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Traditional ditches ("acequias" in Spanish) derive meltwater and infiltrate groundwater providing ecological services downstream in the semi-arid Sierra Nevada range (SE Spain). Therefore, they may act as a nature-based solution by alleviating drought stress in trees growing near ditches by enhancing growth and reducing their intrinsic water-use efficiency (iWUE). Such a mitigation role of acequias is critical given that some oak (Quercus pyrenaica) and pine (Pinus sylvestris) stands reach their xeric distribution limits in Europe. We compared tree-ring width data and wood δ 13 C, a proxy of iWUE, in oak and pine stands located near or far (control) from ditches with different infiltration capacity in two watersheds. We assessed how trees responded to climate data, drought stress, and vegetation greenness through correlations and resilience indices. Oak trees located near ditches grew more and responded less to precipitation, soil moisture, a drought index, and greenness than control trees. In pines, we did not find this pattern, and ditch trees grew more than control trees only during an extremely dry year (1995). Climate-growth correlations suggested a longer growing season in ditch pines. Growth of ditch oaks from the "Acequia Nueva" (AN), with high infiltration capacity, responded more to autumn soil moisture and showed the lowest δ 13 C. Growth was enhanced by cool-wet spring conditions in pines and also by warm-wet conditions in the prior winter in the case of oaks. Control trees showed lower resistance to drought. Control trees presented higher wood δ 13 C values except for old oaks from the "Acequia Grande" (AG) site which may show long-term acclimation. Traditional ditches alleviate drought stress in oak and pine stands subjected to regional xeric climate conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Iron oxide nanoparticles (IONPs) have shown great promise in biomedical applications, particularly as MRI contrast agents due to their magnetic properties and biocompatibility. Although several IONPs have been approved by regulatory agencies as MRI contrast agents, their primary application as negative contrast agents limits their usage. Additionally, there is an emerging need for the development of molecular contrast agents that can specifically target biomarkers, enabling more accurate and sensitive diagnostics. To address these challenges, we exploited the engineerability of proteins to stabilize IONPs with tailored magnetic properties, creating protein-stabilized iron oxide nanoparticles (Prot-IONPs) and leveraged the chemical diversity of proteins to functionalize Prot-IONPs with targeting moieties. As a proof-of-concept, we used alendronate (Ald) to target atherosclerotic plaques in the aorta. Simple protein functionalization allowed targeting while maintaining the stability and relaxation properties of the Prot-IONPs. Prot-IONPs-Ald successfully enabled positive contrast imaging of atherosclerotic plaques in vivo in an atherosclerotic mouse model (ApoE -/- mice on a high-fat diet). This study demonstrates the potential of engineering protein-nanoparticle hybrids as versatile platforms for developing targeted in vivo MRI contrast agents.

Basic Helix-Loop-Helix (bHLH) transcription factors TFEB/TFE3 and HLH-30 are key regulators of autophagy induction and lysosomal biogenesis in mammals and C. elegans, respectively. While much is known about the regulation of TFEB/TFE3, how HLH-30 subcellular dynamics and transactivation are modulated are yet poorly understood. Thus, elucidating the regulation of C. elegans HLH-30 will provide evolutionary insight into the mechanisms governing the function of bHLH transcription factor family. We report here that HLH-30 is retained in the cytoplasm mainly through its conserved Ser201 residue and that HLH-30 physically interacts with the 14-3-3 protein FTT-2 in this location. The FoxO transcription factor DAF-16 is not required for HLH-30 nuclear translocation upon stress, despite that both proteins partner to form a complex that coordinately regulates several organismal responses. Similar as described for DAF-16, the importin IMB-2 assists HLH-30 nuclear translocation, but constitutive HLH-30 nuclear localization is not sufficient to trigger its distinctive transcriptional response. Furthermore, we identify FTT-2 as the target of diethyl maleate (DEM), a GSH depletor that causes a transient nuclear translocation of HLH-30. Together, our work demonstrates that the regulation of TFEB/TFE3 and HLH-30 family members is evolutionarily conserved and that, in addition to a direct redox regulation through its conserved single cysteine residue, HLH-30 can also be indirectly regulated by a redox-dependent mechanism, probably through FTT-2 oxidation., Competing Interests: Declaration of competing interest Authors declare no competing interests, (Copyright © 2024. Published by Elsevier Inc.)

Background: The outstanding capabilities of modern Positron Emission Tomography (PET) to highlight small tumor lesions and provide pathological function assessment are at peril from image quality degradation caused by respiratory and cardiac motion. However, the advent of the long axial field-of-view (LAFOV) scanners with increased sensitivity, alongside the precise time-of-flight (TOF) of modern PET systems, enables the acquisition of ultrafast time resolution images, which can be used for estimating and correcting the cyclic motion. Methods: 0.25 s so-called [ 18 F]FDG PET histo image series were generated in the scope of for detecting respiratory and cardiac frequency estimates applicable for performing device-less data-driven gated image reconstructions. The frequencies of the cardiac and respiratory motion were estimated for 18 patients using Short Time Fourier Transform (STFT) with 20 s and 30 s window segments, respectively. Results: The Fourier analysis provided time points usable as input to the gated reconstruction based on eight equally spaced time gates. The cardiac investigations showed estimates in accordance with the measured pulse oximeter references ( p = 0.97) and a mean absolute difference of 0.4 ± 0.3 beats per minute (bpm). The respiratory frequencies were within the expected range of 10-20 respirations per minute (rpm) in 16 out of 18 patients. Using this setup, the analysis of three patients with visible lung tumors showed an increase in tumor SUV max and a decrease in tumor volume compared to the non-gated reconstructed image. Conclusions: The method can provide signals that were applicable for gated reconstruction of both cardiac and respiratory motion, providing a potential increased diagnostic accuracy.

Large bone defects are a significant health problem today with various origins, including extensive trauma, tumours, or congenital musculoskeletal disorders. Tissue engineering, and in particular bone tissue engineering, aims to respond to this demand. As such, we propose a specific model based on Elastin-Like Recombinamers-based click-chemistry hydrogels given their high biocompatibility and their potent on bone regeneration effect conferred by different bioactive sequences. In this work we demonstrate, using biochemistry, histology, histomorphometry and imaging techniques, the biocompatibility of our matrix and its potent effect on bone regeneration in a model of bone parietal lesion in female New Zealand rabbits., (© 2024. The Author(s).)

Objective . We introduce a versatile methodology for the accurate modelling of PET imaging systems via Monte Carlo simulations, using the Geant4 application for tomographic emission (GATE) platform. Accurate Monte Carlo modelling involves the incorporation of a complete analytical signal processing chain, called the digitizer in GATE, to emulate the different count rates encountered in actual positron emission tomography (PET) systems. Approach . The proposed approach consists of two steps: (1) modelling the digitizer to replicate the detection chain of real systems, covering all available parameters, whether publicly accessible or supplied by manufacturers; (2) estimating the remaining parameters, i.e. background noise level, detection efficiency, and pile-up, using optimisation techniques based on experimental single and prompt event rates. We show that this two-step optimisation reproduces the other experimental count rates (true, scatter, and random), without the need for additional adjustments. This method has been applied and validated with experimental data derived from the NEMA count losses test for three state-of-the-art SiPM-based time-of-flight (TOF)-PET systems: Philips Vereos, Siemens Biograph Vision 600 and GE Discovery MI 4-ring. Main results . The results show good agreement between experiments and simulations for the three PET systems, with absolute relative discrepancies below 3%, 6%, 6%, 7% and 12% for prompt, random, true, scatter and noise equivalent count rates, respectively, within the 0-10 kBq·ml -1 activity concentration range typically observed in whole-body 18 F scans. Significance . Overall, the proposed digitizer optimisation method was shown to be effective in reproducing count rates and NECR for three of the latest generation SiPM-based TOF-PET imaging systems. The proposed methodology could be applied to other PET scanners., (Creative Commons Attribution license.)

Myocardial cardiopathy is one of the highest disease burdens worldwide. The damaged myocardium has little intrinsic repair ability, and as a result, the distorted muscle loses strength for contraction, producing arrhythmias and fainting, and entails a high risk of sudden death. Permanent implantable conductive hydrogels that can restore contraction strength and conductivity appear to be promising candidates for myocardium functional recovery. In this work, we present a printable cardiac hydrogel that can exert functional effects on networks of cardiac myocytes. The hydrogel matrix was designed from poly(vinyl alcohol) (PVA) dynamically cross-linked with gallic acid (GA) and the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT). The resulting patches exhibited excellent electrical conductivity, elasticity, and mechanical and contractile strengths, which are critical parameters for reinforcing weakened cardiac contraction and impulse propagation. Furthermore, the PVA-GA/PEDOT blend is suitable for direct ink writing via a melting extrusion. As a proof of concept, we have proven the efficiency of the patches in propagating the electrical signal in adult mouse cardiomyocytes through in vitro recordings of intracellular Ca 2+ transients during cell stimulation. Finally, the patches were implanted in healthy mouse hearts to demonstrate their accommodation and biocompatibility. Magnetic resonance imaging revealed that the implants did not affect the essential functional parameters after 2 weeks, thus showing great potential for treating cardiomyopathies.

The human Integrator complex is a set of 15 subunits that mediates processing of small nuclear RNAs (snRNAs), and which later participates in splicing messenger RNAs (mRNAs). In addition, it controls the pause and release of RNA polymerase II (RNA pol II) at specific gene promoters in response to growth factors. Mutations in Integrator-complex subunit 6 ( INTS6 ) are associated with different types of tumors. However, the INTS6 gene product does not have a significant prognostic value as a biomarker for tumor progression. Here we show that Integrator-complex deregulation is involved in 8.3% of the colorectal cancer cases diagnosed from the population screen carried out in La Rioja (Spain) from the years 2017 to 2019. Lack of Integrator-complex function, measured by an increased level of unprocessed snRNA, is a prognostic biomarker and correlates with a poorer prognosis in colorectal-cancer patients. The transcriptomic profile of all analyzed colorectal tumors shows a strong alteration of the metabolic state of tumor cells, which compromises standard energy production through mitochondrial respiration, known as the Warburg effect. Furthermore, there is a significant upregulation of genes involved in extracellular matrix organization and collagen rearrangement. This is consistent with tissue reorganization in a growing tumor forming a polyp. Crossing the molecular data generated in this study with the follow-up of patients from population screening indicates that population screening combined with early typing of tumors appears to be the most efficient way to increase patient survival.

The quest for nanomaterial-based imaging probes that can provide positive contrast in MRI is fueled by the necessity of developing novel diagnostic applications with potential for clinical translation that current gold standard probes cannot provide. Although interest in nanomaterials for positive contrast has increased in recent years, their study is less developed than that of traditional negative contrast probes in MRI. In our search for new magnetic materials with enhanced features as positive contrast probes for MRI, we decided to explore the chemical space to comprehensively analyze the effects of different metals on the performance of iron oxide nanomaterials already able to provide positive contrast in MRI. To this end, we synthesized 30 different iron oxide-based nanomaterials. Thorough characterization was performed, including multivariate analysis, to study the effect of different variables on their relaxometric properties. Based on these results, we identified the best combination of metals for in vivo imaging and tested them in different experiments. First, we tested its performance on magnetic resonance angiography using a concentration ten times lower than that clinically approved for Gd. Finally, we studied the capability of these nanomaterials to cross the affected blood-brain barrier in a glioblastoma model. The results showed that the selected nanomaterials provided excellent positive contrast at large magnetic field and were able to accumulate at the tumor site, highlighting the affected tissue., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

The construction sector must incorporate the circular economy to improve sustainability and efficiency. The use of recycled aggregates (RAs) as a substitute for natural aggregates (NAs) is currently being investigated and is expected to yield considerable benefits in the future. The objective of this research is to evaluate the environmental and economic benefits of using recycled coarse aggregates (RCAs) in different 1 m 3 samples of concrete, substituting the natural coarse aggregate (NCAs) with RCAs in different percentages. RCAs generally come from the treatment of construction and demolition wastes (CDWs). However, in this research, the RCAs are the concrete block wastes (CBWs) generated by a concrete production plant. Among the most notable results is that compared to concrete with no RCAs, using alternatives in which RCAs have replaced 50% of the NCAs leads to an average decrease in impact category statistics of -3.30%. In contrast to the existing literature on the subject, the process of producing RCAs generated efficiency improvements in categories such as abiotic depletion of fossil fuels (-58.72%) and global warming potential (-85.13%). This is because the transport process, a key factor in determining the viability of using RAs instead of NAs, was eliminated. In economic terms, there is a slight decrease in the financial cost of producing 1 m 3 of concrete as the quantity of RCAs increases. The maximum decrease was 0.23€/m 3 in the samples studied. Combining both the environmental and economic aspects resulted in a reduction factor of 0.420 g of CO 2 /€cent, which means fewer CO 2 emissions per unit cost when using RCAs. In conclusion, these results are intended to further knowledge in the field of using RAs instead of NAs in order to help the sector achieve sustainability and find an alternative use for a particular type of business waste.

Atherosclerosis, a leading cause of cardiovascular diseases requires approaches to enhance disease monitoring and treatment. Nanoparticles offer promising potential in this area by being customisable to target components or molecular processes within plaques, while carrying diagnostic and therapeutic agents. However, the number of biomarkers available to target this disease is limited. This study investigated the use of sphingomyelin-based nanomicelles triggered by sphingomyelinase (SMase) in atherosclerotic plaques. Accumulation of iron oxide-based nanomicelles in the plaque was demonstrated by fluorescence, MR imaging and electron microscopy. These findings demonstrate the possibility of utilising SMase as a mechanism to retain nanoprobes within plaques, thus opening up possibilities for future therapeutic interventions.

Nowadays, obesity (OB) is one of the most important health problems in population-wide health. In addition to its physical consequences, it is a risk factor for the development of psychological problems, including body dissatisfaction (BD). This is why the treatment of BD is essential for its prevention. However, this has mostly been studied from a quantitative perspective, without focusing on the discomfort experienced by the person and the accompanying thoughts and emotions. In this study, 26 women with obesity (BMI > 30 kg/m 2 ) participated, of whom 16 had high BD and 10 had low BD, as measured by the BSQ questionnaire. The women with high BD underwent six sessions of exposure to their own body in front of a mirror, recording the discomfort experienced with this vision during the session. In addition, all participants recorded positive and negative thoughts towards their body before and after these sessions. After the exposure treatment sessions, a reduction in symptomatology (BD, discomfort when visualizing one's own body) was observed, as well as a change in the thoughts expressed by the participants, both in quantity (fewer negative thoughts) and in quality (a more positive self-perception and/or in more respectful terms used towards themselves). In conclusion, such treatments prove to be effective in reducing subjective discomfort and body-related thoughts in women with obesity.

A significant gap in exposure data for most livestock and zoonotic pathogens is common for several Latin America deer species. This study examined the seroprevalence against 13 pathogens in 164 wild and captive southern pudu from Chile between 2011 and 2023. Livestock and zoonotic pathogen antibodies were detected in 22 of 109 wild pudus (20.18%; 95% CI: 13.34-29.18) and 17 of 55 captive pudus (30.91%; 95% CI: 19.52-44.96), including five Leptospira interrogans serovars (15.38% and 10.71%), Toxoplasma gondii (8.57% and 37.50%), Chlamydia abortus (3.03% and 12.82%), Neospora caninum (0.00% and 9.52%), and Pestivirus (8.00% and 6.67%). Risk factors were detected for Leptospira spp., showing that fawn pudu have statistically significantly higher risk of positivity than adults. In the case of T. gondii , pudu living in "free-range" have a lower risk of being positive for this parasite. In under-human-care pudu, a Pestivirus outbreak is the most strongly suspected as the cause of abortions in a zoo in the past. This study presents the first evidence of Chlamydia abortus in wildlife in South America and exposure to T. gondii , L. interrogans , and N. caninum in wild ungulate species in Chile. High seroprevalence of livestock pathogens such as Pestivirus and Leptospira Hardjo in wild animals suggests a livestock transmission in Chilean template forest.

Introduction: Herpesvirus infections have been highlighted as emerging diseases affecting wildlife health and the conservation of several taxa. Malignant catarrhal fever (MCF) and infectious keratoconjunctivitis (IKC) are two viruses that infect wild ruminants. Nevertheless, epidemiological data on herpesviruses in South American wild ruminants are limited. An outbreak of caprine gammaherpesvirus-2 (CpHV-2) that recently was suspected as the cause of MCF in southern pudus ( Pudu puda ) prompted the need to conduct molecular screenings in Chilean cervids to understand the epidemiology of herpesviruses. The aim of this study was to determine the occurrence and genetic diversity of herpesviruses in free-ranging cervids from Chile., Methods: Herpesvirus infection was assessed in antemortem blood samples ( n = 86) from pudus ( n = 81) and huemuls ( Hippocamelus bisulcus ) ( n = 5), as well as postmortem samples of spleen ( n = 24) and lung ( n = 3) from pudus, using a nested pan-herpesvirus PCR assay., Results: Combining all suitable sample types, DNA of pudu gammaherpesvirus-1 was detected in five pudues and five huemuls, with an overall prevalence of 9.90% ( n = 10/101; 95% CI = 5.11-17.87%). One pudu tested positive for ovine gammaherpesvirus-2 ( n = 1/96; 1.04%; 95% CI = 0.05-6.49%), and one pudu tested positive for a Macavirus sequence with 98.63 similarity to ovine gammaherpesvirus-2 ( n = 96; 1.04%; 95% CI = 0.05-6.49%)., Discussion: To the best of our knowledge, this is the first report of a herpesvirus in huemul and of ovine gammaherpesvirus-2 in Chile. Our results also confirm the active circulation of herpesvirus in free-ranging cervids in Chilean Patagonia, and as such, MCF should be considered as a possible cause of disease in free-ranging Chilean pudus and livestock species. Further research is necessary to develop a plan of systematic monitoring (serological and pathological screening) of herpesviruses in Chilean wild and domestic ruminants to understand their diversity and impact on animal health and conservation., Competing Interests: EH-H and SV-C were employed by Fundacion Buin Zoo. RL was employed by Aumen ONG. VV-W and SC were employed by Parque Zoológico Buin Zoo. CS was employed by Oregon Zoo. AS, AC, and IB were employed by Corporacion Nacional Forestal. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hidalgo-Hermoso, Cabello, Lopez, Vergara-Wilson, Vera, Valencia, Sanchez, Celis, Silva, Cariñanos, Barria, Vicencio, Muñoz-Leal, Aravena, Lagos, Toro-Letelier, Verasay-Caviedes, Garnham, Peña, Sánchez, Moreira-Arce, Vergara, Alegria-Moran and Cortés-Hinojosa.)

Background: Scatter correction (SC) is essential in PET for accurate quantitative imaging. The state-of-the-art SC method is single-scatter simulation (SSS). Although this method is usually robust and accurate, it can fail in some situations, for example when there is motion between the CT and PET scans in PET/CT. Therefore, it is of interest to consider other SC methods., Purpose: In this work, an energy-based scatter estimation (EBS) method is described in detail, tested in phantoms and patients, and compared to SSS., Methods: This version of EBS was developed for list-mode data from Biograph Vision-600 PET/CT scanner. EBS is based on digitized 2D energy histograms in each bin of a coarsely sampled PET sinogram, either with or without time of flight (TOF). The histograms are modeled as a noisy realization of a linear combination of nine basis functions whose parameters were derived from a measurement of the 511-keV photopeak spectrum as well as Monte-Carlo simulations of the scattering process. EBS uses an iterative expectation maximization approach to determine the coefficients in the linear combination, and from this estimates the scatter. The investigation was restricted to 18 F-based PET data in which the acquired number of counts was similar to the levels seen in oncological whole-body PET/CT scans. To evaluate the performance, phantom scans were used that involved the NEMA NU2-2018 protocol, a slab phantom, an NU 2-1994 phantom, a cardiac phantom in an anthropomorphic chest phantom, and a uniformly-filled torso phantom with a bladder phantom slightly outside the axial field of view. Contrast recovery (CR) and other parameters were evaluated in images reconstructed with SSS and EBS. Furthermore, FDG PET scans of seven lung cancer patients were used in the evaluation. Standardized uptake values (SUV) based on SSS and EBS were compared in 27 lesions., Results: EBS and SSS images were visually similar in all cases except the torso + bladder phantom, where the EBS was much closer to the expected uniform image. The NU2-2018 analysis indicated a 2% scatter residual in EBS images compared to 3% with SSS, and 10% higher background variability, which is a surrogate for image noise. The cardiac phantom scan showed that CR was 98.2% with EBS and 99.6% with SSS, and that the SSS sinogram had values greater than the net-true emission sinogram, indicating a slight overcorrection in the case of SSS. In the lesion SUV comparison in patient scans, EBS correlated strongly (R 2  = 0.9973) with SSS, and SUV based on EBS were systematically 0.1 SUV lower. In the case of the torso + bladder phantom portion, the SSS image of the torso + bladder phantom was 299% times hotter than expected in one area, due to scatter estimation error, compared to 16% colder with EBS., Conclusions: In evaluating clinically relevant parameters such as SUV in focal lesions, EBS and SSS give almost the same results. In phantoms, some scatter figures of merit were slightly improved by use of EBS, though an image variability figure of merit was slightly degraded. In typical oncological whole-body PET/CT, EBS may be a suitable replacement for SSS, especially when SSS fails due to technical problems during the scan., (© 2023 American Association of Physicists in Medicine.)

Objective: To analyze the impact, performance, degree of specialization, and collaboration patterns of the worldwide scientific production on tissue engineering in otorhinolaryngology at the level of countries and institutions., Methods: Two different techniques were used, performance and science mapping analyses, using as samples all the available documents regarding tissue engineering focused on otorhinolaryngology applications. The dataset was retrieved from the Core Collection of the Web of Science database from 1900 to 2020. Social structure was analyzed using science mapping analysis with VOSviewer software., Results: The United States was the main producer, followed by Germany, and Japan. Malaysia and Germany had the highest Relative Specialization Index, indicating their greater relative interest in this area compared to other countries. The social structure analysis showed that the United States and Germany had significant co-authorship relationships with other countries. The University of California System, Kyoto University, and Harvard University were the leading institutions producing literature in this field. These latter two institutions showed the largest number of collaborations, although most of them were with institutions within their own country. There was a lack of connections between different communities of research., Conclusion: The United States is the main country driving progress in this research area, housing the most notable institutions. However, significant collaborations between these research centers are currently lacking. Encouraging greater cooperation among these institutions and their researchers would promote the exchange of knowledge, ultimately facilitating and accelerating advancements in this field., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

During the response to different stress conditions, damaged cells react in multiple ways, including the release of a diverse cocktail of metabolites. Moreover, secretomes from dying cells can contribute to the effectiveness of anticancer therapies and can be exploited as predictive biomarkers. The nature of the stress and the resulting intracellular responses are key determinants of the secretome composition, but monitoring such processes remains technically arduous. Hence, there is growing interest in developing tools for noninvasive secretome screening. In this regard, it has been previously shown that the relative concentrations of relevant metabolites can be traced by surface-enhanced Raman scattering (SERS), thereby allowing label-free biofluid interrogation. However, conventional SERS approaches are insufficient to tackle the requirements imposed by high-throughput modalities, namely fast data acquisition and automatized analysis. Therefore, machine learning methods were implemented to identify cell secretome variations while extracting standard features for cell death classification. To this end, ad hoc microfluidic chips were devised, to readily conduct SERS measurements through a prototype relying on capillary pumps made of filter paper, which eventually would function as the SERS substrates. The developed strategy may pave the way toward a faster implementation of SERS into cell secretome classification, which can be extended even to laboratories lacking highly specialized facilities., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Background: The COVID-19 pandemic, caused by SARS-CoV-2 infection, has become the most devastating zoonotic event in recent times, with negative impacts on both human and animal welfare as well as on the global economy. Although SARS-CoV-2 is considered a human virus, it likely emerged from animals, and it can infect both domestic and wild animals. This constitutes a risk for human and animal health including wildlife with evidence of SARS-CoV-2 horizontal transmission back and forth between humans and wild animals., Aim: Molecular surveillance in different wildlife rehabilitation centers and wildlife associated institutions in Chile, which are critical points of animal-human interaction and wildlife conservation, especially since the aim of wildlife rehabilitation centers is to reintroduce animals to their original habitat., Materials and Methods: The survey was conducted in six WRCs and three wildlife associated institutions. A total of 185 samples were obtained from 83 individuals belonging to 15 different species, including vulnerable and endangered species. Each specimen was sampled with two different swabs: one oropharyngeal or nasopharyngeal according to the nostril diameter, and/or a second rectal sample. RNA was extracted from the samples and two different molecular assays were performed: first, a conventional RT-PCR with pan-coronavirus primers and a second SARS-CoV-2 qPCR targeting the N and S genes., Results: All 185 samples were negative for SARS-CoV-2., Clinical Relevance: This study constitutes the first report on the surveillance of SARS-CoV-2 from wildlife treated in rehabilitation centers in Chile, and supports the biosafety procedures adopted in those centers.

Viral diseases jeopardize the health of wildlife in Chile. However, this country lacks health surveillance programs that allow for defining preventive measures to tackle such diseases. The objective of this study was to determine the occurrence and the genetic diversity of pestivirus, herpesvirus and adenovirus in pudus from Chile. Blood samples from wild (n=34) and captive (n=32) pudus were collected between 2011 and 2019 and analyzed through consensus PCR. All the samples were negative to pestivirus and adenovirus. Herpesvirus was confirmed in four captive, and one wild pudu. All four zoo animals share the same sequence for both polymerase and glycoprotein genes. Both sequences share a 100% identity with caprine herpesvirus-2, classifying them in the same cluster as the Macavirus group. In turn, novel sequences of the polymerase and glycoprotein B genes were obtained from the wild pudu. Our study reports the first evidence of CpHV-2 infection in Chile and South American ungulate populations. Further research will be necessary to assess the pathogenicity of CpHV-2 in this species. It is also urgently recommended that molecular, serological and pathological screening should be conducted in Chilean wild and captive pudus to understand the impact of the herpesvirus on their populations.

Introduction: Recent evidence shows a high diversity of infectious agents in wildlife that represent a threat to human, domestic, and wild animal health. In Chile, wild populations of the most common cervid species, pudu ( Pudu puda ), have been reported as hosts for novel pathogens such as Mycoplasma ovis -like and a novel ecotype of Anaplasma phagocytophilum . A better understanding of the epidemiology of this group and other intracellular bacteria that might have cervids as hosts would enlighten their population relevance. This study aimed to determine the occurrence and genetic diversity of Bartonella spp., hemotropic mycoplasmas, and Coxiella burnetii in pudus from Chile., Methods: The DNA was extracted from the blood samples of 69 wild free-ranging and 30 captive pudus from Chile. A combination of real-time (nouG gene for Bartonella and IS1111 element for C. burnetii ) and conventional PCR (16S rRNA for hemotropic Mycoplasma spp. and rpoB, gltA, and ITS for Bartonella spp.) was used for pathogen screening and molecular characterization., Results: DNA of Bartonella spp. was detected in 10.1% [95% CI (5.2-18.2%)] samples, hemotropic Mycoplasma spp. in 1.7% [95% CI (0.08-10.1%)], and C. burnetii in 1.0% [95% CI (0.05-6.3%)] samples. Two sequenced samples were identified as Mycoplasma ovis -like, and one free-ranging pudu was positive for C. burnetii . While one captive and two free-ranging pudus were positive for Bartonella henselae , one wild pudu was co-positive for B. henselae and Bartonella sp., similar to Bartonellae identified in ruminants., Discussion: To the best of our knowledge, this is the first report of B. henselae in wild ungulate species, and C. burnetii and Bartonella spp. in wild ungulate species in South America. Further research will be necessary to evaluate the potential role of pudu as reservoirs of infection and identify the sources for disease transmission among humans and wild and domestic animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hidalgo-Hermoso, Sepúlveda-García, Cabello, Celis, Valencia, Ortiz, Kemec, Moreira-Arce, Orsola, Canales, Garnham, Vera and Muller.)

Anthropogenic environmental change is reducing available habitat for wild species, providing novel selection pressures such as infectious diseases and causing species to interact in new ways. The potential for emerging infectious diseases and zoonoses at the interface between humans, domestic animals, and wild species is a key global concern. In vertebrates, diversity at the major histocompatibility complex MHC is critical to disease resilience, and its study in wild populations provides insights into eco-evolutionary dynamics that human activities alter. In natural populations, variation at MHC loci is partly maintained by balancing selection, driven by pathogenic selective pressures. We hypothesize that MHC genetic diversity differs between guigna populations inhabiting human-dominated landscapes (higher pathogen pressures) versus more natural habitats (lower pathogen pressures). We predict that MHC diversity in guignas would be highest in human-dominated landscapes compared with continuous forest habitats. We also expected to find higher MHC diversity in guignas infected with micro and macro parasites (higher parasite load) versus non infected guignas. We characterized for the first time the genetic diversity at three MHC class I and II exons in 128 wild guignas (Leopardus guigna) across their distribution range in Chile (32-46° S) and Argentina, representing landscapes with varying levels of human disturbance. We integrated MHC sequence diversity with multiple measures of anthropogenic disturbance and both micro and macro parasite infection data. We also assessed signatures of positive selection acting on MHC genes. We found significantly higher MHC class I diversity in guignas inhabiting landscapes where houses were present, and with lower percentage of vegetation cover, and also in animals with more severe cardiorespiratory helminth infection (richness and intensity) and micro-macroparasite co-infection. This comprehensive, landscape-level assessment further enhances our knowledge on the evolutionary dynamics and adaptive potential of vertebrates in the face of emerging infectious disease threats and increasing anthropogenic impacts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Constanza Napolitano reports financial support was provided by Agencia Nacional de Investigación y Desarrollo (ANID). Constanza Napolitano reports financial support was provided by National Geographic Society. Constanza Napolitano reports financial support was provided by Morris Animal Foundation. Constanza Napolitano reports financial support was provided by Mohamed bin Zayed Species Conservation Fund. Constanza Napolitano reports financial support was provided by Endeavour Research Fellowship (Australian government)., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In the energy transition, the promotion of renewable sources entails the development of storage technologies to manage the mismatch between energy production and demand. In this scenario, the use of CAES (Compressed Air Energy Storage) technology enables the efficient and cost-effective storage of large amounts of energy. However, this technology is developed in salt domes who have an inherent risk associated of underground exploration phase. To address this, we propose to develop an infrastructure (iCAES) in abandoned underground mines, where the exploration phase is completed and well known. For its implementation, this paper defines a structure hierarchization method gathers the technical and socio-economic criteria. It involves a multi-criteria problem, and the correct selection of the location must be based on specific mathematical algorithms. For this case the Analytic Hierarchy Process (AHP) from multi-criteria decision making (MCDM) methods allows quantified by means of a scientific and mathematical scale and the assignment of weights, so that it is possible to evaluate different alternatives. This is possible thanks to the application of the AHP model in absolute terms. The information gathering has been based on the specific case study of coal basins in the north of Spain, in the region of León. Considering the proposed methodology, the most suitable alternative locations to implement iCAES in the region of León were identified., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

The use of fibres applied to concrete in order to improve its properties is widely known. Nowadays, research is not only focused on improving mechanical properties but also on the environmental implications. The aim of this research was a mechanical and environmental comparison between different types of fibres. For this purpose, commercial fibres of three materials were used: low carbon steel, modified polyolefins, and glass fibre. In order to improve the sustainability of the sector, we also analysed and compared the performance of using a waste product, such as fibres from machining operations on lathes. For the evaluation of the mechanical properties, compression and flexural tests were carried out. The results show that the use of low carbon steel fibres increases the flexural strength by 4.8%. At the environmental level, and in particular for impact categories such as the Global Warming Potential (GWP), lathe waste fibres prove to be the most suitable. For instance, compared to glass fibres, CO 2 emissions are reduced by 14.39%. This is equivalent to a total of 38 kg CO 2 emissions per m 3 of reinforced concrete. In addition to avoiding the consumption of 482 MJ/m 3 of fossil fuels, the results of the research indicate the feasibility of using waste fibres as a substitute for commercial fibres, contributing to an improved environmental balance without losing mechanical performance.

Tissue engineering is a relatively recent research area aimed at developing artificial tissues that can restore, maintain, or even improve the anatomical and/or functional integrity of injured tissues. Otolaryngology, as a leading surgical specialty in head and neck surgery, is a candidate for the use of these advanced therapies and medicinal products developed. Nevertheless, a knowledge-based analysis of both areas together is still needed. The dataset was retrieved from the Web of Science database from 1900 to 2020. SciMAT software was used to perform the science mapping analysis and the data for the biomedical translation identification was obtained from the iCite platform. Regarding the analysis of the cognitive structure, we find consolidated research lines, such as the generation of cartilage for use as a graft in reconstructive surgery, reconstruction of microtia, or the closure of perforations of the tympanic membrane. This last research area occupies the most relevant clinical translation with the rest of the areas presenting a lower translational level. In conclusion, Tissue engineering is still in an early translational stage in otolaryngology, otology being the field where most advances have been achieved. Therefore, although otolaryngologists should play an active role in translational research in tissue engineering, greater multidisciplinary efforts are required to promote and encourage the translation of potential clinical applications of tissue engineering for routine clinical use., (© 2023. Springer Nature Limited.)

Objective: To analyze the factors associated with the activation of the severe trauma care team (STAT) in patients admitted to the ICU, to measure its impact on care times, and to analyze the groups of patients according to activation and level of anatomical involvement., Design: Prospective cohort study of severe trauma admitted to the ICU. From June 2017 to May 2019. Risk factors for the activation of the STAT analysed with logistic regression and CART type classification tree., Setting: Second level hospital ICU., Patients: Patients admitted consecutively., Interventions: No., Main Variables of Interest: STAT activation. Demographic variables. Injury severity (ISS), intentionality, mechanism, assistance times, evolutionary complications, and mortality., Results: A total of 188 patients were admitted (46.8% of STAT activation), median age of 52 (37-64) years (activated 47 (27-62) vs not activated 55 (42-67) P = 0.023), males 84.0%. No difference in mortality according to activation. The logistic model finds as factors: care (16.6 (2.1-13.2)) and prehospital intubation (4.2 (1.8-9.8)) and severe lower extremity injury (4.4 (1.6-12.3)). Accidental fall (0.2 (0.1-0.6)) makes activation less likely. The CART model selects the type of trauma mechanism and can separate high and low energy trauma., Conclusions: Factors associated with STAT activation were prehospital care, requiring prior intubation, high-energy mechanisms, and severe lower extremity injuries. Shorter care times if activated without influencing mortality. We must improve activation in older patients with low-energy trauma and without prehospital care., (Copyright © 2022 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Carbon Dots (CDs) are luminescent quasi-spherical nanoparticles, possessing water solubility, high biocompatibility, and tunable chemical and physical properties for a wide range of applications, including nanomedicine and theranostics. The evaluation of new purification criteria, useful to achieve more reliable CDs, free from the interference of artifacts, is currently an object of debate in the field. Here, new CDs doped with gadolinium (Gd (III)), named Gd@CNDs, are presented as multifunctional probes for Magnetic Resonance Imaging (MRI). This new system is a case of study, to evaluate and/or combine different purification strategies, as a crucial approach to generate CDs with a better performance. Indeed, these new amorphous Gd@CNDs display good homogeneity, and they are free from emissive side products. Gd@CNDs (7-10 nm) contain 7% of Gd (III) w/w, display suitable and stable longitudinal relaxivity (r 1 ) and with emissive behavior, therefore potentially useful for both MR and fluorescence imaging. They show good biocompatibility in both cellular and in vivo studies, cell permeability, and the ability to generate contrast in cellular pellets. Finally, MRI recording T 1 -weighted images on mice after intravenous injection of Gd@CNDs, show signal enhancement in the liver, spleen, and kidney 30 min postinjection., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Atherosclerosis is a complex disease that can lead to life-threatening events, such as myocardial infarction and ischemic stroke. Despite the severity of this disease, diagnosing plaque vulnerability remains challenging due to the lack of effective diagnostic tools. Conventional diagnostic protocols lack specificity and fail to predict the type of atherosclerotic lesion and the risk of plaque rupture. To address this issue, technologies are emerging, such as noninvasive medical imaging of atherosclerotic plaque with customized nanotechnological solutions. Modulating the biological interactions and contrast of nanoparticles in various imaging techniques, including magnetic resonance imaging, is possible through the careful design of their physicochemical properties. However, few examples of comparative studies between nanoparticles targeting different hallmarks of atherosclerosis exist to provide information about the plaque development stage. Our work demonstrates that Gd (III)-doped amorphous calcium carbonate nanoparticles are an effective tool for these comparative studies due to their high magnetic resonance contrast and physicochemical properties. In an animal model of atherosclerosis, we compare the imaging performance of three types of nanoparticles: bare amorphous calcium carbonate and those functionalized with the ligands alendronate (for microcalcification targeting) and trimannose (for inflammation targeting). Our study provides useful insights into ligand-mediated targeted imaging of atherosclerosis through a combination of in vivo imaging, ex vivo tissue analysis, and in vitro targeting experiments.

The development of functional blood vessels is today a fundamental pillar in the evaluation of new therapies and diagnostic agents. This article describes the manufacture and subsequent functionalization, by means of cell culture, of a microfluidic device with a circular section. Its purpose is to simulate a blood vessel in order to test new treatments for pulmonary arterial hypertension. The manufacture was carried out using a process in which a wire with a circular section determines the dimensions of the channel. To fabricate the blood vessel, cells were seeded under rotary cell culture to obtain a homogeneous cell seeding in the inner wall of the devices. This is a simple and reproducible method that allows the generation of blood vessel models in vitro., (© 2023 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.)

Introduction: Detection and decolonization of Staphylococcus aureus prior to surgery is postulated as an option to reduce the risk of infection in arthroplasties. The aim of this study was to evaluate the effectiveness of a screening program for S. aureus in total knee arthroplasty (TKA) and total hip arthroplasty (THA), the incidence of infection with respect to a historical cohort, and its economic viability., Material and Methods: Pre-post intervention study in patients undergoing primary knee and hip prostheses in 2021, a protocol was carried out to detect nasal colonization by S. aureus and eradication if appropriate, with intranasal mupirocin, post-treatment culture with results three weeks between post-treatment culture and surgery. Efficacy measures are evaluated, costs are analyzed and the incidence of infection is compared with respect to a historical series of patients operated on between January and December 2019, performing a descriptive and comparative statistical analysis., Results: The groups were statistically comparable. Culture was performed in 89%, with 19 (13%) positive patients. Treatment was confirmed in 18, control culture in 14, all decolonized; none suffered infection. One culture-negative patient suffered from Staphylococcus epidermidis infection. In historical cohort: 3 suffered deep infection by S. epidermidis, Enterobacter cloacae, S. aureus. The cost of the program is €1661.85., Conclusion: The screening program detected 89% of the patients. The prevalence of infection in the intervention group was lower than in the cohort, with S. epidermidis being the main microorganism, different from S. aureus described in the literature and in the cohort. We believe that this program is economically viable, as its costs are low and affordable., (Copyright © 2022 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Detection and decolonization of Staphylococcus aureus prior to surgery is postulated as an option to reduce the risk of infection in arthroplasties. The aim of this study was to evaluate the effectiveness of a screening programme for S. aureus in total knee arthroplasty (TKA) and total hip arthroplasty (THA), the incidence of infection with respect to a historical cohort, and its economic viability., Material and Methods: Pre-post intervention study in patients undergoing primary knee and hip prostheses in 2021, a protocol was carried out to detect nasal colonization by S. aureus and eradication if appropriate, with intranasal mupirocin, post-treatment culture with results three weeks between post-treatment culture and surgery. Efficacy measures are evaluated, costs are analyzed and the incidence of infection is compared with respect to a historical series of patients operated on between January and December 2019, performing a descriptive and comparative statistical analysis., Results: The groups were statistically comparable. Culture was performed in 89%, with 19 (13%) positive patients. Treatment was confirmed in 18, control culture in 14, all decolonized; none suffered infection. One culture-negative patient suffered from Staphylococcus epidermidis infection. In historical cohort: three suffered deep infection by S. epidermidis, Enterobacter cloacae, Staphylococcus aureus. The cost of the programme is €1661.85., Conclusion: The screening programme detected 89% of the patients. The prevalence of infection in the intervention group was lower than in the cohort, with S. epidermidis being the main micro-organism, different from S. aureus described in the literature and in the cohort. We believe that this programme is economically viable, as its costs are low and affordable., (Copyright © 2022 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

Birth presents a metabolic challenge to cardiomyocytes as they reshape fuel preference from glucose to fatty acids for postnatal energy production 1,2 . This adaptation is triggered in part by post-partum environmental changes 3 , but the molecules orchestrating cardiomyocyte maturation remain unknown. Here we show that this transition is coordinated by maternally supplied γ-linolenic acid (GLA), an 18:3 omega-6 fatty acid enriched in the maternal milk. GLA binds and activates retinoid X receptors 4 (RXRs), ligand-regulated transcription factors that are expressed in cardiomyocytes from embryonic stages. Multifaceted genome-wide analysis revealed that the lack of RXR in embryonic cardiomyocytes caused an aberrant chromatin landscape that prevented the induction of an RXR-dependent gene expression signature controlling mitochondrial fatty acid homeostasis. The ensuing defective metabolic transition featured blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, leading to perinatal cardiac dysfunction and death. Finally, GLA supplementation induced RXR-dependent expression of the mitochondrial fatty acid homeostasis signature in cardiomyocytes, both in vitro and in vivo. Thus, our study identifies the GLA-RXR axis as a key transcriptional regulatory mechanism underlying the maternal control of perinatal cardiac metabolism., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Research in fluid therapy and perioperative hemodynamic monitoring is difficult and expensive. The objectives of this study were to summarize these topics and to prioritize these topics in order of research importance., Methods: Electronic structured Delphi questionnaire over three rounds among 30 experts in fluid therapy and hemodynamic monitoring identified through the Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section of the Spanish Society of Anesthesiology and Critical Care., Results: 77 topics were identified and ranked in order of prioritization. Topics were categorized into themes of crystalloids, colloids, hemodynamic monitoring and others. 31 topics were ranked as essential research priority. To determine whether intraoperative hemodynamic optimization algorithms based on the invasive or noninvasive Hypotension Prediction Index versus other management strategies could decrease the incidence of postoperative complications. As well as whether the use of renal stress biomarkers together with a goal-directed fluid therapy protocol could reduce hospital stay and the incidence of acute kidney injury in adult patients undergoing non-cardiac surgery, reached the highest consensus., Conclusions: The Fluid Therapy and Hemodynamic Monitoring Subcommittee of the Hemostasis, Transfusion Medicine and Fluid Therapy Section of the Spanish Society of Anesthesiology and Critical Care will use these results to carry out the research., (Copyright © 2023 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Providing historical data on riparian plant biodiversity and physico-chemical parameters of stream water in Mediterranean mountains helps to assess the effects of climate change and other human stressors on these sensitive and critical ecosystems. This database collects data from the main natural headwater streams of the Sierra Nevada (southeastern Spain), a high mountain (up to 3479 m above sea level [m asl]) recognized as a biodiversity super hotspot in the Mediterranean basin. On this mountain, rivers and landscapes depend on snowmelt water, representing an excellent scenario for evaluating global change's impacts. This dataset covers first- to third-order headwater streams at 41 sites from 832 to 1997 m asl, collected from December 2006 to July 2007. Our goal is to supply information on the vegetation associated with streambanks, the essential physico-chemical parameters of stream water, and the physiographic features of the subwatersheds. Riparian vegetation data correspond to six plots sampled at each site, including total canopy, individual number, height and DBH (diameter at breast height) in woody species, and cover percentage for herbs. Physico-chemical parameters were measured in situ (electric conductivity, pH, dissolved O 2 concentration, stream discharge) and determined in the laboratory (alkalinity, soluble reactive phosphate-phosphorus [SRP], total phosphorus [TP], nitrate-nitrogen [ NO 3 - -N], ammonium-nitrogen [ NH 4 + -N], total nitrogen [TN]). Watershed physiographic variables comprise drainage area, minimum altitude, maximum altitude, mean slope, orientation, stream order, stream length, and land cover surface percentage. We recorded 197 plant taxa (67 species, 28 subspecies, and 2 hybrids), representing 8.4% of the Sierra Nevada vascular flora. Due to the botanical nomenclature used, the database can be linked to FloraSNevada database, contributing to Sierra Nevada (Spain) as a laboratory of global processes. This data set can be freely used for non-commercial purposes. Users of these data should cite this data paper in any publications resulting from its use., (© 2023 The Authors. Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Purpose: Clinical ventilation studies are primarily performed with computerized tomography (CT) and more often with single-photon emission Computerized tomography (SPECT) using radiolabelled aerosols, both presenting certain limitations. Here, we investigate the use of the radiofluorinated gas [ 18 F]SF 6 as a positron emission tomography (PET) ventilation marker in an animal model of impaired lung ventilation., Procedures: Sprague-Dawley rats (n = 15) were randomly assigned to spontaneous ventilation (sham group), endotracheal administration of phosphate-buffered saline (PBS group), or endotracheal administration of lipopolysaccharide (LPS group). PET-[ 18 F]SF 6 images (10-min acquisition) were acquired at t = 48 h after LPS or PBS administration under mechanical ventilation. CT images were acquired after each PET session. Volumes of interest were manually delineated in the lungs on CT images, and voxel-by-voxel analysis was carried out on PET images to obtain the corresponding histograms. After the imaging sessions, lungs were harvested to conduct histological analysis., Results: Ventilation studies in sham animals showed uniform distribution of [ 18 F]SF 6 and fast elimination of the radioactivity after discontinuation of the administration. For PBS- and LPS-treated rats, ventilation defects were observed on PET images in some animals, identified as regions with low presence of the radiolabelled gas. Hypoventilated areas co-localized with regions with higher x-ray attenuation than healthy lungs on the CT images, suggesting the presence of oedema and, in some cases, atelectasis. Histograms obtained from PET images showed quasi-Gaussian distributions for control animals, while PBS- and LPS-treated animals demonstrated the presence of hypoventilated voxels. Deviation of the histograms from Gaussian distribution correlated with histological score was obtained by ex vivo histological analysis., Conclusions: [ 18 F]SF 6 is an appropriate marker of regional lung ventilation and may find application in the early diagnose of acute lung disease., (© 2022. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Background: Despite increasing evidence suggesting that pulmonary arterial hypertension (PAH) is a complex disease involving vasoconstriction, thrombosis, inflammation, metabolic dysregulation and vascular proliferation, all the drugs approved for PAH mainly act as vasodilating agents. Since excessive TGF-β signaling is believed to be a critical factor in pulmonary vascular remodeling, we hypothesized that blocking TGFβ-activated kinase 1 (TAK-1), alone or in combination with a vasodilator therapy (i.e., riociguat) could achieve a greater therapeutic benefit. Methods: PAH was induced in male Wistar rats by a single injection of the VEGF receptor antagonist SU5416 (20 mg/kg) followed by exposure to hypoxia (10%O 2 ) for 21 days. Two weeks after SU5416 administration, vehicle, riociguat (3 mg/kg/day), the TAK-1 inhibitor 5Z-7-oxozeaenol (OXO, 3 mg/kg/day), or both drugs combined were administered for 7 days. Metabolic profiling of right ventricle (RV), lung tissues and PA smooth muscle cells (PASMCs) extracts were performed by magnetic resonance spectroscopy, and the differences between groups analyzed by multivariate statistical methods. Results: In vitro , riociguat induced potent vasodilator effects in isolated pulmonary arteries (PA) with negligible antiproliferative effects and metabolic changes in PASMCs. In contrast, 5Z-7-oxozeaenol effectively inhibited the proliferation of PASMCs characterized by a broad metabolic reprogramming but had no acute vasodilator effects. In vivo, treatment with riociguat partially reduced the increase in pulmonary arterial pressure (PAP), RV hypertrophy (RVH), and pulmonary vascular remodeling, attenuated the dysregulation of inosine, glucose, creatine and phosphocholine (PC) in RV and fully abolished the increase in lung IL-1β expression. By contrast, 5Z-7-oxozeaenol significantly reduced pulmonary vascular remodeling and attenuated the metabolic shifts of glucose and PC in RV but had no effects on PAP or RVH. Importantly, combined therapy had an additive effect on pulmonary vascular remodeling and induced a significant metabolic effect over taurine, amino acids, glycolysis, and TCA cycle metabolism via glycine-serine-threonine metabolism. However, it did not improve the effects induced by riociguat alone on pulmonary pressure or RV remodeling. None of the treatments attenuated pulmonary endothelial dysfunction and hyperresponsiveness to serotonin in isolated PA. Conclusion: Our results suggest that inhibition of TAK-1 induces antiproliferative effects and its addition to short-term vasodilator therapy enhances the beneficial effects on pulmonary vascular remodeling and RV metabolic reprogramming in experimental PAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Morales-Cano, Izquierdo-García, Barreira, Esquivel-Ruiz, Callejo, Pandolfi, Villa-Valverde, Rodríguez, Cogolludo, Ruiz-Cabello, Perez-Vizcaino and Moreno.)

Introduction: Patients with pulmonary tuberculosis (PTB) disease and positive sputum cultures are the main source of infection. Culture conversion time is inconsistent and defining the length of respiratory isolation is challenging. The objective of this study is to develop a score to predict the length of isolation period., Methods: A retrospective study was carried out to evaluated risk factors associated with persistent positive sputum cultures after 4 weeks of treatment in 229 patients with PTB. A multivariable logistic regression model was used to determinate predictors for positive culture and a scoring system was created based on the coefficients of the final model., Results: Sputum culture was persistently positive in 40.6%. Fever at consultation (1.87, 95% CI:1.02-3.41), smoking (2.44, 95% CI:1.36-4.37), >2 affected lung lobes (1.95, 95% CI:1.08-3.54), and neutrophil-to-lymphocyte ratio > 3.5 (2.22, 95% CI:1.24-3.99), were significantly associated with delayed culture conversion. Therefore, we assembled a severity score that achieved an area under the curve of 0.71 (95% CI:0.64-0.78)., Conclusions: In patients with smear positive PTB, a score with clinical, radiological and analytical parameters can be used as a supplemental tool to assist clinical decisions in isolation period., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

There is growing evidence that Ph -negative myeloproliferative neoplasms (MPNs) are disorders in which multiple molecular mechanisms are significantly disturbed. Since their discovery, CALR driver mutations have been demonstrated to trigger pathogenic mechanisms apart from the well-documented activation of JAK2/MPL-related pathways, but the lack of experimental models harboring CALR mutations in a JAK2/MPL knockout background has hindered the research on these non-canonical mechanisms. In this study, CRISPR/Cas9 was performed to introduce homozygous patient-like calreticulin mutations in a C. elegans model that naturally lacks JAK2 and MPL orthologs. Whole-genome transcriptomic analysis of these worms was conducted, and some of the genes identified to be associated with processes involved in the pathogenesis of MPNs were further validated by qPCR. Some of the transcriptomic alterations corresponded to typically altered genes and processes in cancer and Ph -negative MPN patients that are known to be triggered by mutant calreticulin without the intervention of JAK2/MPL. However, interestingly, we have also found altered other processes described in these diseases that had not been directly attributed to calreticulin mutations without the intervention of JAK2 or MPL. Thus, these results point to a new experimental model for the study of the JAK2/MPL-independent mechanisms of mutant calreticulin that induce these biological alterations, which could be useful to study unknown non-canonical effects of the mutant protein. The comparison with a calreticulin null strain revealed that the alteration of all of these processes seems to be a consequence of a loss of function of mutant calreticulin in the worm, except for the dysregulation of Hedgehog signaling and flh-3 . Further analysis of this model could help to delineate these mechanisms, and the verification of these results in mammalian models may unravel new potential therapeutic targets in MPNs. As far as we know, this is the first time that a C. elegans strain with patient-like mutations is proposed as a potential model for leukemia research.

Healthy regeneration of tissue relies on a well-orchestrated release of growth factors. Herein, we show the use of synthetic glycosaminoglycans for controlled binding and release of growth factors to induce a desired cellular response. First, we screened glycosaminoglycans with growth factors of interest to determine k on (association rate constant), k off (dissociation rate constant), and K d (equilibrium rate constant). As proof-of-concept, we functionalized an elastin-like recombinamer (ELR) hydrogel with a synthetic glycosaminoglycan and immobilized fibroblast growth factor 2 (FGF2), demonstrating that human umbilical vein endothelial cells cultured on top of ELR hydrogel differentiated into tube-like structures. Taking this concept further, we developed a tunable macroporous ELR cryogel material, containing a synthetic glycosaminoglycan and FGF2 that showed increased blood vessel formation and reduced immune response compared to control when implanted in a subcutaneous mouse model. These results demonstrated the possibility for specific release of desired growth factors in/from a modular 3D scaffold in vitro and in vivo., (© 2022. The Author(s).)

The development of imaging technologies allowing noninvasive observation through solid bodies has represented a breakthrough in medical diagnosis, facilitating the comprehension of biomolecular events underlying disease and the development of more efficient therapeutic approaches. Some of the traditional limitations of these techniques are nowadays fading away thanks to the combination of imaging with nanotechnology, allowing the development of novel functional biomaterials that increase the sensitivity of detection, enable sensitivity to specific targets, and facilitate the combination of therapeutic and diagnostic functions (theragnosis) with molecular platforms functioning simultaneously as imaging probes and drug delivery carriers. The design of such functional biomaterials requires a comprehensive understanding of the principles that govern the generation of signal and modulation of contrast for a given imaging modality to exploit its capabilities to the maximal level. In this sense, magnetic resonance imaging (MRI) is a technique that presents a complex relationship between the detected signal and the physical-chemical properties of its sourcing matter, allowing the generation of multiple image contrasts. Thus, while magnetic resonance imaging is a highly versatile imaging modality, it requires specific knowledge of its physical principles to take advantage of all of its possibilities. This work reviews the origin of the image signal and contrast in MRI and the concepts of relaxometry and MRI contrast agents., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Chronic venous insufficiency (CVI) is a leading vascular disease whose clinical manifestations include varicose veins, edemas, venous ulcers, and venous hypertension, among others. Therapies targeting this medical issue are scarce, and so far, no single venous valve prosthesis is clinically available. Herein, we have designed a bi-leaflet transcatheter venous valve that consists of (i) elastin-like recombinamers, (ii) a textile mesh reinforcement, and (iii) a bioabsorbable magnesium stent structure. Mechanical characterization of the resulting biohybrid elastin-like venous valves (EVV) showed an anisotropic behavior equivalent to the native bovine saphenous vein valves and mechanical strength suitable for vascular implantation. The EVV also featured minimal hemolysis and platelet adhesion, besides actively supporting endothelialization in vitro , thus setting the basis for its application as an in situ tissue engineering implant. In addition, the hydrodynamic testing in a pulsatile bioreactor demonstrated excellent hemodynamic valve performance, with minimal regurgitation (<10%) and pressure drop (<5 mmHg). No stagnation points were detected and an in vitro simulated transcatheter delivery showed the ability of the venous valve to withstand the implantation procedure. These results present a promising concept of a biohybrid transcatheter venous valve as an off-the-shelf implant, with great potential to provide clinical solutions for CVI treatment., Competing Interests: AK is employed by Meotec GmbH. H-WH is employed by Innovative Tomography Products GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 González-Pérez, Acosta, Rütten, Emonts, Kopp, Henke, Bruners, Gries, Rodríguez-Cabello, Jockenhoevel and Fernández-Colino.)

Aim: To evaluate the effect of combining positron range correction (PRC) with point-spread-function (PSF) correction and to compare different methods of implementation into iterative image reconstruction for 124 I-PET imaging., Materials and Methods: Uniform PR blurring kernels of 124 I were generated using the GATE (GEANT4) framework in various material environments (lung, water, and bone) and matched to a 3D matrix. The kernels size was set to 11 × 11 × 11 based on the maximum PR in water and the voxel size of the PET system. PET image reconstruction was performed using the standard OSEM algorithm, OSEM with PRC implemented before the forward projection (OSEM+PRC simplified) and OSEM with PRC implemented in both forward- and back-projection steps (full implementation) (OSEM+PRC). Reconstructions were repeated with resolution recovery, point-spread function (PSF) included. The methods and kernel variation were validated using different phantoms filled with 124 I acquired on a Siemens mCT PET/CT system. The data was evaluated for contrast recovery and image noise., Results: Contrast recovery improved by 2-10% and 4-37% with OSEM+PRC simplified and OSEM+PRC, respectively, depending on the sphere size of the NEMA IQ phantom. Including PSF in the reconstructions further improved contrast by 4-19% and 3-16% with the PSF+PRC simplified and PSF+PRC, respectively. The benefit of PRC was more pronounced within low-density material. OSEM-PRC and OSEM-PSF as well as OSEM-PSF+PRC in its full- and simplified implementation showed comparable noise and convergence. OSEM-PRC simplified showed comparably faster convergence but at the cost of increased image noise., Conclusions: The combination of the PSF and PRC leads to increased contrast recovery with reduced image noise compared to stand-alone PSF or PRC reconstruction. For OSEM-PRC reconstructions, a full implementation in the reconstruction is necessary to handle image noise. For the combination of PRC with PSF, a simplified PRC implementation can be used to reduce reconstruction times., (© 2022. The Author(s).)

Understanding the interplay between order and disorder in intrinsically disorder proteins (IDPs), and its impact on the properties and features of materials manufactured from them, is a major challenge in the design of protein-based synthetic polymers intended for advanced functions. In this paper an elastin-like diblock co-recombinamer amphiphile (Phe-ELR) based on a hydrophobic block containing five phenylalanine (Phe) residues proximal to the carboxyl function of a glutamic acid (Glu) residue upon folding, and with Glu as the guest residue in the hydrophilic part, was engineered and its assembly behaviour compared with another amphiphilic ELR used as control. Phe-ELR was tailored in order to clarify the impact of the presence of aromatic residues in the amino acid sequence, which even in early studies by Urry's group already demonstrated a certain out-of-trend behaviour compared with other apolar amino acids, especially non-aromatic ones, on ELR behaviour. The combination of several experimental techniques indicates strong molecular interactions associated with the Phe residue, thus resulting in limited reversible character of the temperature-induced transitions during sequential thermal cycles, a lower than expected transition enthalpy, and clear differences in its supramolecular assembly with respect to the control ELR. A distinctive pre-aggregated state for the Phe-ELR under any condition of pH and temperature is found. Eventually, this state gives rise to Phe-core micelles or a solid jelly-like material, depending on the concentration, pH and presence of salts. In conclusion, it appears that the presence of aromatic residues and their ability to promote strong inter- and intramolecular interactions at any temperature and pH causes a complete modification of the order-disorder interplay present in other, non-aromatic ELRs. These molecular events have a profound impact on the physical properties of the resulting polymer when compared with other ELRs. This work helps to shed light on the limits that govern intrinsic disorder in ELRs beyond its inverse temperature transition., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Epilepsy is a disabling, chronic brain disease,affecting ~1% of the World's population, characterized by recurrent seizures (sudden, uncontrolled brain activity), which may manifest with motor symptoms (e.g., convulsions) or non-motor symptoms. Temporal lobe epilepsies (TLE) compromising the hippocampus are the most common form of focal epilepsies. Resistance in ~1/3 of epileptic patients to the first line of treatment, i.e., antiepileptic drugs (AEDs), has been an important motivation to seek alternative treatments. Among these, the plant Cannabis sativa (commonly known as marihuana) or compounds extracted from it (cannabinoids) have gained widespread popularity. Moreover, sex differences have been proposed in epilepsy syndromes and in cannabinoid action. In the hippocampus, cannabinoids interact with the CB1R receptor whose membrane levels are regulated by β-Arrestin2, a protein that promotes its endocytosis and causes its downregulation. In this article, we evaluate the modulatory role of WIN 55,212-2 (WIN), a synthetic exogenous cannabinoid on behavioral convulsions and on the levels of CB1R and β-Arrestin2 in female and male adolescent rats after a single injection of the proconvulsant pentylenetetrazol (PTZ). As epilepsies can have a considerable impact on synaptic proteins that regulate neuronal toxicity, plasticity, and cognition, we also measured the levels of key proteins markers of excitatory synapses, in order to examine whether exogenous cannabinoids may prevent such pathologic changes after acute seizures. We found that the exogenous administration of WIN prevented convulsions of medium severity in females and males and increased the levels of phosphorylated CaMKII in the hippocampus. Furthermore, we observed a higher degree of colocalization between CB1R and β-Arrestin2 in the granule cell layer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zirotti Rosenberg, Méndez-Ruette, Gorziglia, Alzerreca, Cabello, Kaufmann, Rambousek, Iturriaga Jofré, Wyneken and Lafourcade.)

Darwin's fox is an opportunistic omnivorous predator native to Chile classified as endangered by the IUCN Red List. Habitat use by Darwin's foxes can be negatively affected by the presence of free-ranging dogs that range freely across native and non-native habitats and can be a source of fox mortality. The objective of this study was to analyze the isotopic similarity of Darwin's fox and sympatric free-ranging dogs in Chiloé Island to determine the impact of anthropogenic environmental alterations on wild predators. We use hair samples to characterise and compare their δ 13 C and δ 15 N values and to evaluate isotopic similarity and isotope niches overlap. A generalised linear model was used to associate the isotope value with landscape variables (forest cover and vegetation type) and distance to the nearest house. We found no significant differences in δ 13 C or δ 15 N values between foxes and dogs, and a marginally significant isotope niche overlap (59.4 %). None of the selected variables at landscape and site scale were related to isotope values. Although our study is not a probe of direct contact between foxes and free-ranging dogs, the high isotopic similarity highlights the risk of pathogen spillover from free-ranging dogs to Darwin's foxes.

Even though enormous efforts and control strategies have been implemented, bovine tuberculosis (TB) remains a significant source of health and socioeconomic concern. The standard method used in TB eradication programs for in vivo detection is the tuberculin skin test. However, the specificity of the tuberculin skin test is affected by infection with non-tuberculous mycobacteria or by vaccination. Thus, some animals are not correctly diagnosed. This study aimed first to identify a plasma metabolic TB profile by high-field (HF) nuclear magnetic resonance (NMR) spectroscopy and second measure this characteristic TB metabolic profile using low-field benchtop (LF) NMR as an affordable molecular technology for TB diagnosis. Plasma samples from cattle diagnosed with TB (derivation set, n = 11), diagnosed with paratuberculosis (PTB, n = 10), PTB-vaccinated healthy control (n = 10) and healthy PTB-unvaccinated control (n = 10) were analyzed by NMR. Unsupervised Principal Component Analysis (PCA) was used to identify metabolic differences between groups. We identified 14 metabolites significantly different between TB and control animals. The second group of TB animals was used to validate the results (validation set, n = 14). Predictive models based on metabolic fingerprint acquired by both HF and LF NMR spectroscopy successfully identified TB versus control subjects (Area under the curve of Receiver Operating Characteristic over 0.92, in both models; Confidence Interval 0.77-1). In summary, plasma fingerprinting using HF and LF-NMR differentiated TB subjects from uninfected animals, and PTB and PTB-vaccinated subjects who may provide a TB-false positive, highlighting the use of LF-NMR-based metabolomics as a complementary or alternative diagnostic tool to the current diagnostic methods., (© 2021 Wiley-VCH GmbH.)

Water availability controls the functioning of dryland ecosystems, driving a patchy vegetation distribution, unequal nutrient availability, soil respiration in pulses, and limited productivity. Groundwater-dependent ecosystems (GDEs) are acknowledged to be decoupled from precipitation, since their vegetation relies on groundwater sources. Despite their relevance to enhance productivity in drylands, our understanding of how different components of GDEs interconnect (i.e., soil, vegetation, water) remains limited. We studied the GDE dominated by the deep-rooted phreatophyte Ziziphus lotus, a winter-deciduous shrub adapted to arid conditions along the Mediterranean basin. We aimed to disentangle whether the groundwater connection established by Z. lotus will foster soil biological activity and therefore soil fertility in drylands. We assessed (1) soil and vegetation dynamics over seasons (soil CO 2 efflux and plant activity), (2) the effect of the patchy distribution on soil quality (properties and nutrient availability), and soil biological activity (microbial biomass and mineralization rates) as essential elements of biogeochemical cycles, and (3) the implications for preserving GDEs and their biogeochemical processes under climate change effects. We found that soil and vegetation dynamics respond to water availability. Whereas soil biological activity promptly responded to precipitation events, vegetation functioning relies on less superficial water and responded on different time scales. Soil quality was higher under the vegetation patches, as was soil biological activity. Our findings highlight the importance of groundwater connections and phreatophytic vegetation to increase litter inputs and organic matter into the soils, which in turn enhances soil quality and decomposition processes in drylands. However, biogeochemical processes are jeopardized in GDEs by climate change effects and land degradation due to the dependence of soil activity on: (1) precipitation for activation, and (2) phreatophytic vegetation for substrate accumulation. Therefore, desertification might modify biogeochemical cycles by disrupting key ecosystem processes such as soil microbial activity, organic matter mineralization, and plant productivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)