Characterization of the Effect of N-(2-Methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, Compound 8, against Leishmania mexicana and Its In Vivo Leishmanicidal Activity.

Chemotherapy currently available for leishmaniasis treatment has many adverse side effects and drug resistance. Therefore, the identification of new targets and the development of new drugs are urgently needed. Previously, we reported the synthesis of a N-(2-methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, named compound 8, with an IC50 value in the micromolar range against L. mexicana, it also inhibited 68.27% the activity of recombinant L. mexicana arginase. Herein, we report studies carried out to characterize the mechanism of action of compound 8, as well as its in vivo leishmanicidal activity. It was shown in our ultrastructural studies that compound 8 induces several changes, such as membrane blebbing, the presence of autophagosomes, membrane detachment and mitochondrial and kinetoplast disorganization, among others. Compound 8 triggers the production of ROS and parasite apoptosis. It reduced 71% of the parasite load of L. mexicana in an experimental model of cutaneous leishmaniasis in comparison with a control. Altogether, the data obtained suggest the potential use of compound 8 in the treatment of cutaneous leishmaniasis.

Structure-Based Optimization of Carbendazim-Derived Tubulin Polymerization Inhibitors through Alchemical Free Energy Calculations.

Carbendazim derivatives, commonly used as antiparasitic drugs, have shown potential as anticancer agents due to their ability to induce cell cycle arrest and apoptosis in human cancer cells by inhibiting tubulin polymerization. Crystallographic structures of α/ß-tubulin multimers complexed with nocodazole and mebendazole, two carbendazim derivatives with potent anticancer activity, highlighted the possibility of designing compounds that occupy both benzimidazole- and colchicine-binding sites. In addition, previous studies have demonstrated that the incorporation of a phenoxy group at position 5/6 of carbendazim increases the antiproliferative activity in cancer cell lines. Despite the significant progress made in identifying new tubulin-targeting anticancer compounds, further modifications are needed to enhance their potency and safety. In this study, we explored the impact of modifying the phenoxy substitution pattern on antiproliferative activity. Alchemical free energy calculations were used to predict the binding free energy difference upon ligand modification and define the most viable path for structure optimization. Based on these calculations, seven compounds were synthesized and evaluated against lung and colon cancer cell lines. Our results showed that compound 5a, which incorporates an α-naphthyloxy substitution, exhibits the highest antiproliferative activity against both cancer lines (SK-LU-1 and SW620, IC50 < 100 nM) and induces morphological changes in the cells associated with mitotic arrest and mitotic catastrophe. Nevertheless, the tubulin polymerization assay showed that 5a has a lower inhibitory potency than nocodazole. Molecular dynamics simulations suggested that this low antitubulin activity could be associated with the loss of the key H-bond interaction with V236. This study provides insights into the design of novel carbendazim derivatives with anticancer activity.

Anti-Diabetic Activity of Glycyrrhetinic Acid Derivatives FC-114 and FC-122: Scale-Up, In Silico, In Vitro, and In Vivo Studies.

Type 2 diabetes (T2D) is one of the most common diseases and the 8th leading cause of death worldwide. Individuals with T2D are at risk for several health complications that reduce their life expectancy and quality of life. Although several drugs for treating T2D are currently available, many of them have reported side effects ranging from mild to severe. In this work, we present the synthesis in a gram-scale as well as the in silico and in vitro activity of two semisynthetic glycyrrhetinic acid (GA) derivatives (namely FC-114 and FC-122) against Protein Tyrosine Phosphatase 1B (PTP1B) and α-glucosidase enzymes. Furthermore, the in vitro cytotoxicity assay on Human Foreskin fibroblast and the in vivo acute oral toxicity was also conducted. The anti-diabetic activity was determined in streptozotocin-induced diabetic rats after oral administration with FC-114 or FC-122. Results showed that both GA derivatives have potent PTP1B inhibitory activity being FC-122, a dual PTP1B/α-glucosidase inhibitor that could increase insulin sensitivity and reduce intestinal glucose absorption. Molecular docking, molecular dynamics, and enzymatic kinetics studies revealed the inhibition mechanism of FC-122 against α-glucosidase. Both GA derivatives were safe and showed better anti-diabetic activity in vivo than the reference drug acarbose. Moreover, FC-114 improves insulin levels while decreasing LDL and total cholesterol levels without decreasing HDL cholesterol.

Nestling sex ratio is unaffected by individual and population traits in the griffon vulture.

Variation in offspring sex ratios is a central topic in animal demography and population dynamics. Most studies have focused on bird species with marked sexual dimorphism and multiple-nestling broods, where the offspring sex ratio is often biased due to different individual or environmental variables. However, biases in offspring sex ratios have been far less investigated in monomorphic and single-egg laying species, and few studies have evaluated long-term and large-scale variations in the sex ratio of nestling vultures. Here, we explore individual and environmental factors potentially affecting the secondary sex ratio of the monomorphic griffon vulture Gyps fulvus. We used information collected at three breeding nuclei from central Spain over a 30-year period (1990-2020) to analyse the effects of nestling age, parental age, breeding phenology, conspecific density, population reproductive parameters, and spatial and temporal variability on nestling sex. Sex ratio did not differ from parity either at the population or the nuclei level. No significant between-year differences were detected, even under highly changing conditions of food availability associated with the mad-cow crisis. We found that tree nesting breeders tend to have more sons than daughters, but as this nesting behavior is rare and we consequently have a small sample size, this issue would require additional examination. Whereas further research is needed to assess the potential effect of breeder identity on nestling sex ratio, this study contributes to understanding the basic ecology and population dynamics of Griffon Vultures, a long-lived species with deferred maturity and low fecundity, whose minor deviations in the offspring sex ratio might imply major changes at the population level.

Large-scale movement patterns in a social vulture are influenced by seasonality, sex, and breeding region.

Quantifying space use and segregation, as well as the extrinsic and intrinsic factors affecting them, is crucial to increase our knowledge of species-specific movement ecology and to design effective management and conservation measures. This is particularly relevant in the case of species that are highly mobile and dependent on sparse and unpredictable trophic resources, such as vultures. Here, we used the GPS-tagged data of 127 adult Griffon Vultures Gyps fulvus captured at five different breeding regions in Spain to describe the movement patterns (home-range size and fidelity, and monthly cumulative distance). We also examined how individual sex, season, and breeding region determined the cumulative distance traveled and the size and overlap between consecutive monthly home-ranges. Overall, Griffon Vultures exhibited very large annual home-range sizes of 5027 ± 2123 km2, mean monthly cumulative distances of 1776 ± 1497 km, and showed a monthly home-range fidelity of 67.8 ± 25.5%. However, individuals from northern breeding regions showed smaller home-ranges and traveled shorter monthly distances than those from southern ones. In all cases, home-ranges were larger in spring and summer than in winter and autumn, which could be related to difference in flying conditions and food requirements associated with reproduction. Moreover, females showed larger home-ranges and less monthly fidelity than males, indicating that the latter tended to use the similar areas throughout the year. Overall, our results indicate that both extrinsic and intrinsic factors modulate the home-range of the Griffon Vulture and that spatial segregation depends on sex and season at the individual level, without relevant differences between breeding regions in individual site fidelity. These results have important implications for conservation, such as identifying key threat factors necessary to improve management actions and policy decisions.

Cuantificar el uso y la segregación del espacio, así como los factores extrínsecos e intrínsecos que los afectan, es crucial para aumentar nuestro conocimiento de la ecología de movimientos de cada especie y diseñar medidas eficaces de gestión y conservación. Esto es especialmente relevante en el caso de especies con gran movilidad y dependientes de recursos tróficos escasos e impredecibles, como son los buitres. En este trabajo se utilizaron datos GPS de 127 buitres leonados Gyps fulvus adultos capturados en cinco regiones de cría diferentes en España para describir los patrones de movimiento (tamaño y fidelidad del área de campeo y distancia acumulada mensual). También examinamos cómo el sexo, la estación del año y la región de cría determinaban la distancia acumulada recorrida y el tamaño y solapamiento entre áreas de campeo mensuales consecutivas. En conjunto, los buitres leonados mostraron un área de campeo anual muy extensa de 5027 ± 2123 km2, una distancia acumulada mensual media de 1776 ± 1497 km y una fidelidad mensual al área de campeo del 67.8 ± 25.5%. Sin embargo, los individuos de las regiones de cría más septentrionales mostraron áreas de campeo más pequeñas y recorrieron distancias mensuales más cortas que los de las más meridionales. En todos los casos, las áreas de campeo fueron mayores en primavera y verano que en otoño e invierno, lo que podría estar relacionado con las diferencias en las condiciones de vuelo y las necesidades tróficas asociadas a la reproducción. Además, las hembras mostraron mayores áreas de campeo y menor fidelidad mensual que los machos, lo que indica que estos últimos tienden a utilizar zonas similares durante todo el año. En conjunto, nuestros resultados indican que tanto los factores extrínsecos como los intrínsecos modulan el área de campeo del buitre leonado y que la segregación espacial depende del sexo y de la estación a nivel individual, sin que existan diferencias relevantes entre las regiones de cría en cuanto a la fidelidad individual al lugar. Estos resultados podrían tener importantes implicaciones para la conservación, como la identificación de los principales factores necesarios para mejorar las medidas de gestión y las decisiones políticas.

Resiliencia y el síndrome de desgaste profesional en enfermeras del Instituto Nacional de Salud del Niño, Lima, 2019 / Resilience and burnout syndrome in nurses of the National Institute of Children's Health, Lima, 2019

Las enfermeras que laboran en el servicio de emergencia y cuidados críticos están expuestas a entornos estresantes siendo vulnerables al síndrome de desgaste profesional. El presente artículo describe las pautas para determinar la relación entre la resiliencia y el síndrome de desgaste profesional en enfermeras del área de servicios críticos del Instituto Nacional de Salud del Niño, Lima, 2019, cuya metodología consiste en el estudio observacional y transversal realizado en enfermeras que laboran en el área de servicios críticos. Se usaron los instrumentos Maslach Burnout Inventory y la Escala de Resiliencia de Wagnild y Young. Para el análisis estadístico, se utilizó el procedimiento de las ecuaciones estructurales ­ SEM, por medio del ajuste de máxima verosimilitud, para lograr obtener las cargas factoriales entre las variables.

A rare complication of jejunal extension of a percutaneous endoscopic gastrostomy tube for levodopa-carbidopa intestinal gel administration.

Direct intestinal administration of levodopa-carbidopa gel has shown good results in selected patients with Parkinson's disease (1, 2). We want to present a complication related to the device necessary for the administration of this drug. A 58-year-old man, diagnosed with Parkinson's disease, treated for six months with levodopa-carbidopa intestinal gel, administered through a percutaneous endoscopic gastrostomy (PEG) tube with jejunal extension, presented at the emergency department for abdominal pain. The patient complained abdominal discomfort that lasted two months. It was described as pain around the umbilical area that radiated to the left lumbar region, worsened after ingestion, and did not subside with conventional analgesia.

Long-term demographic dynamics of a keystone scavenger disrupted by human-induced shifts in food availability.

Scavenging is a key ecological process controlling energy flow in ecosystems and providing valuable ecosystem services worldwide. As long-lived species, the demographic dynamics of vultures can be disrupted by spatiotemporal fluctuations in food availability, with dramatic impacts on their population viability and the ecosystem services provided. In Europe, the outbreak of bovine spongiform encephalopathy (BSE) in 2001 prompted a restrictive sanitary regulation banning the presence of livestock carcasses in the wild on a continental scale. In long-lived vertebrate species, the buffering hypothesis predicts that the demographic traits with the largest contribution to population growth rate should be less temporally variable. The BSE outbreak provides a unique opportunity to test for the impact of demographic buffering in a keystone scavenger suffering abrupt but transient food shortages. We studied the 42-year dynamics (1979-2020) of one of the world's largest breeding colonies of Eurasian griffon vultures (Gyps fulvus). We fitted an inverse Bayesian state-space model with density-dependent demographic rates to the time series of stage-structured abundances to investigate shifts in vital rates and population dynamics before, during, and after the implementation of a restrictive sanitary regulation. Prior to the BSE outbreak the dynamics was mainly driven by adult survival: 83% of temporal variance in abundance was explained by variability in this rate. Moreover, during this period the regulation of population size operated through density-dependent fecundity and subadult survival. However, after the onset of the European ban, a 1-month delay in average laying date, a drop in fecundity, and a reduction in the number of fledglings induced a transient increase in the impact of fledgling and subadult recruitment on dynamics. Although adult survival rate remained constantly high, as predicted by the buffering hypothesis, its relative impact on the temporal variance in abundance dropped to 71% during the sanitary regulation and to 54% after the ban was lifted. A significant increase in the relative impact of environmental stochasticity on dynamics was modeled after the BSE outbreak. These results provide empirical evidence on how abrupt environmental deterioration may induce dramatic demographic and dynamic changes in the populations of keystone scavengers, with far-reaching impacts on ecosystem functioning worldwide.

Incidence, Clinical Characteristics, Risk Factors, and Outcomes of Upper Gastrointestinal Bleeding in Patients With COVID-19: Results of the UMC-19-S12.

OBJECTIVE: The authors investigated the incidence, risk factors, clinical characteristics, and outcomes of upper gastrointestinal bleeding (UGB) in patients with coronavirus disease 2019 (COVID-19), who were attending the emergency department (ED), before hospitalization. METHODS: We retrospectively reviewed all COVID-19 patients diagnosed with UGB in 62 Spanish EDs (20% of Spanish EDs, case group) during the first 2 months of the COVID-19 outbreak. We formed 2 control groups: COVID-19 patients without UGB (control group A) and non-COVID-19 patients with UGB (control group B). Fifty-three independent variables and 4 outcomes were compared between cases and controls. RESULTS: We identified 83 UGB in 74,814 patients with COVID-19 who were attending EDs (1.11%, 95% CI=0.88-1.38). This incidence was lower compared with non-COVID-19 patients [2474/1,388,879, 1.78%, 95% confidence interval (CI)=1.71-1.85; odds ratio (OR)=0.62; 95% CI=0.50-0.77]. Clinical characteristics associated with a higher risk of COVID-19 patients presenting with UGB were abdominal pain, vomiting, hematemesis, dyspnea, expectoration, melena, fever, cough, chest pain, and dysgeusia. Compared with non-COVID-19 patients with UGB, COVID-19 patients with UGB more frequently had fever, cough, expectoration, dyspnea, abdominal pain, diarrhea, interstitial lung infiltrates, and ground-glass lung opacities. They underwent fewer endoscopies in the ED (although diagnoses did not differ between cases and control group B) and less endoscopic treatment. After adjustment for age and sex, cases showed a higher in-hospital all-cause mortality than control group B (OR=2.05, 95% CI=1.09-3.86) but not control group A (OR=1.14, 95% CI=0.59-2.19) patients. CONCLUSIONS: The incidence of UGB in COVID-19 patients attending EDs was lower compared with non-COVID-19 patients. Digestive symptoms predominated over respiratory symptoms, and COVID-19 patients with UGB underwent fewer gastroscopies and endoscopic treatments than the general population with UGB. In-hospital mortality in COVID-19 patients with UGB was increased compared with non-COVID patients with UGB, but not compared with the remaining COVID-19 patients.

A bacteraemia risk prediction model: development and validation in an emergency medicine population.

OBJECTIVE: Design a risk model to predict bacteraemia in patients attended in emergency departments (ED) for an episode of infection. METHODS: This was a national, prospective, multicentre, observational cohort study of blood cultures (BC) collected from adult patients (≥ 18 years) attended in 71 Spanish EDs from October 1 2019 to March 31, 2020. Variables with a p value < 0.05 were introduced in the univariate analysis together with those of clinical significance. The final selection of variables for the scoring scale was made by logistic regression with selection by introduction. The results obtained were internally validated by dividing the sample in a derivation and a validation cohort. RESULTS: A total of 4,439 infectious episodes were included. Of these, 899 (20.25%) were considered as true bacteraemia. A predictive model for bacteraemia was defined with seven variables according to the Bacteraemia Prediction Model of the INFURG-SEMES group (MPB-INFURG-SEMES). The model achieved an area under the curve-receiver operating curve of 0.924 (CI 95%:0.914-0.934) in the derivation cohort, and 0.926 (CI 95%: 0.910-0.942) in the validation cohort. Patients were then split into ten risk categories, and had the following rates of risk: 0.2%(0 points), 0.4%(1 point), 0.9%(2 points), 1.8%(3 points), 4.7%(4 points), 19.1% (5 points), 39.1% (6 points), 56.8% (7 points), 71.1% (8 points), 82.7% (9 points) and 90.1% (10 points). Findings were similar in the validation cohort. The cut-off point of five points provided the best precision with a sensitivity of 95.94%, specificity of 76.28%, positive predictive value of 53.63% and negative predictive value of 98.50%. CONCLUSION: The MPB-INFURG-SEMES model may be useful for the stratification of risk of bacteraemia in adult patients with infection in EDs, together with clinical judgement and other variables independent of the process and the patient.

Correlación entre el estado nutricional y nivel de actividad física en escolares del sur de Sonora, México / Correlation between nutritional status and level of physical activity in School children from southern sonora, México

Resumen Rojo Villa, J.A., Rojo Villa, L.G., y Martínez Félix, J. (2021). Correlación entre el estado nutricional y nivel de actividad física en escolares del sur de Sonora, México. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 19(2), 1-14. La falta de actividad física y presencia de malnutrición son factores importantes que comprometen la salud de toda la población. El estudio tuvo como propósito determinar el grado de asociación entre el estado nutricional y el nivel de actividad física en escolares del sur del estado de Sonora, México. El estudio es de tipo cuantitativo, descriptivo y transversal. La muestra está conformada por 156 estudiantes de nivel primaria ambos sexos (mujeres 48.71% y hombres 51.28%), con rango de edad de 10 a 12 años (10.86 ± 1.56). Las variables evaluadas fueron: nivel de actividad física con el cuestionario PAQ-C, estado nutricional utilizando los percentiles e IMC/E con referencias de la OMS en el año 2007. Los principales resultados indican que el 3.20% de los escolares cuenta con bajo peso; por otra parte, el sobrepeso y obesidad en conjunto suman 19.86% y predomina el sexo masculino con mayor número de casos: el 23.76% cuenta con niveles moderados de actividad física; el sexo femenino cuenta con mayor presencia en los niveles bajos y muy bajos. Se encontró una correlación inversa significativa entre el estado nutricional y nivel de actividad física, tanto en el sexo femenino (r = -0.19; p = .003) como en el masculino (r = -0.55; p < .0001). En conclusión, la asociación entre malnutrición y bajos niveles de actividad física podrían ser considerados para establecer estrategias preventivas y de intervención.

Abstract Rojo Villa, J.A., Rojo Villa, L.G., & Martínez Félix, J. (2021). Correlation between nutritional status and level of physical activity in school children from southern Sonora, México. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 19(2), 1-14. The lack of physical activity and malnutrition are important factors that compromise the health of the entire population. The purpose of the study is to determine the degree of association between the nutritional status and the level of physical activity in school children in southern Sonora, Mexico. The study is quantitative, descriptive, and cross-sectional. The sample is comprised of elementary students of both sexes (female 48.71% and male 51.28%) with ages ranging between 10 and 12 years (10.86 ± 1.56). The evaluated variables included level of physical activity with the PAQ-C questionnaire and nutritional status using BMI/Age percentiles from WHO in 2007. Main results indicate that 3.20% of school children are underweight, while overweight and obesity combined add up to 19.86%, with males having the highest number of cases (23.76% with moderate levels of physical activity) and females having a greater presence at low and very low levels. A significant inverse correlation was found between nutritional status and level of physical activity in both females (r = -0.19; p = .003) and males (r = -0.55; p < .0001). In conclusion, the association between malnutrition and low levels of physical activity could be considered to establish preventive and intervention strategies.

Resumo Rojo Villa, J.A., Rojo Villa, L.G., & Martínez Félix, J. (2021). Correlação entre estado nutricional e nível de atividade física em estudantes do sul de Sonora, México. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 19(2), 1-14. A falta de atividade física e a presença de desnutrição são fatores importantes que comprometem a saúde de toda a população. O objetivo do estudo foi determinar o grau de associação entre o estado nutricional e o nível de atividade física em estudantes do estado de Sonora, no sul do México. O estudo é quantitativo, descritivo e transversal. A amostra é composta por 156 estudantes do ensino fundamental de ambos os sexos (mulheres 48,71% e homens 51,28%), com faixa etária de 10 a 12 anos (10,86 ± 1,56). As variáveis avaliadas foram: nível de atividade física com o questionário PAQ-C, estado nutricional por meio de percentis e IMC/E com referências da OMS em 2007. Os principais resultados indicam que 3,20% dos alunos estão abaixo do peso; por outro lado, o sobrepeso e a obesidade juntos somam 19,86% e o sexo masculino predomina com o maior número de casos: 23,76% apresentam níveis moderados de atividade física; o sexo feminino tem maior presença nos níveis: baixo e muito baixo. Foi encontrada uma correlação inversa significativa entre o estado nutricional e o nível de atividade física, tanto no sexo feminino (r = -0,19; p = 0,003) quanto no masculino (r = -0,55; p <0,0001). Em conclusão, a associação entre desnutrição e os baixos níveis de atividade física pode ser considerada para o estabelecimento de estratégias preventivas e de intervenção.

Multilevel Approach for the Treatment of Giardiasis by Targeting Arginine Deiminase.

Giardiasis represents a latent problem in public health due to the exceptionally pathogenic strategies of the parasite Giardia lamblia for evading the human immune system. Strains resistant to first-line drugs are also a challenge. Therefore, new antigiardial therapies are urgently needed. Here, we tested giardial arginine deiminase (GlADI) as a target against giardiasis. GlADI belongs to an essential pathway in Giardia for the synthesis of ATP, which is absent in humans. In silico docking with six thiol-reactive compounds was performed; four of which are approved drugs for humans. Recombinant GlADI was used in enzyme inhibition assays, and computational in silico predictions and spectroscopic studies were applied to follow the enzyme's structural disturbance and identify possible effective drugs. Inhibition by modification of cysteines was corroborated using Ellman's method. The efficacy of these drugs on parasite viability was assayed on Giardia trophozoites, along with the inhibition of the endogenous GlADI. The most potent drug against GlADI was assayed on Giardia encystment. The tested drugs inhibited the recombinant GlADI by modifying its cysteines and, potentially, by altering its 3D structure. Only rabeprazole and omeprazole decreased trophozoite survival by inhibiting endogenous GlADI, while rabeprazole also decreased the Giardia encystment rate. These findings demonstrate the potential of GlADI as a target against giardiasis.

Synthesis and Cytotoxic Activity of Combretastatin A-4 and 2,3-Diphenyl-2H-indazole Hybrids.

Cancer is the second leading cause of death, after cardiovascular diseases. Different strategies have been developed to treat cancer; however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is still a serious problem, and the development of new active compounds remains a constant need. Taking advantage of the molecular hybridization approach, in the present work we designed, synthesized, and tested the cytotoxic activity of two hybrid compounds and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2H-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2H-indazole and 2,3-dipheny-2H-indazole derivatives under microwave irradiation were implemented. The cytotoxicity assays showed that our designed hybrid compounds possess strong activity, especially compound 5, which resulted even better than the reference drug cisplatin against HeLa and SK-LU-1 cells (IC50 of 0.16 and 6.63 µM, respectively), and it had similar potency to the reference drug imatinib against K562 cells. Additionally, in silico and in vitro studies strongly suggest tubulin as the molecular target for hybrid compound 5.

A Best Practices Case Study for Scientific Collaboration between Researchers and Managers.

Effective engagement among scientists, government agency staff, and policymakers is necessary for solving fisheries challenges, but remains challenging for a variety of reasons. We present seven practices learned from a collaborative project focused on invasive species in the Great Lakes region (USA-CAN). These practices were based on a researcher-manager model composed of a research team, a management advisory board, and a bridging organization. We suggest this type of system functions well when (1) the management advisory board is provided compelling rationale for engagement; (2) the process uses key individuals as communicators; (3) the research team thoughtfully selects organizations and individuals involved; (4) the funding entity provides logistical support and allows for (5) a flexible structure that prioritizes management needs; (6) a bridging organization sustains communication between in-person meetings; and (7) the project team determines and enacts a project endpoint. We predict these approaches apply equally effectively to other challenges at the research-management-policy interface, including reductions of water pollution, transitions to renewable energy, increasing food security, and addressing climate change.

A Tri-Band Cooled Receiver for Geodetic VLBI.

This paper shows a simultaneous tri-band (S: 2.2-2.7 GHz, X: 7.5-9 GHz and Ka: 28-33 GHz) low-noise cryogenic receiver for geodetic Very Long Baseline Interferometry (geo-VLBI) which has been developed at Yebes Observatory laboratories in Spain. A special feature is that the whole receiver front-end is fully coolable down to cryogenic temperatures to minimize receiver noise. It was installed in the first radio telescope of the Red Atlántica de Estaciones Geodinámicas y Espaciales (RAEGE) project, which is located in Yebes Observatory, in the frame of the VLBI Global Observing System (VGOS). After this, the receiver was borrowed by the Norwegian Mapping Autorithy (NMA) for the commissioning of two VGOS radiotelescopes in Svalbard (Norway). A second identical receiver was built for the Ishioka VGOS station of the Geospatial Information Authority (GSI) of Japan, and a third one for the second RAEGE VGOS station, located in Santa María (Açores Archipelago, Portugal). The average receiver noise temperatures are 21, 23, and 25 Kelvin and the measured antenna efficiencies are 70%, 75%, and 60% in S-band, X-band, and Ka-band, respectively.

Incidence, clinical characteristics, risk factors and outcomes of meningoencephalitis in patients with COVID-19.

We investigated the incidence, clinical characteristics, risk factors, and outcome of meningoencephalitis (ME) in patients with COVID-19 attending emergency departments (ED), before hospitalization. We retrospectively reviewed all COVID patients diagnosed with ME in 61 Spanish EDs (20% of Spanish EDs, COVID-ME) during the COVID pandemic. We formed two control groups: non-COVID patients with ME (non-COVID-ME) and COVID patients without ME (COVID-non-ME). Unadjusted comparisons between cases and controls were performed regarding 57 baseline and clinical characteristics and 4 outcomes. Cerebrospinal fluid (CSF) biochemical and serologic findings of COVID-ME and non-COVID-ME were also investigated. We identified 29 ME in 71,904 patients with COVID-19 attending EDs (0.40‰, 95%CI=0.27-0.58). This incidence was higher than that observed in non-COVID patients (150/1,358,134, 0.11‰, 95%CI=0.09-0.13; OR=3.65, 95%CI=2.45-5.44). With respect to non-COVID-ME, COVID-ME more frequently had dyspnea and chest X-ray abnormalities, and neck stiffness was less frequent (OR=0.3, 95%CI=0.1-0.9). In 69.0% of COVID-ME, CSF cells were predominantly lymphocytes, and SARS-CoV-2 antigen was detected by RT-PCR in 1 patient. The clinical characteristics associated with a higher risk of presenting ME in COVID patients were vomiting (OR=3.7, 95%CI=1.4-10.2), headache (OR=24.7, 95%CI=10.2-60.1), and altered mental status (OR=12.9, 95%CI=6.6-25.0). COVID-ME patients had a higher in-hospital mortality than non-COVID-ME patients (OR=2.26; 95%CI=1.04-4.48), and a higher need for hospitalization (OR=8.02; 95%CI=1.19-66.7) and intensive care admission (OR=5.89; 95%CI=3.12-11.14) than COVID-non-ME patients. ME is an unusual form of COVID presentation (<0.5‰ cases), but is more than 4-fold more frequent than in non-COVID patients attending the ED. As the majority of these MEs had lymphocytic predominance and in one patient SARS-CoV-2 antigen was detected in CSF, SARS-CoV-2 could be the cause of most of the cases observed. COVID-ME patients had a higher unadjusted in-hospital mortality than non-COVID-ME patients.