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The sentinel plantation concept consists of assessing the impact of exotic factors, such as pests and pathogens, on plants of interest by planting them out of their native range. This tool is a way to enhance knowledge for pest risk analysis (PRA) by guiding decisions on how quarantine organisms should be regulated and where to focus prevention and surveillance efforts for an early detection. In this study, the sentinel method was used in the case of research on Xylella fastidiosa, a plant pathogenic bacterium that has recently been found established in southern Europe, but whose potential impact and possible host range are still poorly documented in northern areas where the bacterium is not known to occur. To improve knowledge on the susceptibility of potential hosts of X. fastidiosa in northern Europe, a sentinel plantation of Prunus domestica cv. Opal, Quercus petraea and Salix alba was established in the X. fastidiosa-infected area of Majorca. In order to assess the circulation of the bacterium in the sentinel plot and around it, surveys of the local flora and insect vectors were carried out, as well as the planting of a network of rosemary “spy plants”. Symptomatic monitoring and molecular analyses were performed on the sentinel plants for four years. During these years, X. fastidiosa was never detected in our sentinel plants most likely because of the low infectivity pressure recorded in the surroundings. This study underlines the complexity of conducting sentinel plantation assays combined with X. fastidiosa research, highlighting the need for long-term investigation and questioning the efficiency of the sentinel tool. However, this study is placed in perspective with other valuable sentinel plantations. It also highlights the complementarity of the tool and proposes elements to improve or re-orientate the implementation of future sentinel projects.

Culicoides biting midges (Diptera: Ceratopogonidae) are the main vectors of livestock diseases such as bluetongue (BT) which mainly affect sheep and cattle. In Spain, bluetongue virus (BTV) is transmitted by several Culicoides taxa, including Culicoides imicola, Obsoletus complex, Culicoides newsteadi and Culicoides pulicaris that vary in seasonality and distribution, affecting the distribution and dynamics of BT outbreaks. Path analysis is useful for separating direct and indirect, biotic and abiotic determinants of species' population performance and is ideal for understanding the sensitivity of adult Culicoides dynamics to multiple environmental drivers. Start, end of season and length of overwintering of adult Culicoides were analysed across 329 sites in Spain sampled from 2005 to 2010 during the National Entomosurveillance Program for BTV with path analysis, to determine the direct and indirect effects of land use, climate and host factor variables. Culicoides taxa had species-specific responses to environmental variables. While the seasonality of adult C. imicola was strongly affected by topography, temperature, cover of agro-forestry and sclerophyllous vegetation, rainfall, livestock density, photoperiod in autumn and the abundance of Culicoides females, Obsoletus complex species seasonality was affected by land-use variables such as cover of natural grassland and broad-leaved forest. Culicoides female abundance was the most explanatory variable for the seasonality of C. newsteadi, while C. pulicaris showed that temperature during winter and the photoperiod in November had a strong effect on the start of the season and the length of overwinter period of this species. These results indicate that the seasonal vector-free period (SVFP) in Spain will vary between competent vector taxa and geographic locations, dependent on the different responses of each taxa to environmental conditions.

La gobernanza de la salud pública es un sistema de gestión en el que la cultura organizacional, las normas familiares, la formación y las relaciones sindicales serían determinantes de la adherencia al tratamiento como indicador de la calidad del servicio de salud. Se realizó un estudio no experimental, transversal y exploratorio con una selección probabilística de 104 estudiantes asociados con la infección por el VIH. Los resultados muestran que las relaciones en torno al cuidado de los infectados por el VIH determinan la adherencia al tratamiento (β = 0,702, R = 0,645, R2 = 0,080, R2 ajustado = 0,070; p

The public agenda, which reflects the main themes and topics of discussion between the government and the public, has shifted toward debating the pandemic’s impact on public opinion and government initiatives without considering the findings reported in the literature as indicators of the phenomenon. The objective of the present work was to establish the networks inferred from the relationships between findings reported in the literature from 2019 to 2022 regarding political and social actors in the field of social risk communication. The results warn of the prevalence of collateral axes to mobility as a restrictive effect of confinement policies and distancing of people. The analysis of health policies is recommended to anticipate conflict scenarios between the parties involved.

© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.562 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., Objective: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. Methods: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. Results: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). Conclusions: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573., This research was funded by The Netherlands Organisation for Health Research and Development (ZonMw, grant number 10430072110005) and the Dr. C. J. Vaillant Foundation.

The identity and location of vocalization pattern generating (VPG) circuits in mammals is debated. Based on physiological experiments, investigators suggested anterior brainstem circuits in the reticular formation, and anatomic evidence suggested the nucleus retroambiguus (NRA) in the posterior brainstem, or combinations of these sites as the putative mammalian VPG. Additionally, vocalization loudness is a critical factor in acoustic communication. However, many of the underlying neuronal mechanisms are still unknown. Here, we evoked calls by stimulation of the periaqueductal gray in anesthetized male rats, performed a large-scale mapping of vocalization-related activity using the activity marker c-fos, and high-density recordings of brainstem circuits using Neuropixels probes. Both c-fosexpression and recording of vocalization-related activity point to a participation of the NRA in vocalization. More important, among our recorded structures, we found that the NRA is the only brainstem area showing a strong correlation between unit activity and call intensity. In addition, we observed functionally diverse patterns of vocalization-related activity in a set of regions around NRA. Dorsal to NRA, we observed activity specific to the beginning and end of vocalizations in the posterior level of the medullary reticular nucleus, dorsal part, whereas medial and lateral to the NRA, we observed activity related to call initiation. No clear vocalization-related activity was observed at anterior brainstem sites. Our findings suggest a set of functionally heterogeneous regions around the NRA contribute to vocal pattern generation in rats.SIGNIFICANCE STATEMENTVocalization patterns are shaped in the mammalian brainstem, but the identity and location of the circuits involved is debated. Additionally, the neuronal mechanisms of vocal intensity control are still unknown. This study consisted of a large-scale mapping of brainstem vocalization circuits based on the activity marker c-fosand high-density recordings with Neuropixels probes. The results confirm the role of nucleus retroambiguus in call production and point to a key role of neurons in this nucleus in loudness control. Dorsal to the nucleus retroambiguus and in the posterior medulla, the authors identify neurons with activity specific to the beginning and end of vocalizations. The results point to specific neural dials for various aspects of rat vocalization control in the posterior brainstem.

Polycomb repressive complex 2 (PRC2) has oncogenic and tumor-suppressive roles in cancer. There is clinical success of targeting this complex in PRC2-dependent cancers, but an unmet therapeutic need exists in PRC2-loss cancer. PRC2-inactivating mutations are a hallmark feature of high-grade malignant peripheral nerve sheath tumor (MPNST), an aggressive sarcoma with poor prognosis and no effective targeted therapy. Through RNAi screening in MPNST, we found that PRC2 inactivation increases sensitivity to genetic or small-molecule inhibition of DNA methyltransferase 1 (DNMT1), which results in enhanced cytotoxicity and antitumor response. Mechanistically, PRC2 inactivation amplifies DNMT inhibitor–mediated expression of retrotransposons, subsequent viral mimicry response, and robust cell death in part through a protein kinase R (PKR)–dependent double-stranded RNA sensor. Collectively, our observations posit DNA methylation as a safeguard against antitumorigenic cell-fate decisions in PRC2-loss cancer to promote cancer pathogenesis, which can be therapeutically exploited by DNMT1-targeted therapy.Significance:PRC2 inactivation drives oncogenesis in various cancers, but therapeutically targeting PRC2 loss has remained challenging. Here we show that PRC2-inactivating mutations set up a tumor context–specific liability for therapeutic intervention via DNMT1 inhibitors, which leads to innate immune signaling mediated by sensing of derepressed retrotransposons and accompanied by enhanced cytotoxicity.See related commentary by Guil and Esteller, p. 2020.This article is highlighted in the In This Issue feature, p. 2007

Supplementary Data from PRC2-Inactivating Mutations in Cancer Enhance Cytotoxic Response to DNMT1-Targeted Therapy via Enhanced Viral Mimicry

The objective of this paper is to review the theoretical, conceptual and empirical frameworks around the perception of risk as a rational, deliberate, planned and systematic process of contingencies and threats. A documentary and retrospective study was carried out with a non-probabilistic selection of sources indexed in international repositories, considering the journal's impact factor and the author's citation index. A model was established based on the evaluative consensus of expert judges in the subjects, although the research design limited these findings to the study scenario, suggesting the extension of the work towards lines of research concerning normative, technological and strategic trust with respect to to civil protection.

Background: The Enhanced Recovery After Surgery (ERAS) care pathways include evidence-based items designed to accelerate recovery after surgery. Interdisciplinarity is one of the key points of ERAS programs. Objective: To prepare a consensus document among the members of the Nutrition Area of the Spanish Society of Endocrinology and Nutrition (SEEN) and the Spanish Group for Multimodal Rehabilitation (GERM), in which the goal is to homogenize the nutritional and metabolic management of patients included in an ERAS program. Methods: 69 specialists in Endocrinology and Nutrition and 85 members of the GERM participated in the project. After a literature review, 79 statements were proposed, divided into 5 sections: 17 of general characteristics, 28 referring to the preoperative period, 4 to the intraoperative, 13 to the perioperative and 17 to the postoperative period. The degree of consensus was determined through a Delphi process of 2 circulations that was ratified by a consistency analysis. Results: Overall, in 61 of the 79 statements there was a consistent agreement, with the degree of consensus being greater among members of the SEEN (64/79) than members of the GERM (59/79). Within the 18 statements where a consistent agreement was not reached, we should highlight some important nutritional strategies such as muscle mass assessment, the start of early oral feeding or pharmaconutrition. Conclusion: Consensus was reached on the vast majority of the nutritional measures and care included in ERAS programs. Due to the lack of agreement on certain key points, it is necessary to continue working closely with both societies to improve the recovery of the surgical patients.

This scientific opinion focuses on the welfare of laying hens, pullets and layer breeders on farm. The most relevant husbandry systems used in Europe are described. For each system, highly relevant welfare consequences were identified, as well as related animal-based measures (ABMs), and hazards leading to the welfare consequences. Moreover, measures to prevent or correct the hazards and/or mitigate the welfare consequences are recommended. The highly relevant welfare consequences based on severity, duration and frequency of occurrence are bone lesions, group stress, inability to avoid unwanted sexual behaviour, inability to perform comfort behaviour, inability to perform exploratory or foraging behaviour, isolation stress, predation stress, resting problems, restriction of movement, skin disorders and soft tissue lesions and integument damage. The welfare consequences of non-cage compared to cage systems for laying hens are described and minimum enclosure characteristics are described for laying hens, pullets and layer breeders. Beak trimming, which causes negative welfare consequences and is conducted to reduce the prevalence and severity of pecking, is described as well as the risks associated with rearing of non-beak-trimmed flocks. Alternatives to reduce sharpness of the beak without trimming are suggested. Finally, total mortality, plumage damage, wounds, keel bone fractures and carcass condemnations are the most promising ABMs for collection at slaughterhouses to monitor the level of laying hen welfare on farm. Main recommendations include housing all birds in non-cage systems with easily accessible, elevated platforms and provision of dry and friable litter and access to a covered veranda. It is further recommended to implement protocols to define welfare trait information to encourage progress in genetic selection, implement measures to prevent injurious pecking, rear pullets with dark brooders and reduce male aggression in layer breeders.

In this work, we present SaFiDe, a deterministic method to detect eye movements (saccades and fixations) from eye-trace data. We developed this method for human and nonhuman primate data from video- and coil-recorded eye traces and further applied the algorithm to eye traces computed from electrooculograms. All the data analyzed were from free-exploration paradigms, where the main challenge was to detect periods of saccades and fixations that were uncued by the task. The method uses velocity and acceleration thresholds, calculated from the eye trace, to detect saccade and fixation periods. We show that our fully deterministic method detects saccades and fixations from eye traces during free visual exploration. The algorithm was implemented in MATLAB, and the code is publicly available on a GitHub repository. The algorithm presented is entirely deterministic, simplifying the comparison between subjects and tasks. Thus far, the algorithm presented can operate over video-based eye tracker data, human electrooculogram records, or monkey scleral eye coil data.

Objetivo: Avaliar a associação entre o estado nutricional e a presença de sintomas gastrointestinais em pacientes oncológicos em tratamento quimioterápico. Método: Estudo transversal e prospectivo aplicado em 54 pacientes com diagnóstico de qualquer neoplasia maligna, em tratamento quimioterápico, com idade ?18 anos, de ambos os gêneros. Os dados foram coletados em um hospital universitário terciário e foram avaliadas medidas antropométricas, dietéticas e os sintomas gastrointestinais foram avaliados pelo questionário Common Terminology Criteria for Adverse Event (CTCAE). Para todas as análises foi fixado um nível de significância de 5%. Resultados: Os pacientes apresentaram média de idade de 59,3±14,5 anos, sendo a maioria idosos (57,4%) e do sexo feminino (55,6%). O IMC alcançou média de 26,2±5,4 kg/m², sendo identificado uma prevalência de 50% de excesso de peso e obesidade, 35,1% de eutrofia e 14,8% de baixo peso. Foi encontrada maior frequência de idosos com baixo peso quando comparado com adultos. Identificou-se alta prevalência de sintomas gastrointestinais sendo os mais relatados: xerostomia (74%), disosmia (61%), disgeusia (61%), saliva espessa ou gosto metálico na boca (59,2%) e náusea (57,3%). Os participantes apresentaram média de consumo energético de 1.588±688 Kcal/dia e ingestão proteica menor do que recomendado na maioria dos pacientes. Indivíduos com excesso de adiposidade e pacientes com consumo energético maior relataram mais sintomas. Conclusão: Apesar da alta prevalência de sintomas gastrointestinais, indivíduos com câncer em tratamento quimioterápico não apresentaram impactos significativos no estado nutricional.

Neuroprosthetic technology aims to restore nervous system functionality in cases of severe damage or degeneration by recording and stimulating the electrical activity of the neural tissue. One of the key factors determining the quality of the neuroprostheses is the electrode material used to establish electrical communication with the neural tissue, which is subject to strict electrical, electrochemical, and mechanical specifications as well as biological and microfabrication compatibility requirements. This work presents a nanoporous graphene-based thin film technology and its engineering to form flexible neural implants. Bench measurements show that the developed microelectrodes offer low impedance and high charge injection capacity throughout millions of pulses. In vivo electrode performance was assessed in rodents both from brain surface and intracortically showing high-fidelity recording performance, while stimulation performance was assessed with an intrafascicular implant that demonstrated low current thresholds and high selectivity for activating subsets of axons within the sciatic nerve. Furthermore, the tissue biocompatibility of the devices was validated by chronic epicortical and intraneural implantation. Overall, this works describes a novel graphene-based thin film microelectrode technology and demonstrates its potential for high-precision neural interfacing in both recording and stimulation applications.

Xylella fastidiosaWells (1987) (Proteobacteria:Xanthomonadaceae) is a xylem pathogen bacterium transmitted by xylem feeder insects that causes several important plant diseases such as Pierce’s disease in grapes or leaf scorch in almond and olives trees. The bacterium was detected in the Balearic Islands in October 2016, including three subspecies:fastidiosa,multiplexandpauca. The major potential vectors described in the Balearics arePhilaenus spumariusL. andNeophilaenus campestrisFallen (1805). In order to interfere the life cycle of vectors, we tested the effect of mechanical control of the plant cover on the most vulnerable phases, such as nymphs and/or newly emerged adults. For this, we selected four organic orchards in Mallorca, three olive and one vineyard plots. Owners of each selected plot conducted mechanical control according to their common procedures and their own machinery, which in general included cut and tillage of the plant cover during March-April. Nymph abundance per surface (30 sampling points/treatment/orchard x 0,25 m2) was measured in each plot in a weekly basis before and after mechanical control. Our results indicated that either tillage and mowing decreased nymphal density ofX. fastidiosavectors in both types of crops. These results contribute to the integrated pest management of vectors by conducting feasible farm-based management of the regular plant cover.Abstract Figure

Polycyclic aromatic hydrocarbons (PAHs) are the most widespread xenobiotic pollutants in water and their abatement usually involves expensive and energy-consuming treatments. In this work, anthracene (AN) was selected as the recalcitrant model of PAHs and its solar light-stimulated heterogeneous photocatalytic abatement in aerated aqueous media was investigated using a new TiO derived thermoplastic nanocomposite in thin film form. The results were also compared with the benchmark TiO photocatalyst in slurry form. Finally, the possible contribution of reactive intermediates such as hydroxyl radical, AN radical cation and singlet oxygen, was investigated by using a hydroxyl radical trap and laser flash photolysis. Based on the obtained results, a feasible mechanism for AN photodegradation, which involves hydroxyl radical as the key oxidizing species is proposed., This research was funded by the University of Catania (Piano di incentivi per la ricerca di Ateneo, PIACERI–Linea 2).

Este artículo contiene 12 páginas, 2 tablas, 2 figuras., Background: Active surveillance aimed at the early detection of invasive mosquito species is usually focused on seaports and airports as points of entry, and along road networks as dispersion paths. In a number of cases, however, the frst detections of colonizing populations are made by citizens, either because the species has already moved beyond the implemented active surveillance sites or because there is no surveillance in place. This was the case of the frst detection in 2018 of the Asian bush mosquito, Aedes japonicus, in Asturias (northern Spain) by the citizen science platform Mosquito Alert. Methods: The collaboration between Mosquito Alert, the Ministry of Health, local authorities and academic research‑ ers resulted in a multi-source surveillance combining active feld sampling with broader temporal and spatial citizensourced data, resulting in a more fexible and efcient surveillance strategy. Results: Between 2018 and 2020, the joint eforts of administrative bodies, academic teams and citizen-sourced data led to the discovery of this species in northern regions of Spain such as Cantabria and the Basque Country. This raised the estimated area of occurrence of Ae. japonicus from < 900 km2 in 2018 to > 7000 km2 in 2020. Conclusions: This population cluster is geographically isolated from any other population in Europe, which raises questions about its origin, path of introduction and dispersal means, while also highlighting the need to enhance sur‑ veillance systems by closely combining crowd-sourced surveillance with public health and mosquito control agencies’ eforts, from local to continental scales. This multi-actor approach for surveillance (either passive and active) shows high potential efciency in the surveillance of other invasive mosquito species, and specifcally the major vector Aedes aegypti which is already present in some parts of Europe., RE and FB from Mosquito Alert received funding from “la Caixa” Foundation (ID 100010434), under agreement HR18-00336 (Community-Driven Big Data Intel‑ ligence to Fight Mosquito-Borne Disease). This project has also been funded by the European Union’s Horizon 2020 research and innovation program, under the grant agreement 874735 (VEO). Samplings in the Basque Country were funded by the Department of Public Health and the Department of Economic Development and Infrastructures of the Basque Government, and co-funded by the project EU-LIFE 18 IPC/ES/000001 (Urban Klima 2050).

Photosensitized thymine<>thymine (Thy<>Thy) formation and repair can be mediated by carbazole (Cbz). The former occurs from the Cbz triplet excited state via energy transfer, while the latter takes place from the singlet excited state via electron transfer. Here, fundamental insight is provided into the role of the topology and excited state multiplicity, as factors governing the balance between both processes. This has been achieved upon designing and synthesizing different isomers of trifunctional systems containing one Cbz and two Thy units covalently linked to the rigid skeleton of the natural deoxycholic acid. The results shown here prove that the Cbz photosensitized dimerization is not counterbalanced by repair when the latter, instead of operating through-space, has to proceed through-bond., Financial support from the Spanish Government (grant SEV-2016-0683), Generalitat Valenciana (PROMETEO/2017/075 and PROMETEO/2021/077), and Technical University of Valencia (Predoctoral FPI fellowship for P.M.) is gratefully acknowledged. G.S. thanks CTI-CSIC for the use of computational facilities.

We know little about mammalian anemotaxis, wind-sensing. Recently, however, Hartmann and colleagues showed whisker-based anemotaxis in rats. To investigate how whiskers sense airflow, we tracked whisker tips in anesthetized or cadaver rats under no airflow, low airflow and high (fan-blowing) airflow. Whisker tips showed little movement under no airflow conditions and all whisker tips moved during high airflow. Low airflow conditions – most similar to naturally occurring wind stimuli – engaged whisker tips differentially. Most whiskers moved little, the long supraorbital whisker showed maximal displacement and α, A1, β, and γ whiskers also showed movements. The long supraorbital whisker differs from other whiskers in its exposed dorsal position, upward bending, length and thin diameter.Ex vivoextracted long supraorbital whiskers also showed exceptional airflow displacement, suggesting whisker-intrinsic biomechanics mediate the unique airflow-sensitivity. Micro computed tomography revealed that the ring-wulst – the follicle structure receiving the most sensitive afferents – was more complete/ closed in supraorbital and other wind-sensitive whiskers than in non-wind-sensitive whiskers, suggesting specialization of the supraorbital for omni-directional sensing. We localized and targeted the cortical supraorbital whisker representation in simultaneous Neuropixels recordings with D/E-row whisker barrels. Responses to wind-stimuli were stronger in the supraorbital whisker representation than in D/E-row barrel cortex. We assessed the behavioral significance of whiskers in an airflow-sensing paradigm. We observed that rats spontaneously turn towards airflow stimuli in complete darkness. Selective trimming of wind-responsive whiskers diminished airflow turning responses more than trimming of non-wind-responsive whiskers. Lidocaine injections targeted to supraorbital whisker follicles also diminished airflow turning responses compared to control injections. We conclude that supraorbital whiskers act as wind antennae.New and NoteworthyAnimals rely on sensory processing of airflow (anemotaxis) to guide navigation and survival. We examined mechanisms of rat anemotaxis by combining whisker tracking, biomechanical analysis, micro computed tomography of follicle structure, Neuropixels recordings in the barrel field, behavior of airflow turning and whisker interference by trimming and lidocaine injections. This diversity of methods led to a coherent pattern of results. Whiskers greatly differ in their airflow sensitivity and strongly wind-responsive whiskers – in particular long supraorbital whiskers – determine behavioral responses to airflow stimuli in rats.

Contaminants of emerging concern (CECs) constitute a wide class of organic molecules, which are found dissolved in wastewaters. Chemical properties of CECs are as wide as their chemical structures; nevertheless, most of the CECs can be removed from wastewaters using Advanced Oxidation Processes (AOPs). However, there are examples of CECs that have proven recalcitrant to AOPs. In such cases, Advanced Reduction Processes (ARPs) include those techniques able to achieve degradation of contaminants by producing highly reactive reducing radicals. Organic photocatalysts have demonstrated to be an efficient alternative to other types of photocatalysts in AOPs. Moreover, several organic photocatalysts, according to their redox properties, could also act as reductants under appropriate scenarios, a process that has been much less explored than oxidation. As an example, Riboflavin (RF) is a natural water-soluble molecule, well-known as vitamin B2. The photophysical and redox properties of RF have been extensively applied for the oxidative photodegradation of contaminants in water. More recently, the potential of RF has been expanded to the photoreduction of more recalcitrant pollutants. For instance, benzotriazoles UV-stabilizers (BUVSs) constitute a vast family of recalcitrant contaminants, which have been successfully degraded in the presence of a commercially available derivative of RF (2′,3′,4′,5′-tetraacetylated riboflavin, RFTA) and visible light, assisted by an amine, which acts as electron donor to the excited states of RFTA, generating the RFTA.. This species ultimately produces the reduction of the selected BUVSs. Photophysical experiments demonstrated the key role of the radical anion RFTA., and allowed determining the rate constants that were correlated to the observed photodegradations., The authors would like to acknowledge H2020/Marie Skłodowska-Curie Actions under the AQUAlity project (Reference: 765860), Consellería d'Educació, Investigació, Cultura i Esport (PROMETEO/2017/075) and the Spanish Ministry of Science, Innovation and Universities (PID2019–110441RB-C33 financed by MCIN/AEI/10.13039/501100011033) are gratefully acknowledged.

Photosensitization by drugs is directly related with the excited species and the photoinduced processes arising from interaction with UVA light. In this context, the ability of gefitinib (GFT), a tyrosine kinase inhibitor (TKI) used for the treatment of a variety of cancers, to induce phototoxicity and photooxidation of proteins has recently been demonstrated. In principle, photodamage can be generated not only by a given drug but also by its photoactive metabolites that maintain the relevant chromophore. In the present work, a complete study of O-desmorpholinopropyl gefitinib (GFT-MB) has been performed by means of fluorescence and ultrafast transient absorption spectroscopies, in addition to molecular dynamics (MD) simulations. The photobehavior of the GFT-MB metabolite in solution is similar to that of GFT. However, when the drug or its metabolite are in a constrained environment, i.e. within a protein, their behavior and the photoinduced processes that arise from their interaction with UVA light are completely different. For GFT in complex with human serum albumin (HSA), locally excited (LE) singlet states are mainly formed; these species undergo photoinduced electron transfer with Tyr and Trp. By contrast, since GFT-MB is a phenol, excited state proton transfer (ESPT) to form phenolate-like excited species might become an alternative deactivation pathway. As a matter of fact, the protein-bound metabolite exhibits higher fluorescence yields and longer emission wavelengths and lifetimes than GFT@HSA. Ultrafast transient absorption measurements support direct ESPT deprotonation of LE states (rather than ICT), to form phenolate-like species. This is explained by MD simulations, which reveal a close interaction between the phenolic OH group of GFT-MB and Val116 within site 3 (subdomain IB) of HSA. The reported findings are relevant to understand the photosensitizing properties of TKIs and the role of biotransformation in this type of adverse side effects., Financial support from the Spanish Ministry of Science and Innovation (RYC-2015-17737, BEAGAL 18/00211, PID2020-115010RB-I00/AEI/10.13039/501100011033, FPU19/00048, PID2019-105512RB-I00/AEI/10.13039/501100011033), the Xunta de Galicia (ED431C 2021/29), the Centro singular de investigación de Galicia accreditation 2019–2022 (ED431G 2019/03), and the European Regional Development Fund (ERDF) is gratefully acknowledged. All authors are grateful to the Centro de Supercomputación de Galicia (CESGA) for use of the Finis Terrae computer.

The sentinel plantation concept consists of assessing the impact of exotic factors, such as pests and pathogens, on plants of interest by planting them out of their native range. This tool is a way to enhance knowledge for pest risk analysis (PRA) by guiding decisions on how quarantine organisms should be regulated and where to focus prevention and surveillance efforts for an early detection. In this study, the sentinel method was used in the case of research on Xylella fastidiosa, a plant pathogenic bacterium that has recently been found established in southern Europe, but whose potential impact and possible host range are still poorly documented in northern areas where the bacterium is not known to occur. To improve knowledge on the susceptibility of potential hosts of X. fastidiosa in northern Europe, a sentinel plantation of Prunus domestica cv. Opal, Quercus petraea and Salix alba was established in the X. fastidiosa-infected area of Majorca. In order to assess the circulation of the bacterium in the sentinel plot and around it, surveys of the local flora and insect vectors were carried out, as well as the planting of a network of rosemary “spy plants”. Symptomatic monitoring and molecular analyses were performed on the sentinel plants for four years. During these years, X. fastidiosa was never detected in our sentinel plants most likely because of the low infectivity pressure recorded in the surroundings. This study underlines the complexity of conducting sentinel plantation assays combined with X. fastidiosa research, highlighting the need for long-term investigation and questioning the efficiency of the sentinel tool. However, this study is placed in perspective with other valuable sentinel plantations. It also highlights the complementarity of the tool and proposes elements to improve or reorient the implementation of future sentinel projects.

Dissertação de Mestrado em Estudos Artísticos apresentada à Faculdade de Letras Na Biblioteca Geral da Universidade de Coimbra encontra-se uma tradução do famoso tratado de cantochão de Juan Martínez que terá servido de referência para um caso de sucesso dentro da imprensa musical portuguesa. Procurámos, com este trabalho, torná-lo acessível ao leitor moderno e compreender melhor o seu processo editorial.Para tal, começámos por fazer uma análise sistemática dos principais estudos que nos podiam ajudar para o processo de investigação. Depois, apresentámos o contexto que precedeu este impresso e dedicámo-nos à análise detalhada do mesmo. De seguida, debruçámo-nos sobre o fenómeno editorial que se seguiu, protagonizado pela Universidade de Coimbra.Ao longo da dissertação procurámos cruzar a bibliografia sobre o enquadramento da impressão e comercialização do tratado com os exemplares que nos chegaram. Inserimos a obra num grupo de obras pioneiras do mesmo género e comparámos todas as edições conhecidas desta versão portuguesa entre si.Perante este exercício ficou evidente, não só o destaque da tradução da obra de Martinez dentro do espectro português como também um rico percurso editorial onde vemos uma procura pela melhoria desta obra , com acrescentos e alterações, ao longo do tempo.No final deste trabalho, verificámos que a versão portuguesa de Martínez se tornaria numa obra acessível a um grande público, mas os acrescentos de Bernal dotaram-na de algumas preocupações mais características do ofício sacerdotal. Esta combinação aparenta um especial sucesso dadas as sucessivas reimpressões que verificou no primeiro quartel do séc. XVII. Futuras investigações poderão encontrar no repertório de Martínez e nos acrescentos de Bernal um pertinente objeto de estudo. In the Biblioteca Geral da Universidade de Coimbra there is a translation of the famous plainchant treaty by Juan Martínez that may have served as a reference for a success story within the Portuguese musical press. With this work, we sought to make it accessible to the modern reader and better understand its editorial process.To do so, we started by making a systematic analysis of the main studies that could help us in the investigation process. Then, we presented the context that preceded this book and dedicated ourselves to a detailed analysis of it. Next, we focused on the publishing phenomenon that followed, led by the Universidade de Coimbra.Throughout the thesis we tried to cross the bibliography on the framework of printing and commercialization of the treaty with the copies that reached us. We placed the work in a group of pioneering works of the same genre and compared all known editions of this portuguese version with each other.Towards this exercise, it was evident not only the prominence of the translation of Martinez's work within the portuguese spectrum, but also a rich editorial path where we see a search for improvement of this work, with additions and changes, over time.Finally, it would seem that Martínez Portuguese version has reached a wide audience, enriched with Bernal's additions concerning the priestly office. A successful combination which has given place to several reprints during the 17th-century. Future investigations may find in Martínez's repertoire and Bernal's additions a relevant object of study.

The discovery of three subspecies ofXylella fastidiosain Europe has triggered major attention on the potential spread up North of the bacteria. Assessing the susceptibility of a previously unexposed European flora is a key element that remains widely unknown. Under biosafety facility, we evaluated the susceptibility of Salicaceae such asPopulus tremula, Populus canescens, Salix albaandSalix capreaby mechanically inoculating the KLN59.3 GFP-labelledX. fastidiosaat 22 °C and at 28 °C. Bacterial movement and multiplication in plants were investigated by PCR, real-time PCR, confocal or scanning electron microscopy. Nine months post-inoculation, 100 % of the plants tested positive forX. fastidiosa, with the exception of 57% forP. canescensunder the 22 °C-growing conditions. Bacteria were detected up to 120 cm from the inoculation point forS. alba. They were detected in the roots of all species and were successfully isolated forS. albaandP. tremula. Estimates of average CFU/g of plant tissue per species ranged from 1.5E + 03 to 3.5E + 06, with the lowest figures forP. canescensand the highest forP. tremulatogether with high number of totally obstructed vessels observed by confocal microscopy. The possibility of insect transmission was also evaluated using an experimental set up based on Mallorca Island. There, transmission byP. spumariusof bothX. fastidiosaST1 and ST81 was proven onS. alba. We thus demonstrated that indigenous European Salicaceae such asS. albaorP. tremulaare new potential hosts forX. fastidiosa.

Phenols are regarded as highly toxic chemicals. Their effects are difficult to study in in vitro systems because of their ambiguous fate (degradation, auto-oxidation and volatility). In the course of in vitro studies of a series of redox-cycling phenols, we found evidences of cross-contamination in several in vitro high-throughput test systems, in particular by trimethylbenzene-1, 4-diol/trimethylhydroquinone (TMHQ) and 2,6-di-tertbutyl-4-ethylphenol (DTBEP), and investigated in detail the physicochemical basis for such phenomenon and how to prevent it. TMHQ has fast degradation kinetics followed by significant diffusion rates of the resulting quinone to adjacent wells, other degradation products being able to air-diffuse as well. DTBEP showed lower degradation kinetics, but a higher diffusion rate. In both cases the in vitro toxicity was underestimated because of a decrease in concentration, in addition to cross-contamination to neighbouring wells. We identified four degradation products for TMHQ and five for DTBEP indicating that the current effects measured on cells are not only attributable to the parent phenolic compound. To overcome these drawbacks, we investigated in detail the physicochemical changes occurring in the course of the incubation and made use of gas-permeable and non-permeable plastic seals to prevent it. Diffusion was greatly prevented by the use of both plastic seals, as revealed by GC–MS analysis. Gas non-permeable plastic seals, reduced to a minimum compounds diffusion as well oxidation and did not affect the biological performance of cultured cells. Hence, no toxicological cross-contamination was observed in neighbouring wells, thus allowing a more reliable in vitro assessment of phenol-induced toxicity., The authors wish to acknowledge the support of the European Union’s Horizon 2020 research and innovation 493 program under Grant Agreement No 681002 (EU-ToxRisk). We are indebted to CIBEREHD (ISCIII), for supporting our research program on hepatotoxicity of xenobiotics. L.T. was supported by the Miguel 494 Servet I Program financed by the Institute of Health Carlos III (Plan Estatal de I+D+i 2013-2016) 495 and co-financed by the European Regional Development Fund "A way to achieve Europe" (FEDER) 496 through grant CP16/00097. TMS acknowledges her personal predoctoral grant (FI18/00260, 497 ISCIII, Spain).

European guidelines for testing attractant and repellent efficacy (i.e., Product type 19 [PT19]) have been in revision since 2017. A key topic of discussion is the current approach to evaluating topical repellents. The European Chemical Agency has stated field testing should be avoided because of mosquito-borne disease risks. However, the most common laboratory method, the arm-in-cage (AIC) test, may limit the reliable extrapolation of lab results to field conditions. This study’s main goal was to assess alternative laboratory methods for evaluating topical mosquito repellents that use mosquito landing rates more representative of those in the field. The study took place at three European testing labs using 30 study participants per test and the mosquito, Aedes albopictus (Skuse, 1894, Diptera: Culicidae). In phase 1, a conventional AIC test and a sleeved AIC test were performed. Respectively, the arm area exposed was 600 and 100 cm2, and cage volume was 0.040 and 0.064 m3. Mosquito density was the same for both: 1 female/840 cm3. In phase 2, room-based testing (40 ± 5 mosquitoes in 25–30 m3) was used as a proxy for field testing. The mosquito repellent employed was 15% N,N-diethyl-m-toluamide in ethanol at two doses: 1 and 0.5 g/600 cm2. The protection times measured at each laboratory were analyzed both separately and together using nonparametric (Kruskal–Wallis) test. The two alternatives methods showed to be potential alternatives to the current AIC method recreated field mosquito landing rates and achieved reproducible protection times across laboratories., Graphical Abstract Graphical Abstract

Several pathogens are known to be transmitted by arthropods. One of the most relevant, in economic terms, affecting animals is bluetongue virus. Its known vectors are several species of Culicoides midges. In Europe, the considered main vector species are Culicoides imicola and Culicoides obsoletus, though other species may be implicated at different levels. In the present work, the activity of these vector species between sunset and sunrise from May to November is analyzed according to their captures in a rotator bottle collector adapted to a light trap. Additionally, the Culicoides populations of two areas in Mallorca (Spain) with different characteristics (rural vs. urban) are compared. The results indicated that June is the month of higher abundance of C. obsoletus in our climatic conditions—being active during the first three hours after sunset. Conversely, C. imicola reached the maximum level of captures during October, and captures were more evenly distributed during the night. Collections from the two areas revealed that Culicoides populations were composed by the same species; however, abundance and sex ratio presented marked differences. These results add valuable insight into the ecology of Culicoides and may be used to design more accurate strategies to control diseases associated with Culicoides.

9 Pág., Phlebotomine sand flies are vectors of several diseases of importance for public health, including leishmaniosis, bartonellosis, and sand fly fevers. An entomological survey on blood-feeding Diptera was conducted in June–November 2020–2021 to know the diversity of insect vectors in Mallorca (Balearic Islands, Spain). Among the vectors collected, Phlebotomus (Larroussius) perfiliewi Parrot, 1930 was found being the first record of this species in Spain. Phlebotomus perfiliewi s.l. is one of the main vectors of Leishmania infantum in the Mediterranean Basin and Central Asia. The identification of this species was confirmed by both morphological features and DNA barcoding. Phylogenetic analyses showed that the specimens captured were Ph. perfiliewi s.s. (99.85–100% homologues from Italy and Algeria specimens), with a sequence divergence of 0.17%. The cytochrome c oxidase subunit I gene clearly separates the three species that make up the Ph. perfiliewi species complex. In addition, we also provide a brief discussion about their identification remarks, phylogenetic relationships, and vector status., This study was funded by the Agriculture, Fisheries and Food council through the project num. BIA08/20-2 from the agricultural and fishing guarantee fund (FOGAIBA) of the Government of the Balearic Islands. Samplings were supported by own resources of ZAP-UIB and FOGAIBA. R.G.L. was initially supported by a Margalida Comas contract from the Government of the Balearic Islands and from the European Regional Development Fund (FEDER) (REF- PD/038/2019) and he is currently funded by a Juan de la Cierva 2019 Formación contract (FJC2019-041291-I) from the Ministry of Science and Innovation.

No hay resúmenes disponibles. Investigaciones UCA, Año. 1, Vol. 1, 2019-2020: 380-383.

Polycomb Repressive Complex 2 (PRC2) establishes and maintains di- and tri-methylation at histone 3 at lysine 27 (H3K27me2/3) in the genome and plays oncogenic and tumor suppressor roles in context-dependent cancer pathogenesis. While there is clinical success of therapeutically targeting PRC2 core component, EZH2, in PRC2-dependent cancers (e.g., follicular lymphoma, epithelioid sarcoma), it remains an unmet therapeutic bottleneck in PRC2-inactivated cancer. Biallelic inactivating mutations in PRC2 core components are a hallmark feature of high-grade malignant peripheral nerve sheath tumor (MPNST), an aggressive subtype of sarcoma with poor prognosis and no effective targeted therapeutics. Using a custom RNAi-based drop out screen, we observed that PRC2-inactivation is synthetic lethal with DNA methyltransferase 1 (DNMT1) downregulation; we further observed that small molecule DNMT inhibitors (DNMTis) resulted in enhanced cytotoxicity and antitumor response in PRC2-loss cancer context in vitro and in vivo. Mechanistically, DNMTi-mediated de-repression of retrotransposons (e.g., endogenous retroviral elements (ERVs)/LTR, LINE, SINE) and gene targets is partly restricted by PRC2, which potentially contributes to limited therapeutic activity in PRC2-wild-type (wt) cancer context. In contrast, DNMTi treatment synergizes with PRC2 inactivation and cooperatively amplifies the expression of retrotransposons (e.g., ERV/LTR, LINE, SINE), and subsequent viral mimicry response that promotes robust cell death in part through PKR-dependent double stranded-RNA (dsRNA) sensing. Collectively, our observations posit DNA methylation as a safeguard against anti-tumorigenic cell fate decisions in the context of PRC2-inactivation to promote cancer pathogenesis. Further, they identified a novel targeted therapeutic strategy in PRC2-inactivated MPNST and delineated the PRC2-inactivated cancer context for future preclinical exploration and clinical investigation of DNMT1-targeted therapies in cancer.SIGNIFICANCEPRC2-inactivation drives oncogenesis in various cancers but therapeutically targeting PRC2-loss has remained challenging. Here we show that PRC2 inactivating mutations sets up a tumor context-specific liability for synthetic lethal interaction with genetic and therapeutic inhibition of DNMT1. DNMT1 inhibitor-induced cytotoxicity in PRC2-loss cancer context is accompanied by innate immune signaling signature through PKR-mediated sensing of endogenous retrotransposons. These observations posit a therapeutic window via direct anti-tumor effect by DNMT1 inhibitors in PRC2-loss cancers, and point to potentials to be combined with innovative immunotherapeutic strategies to capitalize on innate immune signaling activation.

Immune checkpoint blockade (ICB) has demonstrated clinical success in “inflamed” tumors with significant T-cell infiltrates, but tumors with an immune-desert tumor microenvironment (TME) fail to benefit. The tumor cell-intrinsic molecular mechanisms of the immune-desert phenotype remain poorly understood. Here, we demonstrate that inactivation of the Polycomb-repressive complex 2 (PRC2) core components, EED or SUZ12, a prevalent genetic event in malignant peripheral nerve sheath tumor (MPNST) and sporadically in other cancer types, drives a context-dependent immune-desert TME. PRC2 inactivation reprograms the chromatin landscape that leads to a cell-autonomous shift from primed baseline signaling-dependent cellular responses (e.g., interferon γ) to PRC2-regulated development and cellular differentiation transcriptional programs. Further, PRC2 inactivation reprograms the TME, leads to diminished tumor immune infiltrates and immune evasion through reduced chemokine production and impaired antigen presentation and T-cell priming, and confers ICB primary resistance through blunted T-cell recruitment in vivo. We demonstrate that strategies that enhancing innate immunity via intratumoral delivery of inactivated modified vaccinia virus Ankara (MVA) leads to increased tumor immune infiltrates and sensitizes PRC2-loss tumors to ICB. Our results provide novel molecular mechanisms of context-dependent dysfunctional epigenetic reprogramming that underline the immune-desert phenotype in MPNST and other cancers with PRC2 inactivation. Importantly, our findings highlight genetic-inactivation of PRC2 as a novel context-dependent ICB therapeutic resistance biomarker in cancer, and caution that therapeutic strategies that non-selectively target PRC2 in the host may lead to undesirable context-dependent immune evasion and ICB resistance in tumors. Our studies also point to intratumoral delivery of immunogenic therapeutic viruses as an initial strategy to modulate the immune-desert TME and capitalize on the clinical benefit of ICB.

(1) To determine probabilities of immediate postoperative new motor deficits after no, reversible, and irreversible motor evoked potentials (MEP) deteriorations and (2) to calculate the same outcome considering whether MEP deteriorations were followed by surgical interventions in the absence of confounding factors.We analyzed MEPs from 513 surgeries. Four-limb MEPs were evoked by transcranial electrical stimulation. Baseline recordings were obtained before skin incision and updated before instrumentation. Motor evoked potentials deteriorations were considered significant whenever they showed a persistent, reversible, or irreversible amplitude decrease of80% of the baseline values.Nine patients showed postoperative new motor deficits. Probabilities of postoperative new motor deficits were null, 2.8%, and 36.8% with no, reversible, and irreversible MEP deteriorations, respectively. The risk of immediate postoperative new motor deficits was significantly lower (P = 0.0002) in reversible MEP compared with irreversible MEP deteriorations. In patients showing reversible/irreversible MEP deteriorations in the absence of confounding factors, surgical interventions compared with nonsurgical interventions significantly decreased the risk of immediate postoperative new motor deficits (P = 0.0216).This study shows that probabilities of immediate postoperative new motor deficits increase with the severity of intraoperative MEP changes. In addition, our results support the value of surgical interventions triggered by MEP deteriorations to reduce postoperative adverse motor outcomes.

Los himnos representan un concepto, una manera de organización, un sentido de pertenencia, una forma de percibir una identidad y una cultura nacional. Una tarea común de historiadores y educadores es analizar, interpretar y comprender los mitos y símbolos nacionales. Los mensajes de los himnos llegan a la ciudadanía cada vez que se entonan y su repetición es, junto con las banderas, muy superior al uso del resto de los símbolos nacionales. De ahí su importancia en el desarrollo de los nacionalismos y como medio de educación. El objetivo de esta investigación es examinar las letras de los himnos de las naciones de Europa, reconocidas por la ONU, y explicar su vinculación con los elementos estructurantes del nacionalismo étnico. Mediante un análisis cualitativo de esos cincuenta himnos en su versión extensa, se seleccionaron todos sus términos (466) vinculados con los ejes temáticos del nacionalismo étnico y se estableció una relación directa entre estos y su contenido global. Esta concepción nacionalista no está reflejada en cada una de las letras, pero sí lo está en el conjunto de todas ellas, la cual puede ser beligerante y contravenir el ejercicio de los derechos humanos., National anthems represent a concept, a way of organization, a sense of belonging, a form of perceiving a national identity and culture. A common task of historians and educators is to analyze, interpret, and understand national myths and symbols. The messages of these anthems reach the citizens every time they are sung. The repetition of these symbols, together with flags, is far superior to the use of other national symbols, hence their importance in the development of nationalisms and as a means of education and enculturation. In this sense, the general objective of this work is to study the role of the anthems of European nations, recognized by the UN, in the education of ethnic nationalism. Through a qualitative analysis of fifty anthems in their extended versions, all the terms (466) linked to the thematic axes of ethnic nationalism were selected from the lyrics, and a direct relationship was established between their overall content and nationalism. This nationalist conception is not reflected in every one of the lyrics, but it is reflected in the anthems as a whole; this ethnic nationalism can be belligerent and contravene the exercise of human rights., Os hinos representam um conceito, uma forma de organização, um sentimento de pertencimento, uma forma de perceber uma identidade e uma cultura nacional. Uma tarefa comum de historiadores e educadores é analisar, interpretar e compreender os mitos e símbolos nacionais. As mensagens dos hinos chegam ao público cada vez que são cantados e a sua repetição, juntamente com as bandeiras, é muito superior ao uso dos restantes símbolos nacionais. Daí sua importância no desenvolvimento dos nacionalismos e como meio de educação. O objetivo desta pesquisa é examinar as letras dos hinos das nações da Europa, reconhecidos pela ONU, e explicar sua vinculação com os elementos estruturantes do nacionalismo étnico. Por meio de uma análise qualitativa desses cinquenta hinos em sua versão ampliada, foram selecionados todos os seus termos (466) vinculados aos eixos temáticos do nacionalismo étnico e estabelecida uma relação direta entre eles e seu conteúdo global. Essa concepção nacionalista não se reflete em cada uma das letras, mas no conjunto de todas elas, o que pode ser beligerante e violar o exercício dos direitos humanos.

Culicoides Latreille (Diptera: Ceratopogonidae) transmit arboviruses affecting wild and domestic ruminants such as bluetongue (BTV) and Schmallenberg virus (SBV). The sub-adult development and lifespan of Culicoides obsoletus s.s. (Meigen), Culicoides circumscriptus Kieffer and Culicoides paolae Boorman were examined at three different temperatures under laboratory conditions. Insects were collected from field between spring and autumn 2015 in two livestock farms located in Majorca (Spain). Gravid females were held individually at 18, 25 or 30 °C. Low temperatures increased the adult lifespan, time to oviposit and rate of development, whereas high temperatures increased the number of eggs, successful pupation and adult emergence as well as the larvae growth rate. The results showed that C. obsoletus s.s. have optimum development at 18 °C, whereas the optimal rearing temperature for C. circumscriptus and C. paolae was under warmer conditions of 25-30 °C. Variations in temperature/humidity and assays with different materials and substrates for oviposition should be considered in future studies. Understanding the requirements of the different species of Culicoides optimizing the results should be of special interest for predicting environmental change effects on these species, in addition to determining the rearing conditions for candidate Culicoides vectors.

Rats have elaborate cognitive capacities for playing Hide & Seek. Playing Hide & Seek strongly engages medial prefrontal cortex and the activity of prefrontal cortex neurons reflects the structure of the game. We wondered if prefrontal neurons would also show a mirroring of play-related neural activity. Specifically, we asked how does the activity in the rat medial prefrontal cortex differ when the animal plays itself versus when it observes others playing. Consistent with our previous work, when the animal plays itself we observed medial prefrontal cortex activity that was sharply locked to game events. Observing play, however, did not lead to a compara-ble activation of rat medial prefrontal cortex. Firing rates during observing play were lower than during real play. The modulation of responses in medial prefrontal cortex by game events was strong during playing Hide & Seek, but weak during observing Hide & Seek. We conclude the rat prefrontal cortex does not mirror play events under our experimental conditions.

This study linked the fermentation index of two varieties of cocoa beans: CCN 51 and ICS 6 with electrical conductivity (EC) of the water where they were immersed using a laboratory conductimeter. Mixtures of 11 fermented cocoa beans and unfermented were performed in order to obtain fermentation index from 0% (unfermented beans) to that reached by the fermented cocoa beans. Immersion times tested for determination of the electrical conductivity were 90 and 180 minutes. The results of electrical conductivity for CCN 51 and ICS 6 were 56.1 ± 12.0 to 1375.0 ± 28.0 mS/cm and 150.0 ± 19.9 to 1199.3 ± 44.5 mS/cm, respectively. Subsequent conductivity values ​​did not represent significant increases over time. The relationship between the fermentation index and electrical conductivity for CCN 51 showed positive trend, achieving a R2 = 63.1%. The following function by regression: EC (CCN-51) = 1196 + 10.83 * (FI) – 0.06 *(FI)2 got a model with significant adjustment to be used to determine its fermentation index.

Presence of diabetes (types 1 and 2) increases the risk of atherosclerotic cardiovascular disease. Despite adequate metabolic control and treatment of vascular risk factors until the goals recommended by the clinical practice guidelines are achieved, residual cardiovascular risk may be very high in some patients with diabetes. Stratifying the vascular risk for each patient as precisely as possible is therefore necessary. Consolidated strategies to improve patient prognosis include aggressive reduction of LDL cholesterol, blood pressure control, achievement of the best HbA1c control possible without inducing hypoglycemia, use of hypoglycemic drugs shown to have cardiovascular benefits, and use of platelet aggregation inhibitors in patients with greater initial risk. Emerging strategies for patients with very high or extreme risk would include use of drugs intended to decrease triglyceride-rich lipoproteins and inflammation.

Background Culicoides biting midges transmit viruses resulting in disease in ruminants and equids such as bluetongue, Schmallenberg disease and African horse sickness. In the past decades, these diseases have led to important economic losses for farmers in Europe. Vector abundance is a key factor in determining the risk of vector-borne disease spread and it is, therefore, important to predict the abundance of Culicoides species involved in the transmission of these pathogens. The objectives of this study were to model and map the monthly abundances of Culicoides in Europe. Methods We obtained entomological data from 904 farms in nine European countries (Spain, France, Germany, Switzerland, Austria, Poland, Denmark, Sweden and Norway) from 2007 to 2013. Using environmental and climatic predictors from satellite imagery and the machine learning technique Random Forests, we predicted the monthly average abundance at a 1 km2 resolution. We used independent test sets for validation and to assess model performance. Results The predictive power of the resulting models varied according to month and the Culicoides species/ensembles predicted. Model performance was lower for winter months. Performance was higher for the Obsoletus ensemble, followed by the Pulicaris ensemble, while the model for Culicoides imicola showed a poor performance. Distribution and abundance patterns corresponded well with the known distributions in Europe. The Random Forests model approach was able to distinguish differences in abundance between countries but was not able to predict vector abundance at individual farm level. Conclusions The models and maps presented here represent an initial attempt to capture large scale geographical and temporal variations in Culicoides abundance. The models are a first step towards producing abundance inputs for R0 modelling of Culicoides-borne infections at a continental scale.

Photosensitised biphotonic irradiation of DNA has been rarely addressed, probably due to the difficulties in the experimental design. This is associated with the selection of nucleobases and sensitisers with appropriate absorption spectra and photochemical reactivity, in combination with a laser source emitting intense UVA light of the adequate wavelength. The present paper presents a new strategy involving absorption of a first UVA photon by an adequate sensitiser followed by triplet energy transfer to a pyrimidine (Pyr) derivative and absorption of a second UVA photon by the resulting Pyr triplet excited state. The feasibility of the proposed strategy has been demonstrated using two model reactions: (i) the Norrish-Yang photocyclisation of a tert-butyluracil and (ii) the photohydration of its uracil analogue, lacking the tert-butyl substituent., Financial support by the Spanish Government (O. R-A. for FPU14/05294) and Generalitat Valenciana (PROMETEO/2017/075) is gratefully acknowledged. We also thank Dr Lhiaubet-Vallet for her help with the UPLC-MS/MS experiments.