The therapeutic efficacy was evaluated in Caenorhabditis elegans grown under high glucose conditions. In this model, worms treated with insulin-loaded in PPA-NPs displayed a longer lifespan than those treated with insulin free or nanoencapsulated in NPs. This finding was associated with a significant reduction in the formation of reactive oxygen species (ROS) as well as an important decrease in the glucose and fat content in worms. These effects would be related with the mucus-permeating ability of PPA-NPs that would facilitate the passage through the intestinal peritrophic-like dense layer of worms (similar to mucus) and, thus, the absorption of insulin.

Background Alpha klotho (α-Klotho) is an anti-aging protein recognized as a humoral factor with anti-oxidant and anti-inflammatory effects, showing a bidirectional relationship with inflammation, a main pathophysiologic factor in atherosclerosis. A decrease in Klotho has been associated to cardiovascular disease (CVD), but no previous studies have investigated the relationship between inflammatory bowel disease (IBD), a risk factor for CVD, and Klotho levels. Therefore, we assessed if the serum levels of Klotho differ between patients with IBD and controls, and how this protein is related to the clinical and laboratory characteristics of the disease, subclinical atherosclerosis and metabolic risk factors. Methods Cross-sectional multicentric study that included 251 individuals: 191 IBD patients and 60 healthy controls was conducted. Serum Klotho levels were determined by commercial ELISA immunoassay (IBL International GmbH Laboratories). In the IBD patients disease activity was evaluated using CDAI for Crohn's disease, partial Mayo (pMayo) for ulcerative colitis, specific laboratory parameters, determination of the Systematic Coronary Risk Evaluation (SCORE), and the presence of subclinical atherosclerosis was assessed using carotid ultrasound for identifying carotid plaque and measurement of carotid intima-media thickness. Results Serum Klotho levels were significantly higher in the IBD group: 734.31 pg/ml vs. 484.17 pg/ml (p Conclusion Patients with IBD had higher Klotho levels than healthy controls, with an inverse and significant relationship with the SCORE in the IBD patients. Further studies are necessary to clarify the role of Klotho in IBD.

Ultrasound molecular imaging with targeted microbubbles (MBs) can be used to noninvasively diagnose, monitor, and study the progression of different endothelial-associated diseases. Acoustic radiation force (

In swimming, the beneficial effects of the in-water warm-up are often undermined by the long transition periods before competition (≥ 20 min). For that reason, studies comparing the effects of in-water warm-ups followed by dryland activities have been conducted in the swimming literature. This has brought conflicting evidence due to large combinations of supervised and unsupervised warm-up procedures used. Therefore, a scoping review was performed to discuss (1) why warm-up strategies are important for competitive swimming; to identify (2) what are the different warm-up approaches available in the literature, and; to establish (3) what are the main conclusions, considerations and gaps that should be addressed in further research to provide clearer guidance for interventions. The search was conducted on PubMed, Web of Science, Scopus, and SPORTDiscus databases. To be considered eligible, studies must have assessed acute short-term responses of warm-up procedures in swimmers by using randomized controlled trials or pre-post study designs. A total of 42 articles were included in this review. The effectiveness of warm-up responses was evaluated based on the inclusion or not of warm-up, the type of conditioning activity (in-water exercise, inwater exercise combined with dryland or dryland exercise only), its duration, and intensity. (1) Warm-up mechanisms have been mainly related to temperature changes associated to cardiovascular adaptations and short-term specific neuromuscular adaptations. Thus, maintaining muscle activity and body temperature during the transition phase immediately prior to competition could help swimmers’ performance; (2) the most common approach before a race usually included a moderate mileage of in-water warm-up (~ 1000 m) performed at an intensity of ≤ 60% of the maximal oxygen consumption, followed by dryland protocols to keep the muscle activity and body temperature raised during the transition phase. Dryland activities could only optimize performance in sprint swimming if performed after the in-water warm-up, especially if heated clothing elements are worn. Using tethered swimming and hand-paddles during warm-ups does not provide superior muscular responses to those achieved by traditional in-water warm-ups, possibly because of acute alterations in swimming technique. In contrast, semi-tethered resisted swimming may be considered as an appropriate stimulus to generate post-activation performance enhancements; (3) nothing has yet been investigated in backstroke, butterfly or individual medley, and there is a paucity of research on the effects of experimental warm-ups over distances greater than 100 m. Women are very under-represented in warm-up research, which prevents conclusions about possible sex-regulated effects on specific responses to the warm-up procedures., Agencia de Innovacion y Desarrollo de Andalucia, European Commission, SWIM FOR LIFE B-SEJ-164-UGR20, Spanish Government FPU17/02761 FPU19/02477

The fate and presence of nanoplastics in wastewater treatment systems is a topic of increasing interest. Furthermore, challenges related to their quantification and identification have made it difficult to set up experimental conditions and compare results between studies. In this study, the effect of 100 nm polystyrene nanoplastics on activated sludge was evaluated. A concentration of 2 μg/L was used to continuously feed a sequencing batch reactor (SBR-NPs). Under the experimental conditions used in this study, no changes were observed in the process performance of the SBR-NPs compared to the reactor used as a control. Neither nitrification nor organic matter removal efficiency, which was 96% for both SBRs, were affected by the presence of 100 nm polystyrene nanoplastics, which suggests that the tested nanoplastics were not sufficiently toxic to the biomass. Although no significant differences in the relative abundances of predominant phyla between SBR-Control and SBR-NPs were observed, a slight shift in the relative abundance of Patescibacteria (1.5 ± 0.6% and 3.7 ± 0.8% in SBR-Control and SBR-NPs, respectively, at the end of the test) occurred. The higher abundance of this phylum in SBR-NPs compared to SBR-Control may suggest that these bacteria have some sensitivity to the presence of 100 nm polystyrene nanoplastics. Furthermore, even with the absence of nitrification inhibition, it was observed stagnation of the growth of Nitrotoga bacteria in SBR-NPs, which also suggests that the polystyrene nanoplastics could have an inhibitory effect on these cells and an impact on nitrification in the long term.

Neurodegenerative disorders are a critical affection with a high incidence around the world. Currently, there are no effective treatments to solve this problem. However, the application of mesenchymal stem cells (MSCs) and antioxidants in neurodegenerative diseases has shown to be a promising tool due to their multiple therapeutic effects. This work aimed to evaluate the effects of a combination of resveratrol (RSV) and coenzyme Q10 (CoQ10) on the proliferation and differentiation of MSC and the protector effects in induced damage. To characterize the MSCs, we performed flow cytometry, protocols of cellular differentiation, and immunocytochemistry analysis. The impact of RSV + CoQ10 in proliferation was evaluated by supplementing 2.5 and 10 μM of RSV + CoQ10 in a cellular kinetic for 14 days. Cell viability and lactate dehydrogenase levels (LDH) were also analyzed. The protective effect of RSV + CoQ10 was assessed by supplementing the treatment to damaged MSCs by 1-methyl-4-phenylpyridinium (MPP+); cellular viability, LDH, and reactive oxygen species (ROS) were evaluated.. MSCs expressed the surface markers CD44, CD73, CD90, and CD105 and showed multipotential ability. The combination of RSV + CoQ10 increased the proliferation potential and cell viability and decreased LDH levels. In addition, it reverted the effect of MPP+-induced damage in MSCs to enhance cell viability and decrease LDH and ROS. Finally, RSV + CoQ10 promoted the differentiation of neural progenitors. The combination of RSV + CoQ10 represents a potential treatment to improve MSCs capacities and protect against neurodegenerative damage.

Silver nanoparticles (AgNPs) synthesized with plants are widely used in different industries, such as the medical, industrial, and food industries; however, their hazards and risks remain unclear. Here, we aimed to evaluate the toxicological effects of AgNPs in both in vitro and in vivo models. Previously, we developed and characterized green synthesized AgNPs based on

In this paper, we present an apparatus for studies into the photodetachment process of atomic negative ions. State-selective detection of the residual atom following the initial photodetachment step is achieved by combining resonant laser excitation of the photo-detached atom with electric field ionization. The resonance ionization technique in combination with a co-linear ion–laser beam geometry gives an experimental apparatus that has both high selectivity and sensitivity. In addition to measurements of a single selected partial photodetachment channel, the apparatus also can be used to study a manifold of photodetachment channels in which the residual atom is left in a high-lying Rydberg state and for investigation of the double electron-detachment process. Ion-optical simulations in SIMION are used to illustrate the operation of the apparatus for studying such processes. Successful performance of the apparatus against the simulation is demonstrated by a high resolution study of the photodetachment of cesium, where the sharp s-wave threshold of the photodetachment processes leaving the residual atom in the excited 6 p state was investigated.

Soil is an essential component in viticulture. The study reported here concerns the assessment of the morphology chemical and physicochemical features of typical, well-developed and representative evolved Mediterranean soils near Anchuras (Spain, southern Europe), a site with soils that developed on old landforms (Plio-Quaternary) called ‘raña’ and/or ‘rañizo’. The soils under study were described and sampled by conducting soil surveys. Selected soil properties, such as texture, bulk density, pH, electrical conductivity (EC), cation exchange capacity (CEC) and contents of organic matter, nutrients, etc., were analysed using standard procedures. The results showed that these landscape surfaces were, linked with specific soil properties such as low pH (from 4.4 to 5.3) and EC (from 0.15 to 0.02 dSm 1 ), clay contents (20.1%–48.8%), high CEC (26–39 cmol/kg), and low base saturation values (from 11.2% to 17.2%), and have an adequate and singular pedological potential in relation to the ‘terroir’ or ‘terron’ concepts that meet suitability criteria. Furthermore, the information provided by this study, fundamentally through the weathering indices, supports the role of soil-forming factors and their influence on soil properties. In addition, as these landforms and underlying materials have abundant and extensive rock fragments, the role of these soils in the context of vineyard growth and development has been investigated, This research was supported by the Winerin Eldoze (Project number UCTR180065)

The aim was to evaluate the potential of nanocarriers, based on the coating of zein nanoparticles (ZNP) with a Gantrez® AN-PEG conjugate (GP), for the oral delivery of insulin. ZNP-GP displayed less negative surface charge and a 14-fold higher diffusion coefficient in pig intestinal mucus than ZNP. Both nanoparticles showed a spherical shape and an insulin load of 77.5 µg/mg. Under simulated gastric conditions, ZNP-GP released significantly lower amount of insulin than ZNP, while under simulated intestinal conditions, both types of nanoparticles displayed similar behaviour. In Caenorhabditis elegans wild-type N2, grown under high glucose conditions, insulin treatments reduced glucose and fat accumulation without altering the growth rate, the worm length, or the pumping rate. The effect was significantly greater (p

The root rot of holm and cork oaks caused by Phytophthora cinnamomi is one of the main phytosanitary problems in dehesas and montados, open woodlands of the Southern Iberian Peninsula. Biofumigation with seed meals rich in sinigrin is a promising technique to diminish the impact of this disease, but verification of its effectiveness is necessary before applying it in the field. The effectiveness to reduce sporangial production of P. cinnamomi and to control disease in holm and cork oak plants of biofumigation with non-defatted seed meal of Brassica juncea and pellets of defatted seed meal of Brassica carinata, combined or not with calcium carbonate, was tested in experimental conditions. The combinations of biofumigant materials and CaCO3 in vitro experiments were more effective in reducing the production of sporangia than the application separately, even with high doses of biofumigants. In plant experiments, none of the treatments significantly reduced disease symptoms in holm oak plants. In cork oak plants, the most effective treatment was seed meal of B. juncea (1.34 g L−1 of substrate) combined with CaCO3 (1.5 g L−1of substrate), although treatments with both doses of B. juncea seed meal (1.34 and 2.68 g L−1 of substrate) and with pellets of B. carinata (1.5 g L−1 of substrate) combined with CaCO3 (1.5 g L−1 of substrate) also significantly reduced root symptom severity in contrast with the inoculated control. Biofumigation with B. juncea seed meal or with B. carinata pellets, combined with the application of CaCO3 can be a tool to integrate control strategies into the disease in the dehesas.

In this work, a bioactive persimmon extract was produced from discarded fruits. A central composite design was used to evaluate the effect of different extraction parameters and ripeness stages of persimmon fruits on the total phenolic content and antioxidant activity of the resulting extracts. Significantly greater phenolic contents were obtained from immature persimmon (IP) fruits. The optimum IP extract with the conditions set by the experimental design was industrially up-scaled and its composition and functional properties were evaluated and compared with those obtained under lab-scale conditions. Both extracts contained significant protein (>20%) and phenolic contents (∼11–27 mg GA/g dry extract) and displayed significant antiviral activity against murine norovirus and hepatitis A virus. Moreover, the extract showed no toxicity and significantly reduced the fat content and the cellular ageing of Caenorhabditis elegans (C. elegans) without affecting the worm development. These effects were mediated by down-regulation of fat-7, suggesting an anti-lipogenic activity of this extract., This work was financially supported by the grant RTI-2018-094268-B-C22 (MCI/AEI/FEDER, EU). Mendez D. A. is supported by the Ministry of Science, Technology and Innovation (Minciencias) of the Colombian Government (783-2017). M. J. Fabra and A. Martinez-Abad are recipients of Ramon y Cajal (RYC-2014-158) and Juan de la Cierva (IJDC-2017-31255), respectively, from the Spanish Ministry of Economy, Industry and Competitiveness. We also appreciate the funding of the CERCA program (Centres de Recerca de Catalunya) of the Generalitat de Catalunya and from the CIEN project “BIOPRO” from CDTI.

Paroxysmal nocturnal hemoglobinuria is a rare non malignant clonal disease, caused by an acquired somatic mutation in a variable number of hematopoietic stem cells, whose consequence is an abnormal sensitivity of blood cells to complement-mediated lysis. It manifests as intravascular hemolytic anemia, a variable degree of bone marrow insufficiency and high thrombotic risk. The effective management of the disease is based on an adequate diagnosis and clinical and laboratory follow-up. Flow cytometry is the method of choice for diagnosis and monitoring of the patient. The only curative treatment is hematopoietic stem cell transplantation. Eculizumab is the first specific treatment approved for this disease. We present the case of a patient diagnosed with paroxysmal nocturnal hemoglobinuria, wo has recently started treatment with eculizumab. We show the clinical and analytical evolution during the first months of treatment as an assessment of is benefit.

Ultrasound-mediated microbubble destruction (UMMD) is a promising strategy to improve local drug delivery in specific tissues. However, acoustic cavitation can lead to harmful bioeffects in endothelial cells. We investigated the side effects of UMMD treatment on vascular function (contraction and relaxation) and endothelium integrity of ex vivo Wistar rat arteries. We used an isolated organ system to evaluate vascular responses and confocal microscopy to quantify the integrity and viability of endothelial cells. The arteries were exposed for 1-3 min to ultrasound at a 100 Hz pulse-repetition frequency, 0.5 MPa acoustic pressure, 50% duty cycle and 1%-5% v/v microbubbles. The vascular contractile response was not affected. The acetylcholine-dependent maximal relaxation response was reduced from 78% (control) to 60% after 3 min of ultrasound exposure. In arteries treated simultaneously with 1 min of ultrasound exposure and 1%, 2%, 3% or 5% microbubble concentration, vascular relaxation was reduced by 19%, 58%, 80% or 93%, respectively, compared with the control arteries. Fluorescent labeling revealed that apoptotic death, detachment of endothelial cells and reduced nitric oxide synthase phosphorylation are involved in relaxation impairment. We demonstrated that UMMD can be a safe technology if the correct ultrasound and microbubble parameters are applied. Furthermore, we found that tissue-function evaluation combined with cellular analysis can be useful to study ultrasound-microbubble-tissue interactions in the optimization of targeted endothelial drug delivery.

The aim of CONFIDENCE WP2 is to improve the situation awareness in the early phase of a nuclear accident by trying to reduce the uncertainty in individual dose assessment when dealing with external and internal exposures. Main WP2 research actions to improve external dosimetry in this emergency frame were the development of destruction-free protocols using electronic components in smartphones for external dose measurements, Monte Carlo (MCNP) calculations for organ dose assessment with associated uncertainties and the organization of a workshop for integration of biodosimetry into emergency response. On the other hand, one of the main concerns after the release of radioactive material in case of a nuclear reactor accident is the intake of radioiodines in workers and population. A smartphone/tablet application for direct calculation of thyroid doses from monitoring data of the content of 131I (and 132I) in the thyroid was developed during the project (Prototype of processing unit for thyroid dose monitor [IDOSE]). Up to date age-dependent ICRP dose per content values are used by this tool, allowing a rapid screening of exposed persons. A sensitivity analysis on thyroid doses was carried out, considering 16 exposure scenarios leading to 16 different dose estimates, using ICRP56/119 (ICRP60) vs. ICRP130/137 iodine models for adults, varying the time of intake, the time pattern (acute vs. chronic) and considering not well defined relative abundance of short-lived radioiodines and 132Te. Real cases of Europeans contaminated in Japan shortly after the Fukushima NPP accident (low doses), and artificial cases of high doses generated to see the impact of the different parameters in this study, were used for applying this multi-intake scenario approach. Main conclusions of the study are presented here.

Funding: This study was supported by grants awarded by the Ministry of Economy, Industry and Competitiveness (Spanish Agency of Research) and the European Regional Development Fund (ERDF); DEP2014-59707-P “SWIM: Specific Water Innovative Measurements applied to the development of International Swimmers in Short Swimming Events (50 and 100 m), by the Ministry of Science, Innovation and Universities (Spanish Agency of Research) and the European Regional Development Fund (ERDF); PGC2018-102116-B-I00 “SWIM II: Specific Water Innovative 10 J. J. RUIZ-NAVARRO ET AL. Measurements: Applied to the performance improvement” and the Spanish Ministry of Education, Culture and Sport: FPU17/02761 grant. This article is a part of an international thesis belonging to the Program of PhD in Biomedicine (B11.56.1), from the University of Granada, Granada (Spain). This study aimed 1) to examine variables that may quantify the ability to apply force in the water and 2) to test their relationship with free swimming performance. Sixteen regional-level swimmers participated in this study. Average (Favg) and maximum (Fmax) forces were measured for 30 s arm stroke tethered swimming in a flume at zero and 1.389 m/s water flow speeds. The maximum and average force’s relative changes (ΔFmax and ΔFavg, respectively) were calcu-lated between tethered swimming at zero and 1.389 m/s water flow speeds. Free swimming speeds were obtained from 25, 50, and 100 m front crawl trials, and were correlated with ΔFmax and ΔFavg. A negative correlation was found between ΔFmax and 25, 50 and 100 m speeds (r = -0.84, r = -0.74, r = -0.55; p < 0.05, respectively) and ΔFavg correlated negatively with 25 and 50 m speeds (r = -0.63, r = -0.54; p < 0.05, respectively), but it did not correlate with 100 m swimming speed. The relative change in force could be used to quantify the ability to apply force in the water. This could aid coaches to understand if changes in swimmers’ ability to apply force in the water contribute to improvements in performance. info:eu-repo/semantics/publishedVersion

Microbubbles (1–10 µm diameter) have been used as conventional ultrasound contrast agents (UCAs) for applications in contrast-enhanced ultrasound (CEUS) imaging. Nanobubbles (

We report for the first time the association of Haemophilus pittmaniae and Haemophilus sputorum with urethritis in men who have sex with men and who engage in unprotected intercourse. A search for genital pathogens was conducted using urethral exudate cultures and PCR tests for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma spp., and Ureaplasma spp. Recovered microorganisms were identified by MALDI-TOF mass spectrometry, and their susceptibility was evaluated by diffusion gradient test. H. pittmaniae and H. sputorum were isolated. They both proved susceptible to ampicillin, cefixime, and trimethoprim/sulfamethoxazole. H. pittmaniae was also susceptible to tetracycline and H. sputorum to moxifloxacin. The increased frequency of potentially resistant Haemophilus spp. isolates in genital exudates highlights the need for greater surveillance of these microorganisms and for their consideration in the differential diagnosis of genital system infections.

Microbubbles are 1–10 μm diameter gas-filled acoustically-active particles, typically stabilized by a phospholipid monolayer shell. Microbubbles can be engineered through bioconjugation of a ligand, drug and/or cell. Since their inception a few decades ago, several targeted microbubble (tMB) formulations have been developed as ultrasound imaging probes and ultrasound-responsive carriers to promote the local delivery and uptake of a wide variety of drugs, genes, and cells in different therapeutic applications. The aim of this review is to summarize the state-of-the-art of current tMB formulations and their ultrasound-targeted delivery applications. We provide an overview of different carriers used to increase drug loading capacity and different targeting strategies that can be used to enhance local delivery, potentiate therapeutic efficacy, and minimize side effects. Additionally, future directions are proposed to improve the tMB performance in diagnostic and therapeutic applications.

Research into various proteins capable of blocking metabolic pathways has improved the detection and treatment of multiple pathologies associated with the malfunction and overexpression of different metabolites. However, antigen-binding proteins have limitations. To overcome the disadvantages of the available antigen-binding proteins, the present investigation aims to provide chimeric antigen-binding peptides by binding a complementarity-determining region 3 (CDR3) of variable domains of new antigen receptors (VNARs) with a conotoxin. Six non-natural antibodies (NoNaBodies) were obtained from the complexes of conotoxin cal14.1a with six CDR3s from the VNARs of Heterodontus francisci and two NoNaBodies from the VNARs of other shark species. The peptides cal_P98Y vs. vascular endothelial growth factor 165 (VEGF165), cal_T10 vs. transforming growth factor beta (TGF-β), and cal_CV043 vs. carcinoembryonic antigen (CEA) showed in-silico and in vitro recognition capacity. Likewise, cal_P98Y and cal_CV043 demonstrated the capacity to neutralize the antigens for which they were designed.

This study was supported by the Ministry of Economy, Industry and Competitiveness (Spanish Agency of Research) and the European Regional Development Fund (ERDF); PGC2018-102116-B-I00 ‘SWIM II: Specific Water Innovative Measurements: Applied to the performance improvement’ and the Spanish Ministry of Education, Culture and Sport: FPU17/02761, FPU16/02629, and FPU19/02477 grant. This article is a part of an international thesis belonging to the Program of PhD in Biomedicine (B11.56.1), from the University of Granada, Granada (Spain), The level of expertise must be defined for the sample studied when report research in sport. Concretely in swimming, apart from the participants’ background, the competitive status is based on the level that swimmers participate. Thus, the International Swimming Federation (FINA) points are added to improve the sample level characterization. The aim of this study was two-fold: 1) to assess whether national and regional swimmers from different countries differ in their performance level (based on FINA points), and 2) to propose a model that allows standardizing the research results in swimming. The FINA points of 5876 participants (males = 2962 and females = 2914) in 100 m butterfly, backstroke, breaststroke, and freestyle were retrieved from nationals (n = 21) and regionals (n = 44) swimming competitions. One-way analysis of variance was conducted to test the difference in FINA points between swimmers of different countries. Significant disparities (100 to 350 FINA points; p, Spanish Ministry of Education, Culture and Sport: FPU17/02761, FPU16/02629, and FPU19/02477, Ministry of Economy, Industry and Competitiveness (Spanish Agency of Research) and the European Regional Development Fund (ERDF); PGC2018-102116-B-I00 ‘SWIM II: Specific Water Innovative Measurements: Applied to the performance improvement

While it is widely recognized that microstructure plays an important role in the performance of organic photovoltaics (OPV), systematic studies are often challenging, as varying the molecular packing through typical chemical means (such as sidechain tuning) often affects the molecular energy levels, thus preventing a clear correlation. In this work we present the synthesis of three perylene imide (PI) based electron acceptors with almost identical energy levels, but distinct packing tendencies. We confirm our initial hypothesis by measuring solution and solid-state absorption, cyclic voltammetry as well as characterizing the films by grazing incident wide angle X-ray scattering (GIWAXS). In a second step, we repeat the characterization of the three materials in blends with two polymer donors, namely PCDTBT or PBDBT, whose energy levels are well aligned with those of the PI acceptors, and which, additionally, exhibit different degrees of structural order. We show how the initial strong difference between acceptors is partially blurred in blends, but still critical. Finally, we correlate our structural data with OPV devices made with the corresponding six blends. Our data suggest that a good donor acceptor marriage should ensure good energy alignment but also exhibit complementary crystallization tendencies of the two components., The authors acknowledge financial support from the Spanish Ministry of Science and Innovation through the Severo Ochoa” Program for Centers of Excellence in R&D (No. CEX2019-000917-S), and projects PGC2018-095411-B-I00, PID2019-106268GB-C33 and PID2019-110305GB-I00, as well as the European Commission through the Horizon 2020 Marie Sklodowska-Curie ITN Programme, SEPOMO, Grant Number: 722651, and the UCM (INV.GR.00.1819.10759). E.G. specially acknowledges Comunidad de Madrid and Universidad Complutense de Madrid for a post-doctoral contract (CT20/19- CT21/19/PEJD-2018-POST/IND-8661PAI). M.J.A.N. acknowledges URJC for a post-doctoral contract. R.P.O and A.H. also acknowledge support from Junta de Andalucía (projects UMA18-FEDERJA-080). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).

The investigation of caloric effects linked to first-order structural transitions in Heusler-type alloys has become a subject of considerable current interest due to their potential utilization as refrigerants in solid-state cooling devices. This study is mainly motivated by the possibility of developing refrigeration devices of improved energy efficiency with a reduced environmental impact. We produced partially textured and isotropic bulk samples of the Heusler-type magnetic shape memory alloy Ni55Fe11Mn7Ga27 by arc melting and spark plasma sintering (SPS), respectively. Their structural, microstructural, and phase transition characteristics and magnetocaloric and elastocaloric effects, associated with first-order martensitic transformation (MT), were studied. The elemental chemical compositions of both samples were close to nominal, and a martensitic-like structural transformation appeared around room temperature with similar starting and finishing structural transition temperatures. At room temperature, austenite exhibited a highly ordered L21-type crystal structure. The partial grain orientation and isotropic nature of the arc-melted and SPS samples, respectively, were revealed by X-ray diffraction and SEM observations of the microstructure. For the arc-melted sample, austenite grains preferentially grew in the (100) direction parallel to the thermal gradient during solidification. The favorable effect of the texture on the elastocaloric response was demonstrated. Finally, due to its partial grain orientation, the arc-melted bulk sample showed superior values of maximum magnetic entropy change (|ΔSM|max = 18.6 Jkg−1K−1 at 5 T) and elastocaloric adiabatic temperature change (|ΔTadme|max = 2.4 K at 120 MPa) to those measured for the SPS sample (|ΔSM|max = 8.5 Jkg−1K−1 and (|ΔTadme|max = 0.8 K).

Introduction and Objectives: The treatment of vulnerable populations must be prioritized to accomplish the WHO HCV elimination goals by 2030, including patients with mental health disorders, incarcerated patients or homeless patients. Simplifying the treatment cascade and rapid treatment start is key to achieving this goal, even more so in the COVID-19 era. Sofosbuvir/velpatasvir (SOF/VEL) is a protease inhibitor-free, pangenotypic, panfibrotic, single duration, single tablet regimen, to be taken without regards to food and with limited drug-drug interactions, allowing treatment simplification. Purpose: This real world data (RWD) analysis evaluates the effectiveness and safety of SOF/VEL for 12 weeks in a heterogeneous HCV population who suffer a mental health disorder, are incarcerated, or homeless. Materials and Methods: 33 clinical cohorts across Australia, Canada, Europe & USA included 1,888 patients, 280 of them (from 6 clinical cohorts) were treated in Canada and overall managed following local standards of care. Adults were included if SOF/VEL for 12 weeks was started before November 2019 and completed while suffering a mental health disorder, being incarcerated or homeless, irrespective of genotype (GT), presence of compensated cirrhosis (CC) or treatment experience. Exclusion criteria were history of decompensation, prior NS5A-inhibitor exposure, treatment duration >12 weeks or addition of ribavirin. Sustained virological response (SVR; ≥12 weeks after end-of-treatment) and time to treatment initiation were assessed. Results: Overall analysis includes 1,888 (71.3% male) patients (1,422 with a mental health disorder, 526 incarcerated, 153 homeless) aged 50 years, 24.4% were taking antipsychotic drugs and 52.2% of patients had former or current intravenous drug use. 43.2% patients had HCV GT1, 11.6% GT2, 36.3% GT3, 5.9% GT4-6, and 3.0% mixed/unknown GT. 19.0% patients had CC and 12.4% were treatment-experienced. In 257 patients (13.6%), SVR was not evaluated due to non-virological or unknown reasons; 79.9% of those were lost to follow-up (LTFU). When SVR was measured, 98.0% (n=1598/1631) achieved SVR, with 97.6%, 98.9% and 100% in patients with a mental health disorder, incarcerated or homeless patients, respectively. SVR was 98.5% in non-cirrhotic and 95.4% in CC patients. SVR remained >95% under antipsychotic use or coexistence of two negative factors of non-response such as GT3 plus active drug use or psychiatric disorder. SVR was similar, irrespective of time from diagnosis to treatment. Detailed analysis of the Canadian cohort data will be presented at the conference. Conclusion: A test-and-treat strategy, easily implemented with SOF/VEL, and supported by the AASLD/ALEH/APASL/EASL joint call to action, could further enhance the population-level efficacy of HCV therapy by reducing the rate of non-virologic failure due to LTFU and related factors.

Small islands that support urban communities provide a unique opportunity to study the urban water cycle, its energy needs, and possible links to renewable energy. In this paper, models for an energy generation system and the processes in the urban water cycle are formulated. These are combined and then used to determine optimal parameters for 12 different possible alternatives in two scenarios.

[Objectives] The number of people aged ≥60 y is increasing worldwide, so establishing a relationship between lifestyle and health-associated factors, such as gut microbiota in an older population, is important. This study aimed to characterize the gut microbiota of a presenior population, and analyze the association between some bacteria and quality of life with the Short Form (SF) 36 questionnaire., [Methods] Participants were adult men and women ages 50 to 80 y (n = 74). In addition to the SF-36 questionnaire, fecal samples were collected in cryotubes, and 16S RNA gene sequencing was performed to characterize microbial features. Participants were classified into two groups according to SF-36 punctuation. Linear and logistic regression models were performed to assess the possible association between any bacterial bowl and SF-36 score. Receiver operating characteristics curves were fitted to define the relative diagnostic strength of different bacterial taxa for the correct determination of quality of life., [Results] A positive relationship was established between SF-36 score and Actinobacteria (P = 0.0310; R = 0.2510) compared with Peptostreptococcaceae (P = 0.0259; R = –0.2589), which increased with decreasing quality of life. Logistic regressions models and receiver operating characteristics curves showed that the relative abundance of Actinobacteria and Peptostreptococcaceae may be useful to predict quality of life in a presenior population (area under the curve: 0.71)., [Conclusions] Quality of life may be associated with the relative abundance of certain bacteria, especially Actinobacteria and Peptostreptococcaceae, which may have a specific effect on certain markers and health care, which is important to improve quality of life in older populations., The authors express their gratitude to the NUTRIPRECISION consortium associated with the project “Strategies for improving the quality of life of presenior and senior populations based on precision nutrition”. The authors gratefully acknowledge the financial support from CDTI through the Programa Estratégico CIEN (IDI-20160734), cofounded by the European Regional Development Fund. The physician (B.E. Martínez de Morentin), dietitians (M. Hernández, N. Hernández), nurses (C. Castejón, S. Pérez), and technicians (V. Ciaurriz, M. Zabala) are thanked for their contribution to the Nutriprecision project. Begoña de Cuevillas appreciates the predoctoral grant received from Congelados de Navarra.

A photoacoustic contrast mechanism is presented based on the photoacoustic fluctuations induced by microbubbles flowing inside a micro vessel filled with a continuous absorber. It is demonstrated that the standard deviation of a homogeneous absorber mixed with microbubbles increases non-linearly as the microbubble concentration and microbubble size is increased. This effect is then utilized to perform photoacoustic fluctuation imaging with increased visibility and contrast of a blood flow phantom., 12 pages

The study reported here concerns the geochemical distributions of macro- and trace elements (including potentially toxic elements, PTEs) in the vineyard soils of Alcubillas, which is one of the oldest, albeit not world-renowned, wine-growing areas in La Mancha (Central Spain). Soil and leaf samples were analyzed by X-ray fluorescence spectrometry to ascertain the levels of various elements in the soil and the plant. The potential toxicity of the elements was assessed with regard to the development of the vineyard. Despite the fact that fertilizers and pesticides are employed in the vineyards in this area, the results showed that the levels of trace elements in the soil samples did not exceed the reference values according the pedogeochemical values for the region and Spain. This finding suggests that the study area is not polluted, and therefore, there are hardly any traces of anthropogenic contamination. The Biological Absorption Coefficient (BAC) was calculated to assess the assimilation of various elements from the soil to the leaves, and differences were found in the element absorption capacity of the vines. Some elements were not taken up by Vitis vinifera despite elements like Zr and Rb being present in relatively high concentrations in the soil. The production in these soils does not represent a threat to human health or the ecosystem, because the farmers in this area are extremely careful to preserve the environment and they only farm to achieve moderate yields of grapes per hectare.