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Abstract Background Climate change is driving the occurrence of several infectious diseases. Within a One Health action to complement the ongoing preventive chemotherapy initiative against human fascioliasis in the Northern Bolivian Altiplano hyperendemic area, field surveys showed a geographical expansion of its lymnaeid snail vector. To assess whether climate change underlies this spread of the infection risk area, an in-depth analysis of the long-term evolution of climatic factors relevant for Fasciola hepatica development was imperative. Methods We used monthly climatic data covering at least a 30-year period and applied two climatic risk indices, the water-budget-based system and the wet–day index, both of verified usefulness for forecasting fascioliasis transmission in this endemic area. To reveal the long-term trends of the climatic factors and forecast indices, we applied procedures of seasonal-trend decomposition based on locally weighed regression and trend analysis on the basis of linear models. To further demonstrate the changes detected, we depicted selected variables in the form of anomalies. Results This study revealed a notorious climatic change affecting most of the hyperendemic area, with a strong impact on crucial aspects of the fascioliasis transmission. Trends in maximum and mean temperatures show significant increases throughout the endemic area, while trends in minimum temperatures are more variable. Precipitation annual trends are negative in most of the localities. Trends in climatic risk indices show negative trends at lower altitudes or when farther from the eastern Andean chain. However, monthly and yearly values of climatic risk indices indicate a permanent transmission feasibility in almost every location. Conclusions Warmer temperatures have enabled lymnaeids to colonize formerly unsuitable higher altitudes, outside the endemicity area verified in the 1990s. Further, drier conditions might lead to an overexploitation of permanent water collections where lymnaeids inhabit, favoring fascioliasis transmission. Therefore, the present preventive chemotherapy by annual mass treatments is in need to widen the area of implementation. This study emphasizes the convenience for continuous monitoring of nearby zones for quick reaction and appropriate action modification. Graphical Abstract

Abstract Background Common bean (Phaseolus vulgaris) is one of the main nutritional resources in the world, and a low environmental impact source of protein. However, the majority of its cultivation areas are affected by drought and this scenario is only expected to worsen with climate change. Stomatal closure is one of the most important plant responses to drought and the MYB60 transcription factor is among the key elements regulating stomatal aperture. If targeting and mutating the MYB60 gene of common bean would be a valuable strategy to establish more drought-tolerant beans was therefore investigated. Results The MYB60 gene of common bean, with orthology to the Arabidopsis AtMYB60 gene, was found to have conserved regions with MYB60 typical motifs and architecture. Stomata-specific expression of PvMYB60 was further confirmed by q-RT PCR on organs containing stomata, and stomata-enriched leaf fractions. Further, function of PvMYB60 in promoting stomata aperture was confirmed by complementing the defective phenotype of a previously described Arabidopsis myb60-1 mutant. Conclusions Our study finally points PvMYB60 as a potential target for obtaining more drought-tolerant common beans in the present context of climate change which would further greatly contribute to food security particularly in drought-prone countries.

Background: Species hybridization represents a real concern in terms of parasite transmission, epidemiology and morbidity of schistosomiasis. It is greatly important to better understand the impact of species hybridization for the clinical management. Methods: A prospective observational study was carried out in sub-Saharan migrants who were diagnosed with confirmed genitourinary schistosomiasis. A tailored protocol was applied, including Schistosoma serology, a specific urine LAMP tests for schistosomiasis and an ultrasound examination before treatment with praziquantel. A scheduled follow-up was performed at 3, 6 and 12 months to monitor treatment response, comparing patients carriers of Schistosoma hybrids with carriers of only genetically pure forms. Results: A total of 31 male patients from West Africa were included in the study with a mean age of 26.5 years. Twelve (38.7 %) of the patients were carriers of Schistosoma hybrids. As compared with patients infected with S. haematobium alone, hybrid carriers had lower haemoglobin levels (13.8 g/dL [SD 1.8] vs 14.8 g/dL [SD 1.4], p = 0.04), a greater frequency of hematuria (100 % vs 52.6 %, p = 0.005), a higher ultrasound score (2.64, SD 2.20 vs 0.89, SD 0.99; p = 0.02). However, the presence of hybrids did not result in differences in clinical and analytical responses after treatment. Conclusions: The presence of Schistosoma hybrids seems to cause increased morbidity in infected individuals. However, it does not appear to result in differences in diagnostic tests or in clinical and analytical responses after treatment.

Abstract Background The convergence of hypervirulence and carbapenem resistance in the bacterial pathogen Klebsiella pneumoniae represents a critical global health concern. Hypervirulent K. pneumoniae (hvKp) strains, frequently from sequence type 23 (ST23) and having a K1 capsule, have been associated with severe community-acquired invasive infections. Although hvKp were initially restricted to Southeast Asia and primarily antibiotic-sensitive, carbapenem-resistant hvKp infections are reported worldwide. Here, within the carbapenemase production Enterobacterales surveillance system headed by the Chilean Public Health Institute, we describe the isolation in Chile of a high-risk ST23 dual-carbapenemase-producing hvKp strain, which carbapenemase genes are encoded in a single conjugative plasmid. Results Phenotypic and molecular tests of this strain revealed an extensive resistance to at least 15 antibiotic classes and the production of KPC-2 and VIM-1 carbapenemases. Unexpectedly, this isolate lacked hypermucoviscosity, challenging this commonly used hvKp identification criteria. Complete genome sequencing and analysis confirmed the K1 capsular type, the KpVP-1 virulence plasmid, and the GIE492 and ICEKp10 genomic islands carrying virulence factors strongly associated with hvKp. Although this isolate belonged to the globally disseminated hvKp clonal group CG23-I, it is unique, as it formed a clade apart from a previously reported Chilean ST23 hvKp isolate and acquired an IncN KPC-2 plasmid highly disseminated in South America (absent in other hvKp genomes), but now including a class-I integron carrying bla VIM−1 and other resistance genes. Notably, this isolate was able to conjugate the double carbapenemase plasmid to an E. coli recipient, conferring resistance to 1st -5th generation cephalosporins (including combinations with beta-lactamase inhibitors), penicillins, monobactams, and carbapenems. Conclusions We reported the isolation in Chile of high-risk carbapenem-resistant hvKp carrying a highly transmissible conjugative plasmid encoding KPC-2 and VIM-1 carbapenemases, conferring resistance to most beta-lactams. Furthermore, the lack of hypermucoviscosity argues against this trait as a reliable hvKp marker. These findings highlight the rapid evolution towards multi-drug resistance of hvKp in Chile and globally, as well as the importance of conjugative plasmids and other mobile genetic elements in this convergence. In this regard, genomic approaches provide valuable support to monitor and obtain essential information on these priority pathogens and mobile elements.

Fascioliasis is a snail-borne zoonotic disease with impact on the development of human subjects and communities. It is caused by two liver-infecting fasciolid trematode species, the globally-distributed Fasciola hepatica and the Africa/Asia-restricted but more pathogenic, larger F. gigantica. Fasciola gigantica is the cause of endemicity in livestock throughout the warm lowlands from Pakistan to southeastern Asia since old times. Human fascioliasis is emerging in this region at present, with an increase of patient reports. Complete sequences of rDNA ITS-1 and ITS-2 spacers and mtDNA nad1 and cox1 genes were obtained from fasciolid eggs found in the endoscopic bile aspirate from a patient of Arunachal Pradesh, northeastern India. Egg measurements, pronounced ITS heterozygosity, and pure F. gigantica mtDNA haplotypes demonstrate an infection by a recent F. gigantica-like hybrid. Sequence identities and similarities with the same DNA markers found in livestock from Bangladesh prove the human-infecting fasciolid to present identical ITSs and nad1 haplotypes and only one silent transversion in cox1 when compared to a widely-spread combined haplotype in animals. In northeastern India and Bangladesh, human fascioliasis emergence appears linked to increasing livestock prevalences due to: ruminant importation from other countries because of the increasing demand of rapidly growing human populations; numerous livestock movements, including transborder corridors, due to the uncontrolled small-scale household farming practices; and man-made introduction of F. hepatica with imported livestock into an area originally endemic for F. gigantica leading to frequent hybridization. Sequences, phylogenetic trees, and networks indicate that the origins of intermediate/hybrid fasciolids and factors underlying human infection risk differ in eastern and western South Asia. The emergence scenario in southern China and Vietnam resembles the aforementioned of northeastern India and Bangladesh, whereas in Pakistan it is linked to increasing monsoon rainfall within climate change combined with an impact of an extensive irrigation system. Past human-guided movements of pack animals along the western Grand Trunk Road and the eastern Tea-Horse Road explain the F. gigantica mtDNA results obtained. Physicians should be aware about these emerging scenarios, clinical pictures, diagnostic techniques and treatment. Government authorities must appropriately warn health professionals, ensure drug availability and improve livestock control.

Frailty is a geriatric syndrome associated with the lack of physiological reserve and consequent adverse outcomes (therapy complications and death) in older adults. Recent research has shown associations between heart rate (HR) dynamics (HR changes during physical activity) with frailty. The goal of the present study was to determine the effect of frailty on the interconnection between motor and cardiac systems during a localized upper-extremity function (UEF) test. Fifty-six individuals aged 65 or above were recruited and performed the previously developed UEF test consisting of 20-s rapid elbow flexion with the right arm. Frailty was assessed using the Fried phenotype. Wearable gyroscopes and electrocardiography were used to measure motor function and HR dynamics. In this study, the interconnection between motor (angular displacement) and cardiac (HR) performance was assessed, using convergent cross-mapping (CCM). A significantly weaker interconnection was observed among pre-frail and frail participants compared to non-frail individuals (p < 0.01, effect size = 0.81 ± 0.08). Using logistic models, pre-frailty and frailty were identified with sensitivity and specificity of 82%–89%, using motor, HR dynamics, and interconnection parameters. Findings suggested a strong association between cardiac-motor interconnection and frailty. Adding CCM parameters in a multimodal model may provide a promising measure of frailty.

Introduction: A comprehensive pathophysiological mechanism to explain the relationship between high-salt intake and hypertension remains undefined. Evidence suggests that chloride, as the accompanying anion of sodium in dietary salt, is necessary to develop hypertension. We evaluated whether reducing dietary Cl− while keeping a standard Na+ intake modified blood pressure, cardiac hypertrophy, renal function, and vascular contractility after angiotensin II (AngII) infusion. Methods: C56BL/6J mice fed with standard Cl− diet or a low-Cl− diet (equimolar substitution of Cl− by a mixture of Na+ salts, both diets with standard Na+ content) received AngII (infusion of 1.5 mg/kg/day) or vehicle for 14 days. We measured systolic blood pressure (SBP), glomerular filtration rate (GFR), natriuretic response to acute saline load, and contractility of aortic rings from mice infused with vehicle and AngII, in standard and low-Cl− diet. Results: The mice fed the standard diet presented increased SBP and cardiac hypertrophy after AngII infusion. In contrast, low-Cl− diet prevented the increase of SBP and cardiac hypertrophy. AngII-infused mice fed a standard diet presented hampered natriuretic response to saline load, meanwhile the low-Cl− diet preserved natriuretic response in AngII-infused mice, without change in GFR. Aortic rings from mice fed with standard diet or low-Cl− diet and infused with AngII presented a similar contractile response. Conclusion: We conclude that the reduction in dietary Cl− as the accompanying anion of sodium in salt is protective from AngII pro-hypertensive actions due to a beneficial effect on kidney function and preserved natriuresis.

This paper aims to analyse the spatial interaction of Romanian Cities from 1948 to 2021 trying to perceive if, along seven decades of quite different political regimes - from Central Planning to Market Interaction-, there have been changes in the logic of spatial interaction between City Regions. The study looks into the economic-demographic evolution of Romanian city regions and tests whether, throughout time, adding to the role of the economic base, their evolution follows a logic of size maximization, or a logic of maximization of interaction flows subject to the spatial structure of Romanian cities. Results show that the logic of spatial interaction changed during the period. Except for the first periods from 1948-1956-1966, the spatial evolution of Romanian City Regions is better explained by a logic of size maximization, either in the period of Central Planning (1966-1992) or in the period of Market Interaction where the population of the previous period, or the logic of size maximization, has a strong effect in the relative performance of city-regions when compare with the logic of maximization of interaction flows. Furthermore, exports play a more reduced role in regional growth when space is appropriately integrated.

Background: The Chilean population has experienced increased longevity in recent decades, leading to an increased incidence of and mortality from neurodegenerative diseases such as Parkinson’s disease (PD). PD is a chronic degenerative condition that affects the central nervous system. The main objective of this research is to evaluate the effect of 12-week programs of tonic, isometric, and isometric/vibratory muscular strength training while controlling the manipulation of the intensity variable on motor and non-motor symptomatology in PD patients. The secondary objective is to assess the levels of muscular strength in PD patients and their relationship with motor and non-motor symptomatology. Methods: A parallel-group, randomized trial will randomly assign (n = 34) people of both sexes with Parkinson’s disease between stages I–III Hoehn and Yahr (H&Y), aged between 50 and 70 years to one of the experimental groups, in which they will undergo a total of 24 strength training sessions during 12 weeks. During the intervention period, the participants will be advised not to undertake additional exercise programs, to avoid substances that may disrupt metabolism and circadian cycles, and to maintain their medication regimen. The primary or motor evaluation of rest tremor will be performed with an accelerometer (Actigraphy), balance with the Mini-BESTest balance test, gait speed with the Ten Meters Walk Test, and non-motor symptomatology through anxiety, depression (MDS-UPDRS), and quality of life (PDQ-39) questionnaires. The Secondary evaluation of muscle strength will be performed with a functional electromechanical dynamometer. Discussion: Established as a hypothesis is that manipulating intensity variables in 12-week tonic, isometric, and isometric/vibratory muscle strength training programs has an effect on motor and non-motor symptomatology in people with Parkinson’s disease. The research will establish the extent to which controlled muscular strength training has an effect on relevant factors related to motor and non-motor symptomatology.

The purpose of the study was to analyze the test–retest reliability of an isometric and isometric/vibratory muscular strength protocol in the bilateral seated bench press (BSBP), bilateral seated rowing (BSR), unilateral seated right knee extension (USKER), and left knee extension (USKEL) tests controlled using functional electromechanical dynamometry (FEMD) in healthy young adults. A repeated measures design was used to determine the reliability of a muscular strength protocol in isometric and isometric vibration modes with FEMD. No significant differences were found in test–retest analysis (p > 0.05; ES < 0.20); and high reliability (CV = 4.65–5.02%; ICC = 0.99–0.98) was found for BSBP measures, and acceptable reliability (CV = 3.71–9.61%; ICC = 0.98–0.95) was found for BSR, USKER, and USKEL. Furthermore, the coefficients between the two measures were strong (r = 0.963–0.839) and highly significant (p = 0.001) for maximal strength in the isometric and maximal isometric/vibratory assessment of muscle strength in all muscle strength tests. This study demonstrates that isometric and maximal isometric/vibratory strength in the BSBP, BSR, USKER, and USKEL tests can be measured with high reliability and reproducibility using the FEMD.

Fascioliasis causes high economic losses in livestock and underlies public health problems in rural areas, mainly of low-income countries. The increasing animal infection rates in Bangladesh were assessed, by focusing on host species, different parts of the country, and rDNA sequences. Fasciolid flukes were collected from buffaloes, cattle, goats and sheep from many localities to assess prevalences and intensities of infection. The nuclear rDNA internal transcribed spacer (ITS) region including ITS-1 and ITS-2 spacers was analyzed by direct sequencing and cloning, given the detection of intermediate phenotypic forms in Bangladesh. The 35.4% prevalence in goats and 55.5% in buffaloes are the highest recorded in these animals in Bangladesh. In cattle (29.3%) and sheep (26.8%) prevalences are also high for these species. These prevalences are very high when compared to lowlands at similar latitudes in neighboring India. The high prevalences and intensities appear in western Bangladesh where cross-border importation of animals from India occur. The combined haplotype CH3A of Fasciola gigantica widely found in all livestock species throughout Bangladesh fits its historical connections with the western Grand Trunk Road and the eastern Tea-Horse Road. The “pure” F. hepatica sequences only in clones from specimens showing heterozygotic positions indicate recent hybridization events with local “pure” F. gigantica, since concerted evolution did not yet have sufficient time to homogenize the rDNA operon. The detection of up to six different sequences coexisting in the cloned specimens evidences crossbreeding between hybrid parents, indicating repeated, superimposed and rapidly evolving hybridization events. The high proportion of hybrids highlights an increasing animal infection trend and human infection risk, and the need for control measures, mainly concerning goats in household farming management. ITS-1 and ITS-2 markers prove to be useful for detecting recent hybrid fasciolids. The introduction of a Fasciola species with imported livestock into a highly prevalent area of the other Fasciola species may lead to a high nucleotide variation in the species-differing positions in the extremely conserved fasciolid spacers. Results suggest that, in ancient times, frequent crossbreeding inside the same Fasciola species gave rise to the very peculiar characteristics of the present-day nuclear genome of both fasciolids.

Resumen: Introducción: la integridad académica se define como la adopción por parte del estudiantado de valores que rigen su formación profesional como la honestidad, la confianza, la responsabilidad, el respeto y la justicia. En los programas de farmacia las faltas a la integridad académica llegan hasta el 90%, encontrándose entre los principales factores las razones socioeconómicas, personales y académicas. El objetivo de este estudio fue evaluar los factores que influyen en la integridad académica del alumnado de Química y Farmacia de la Universidad Católica del Norte. Métodos: estudio descriptivo de corte transversal, que incluyó al estudiantado de Química y Farmacia, a quienes se les aplicó una encuesta de 31 enunciados con respuesta en escala tipo Likert, que permitió recopilar los factores que influyen en la integridad académica. Resultados: de los 113 estudiantes, 60,2% fueron mujeres, edad promedio 23,1 ± 3,2 años y 16 (14,1%) correspondieron a las cohortes 2020-2021. Las principales motivaciones que percibió el alumnado para cometer actos deshonestos fueron razones «socioeconómicas, socioculturales y familiares» y «características personales», como el miedo a perder la beca, salir eliminado de la carrera o reprobar el curso. La comparación de las cohortes 2020-2021 con el resto de las generaciones evidenció diferencias significativas en las percepciones agrupadas en la categoría «socioeconómicas, socioculturales y familiares» (p = 0,002). Conclusión: reconocer las causas de la deshonestidad académica permiten focalizar la implementación de estrategias preventivas hacia el desarrollo de una cultura de integridad académica y de habilidades actitudinales de autoeficacia en el estudiantado, que contribuyan a una formación y desempeño ético profesional. Abstract: Introduction: Academic integrity is defined as the adoption by the student body of values that govern their professional training such as honesty, trust, fairness, respect, responsibility, and courage. In pharmacy programs, lack of academic integrity reaches up to 90%, with socioeconomic, personal, and academic reasons being among the main factors. The objective of this study was to evaluate the factors that influence academic integrity of Chemistry and Pharmacy students at the Universidad Católica del Norte. Methods: Descriptive cross - sectional study, which included Pharmacy students, to whom a survey of 31 statements with responses on a Likert-type scale was applied, which allowed us to collect the factors that influence academic integrity. Results: Out of a total of 113 students, 60.2% were female, average age of 23.1 ± 3.2 years, and 16 (14.1%) corresponded to the 2020-2021 cohorts. The main motivations to commit dishonest acts perceived by the students were “socioeconomic, socio-cultural and family” reasons as well as “personal characteristics”, such as the fear of losing scholarships, failing a course and fear of career failure. The comparison between 2020-2021 cohorts and the rest of the generations showed significant differences in the ''socioeconomic, sociocultural and family'' grouped perceptions category (p = 0.002). Conclusion: Recognizing the causes of academic dishonesty allows us to implement preventive strategies that focus towards the development of an academic integrity based culture and attitudinal skills of self-efficacy in the student body, which contribute to an ethical professional training and performance.

ABSTRACT Multidrug- and carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are critical threats to global health and key traffickers of resistance genes to other pathogens. Despite the sustained increase in CR-Kp infections in Chile, few strains have been described at the genomic level, lacking details of their resistance and virulence determinants and the mobile elements mediating their dissemination. In this work, we studied the antimicrobial susceptibility and performed a comparative genomic analysis of 10 CR-Kp isolates from the Chilean surveillance of carbapenem-resistant Enterobacteriaceae. High resistance was observed among the isolates (five ST25, three ST11, one ST45, and one ST505), which harbored 44 plasmids, most carrying genes for conjugation and resistance to several antibiotics and biocides. Ten plasmids encoding carbapenemases were characterized, including novel plasmids or variants with additional resistance genes, a novel genetic environment for bla KPC-2, and plasmids widely disseminated in South America. ST25 K2 isolates belonging to CG10224, a clone traced back to 2012 in Chile, which recently acquired bla NDM-1, bla NDM-7, or bla KPC-2 plasmids stood out as high-risk clones. Moreover, this corresponds to the first report of ST25 and ST45 Kp producing NDM-7 in South America and ST505 CR-Kp producing both NDM-7 and KPC-2 worldwide. Also, we characterized a variety of genomic islands carrying virulence and fitness factors. These results provide baseline knowledge for a detailed understanding of molecular and genetic determinants behind antibiotic resistance and virulence of CR-Kp in Chile and South America. IMPORTANCE In the ongoing antimicrobial resistance crisis, carbapenem-resistant strains of Klebsiella pneumoniae are critical threats to public health. Besides globally disseminated clones, the burden of local problem clones remains substantial. Although genomic analysis is a powerful tool for improving pathogen and antimicrobial resistance surveillance, it is still restricted in low- to middle-income countries, including Chile, causing them to be underrepresented in genomic databases and epidemiology surveys. This study provided the first 10 complete genomes of the Chilean surveillance for carbapenem-resistant K. pneumoniae in healthcare settings, unveiling their resistance and virulence determinants and the mobile genetic elements mediating their dissemination, placed in the South American and global K. pneumoniae epidemiological context. We found ST25 with K2 capsule as an emerging high-risk clone, along with other lineages producing two carbapenemases and several other resistance and virulence genes encoded in novel plasmids and genomic islands.

Context: The inappropriate use of antimicrobials is a public worldwide health problem that causes increased morbidity and mortality, bacterial resistance, and care costs and hospitalizations. Aims: To evaluate the prescription of antimicrobials in patients treated at a Cuban cancer hospital, based on clinical indicators and pharmacotherapeutics. Methods: Retrospective descriptive study of prescription-indication of antimicrobials, during the period of January-December 2018, in a Cuban cancer hospital. Hospitalized patients with antimicrobial treatment were included in the study. The determination of prevalent microorganisms and bacterial resistance was analyzed through the book of infection control and antibiograms. The adequate and inadequate categories of prescriptions based on clinical and pharmacotherapeutic indicators were established to evaluate the prescription. Results: In a sample of 50 patients, laryngeal cancer (40%), surgical wound infection (48%), and beta-lactam pharmacological group (46.4%) prevailed. Eight germs were isolated, with a predominance of Pseudomonas aeruginosa (26.3%) with gentamicin resistance (66.7%). Staphylococcus spp. presented resistance to ciprofloxacin (63.6%) and amikacin (54.5%). Escherichia coli exhibited resistance to gentamicin (66.7%) and ciprofloxacin (55.6%). Appropriate prescriptions predominated (52%), with the indicator ‘indication and therapeutic scheme’ being the most difficult. Conclusions: The inappropriate use of antimicrobials constitutes a problem in cancer patients and highlights the need to implement actions that contribute to raising the quality of prescriptions to prevent microbial resistance.

We demonstrate strong dispersive coupling between a fluxonium superconducting qubit and a 690 megahertz mechanical oscillator, extending the reach of circuit quantum acousto-dynamics (cQAD) experiments into a new range of frequencies. We have engineered a qubit-phonon coupling rate of g≈2π×14MHz, and achieved a dispersive interaction that exceeds the decoherence rates of both systems while the qubit and mechanics are highly nonresonant (Δ/g≳10). Leveraging this strong coupling, we perform phonon-number-resolved measurements of the mechanical resonator and investigate its dissipation and dephasing properties. Our results demonstrate the potential for fluxonium-based hybrid quantum systems, and a path for developing new quantum sensing and information processing schemes with phonons at frequencies below 700 MHz to significantly expand the toolbox of cQAD.

Salar de Ascotán is a high-altitude arsenic-rich salt flat exposed to high ultraviolet radiation in the Atacama Desert, Chile. It hosts unique endemic flora and fauna and is an essential habitat for migratory birds, making it an important site for conservation and protection. However, there is limited information on the resident microbiota’s diversity, genomic features, metabolic potential, and molecular mechanisms that enable it to thrive in this extreme environment. We used long- and short-read metagenomics to investigate the microbial communities in Ascotán’s water, sediment, and soil. Bacteria predominated, mainly Pseudomonadota, Acidobacteriota, and Bacteroidota, with a remarkable diversity of archaea in the soil. Following hybrid assembly, we recovered high-quality bacterial (101) and archaeal (6) metagenome-assembled genomes (MAGs), including representatives of two putative novel families of Patescibacteria and Pseudomonadota and two novel orders from the archaeal classes Halobacteriota and Thermoplasmata. We found different metabolic capabilities across distinct lineages and a widespread presence of genes related to stress response, DNA repair, and resistance to arsenic and other metals. These results highlight the remarkable diversity and taxonomic novelty of the Salar de Ascotán microbiota and its rich functional repertoire, making it able to resist different harsh conditions. The highly complete MAGs described here could serve future studies and bioprospection efforts focused on salt flat extremophiles, and contribute to enriching databases with microbial genome data from underrepresented regions of our planet.

La investigación tuvo como propósito analizar la formación en competencias investigativas en tiempos de COVID-19 en el área contable en el contexto de la Universidad Técnica Luis Vargas Torres, de Esmeraldas, Ecuador. El enfoque fue cualitativo, bajo el método fenomenológico, los informantes clave fueron los estudiantes de la carrera contabilidad de la Universidad, realizando un muestreo intencional basado en criterios. La técnica de recolección de datos aplicada fue la entrevista y la triangulación para la validez interna, el procedimiento realizado fue a través de las etapas del método fenomenológico, y la técnica para el análisis de resultados fue la categorización. Entre los resultados surgen dos categorías emergentes: formación desde la virtualidad y la vinculación con el área contable. Se concluye que, ante la interrupción de las actividades educativas como consecuencia de la emergencia sanitaria por el COVID-19, surge un escenario para la investigación con base en la formación de competencias investigativas, proceso mediado por la virtualidad para aprender los distintos paradigmas y métodos cuya aplicación permita al estudiante obtener resultados coherentes con el área contable, con la realimentación necesaria para garantizar la sostenibilidad del proceso durante la pandemia y en tiempos de post pandemia. The purpose of the research was to analyze the training in research competences in times of COVID-19 in the accounting area in the context of the Luis Vargas Torres Technical University, from Esmeraldas, Ecuador. The approach was qualitative, under the phenomenological method, the key informants were the accounting students of the University, carrying out an intentional sampling based on criteria. The data collection technique applied was the interview and triangulation for internal validity, the procedure carried out was through the stages of the phenomenological method, the technique for the analysis of results was the categorization. Among the results, two emerging categories emerge: training from virtuality and the link with the accounting area. It is concluded that, given the interruption of educational activities as a result of the health emergency caused by COVID-19, a scenario for research arises based on the formation of investigative competences, a process mediated by virtuality to learn the different paradigms and methods whose the application allows the student to obtain consistent results with the accounting area, with the necessary feedback to guarantee the sustainability of the process during the pandemic and in post-pandemic times.

An improved numerical formulation for a self-centering frictional damper is presented. This was experimentally validated through quasi-static tests carried out on a steel-made prototype of the damper. Its design is ad hoc for implementation in the seismic protection of industrial storage racks. The conceptual model of the device was adjusted to the prototype built. The formulation of the analytical model, a parametric analysis of it, and the validation with experimental results are presented. The improvement of the model presented here explicitly considers elements included in the prototype, such as a system of load transmission rings and the friction between all of the components that slide or rotate relatively. In the experimental validation, the parameters of the improved model were determined. The numerical predictions for the improved model were contrasted with those obtained with the original one and with the experimental results. This demonstrates that the improvement leads to a better adjustment of the numerical predictions concerning the experimental measurements, which is useful for nonlinear analysis. The device withstood forces of considerable magnitude in addition to dissipating enough energy per load–unload cycle to be effective in the seismic protection of industrial storage racks.

This paper departs from the regional resilience concept - as part of a broad strand of literature on non-linear dynamic systems in a space-economy - and introduces the notion of prosilience to highlight the policy challenge of developing radically new and innovative strategies for regions in decline. The mining industry will be used as an illustrative case. The notion of phoenix regions is put forward to argue that an external disruption or shock in an established industrial sector in a region necessitates unconventional survival strategies oriented towards entirely new market demands and based on totally different product packages. Ansoff's model on product diversification in competitive markets forms an inspiration source for the Schumpeterian 'creative destruction' proposition advocated in this study. An illustrative case study is concisely described in the present paper, viz. the South-Limburg coal mining region in the Southern part of the Netherlands. Smart prosilience trajectories supported in particular by evidence-based decision support tools are sketched for such depressed regions, based on the so-called Pentagon intervention model. The paper is concluded with some general policy lessons for an intelligent transformation of regions in decline.

In recent studies, primary aldosteronism (PA) has been reported as the most common etiology for secondary hypertension of endocrine origin, accounting for approximately 10% of cases. In PA, excess aldosterone production can lead to deleterious effects at the cardiovascular (CV) and renal levels by activating mineralocorticoid receptors, which involves an increase in pro-inflammatory and pro-fibrotic mediators. Among these mediators, neutrophil gelatinase–associated lipocalin (NGAL), a secretion glycoprotein belonging to the lipocalin superfamily, has been closely linked to CV and renal damage in several pathological conditions. Because NGAL can be detected in biofluids such as plasma and urine, it has been proposed as a damage biomarker for target tissues and has also been studied for its role in hypertension and associated with PA. NGAL is produced by many different cell types, can be carried on extracellular vesicles, and is modulated by microRNAs, which would support its use as a biomarker for endocrine hypertension due to PA. Over the last decade, studies have shown that NGAL is necessary for the development of aldosterone-induced hypertension and that is associated with end-organ damage. In addition, it has been proposed that some mechanisms are dependent on the activation of immune cells, such as dendritic cells and macrophages, where the release of specific cytokines (i.e., interleukin [IL]-23) or chemokines (i.e., CCL-5) induced by aldosterone would depend on NGAL. Subsequently, this activates the T helper (Th) lymphocytes, such as Th17 and Th2, resulting in CV and renal fibrosis due to the high aldosterone levels. Although the immune system has been closely associated with essential hypertension, its participation in endocrine hypertension has not been fully elucidated. This review discusses the link between NGAL and endocrine hypertension, particularly in the context of PA, and their possible regulators and mechanisms, with a focus on its role as an immunomodulator.

Grapevine is a fruit crop of major significance worldwide. Fungal attacks are one of the most relevant factors affecting grapevine yield and fruit quality, and powdery mildew caused by Erysiphe necator is one of the most harmful fungal diseases for this fruit-bearing species. Incorporating resistance genes such as Run1 and Ren1 in new vine selections offers a sustainable alternative to control the disease. These combined loci produce an immune response that prevents the development of the disease. However, to date studies are lacking concerning whether this response generates alterations in the physiological and antioxidant parameters of resistant plants in the presence of the fungus or if it has an associated energy cost. Therefore, the main goal of our research was to determine if Run1Ren1 plants present alterations in their physiological and biochemical parameters in the presence of the fungus. To achieve this target, a previously characterized resistant Run1Ren1 genotype and the susceptible Carménère cultivar were analyzed. We evaluated photochemical parameters (Fv’/Fm’, ΦPSII and ETR), net photosynthesis (Pn), photosynthetic pigments, transpiration (E), stomatal conductance (gs), oxidative stress parameters (MDA), antioxidant activity, and phenols. Our results show that the physiological parameters of Run1Ren1 plants were not negatively affected by the fungus at 10 days post-inoculation, contrasting with alterations observed in the susceptible plants. Therefore, we propose that the resistance response triggered by Run1Ren1 is physiologically and biochemically advantageous to grapevines by preventing the development of powdery mildew infection.

Fascioliasis is a highly pathogenic disease affecting humans and livestock worldwide. It is caused by the liver flukes Fasciola hepatica transmitted by Galba/Fossaria lymnaeid snails in Europe, Asia, Africa, the Americas and Oceania, and F. gigantica transmitted by Radix lymnaeids in Africa and Asia. An evident founder effect appears in genetic studies as the consequence of their spread by human-guided movements of domestic ruminants, equines and Old World camelids in the post-domestication period from the beginning of the Neolithic. Establishing the geographical origins of fasciolid expansion is multidisciplinary crucial for disease assessment. Sequencing of selected nuclear ribosomal and mitochondrial DNA markers of F. nyanzae infecting hippopotamuses (Hippopotamus amphibius) in South Africa and their comparative analyses with F. hepatica and F. gigantica, and the two Fascioloides species, Fs. jacksoni from Asian elephants and Fs. magna from Holarctic cervids, allow to draw a tuned-up evolutionary scenario during the pre-domestication period. Close sequence similarities indicate a direct derivation of F. hepatica and F. gigantica from F. nyanzae by speciation after host capture phenomena. Phylogenetic reconstruction, genetic distances and divergence estimates fully fit fossil knowledge, past interconnecting bridges between continents, present fasciolid infection in the wild fauna, and lymnaeid distribution. The paleobiogeographical analyses suggest an origin for F. gigantica by transfer from primitive hippopotamuses to grazing bovid ancestors of Reduncinae, Bovinae and Alcelaphinae, by keeping the same vector Radix natalensis in warm lowlands of southeastern Africa in the mid-Miocene, around 13.5 mya. The origin of F. hepatica should have occurred after capture from primitive, less amphibious Hexaprotodon hippopotamuses to mid-sized ovicaprines as the wild bezoar Capra aegagrus and the wild mouflon Ovis gmelini, and from R. natalensis to Galba truncatula in cooler areas and mountainous foothills of Asian Near East in the latest Miocene to Early Pliocene, around 6.0 to 4.0 mya and perhaps shortly afterwards.

Abstract Background Aedes albopictus is a very invasive mosquito, which has recently colonized tropical and temperate regions worldwide. Of concern is its role in the spread of emerging or re-emerging mosquito-borne diseases. Ae. albopictus from south-western Europe and Brazil were studied to infer genetic and phenetic diversity at intra-individual, intra-population and inter-population levels, and to analyse its spread. Methods Genotyping was made by rDNA 5.8S-ITS-2 and mtDNA cox1 sequencing to assess haplotype and nucleotide diversity, genetic distances and phylogenetic networks. Male and female phenotyping included combined landmark-and outlined-based geometric morphometrics of wing size and shape. Results Specimens from seven populations from Spain, France and Brazil provided 12 cox1 and 162 5.8S-ITS-2 haplotypes, with great genetic variability difference between both markers (0.9% vs 31.2%). Five cox1 haplotypes were shared with other countries, mainly Italy, USA and China, but none was shared between Europe and Brazil. The 5.8S-ITS-2 showed 2–7 intra-individual (mean 4.7) and 16–34 intra-/inter-population haplotypes (24.7), including haplotypes shared between Spain, France and Brazil. A 4.3% of ITS-2 haplotypes were shared, mainly with Italy, USA and Thailand, evidencing worldwide spread and introductions from areas where recent outbreaks of Ae. albopictus-transmitted pathogens occurred. Wing size showed sex differences. Wing shape distinguished between Brazilian and European specimens. Both genetic and morphometric markers showed differences between insular Spain and continental Spain, France and Brazil. Conclusions ITS-2 proves to be a useful marker to assess Ae. albopictus spread, providing pronouncedly more information than cox1, including intra-individual, intra-population and inter-population levels, furnishing a complete overview of the evolutionary exchanges followed by this mosquito. Wing morphometry proves to be a useful phenotyping marker, allowing to distinguish different populations at the level of both male and female specimens. Results indicate the need for periodic surveillance monitorings to verify that no Ae. albopictus with high virus transmission capacity is introduced into Europe. Graphic Abstract

Resumen: Introducción: más de la mitad del alumnado universitario comete fraude o plagio en las actividades académicas, llegando hasta el 90% en estudiantes de Farmacia. No existen publicaciones en Chile que aborden la integridad académica. El objetivo de este estudio fue evaluar la percepción sobre las conductas relacionadas a la integridad académica en el alumnado de Licenciatura en Química y Farmacia de la Universidad Católica del Norte, Chile. Métodos: estudio no probabilístico por conveniencia, cuantitativo, descriptivo y transversal, que aplicó una encuesta, distribuida por correo electrónico y redes sociales, con 11 situaciones de simulación escrita que mostraban conductas deshonestas, validada por pares expertos; donde el estudiantado debía reconocer quien había cometido la falta e indicar si la habían presenciado en la universidad. Resultados: de los 126 estudiantes, 60% fueron mujeres, edad promedio 22,9 ± 3,2 años y 21 (16,7%) correspondieron a las cohortes 2020-2021. El 98,8% reconoció el plagio en los escenarios de simulación escritos; la conducta menos reconocida fue encubrimiento (58,7%; p < 0,0001). El 90% indicó que presenció en la universidad una situación que involucraba engaño y encubrimiento. La comparación de las cohortes 2020-2021 con el resto de las generaciones no evidenció diferencias estadísticamente significativas en una situación de encubrimiento (p = 0,115) y de colusión (p = 0,186). Conclusión: implementar estrategias preventivas que promuevan la formación ética, permitirá al alumnado detectar actitudes deshonestas en contextos universitarios, contribuyendo positivamente en su formación profesional. Abstract: Introduction: Over 50% of college students commit either fraud or plagiarism in their academic activities, reaching up to 90% among pharmacy students. There are no articles available in Chile to address academic integrity. The aim of this Study is to assess the perception on the conducts that relate to academic integrity of pharmacist students of the Universidad Católica del Norte, Chile. Method: A quantitative, descriptive, cross-sectional and non-probabilistic study for convenience sample, in which an email and social network distributed expert peers aproved survey was conducted, including 11 written simulations showing dishonest conducts; students were required to recognize in every situation the person accountable of misconduct and to point out if they had witnessed these conducts during their college career. Results: Out of a total of 126 students, 60% where female, average age of 22.9±3.2 years and 21 (16.7%) belonged to the 2020-2021 cohort. 98.8% of the students recognized plagiarism in the written simulation scenarios; the least recognized conduct was concealment (58.7%; p

Mediante un modelamiento de insumo-producto para medir sensibilidades y cambios estructurales de la producción, este estudio analiza cómo han evolucionado éstos en la economía chilena, y, en especial, la importancia que tiene el sector de la minería del cobre en este proceso. La información utilizada proviene de la Organización para la Cooperación y el Desarrollo Económicos (OCDE) y abarca un horizonte de 11 años (de 2005 a 2015). El estudio revela la importancia que el cobre tiene para el desarrollo de la economía chilena, lo cual se manifiesta en los cambios ocurridos en los tipos de relaciones formados en la oferta y la demanda de insumos que tiene esta actividad. Adicionalmente, los resultados muestran un debilitamiento en las sensibilidades vinculadas con las relaciones de la industria manufacturera, efecto conocido en la literatura de insumo-producto como hollowing-out; esto es, en el debilitamiento de la complejidad de los encadenamientos productivos de la industria, que implica una reducción en la sensibilidad de los vínculos directos; indirectos locales y globales, y totales con el resto del sistema productivo.

Abstract Background Fascioliasis is a snail-borne zoonotic trematodiasis emerging due to climate changes, anthropogenic environment modifications, and livestock movements. Many areas where Fasciola hepatica is endemic in humans have been described in Latin America altitude areas. Highest prevalences and intensities were reported from four provinces of the northern Bolivian Altiplano, where preventive chemotherapy is ongoing. New strategies are now incorporated to decrease infection/re-infection risk, assessment of human infection sources to enable efficient prevention measures, and additionally a One Health initiative in a selected zone. Subsequent extension of these pilot interventions to the remaining Altiplano is key. Methods To verify reproducibility throughout, 133 specimens from 25 lymnaeid populations representative of the whole Altiplano, and 11 used for population dynamics studies, were analyzed by rDNA ITS2 and ITS1 and mtDNA cox1 and 16S sequencing to assess their classification, variability and geographical spread. Results Lymnaeid populations proved to belong to a monomorphic group, Galba truncatula. Only a single cox1 mutation was found in a local population. Two cox1 haplotypes were new. Comparisons of transmission foci data from the 1990’s with those of 2018 demonstrated an endemic area expansion. Altitudinal, northward and southward expansions suggest movements of livestock transporting G. truncatula snails, with increasing temperatures transforming previously unsuitable habitats into suitable transmission areas. Transmission foci appear to be stable when compared to past field observations, except for those modified by human activities, including construction of new roads or control measures undertaken in relation to fascioliasis. Conclusions For a One Health initiative, the control of only one Fasciola species and snail vector species simplifies efforts because of the lower transmission complexity. Vector monomorphism suggests uniformity of vector population responses after control measure implementation. Hyperendemic area outer boundary instability suggests a climate change impact. All populations outside previously known boundaries were close to villages, human dwellings and/or schools, and should therefore be considered during disease control planning. The remarkable southward expansion implies that a fifth province, Aroma, should now be included within preventive chemotherapy programmes. This study highlights the need for lymnaeid molecular identification, transmission foci stability monitoring, and potential vector spread assessment.

Vector-borne diseases (VBDs) pose a major threat to human and animal health, with more than 80% of the global population being at risk of acquiring at least one major VBD. Being profoundly affected by the ongoing climate change and anthropogenic disturbances, modelling approaches become an essential tool to assess and compare multiple scenarios (past, present and future), and further the geographic risk of transmission of VBDs. Ecological niche modelling (ENM) is rapidly becoming the gold-standard method for this task. The purpose of this overview is to provide an insight of the use of ENM to assess the geographic risk of transmission of VBDs. We have summarised some fundamental concepts and common approaches to ENM of VBDS, and then focused with a critical view on a number of crucial issues which are often disregarded when modelling the niches of VBDs. Furthermore, we have briefly presented what we consider the most relevant uses of ENM when dealing with VBDs. Niche modelling of VBDs is far from being simple, and there is still a long way to improve. Therefore, this overview is expected to be a useful benchmark for niche modelling of VBDs in future research.

Schistosome eggs play a key role in schistosomiasis diagnosis and research. The aim of this work is to morphogenetically study the eggs of Schistosoma haematobium found in sub-Saharan migrants present in Spain, analyzing their morphometric variation in relation to the geographical origin of the parasite (Mali, Mauritania and Senegal). Only eggs considered “pure” S. haematobium by genetic characterization (rDNA ITS-2 and mtDNA cox1) have been used. A total of 162 eggs obtained from 20 migrants from Mali, Mauritania and Senegal were included in the study. Analyses were made by the Computer Image Analysis System (CIAS). Following a previously standardized methodology, seventeen measurements were carried out on each egg. The morphometric analysis of the three morphotypes detected (round, elongated and spindle) and the biometric variations in relation to the country of origin of the parasite on the egg phenotype were carried out by canonical variate analysis. Mahalanobis distances, when all egg measurements were analyzed, showed differences between: (i) Mali-Mauritania, Mali-Senegal and Mauritania-Senegal in the round morphotype; (ii) Mali-Mauritania and Mauritania-Senegal in the elongated morphotype; and (iii) Mauritania-Senegal in the spindle morphotype. Mahalanobis distances, when spine variables were analyzed, showed differences between Mali-Senegal in the round morphotype. In conclusion, this is the first phenotypic study performed on individually genotyped “pure” S. haematobium eggs, allowing the assessment of the intraspecific morphological variations associated with the geographical origin of the schistosome eggs.

The Northern Bolivian Altiplano is the human fascioliasis hyperendemic area where the highest prevalences and intensities in humans have been reported. Preventive chemotherapy was implemented in the last ten years. Surveillance showed high human infection and re-infection rates in between the annual triclabendazole monodose treatments. A complementary One Health control action was launched to decrease the infection risk. Among the multidisciplinary axes, there is the need to establish animal reservoir species priorities for a more efficient control. Laboratory and field studies were performed for the first time to assess the Fasciola hepatica transmission capacity of the pig and its potential reservoir role. The experimental follow-up of altiplanic pig isolates through altiplanic Galba truncatula snail vector isolates were performed at different miracidial doses and different day/night temperatures. Experiments included egg embryonation, miracidial infectivity, lymnaeid snail infection, intramolluscan larval development, cercarial production, chronobiology of the cercarial shedding, vector survival to infection, metacercarial infectivity of mammal host, and adult stage development. Surveys included the assessment of prevalence, intensity, egg measurements and egg shedding rates in nature. Pig contribution was evaluated by comparing with the main altiplanic reservoirs sheep and cattle. Results demonstrated that the pig assures the whole F. hepatica life cycle and participates in its transmission in this area. The fast egg embryonation, high cercarial production, long multi-wave shedding chronobiological pattern in monomiracidial infections at permanent 20 °C temperature, and the high daily egg outputs per pig are worth mentioning. The high infection risk suggests early infection of freely running piglets and evolutionary long-term adaptation of the liver fluke to this omnivorous mammal, despite its previously evoked resistance or non-suitability. Genetic, physiological and immune similarities with humans may also underlie the parasite adaptation to humans in this area. The pig should be accordingly included for appropriate control measures within a One Health action against human fascioliasis. The pig should henceforth be considered in epidemiological studies and control initiatives not only in fascioliasis endemic areas with human infection risk on other Andean countries, but also in rural areas of Latin America, Africa and Asia where domestic pigs are allowed to run freely.

Las “aguas de contacto mineras” en Chile contaminan largas zonas del territorio nacional y sus efectos actualmente son permanentes porque no pueden ser modificados o recuperar las aguas. Se requiere de una reacción rápida del Ser humano, sea de prevención para modificar los efectos o sea de recuperación de las mismas evitando efectos permanentes. Las aguas de contacto mineras producen efectos negativos que no son instantáneos sino, se van acumulando y generando una “bola de nieve” al pasar el tiempo, su existencia es un peligro. Asimismo, existe un vacío legal, porque las “aguas de contacto mineras” requieren, a su vez, los requisitos legales y reglamentarios de prevención de las mismas y en caso de existencia de un tratamiento de descontaminación especial no regulados por el legislador en leyes generales o específicas. Las posibles soluciones obligan al Estado a la búsqueda de prevención y descontaminación de las mismas al haberse producido éstas.

Este artículo aborda el problema de la representación de víctimas y victimarios en el espacio público. Pretendemos reflexionar sobre la interpretación de los perpetradores a partir de la noción de lo monstruoso. La categoría estética de lo monstruoso tiene la deficiencia de no abordar de modo apropiado el objeto que se califica como tal. Luego, mostraremos cómo esta cuestión ha estado también a la base de la discusión museográfica a través del análisis de una de las experiencias supuestamente más exitosas de transición memorial: la desnazificación en Alemania. Veremos cómo, en este caso, la representación de los perpetradores ha oscilado entre el monstruo y el humano, dando lugar a respuestas estéticas que evidencian la necesidad de cuestionar cualquier a priori histórico al analizar la violencia de Estado.

We explored the effects of ultraviolet B radiation (UV-B) on the developmental dynamics of microRNAs and phased small-interfering-RNA (phasi-RNAs)-producing loci by sequencing small RNAs in vegetative and reproductive organs of grapevine (Vitis vinifera L.). In particular, we tested different UV-B conditions in in vitro-grown plantlets (high-fluence exposition) and in berries from field-grown (radiation filtering) and greenhouse-grown (low- and high-fluence expositions) adult plants throughout fruit development and ripening. The functional significance of the observed UV-coordinated miRNA responses was supported by degradome evidences of ARGONAUTE (AGO)-programmed slicing of mRNAs. Co-expression patterns of the up-regulated miRNAs miR156, miR482, miR530, and miR828 with cognate target gene expressions in response to high-fluence UV-B was tested by q-RT-PCR. The observed UV-response relationships were also interrogated against two published UV-stress and developmental transcriptome datasets. Together, the dynamics observed between miRNAs and targets suggest that changes in target abundance are mediated transcriptionally and, in some cases, modulated post-transcriptionally by miRNAs. Despite the major changes in target abundance are being controlled primarily by those developmental effects that are similar between treatments, we show evidence for novel miRNA-regulatory networks in grape. A model is proposed where high-fluence UV-B increases miR168 and miR530 that target ARGONAUTE 1 (AGO1) and a Plus-3 domain mRNA, respectively, while decreasing miR403 that targets AGO2, thereby coordinating post-transcriptional gene silencing activities by different AGOs. Up-regulation of miR3627/4376 could facilitate anthocyanin accumulation by antagonizing a calcium effector, whereas miR395 and miR399, induced by micronutrient deficiencies known to trigger anthocyanin accumulation, respond positively to UV-B radiation. Finally, increases in the abundance of an anthocyanin-regulatory MYB-bHLH-WD40 complex elucidated in Arabidopsis, mediated by UV-B-induced changes in miR156/miR535, could contribute to the observed up-regulation of miR828. In turn, miR828 would regulate the AtMYB113-ortologues MYBA5, A6 and A7 (and thereby anthocyanins) via a widely conserved and previously validated auto-regulatory loop involving miR828 and phasi TAS4abc RNAs.

Diabetes mellitus (DM) causes high glucose (HG) levels in the plasma and urine. The (pro)renin receptor (PRR) is a key regulator of renal Na+ handling. PRR is expressed in intercalated (IC) cells of the collecting duct (CD) and binds renin to promote angiotensin (Ang) II formation, thereby contributing to Na+ reabsorption. In DM, the Kreb's cycle is in a state of suppression in most tissues. However, in the CD, expression of glucose transporters is augmented, boosting the Kreb's cycle and consequently causing α-ketoglutarate (αKG) accumulation. The αKG receptor 1 (OXGR1) is a Gq-coupled receptor expressed on the apical membrane of IC cells of the CD. We hypothesize that HG causes αKG secretion and activation of OXGR1, which increases PRR expression in CD cells. This effect then promotes intratubular AngII formation and Na+ reabsorption. To test this hypothesis, streptozotocin (STZ)-induced diabetic mice were treated with or without montelukast (ML), an OXGR1 antagonist, for 6 days. STZ mice had higher urinary αKG and PRR expression along with augmented urinary AngII levels and Na+ retention. Treatment with ML prevented all these effects. Similarly, primary cultured inner medullary CD cells treated with HG showed increased PRR expression, while OXGR1 antagonist prevented this effect. αKG increases PRR expression, while treatments with ML, PKC inhibition, or intracellular Ca2+ depletion impair this effect. In silico analysis suggested that αKG binds to mouse OXGR1. These results indicate that HG conditions promote increased levels of intratubular αKG and OXGR1-dependent PRR upregulation, which impact AngII formation and Na+ reabsorption.

Abstract Fascioliasis is a freshwater snail-borne zoonotic disease. The Northern Bolivian Altiplano is a very high altitude endemic area where the highest human prevalences and intensities have been reported. Preventive chemotherapy by treatment campaigns is yearly applied. However, liver fluke infection of cattle, sheep, pigs and donkeys assures endemicity and consequent human infection and re-infection risks. A One Health action has therefore been implemented. Activity concerns lymnaeid vectors and environment diversity. Studies included growth, egg-laying and life span in laboratory-reared lymnaeids. Different habitat types and influencing factors were assessed. All populations proved to belong to Galba truncatula by rDNA sequencing. Analyses comprised physico-chemical characteristics and monthly follow-up of water temperature, pH and quantity, and lymnaeid abundance and density. Population dynamics in the transmission foci differed. Mean environmental temperature was lower than fluke development minimum temperature threshold, but water temperature was higher, except during winter. A two generations/year pattern appeared in permanent water habitats, and one generation/year pattern in habitats drying out for months. The multidisciplinary control measures can be extended from one part of the endemic area to another. These studies, made for the first time at very high altitude, constitute a baseline useful for fascioliasis control in other countries.

Grapevine (Vitis vinifera) is one of the main fruit crops worldwide. In 2020, the total surface area planted with vines was estimated at 7.3 million hectares. Diverse pathogens affect grapevine yield, fruit, and wine quality of which powdery mildew is the most important disease prior to harvest. Its causal agent is the biotrophic fungus Erysiphe necator, which generates a decrease in cluster weight, delays fruit ripening, and reduces photosynthetic and transpiration rates. In addition, powdery mildew induces metabolic reprogramming in its host, affecting primary metabolism. Most commercial grapevine cultivars are highly susceptible to powdery mildew; consequently, large quantities of fungicide are applied during the productive season. However, pesticides are associated with health problems, negative environmental impacts, and high costs for farmers. In paralleled, consumers are demanding more sustainable practices during food production. Therefore, new grapevine cultivars with genetic resistance to powdery mildew are needed for sustainable viticulture, while maintaining yield, fruit, and wine quality. Two main gene families confer resistance to powdery mildew in the Vitaceae, Run (Resistance to Uncinula necator) and Ren (Resistance to Erysiphe necator). This article reviews the powdery mildew resistance genes and loci and their use in grapevine breeding programs.

A One Health initiative has been implemented for fascioliasis control in a human hyperendemic area for the first time. The area selected for this multidisciplinary approach is the Northern Bolivian Altiplano, where the highest prevalences and intensities in humans have been reported. Within the strategic intervention axis of control activities concerning animal reservoirs, complete experimental studies, and field surveys have been performed to assess the fascioliasis transmission capacity and epidemiological role of the donkey for the first time. Laboratory studies with altiplanic donkey-infecting Fasciola hepatica and altiplanic Galba truncatula snail vector isolates demonstrate that the donkey assures the viability of the whole fasciolid life cycle. Several aspects indicate, however, that F. hepatica does not reach, in the donkey, the level of adaptation it shows in sheep and cattle in this high altitude hyperendemic area. This is illustrated by a few-day delay in egg embryonation, longer prepatent period despite similar miracidial infectivity and shorter patent period in the intramolluscan development, lower cercarial production per snail, different cercarial chronobiology, shorter snail survival after shedding end, shorter longevity of shedding snails, and lower metacercarial infectivity in Wistar rats. Thus, the role of the donkey in the disease transmission should be considered secondary. Field survey results proved that liver fluke prevalence and intensity in donkeys are similar to those of the main reservoirs sheep and cattle in this area. Fasciolid egg shedding by a donkey individual contributes to the environment contamination at a rate similar to sheep and cattle. In this endemic area, the pronounced lower number of donkeys when compared to sheep and cattle indicates that the epidemiological reservoir role of the donkey is also secondary. However, the donkey plays an important epidemiological role in the disease spread because of its use by Aymara inhabitants for good transport, movements, and travel from one locality/zone to another, a repercussion to be considered in the present geographical spread of fascioliasis in the Altiplano due to climate change. Donkey transport of parasite and vector, including movements inside the zone under control and potential introduction from outside that zone, poses a problem for the One Health initiative.

The Northern Bolivian Altiplano is the human fascioliasis hyperendemic area where the highest prevalences and intensities of infection by Fasciola hepatica in humans have been reported. Four animal species are the reservoir species for F. hepatica in this area, namely, sheep, cattle, pigs, and donkeys. Livestock for the Aymara inhabitants is crucial because vegetable cultures are not viable due to the inhospitality of the very high altitude of 3,820–4,100 m. A One Health initiative has been implemented in this area in recent years, as the first such control action in a human endemic area ever. Among the different control axes included, special focus is devoted to the two main reservoirs sheep and cattle. Egg embryonation, miracidial infectivity, intramolluscan development, cercarial production, infected snail survival, and metacercarial infectivity were experimentally studied in altiplanic sheep and cattle isolates. These laboratory studies were performed using altiplanic isolates of the lymnaeid species Galba truncatula, the only vector present in the hyperendemic area. Experiments were made at constant 12 h day/12 h night and varying 20/20°C and 22/5°C photoperiods. Infections were implemented using mono-, bi-, and trimiracidial doses. Results demonstrate that sheep and cattle have the capacity to assure F. hepatica transmission in this very high-altitude area. Field surveys included prevalence studies by coprology on fecal samples from 1,202 sheep and 2,690 cattle collected from different zones of the Northern Bolivian Altiplano. Prevalences were pronouncedly higher and more homogeneous in sheep (63.1%; range: 38.9–68.5%) than in cattle (20.6%; range: 8.2–43.3%) in each one of the different zones. Although similarities between the prevalences in sheep and cattle appeared in the zones of the highest and lowest infection rates, this disappeared in the other zones due to cattle treatments. Comparison with past surveys demonstrates that this hyperendemic area is stable from the disease transmission point of view. Therefore, the control design should prioritize sheep and cattle within the One Health action. Studies performed in the Bolivian Altiplano furnish a baseline for future initiatives to assess the transmission and epidemiological characteristics of fascioliasis in the way for its control in other high altitude Andean endemic areas.

Head motion induced by impacts has been deemed as one of the most important measures in brain injury prediction, given that the vast majority of brain injury metrics use head kinematics as input. Recently, researchers have focused on using fast approaches, such as machine learning, to approximate brain deformation in real time for early brain injury diagnosis. However, training such models requires large number of kinematic measurements, and therefore data augmentation is required given the limited on-field measured data available. In this study we present a principal component analysis-based method that emulates an empirical low-rank substitution for head impact kinematics, while requiring low computational cost. In characterizing our existing data set of 537 head impacts, each consisting of 6 degrees of freedom measurements, we found that only a few modes, e.g., 15 in the case of angular velocity, is sufficient for accurate reconstruction of the entire data set. Furthermore, these modes are predominantly low frequency since over 70% of the angular velocity response can be captured by modes that have frequencies under 40 Hz. We compared our proposed method against existing impact parametrization methods and showed significantly better performance in injury prediction using a range of kinematic-based metrics—such as head injury criterion (HIC), rotational injury criterion (RIC), and brain injury metric (BrIC)—and brain tissue deformation-based metrics—such as brain angle metric (BAM), maximum principal strain (MPS), and axonal fiber strains (FS). In all cases, our approach reproduced injury metrics similar to the ground truth measurements with no significant difference, whereas the existing methods obtained significantly different (p < 0.01) values as well as substantial differences in injury classification sensitivity and specificity. This emulator will enable us to provide the necessary data augmentation to build a head impact kinematic data set of any size. The emulator and corresponding examples are available on our website1.

We present a comprehensive architectural analysis for a proposed fault-tolerant quantum computer based on cat codes concatenated with outer quantum error-correcting codes. For the physical hardware, we propose a system of acoustic resonators coupled to superconducting circuits with a two-dimensional layout. Using estimated physical parameters for the hardware, we perform a detailed error analysis of measurements and gates, including cnot and Toffoli gates. Having built a realistic noise model, we numerically simulate quantum error correction when the outer code is either a repetition code or a thin rectangular surface code. Our next step toward universal fault-tolerant quantum computation is a protocol for fault-tolerant Toffoli magic state preparation that significantly improves upon the fidelity of physical Toffoli gates at very low qubit cost. To achieve even lower overheads, we devise a new magic state distillation protocol for Toffoli states. Combining these results together, we obtain realistic full-resource estimates of the physical error rates and overheads needed to run useful fault-tolerant quantum algorithms. We find that with around 1000 superconducting circuit components, one could construct a fault-tolerant quantum computer that can run circuits, which are currently intractable for classical computers. Hardware with 18 000 superconducting circuit components, in turn, could simulate the Hubbard model in a regime beyond the reach of classical computing.

This study contributes to the debate on accessibility of higher education in Chile, with a special focus on the geospatial dimension of access to university studies. This paper addresses the central question of whether geography (physical distance and neighborhood effects) plays a significant role in determining the accessibility of higher education to students in Chile. We use Heckman probit-type (Heckit) models to adjust for selection during application for higher education—that is, pre-selection among applications to study at university and, ultimately, admission (or denial) to a higher educational institution. Of all high school graduates who took the university selection test (PSU), only 37.9% were able to attend higher education. The results show that the geospatial elements—neighborhood characteristics and distance from the city of Santiago—have a significant local effect on the student’s application and access to Chilean universities. Specifically, the most significant local range for each candidate is 300 neighbors. We also find that, when distance to the capital city increases, the probability of applying to university increases to a threshold of 1400 km, at which point probability begins to decrease.

El presente artículo trata de sistematizar la intervención de la persona jurídica en el proceso, haciendo referencia a las situaciones más trascendentes en que se encontrará el investigado, desde su personación y actuación en las distintas fases de la instrucción, hasta el desarrollo del juicio. Se trata así, de su personación, declaración, la posible conformidad, caso de incomparecencia y una especial atención a las medidas cautelares que puede ser objeto la persona jurídica.

South American camelids are definitive hosts of Fasciola hepatica. However, their capacity to participate in the transmission and epidemiology of fascioliasis has never been appropriately studied. Therefore, an F. hepatica isolate from Argentine llama is for the first time analyzed using Galba truncatula lymnaeids from Bolivia. Experimental follow-up studies included egg embryogenesis, miracidial infection of lymnaeid snails, intramolluscan larval development, cercarial production, chronobiology of cercarial shedding, vector survival to infection, and metacercarial infectivity of mammal host. Shorter prepatent and patent periods were leading to markedly lower cercarial production, shorter cercarial shedding, and a higher negative impact on snail survival. The usually low liver fluke prevalences and intensities and low daily fecal outputs indicate that llamas do not substantially contribute to fascioliasis transmission. The defecating behavior in dung piles far from freshwater collections prevents lymnaeid infection by eggs shed by this camelid. All results suggest the reservoir role of the llama to be negligible and, therefore, no priority within control measures in endemic areas. However, llamas may play a disease-spreading role if used as pack animals in rural areas. In the Northern Bolivian Altiplano human hyperendemic area, neither llamas nor alpacas should be considered for control measures within a One Health action.

Quantitative coprological analyses of children were performed in Alexandria and Behera governorates, Egypt, to ascertain whether individual intensities in the Nile Delta lowlands reach high levels as those known in hyperendemic highland areas of Latin America. Analyses focused on subjects presenting intensities higher than 400 eggs per gram of faeces (epg), the high burden cut-off according to WHO classification. A total of 96 children were found to shed between 408 and 2304 epg, with arithmetic and geometric means of 699.5 and 629.07 epg, respectively. Intensities found are the highest hitherto recorded in Egypt, and also in the whole Old World. A total of 38 (39.6%) were males and 58 (60.4%) were females, with high intensities according to gender following a negative binomial distribution. The high burden distribution shows a peak in the 7–10 year-old children group, more precocious in females than males. Results showed high burdens in winter to be remarkably higher than those known in summer. The fascioliasis scenario in Egyptian lowlands shows similarities to highlands of Bolivia and Peru. Diagnostic methods, pathogenicity and morbidity in high burdens should be considered. The need for an appropriate quantitative assessment of heavy infected children to avoid post-treatment colic episodes is highlighted.

Fascioliasis is a disease caused by Fasciola hepatica worldwide transmitted by lymnaeid snails mainly of the Galba/Fossaria group and F. gigantica restricted to parts of Africa and Asia and transmitted by Radix lymnaeids. Concern has recently risen regarding the high pathogenicity and human infection capacity of F. gigantica. Abnormally big-sized fasciolids were found infecting sheep in Ecuador, the only South American country where F. gigantica has been reported. Their phenotypic comparison with F. hepatica infecting sheep from Peru, Bolivia and Spain, and F. gigantica from Egypt and Vietnam demonstrated the Ecuadorian fasciolids to have size-linked parameters of F. gigantica. Genotyping of these big-sized fasciolids by rDNA ITS-2 and ITS-1 and mtDNA cox1 and nad1 and their comparison with other countries proved the big-sized fasciolids to belong to F. hepatica. Neither heterozygotic ITS position differentiated the two species, and no introgressed fragments and heteroplasmic positions in mtDNA were found. The haplotype diversity indicates introductions mainly from other South American countries, Europe and North America. Big-sized fasciolids from Ecuador and USA are considered to be consequences of F.gigantica introductions by past livestock importations. The vector specificity filter due to Radix absence should act as driving force in the evolution in such lineages.

This paper develops a methodology using business intelligence (data warehouse) and OLAP tools (Online Analytical Processing) to match individuals from a household survey data to a census one. In order to geo-reference the household data, the method takes advantage of the geographical information of the census. Using the 2003 Household Survey and the 2002 Chilean Census of Population and Housing, the average household income is projected to intra-municipality levels and the results are compared to Elbers et al. (2003) methodology. The results show that the proposed methodology allows for taking into account and display the impact of intra-municipality heterogeneity and the spatial interaction among the spatial units.

In this theoretical note, we propose the GProbit model as an alternative to gravity models to estimate grouped-data flows. This is a model based on the random utility theory, which is consistent with the principle of population behavior. Instead of migrant counts, the dependent variable of the GProbit model of flows consists of a number of observed proportions. It allows explaining the propensity to migrate from any origin to a destination, which is an interesting relative concept not affected by the size effect. For this reason, it is expected to have better fit and less problems of non-normality, as illustrated by an application for the internal migration flows of the Spanish regions.

Renal diseases are a global health concern, and nearly 24% of kidney disease patients are overweight or obese. Particularly, increased body mass index has been correlated with oxidative stress and urinary albumin excretion in kidney disease patients, also contributing to increased cardiovascular risk. Albumin is the main plasma protein and is able to partially cross the glomerular filtration barrier, being reabsorbed mainly by the proximal tubule through different mechanisms. However, it has been demonstrated that albumin suffers different posttranslational modifications, including oxidation, which appears to be tightly linked to kidney damage progression and is increased in obese patients. Plasma-oxidized albumin levels correlate with a decrease in estimated glomerular filtration rate and an increase in blood urea nitrogen in patients with chronic kidney disease. Moreover, oxidized albumin in kidney disease patients is independently correlated with higher plasma levels of transforming growth factor beta (TGF-β1), tumor necrosis factor (TNF-α), and interleukin (IL)-1β and IL-6. In addition, oxidized albumin exerts a direct effect on neutrophils by augmenting the levels of neutrophil gelatinase-associated lipocalin, a well-accepted biomarker for renal damage in patients and in different experimental settings. Moreover, it has been suggested that albumin oxidation occurs at early stages of chronic kidney disease, accelerating the patient requirements for dialytic treatment during disease progression. In this review, we summarize the evidence supporting the role of overweight- and obesity-induced oxidative stress as a critical factor for the progression of renal disease and cardiovascular morbimortality through albumin oxidation.

O ano de 1968 marcou um ponto de inflexão no mundo ocidental por causa de uma série de acontecimentos críticos que consolidara o que podia denominar-se como autoconsciência da era global. Esta subjetivação da condição global da sociedade ocidental irrompeu com força por meio de fenômenos que remontam a anos anteriores; entretanto, foi em 1968, quando tanto a frequência quanto a envergadura de acontecimentos de âmbito mundial criaram uma verdadeira atmosfera revolucionária. Entre eles, os conflitos estudantis ao redor do mundo assumiram um papel importante como catalisadores de uma consciência global de transformação, cujo ápice teve lugar durante os meses de maio e junho em Paris, quando as notícias das revoltas dos estudantes da Sorbonne chegaram às principais capitais do mundo, gerando uma vasta discussão intelectual sobre o alcance dessas manifestações e os efeitos das mesmas nos diversos âmbitos locais. No caso do Chile, sua recepção foi muito importante em diversos âmbitos do campo intelectual nacional, desde a ala mais conservadora até à esquerda, que apenderam as lições dos eventos parisienses, seja para analisar, criticar ou legitimar as manifestações nas universidades chilenas e o processo de reforma universitária que havia começado alguns anos antes.

La investigación que se presenta en el presente artículo tiene como objetivo relacionar tres grupos de variables: utilidad per cápita, participación de mercado y estructura de capital per cápita; con el fin de mostrar la correlación de cada una de estas variables en 17 industrias del sector agrícola ecuatoriano. Los datos que se utilizaron para el análisis de esta correlación fueron los publicados por el Instituto Nacional de Estadísticas y Censos INEC, correspondientes al último Censo Nacional Económico, realizado en el año 2010. Los resultados muestran que existen correlaciones significativas a niveles de 1% y 5%, entre las variables: utilidad per cápita y participación de mercado, y entre las variables: utilidad per cápita y estructura de capital per cápita, en los sectores de cultivo de cereales (excepto arroz), legumbres y semillas oleaginosas, cultivos de arroz, cultivo de frutas tropicales y subtropicales, cultivo de frutas con hueso y con pepa y cultivo de especias y de plantas aromáticas, medicinales y farmacéuticas.