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Abstract PI3K/AKT/mTOR pathway is implicated in breast cancer progression and recurrence. The identification of PIK3CA and AKT1 mutations and loss of PTEN serve as selection criterion for targeted therapies involving selective inhibitors. However, they do not consistently align with pathway activation, and high-cost determinations limit their routine application. PI3K-downstream epigenetic regulatory mechanisms broaden the alterations that amplify pathway activity and, consequently, sensitivity to selective inhibitors. In this retrospective observational study, conducted within a cohort of early-stage breast cancer patients, we determined phosphorylated ribosomal protein S6 (pS6) at Ser240/244 by immunohistochemistry as an indicator of PI3K pathway activation. Log-Rank test and Cox proportional hazards regression were used to analyze the clinical relevance of pS6, alone and together with clinicopathological variables, regarding recurrence-free survival. ROC curves and the area under the curves were used to evaluate the calibration and discrimination properties of uni- and multivariate models. Our results show that a high percentage of pS6 positive tumor cells was associated with an unfavorable prognosis in a cohort of 129 hormone receptor positive/HER2 negative breast cancer patients (Hazard Ratio = 5.92; Log-Rank p = 9.5e-08; median follow-up = 53 months). When assessed in combination with lymph node status, the predictive capacity was higher compared to both univariate models individually. In conclusion, pS6 could represent a novel independent marker for predicting recurrence risk in luminal breast cancer.

Abstract Background Increased cancer stem cell (CSC) content and SOX2 overexpression are common features in the development of resistance to therapy in hormone-dependent breast cancer, which remains an important clinical challenge. SOX2 has potential as biomarker of resistance to treatment and as therapeutic target, but targeting transcription factors is also challenging. Here, we examine the potential inhibitory effect of different polyoxometalate (POM) derivatives on SOX2 transcription factor in tamoxifen-resistant breast cancer cells. Methods Various POM derivatives were synthesised and characterised by infrared spectra, powder X-ray diffraction pattern and nuclear magnetic resonance spectroscopy. Estrogen receptor (ER) positive breast cancer cells, and their counterparts, which have developed resistance to the hormone therapy tamoxifen, were treated with POMs and their consequences assessed by gel retardation and chromatin immunoprecipitation to determine SOX2 binding to DNA. Effects on proliferation, migration, invasion and tumorigenicity were monitored and quantified using microscopy, clone formation, transwell, wound healing assays, flow cytometry and in vivo chick chorioallantoic membrane (CAM) models. Generation of lentiviral stable gene silencing and gene knock-out using CRISPR-Cas9 genome editing were applied to validate the inhibitory effects of the selected POM. Cancer stem cell subpopulations were quantified by mammosphere formation assays, ALDEFLUOR activity and CD44/CD24 stainings. Flow cytometry and western blotting were used to measure reactive oxygen species (ROS) and apoptosis. Results POMs blocked in vitro binding activity of endogenous SOX2. [P2W18O62]6− (PW) Wells-Dawson-type anion was the most effective at inhibiting proliferation in various cell line models of tamoxifen resistance. 10 µM PW also reduced cancer cell migration and invasion, as well as SNAI2 expression levels. Treatment of tamoxifen-resistant cells with PW impaired tumour formation by reducing CSC content, in a SOX2-dependent manner, which led to stem cell depletion in vivo. Mechanistically, PW induced formation of reactive oxygen species (ROS) and inhibited Bcl-2, leading to the death of tamoxifen-resistant cells. PW-treated tamoxifen-resistant cells showed restored sensitivity to tamoxifen. Conclusions Together, these observations highlight the potential use of PW as a SOX2 inhibitor and the therapeutic relevance of targeting SOX2 to treat tamoxifen-resistant breast cancer.

Abstract Legacy phosphorus (P) is a reservoir of sparingly available P, and its recovery could enhance sustainable use of nonrenewable mineral fertilizers. Domestication has affected P acquisition, but it is unknown if subsequent breeding efforts, like the Green Revolution (GR), had a similar effect. We examined how domestication and breeding events altered P acquisition by growing wild, traditional (pre-GR), and modern (post-GR) tomato in soil with legacy P but low bioavailable P. Wild tomatoes, particularly accession LA0716 (Solanum pennellii), heavily cultured rhizosphere P solubilizers, suggesting reliance on microbial associations to acquire P. Wild tomato also had a greater abundance of other putatively beneficial bacteria, including those that produce chelating agents and antibiotic compounds. Although wild tomatoes had a high abundance of these P solubilizers, they had lower relative biomass and greater P stress factor than traditional or modern tomato. Compared to wild tomato, domesticated tomato was more tolerant to P deficiency, and both cultivated groups had a similar rhizosphere bacterial community composition. Ultimately, this study suggests that while domestication changed tomato P recovery by reducing microbial associations, subsequent breeding processes have not further impacted microbial P acquisition mechanisms. Selecting microbial P-related traits that diminished with domestication may therefore increase legacy P solubilization.

Introducción: los glucocorticoides (GC) han sido ampliamente utilizados en el tratamiento de patologías oculares debido a sus efectos antiinflamatorios y anti-angiogénicos. Se ha sugerido que el mecanismo de acción antiangiogénico de los GC puede estar relacionado con la enzima fosfatidilinositol-3-cinasa (PI3K), la cual desempeña un papel crucial en la angiogénesis mediada por el receptor nicotínico de acetilcolina alfa 7 (α7-nAChR). La PI3K es una enzima lipoproteica heterodimérica compuesta por las subunidades; reguladora (p85) y catalítica (p110). Objetivo: esta revisión examina la evidencia de la interrelación entre los GC, y la vía de señalización de PI3K activada por α7-nAChR en la angiogénesis “in vitro”. Metodología: se realizó una revisión bibliográfica utilizando los motores de búsqueda PubMed y Web of Science, relacionando los conceptos “endothelial cell”, “α7-nAChR”, “PI3K”, y “glucocorticoid”. Resultados: se seleccionaron 30 artículos que informaron sobre la expresión de α7-nAChR y PI3K en células endoteliales humanas. Además, del efecto de dexametasona sobre las subunidades de PI3K y Akt en modelos humano, murino y porcino. A partir de estos hallazgos, se propuso un mecanismo mediante el cual los GC ejercen su efecto antiangiogénico a través de la modulación en la expresión de la subunidad inhibitoria p85 de PI3K activada por α7-nAChR en células endoteliales humanas. Conclusión: los antecedentes evidencian que dexametasona, ejerce su mecanismo de acción anti-angiogénico mediante el incremento de la expresión de la subunidad inhibitoria p85 de PI3K activada por α7-nAChR. Estos hallazgos podrían contribuir a explicar la posible falla terapéutica en el área oftalmológica en pacientes fumadores.

Resumen Introducción: Los camioneros de la empresa “Nortev Spa” se exponen diariamente a situaciones de alto riesgo, debido a que se encuentran manejando, corren el riesgo de afectar su salud, ya que pueden verse involucrados en accidentes de tránsito, poniendo en riesgo sus vidas y las de otras personas en la carretera generando lesiones y/o la muerte de ellas. Indirectamente su salud se ve afectada de otras maneras. Objetivo: Determinar patologías prevalentes que afectan la salud de camioneros pertenecientes a una empresa chilena. Método: estudio descriptivo de corte transversal, con muestra de 29 camioneros. Para la recogida de datos se aplicó la encuesta que tiene por nombre “Patologías prevalentes que afectan el desempeño laboral de los transportistas”, validada en Argentina 2016. Resultados: Entre los resultados se destaca que el 48,3% (14 trabajadores) de los camioneros sufren de dolor de espalda, seguido de estrés con un 34,5% (10 trabajadores) siendo más frecuente en hombres 96,6% (28 trabajadores). Conclusiones: Se puede concluir que debido a las extensas jornadas de trabajo la salud de la mayoría de los camioneros se ve afectada de manera directa, presentando molestias musculoesqueléticas lo que podría estar relacionado con la edad y los hábitos de vida que tienen.

Pressure injuries, or pressure ulcers, are a common problem that may lead to infections and major complications, besides being a social and economic burden due to the costs of treatment and hospitalization. While surgery is sometimes necessary, this also has complications such as recurrence or wound dehiscence. Among the newer methods of pressure injury treatment, advanced therapies are an interesting option. This study examines the healing properties of bone marrow mononuclear cells (BM-MNCs) embedded in a plasma-based scaffold in a mouse model. Pressure ulcers were created on the backs of mice (2 per mouse) using magnets and assigned to a group of ulcers that were left untreated (Control, n = 15), treated with plasma scaffold (Plasma, n = 15), or treated with plasma scaffold containing BM-MNC (Plasma + BM-MNC, n = 15). Each group was examined at three time points (3, 7, and 14 days) after the onset of treatment. At each time point, animals were subjected to biometric assessment, bioluminescence imaging, and tomography. Once treatment had finished, skin biopsies were processed for histological and wound healing reverse transcription polymerase chain reaction (RT-PCR) array studies. While wound closure percentages were higher in the Plasma and Plasma + BM-MNC groups, differences were not significant, and thus descriptive data are provided. In all individuals, the presence of donor cells was revealed by immunohistochemistry on posttreatment onset Days 3, 7, and 14. In the Plasma + BM-MNC group, less inflammation was observed by positron emission tomography–computed tomography (PET/CT) imaging of the mice at 7 days, and a complete morphometabolic response was produced at 14 days, in accordance with histological results. A much more pronounced inflammatory process was observed in controls than in the other two groups, and this persisted until Day 14 after treatment onset. RT-PCR array gene expression patterns were also found to vary significantly, with the greatest difference noted between both treatments at 14 days when 11 genes were differentially expressed.

Abstract Interspecific and intraspecific competition and facilitation have been a focus of study in plant-plant interactions, but their influence on plant recruitment of soil microbes is unknown. In this greenhouse microcosm experiment, three cover crops (alfalfa, brassica, and fescue) were grown alone, in paired mixtures, and all together under different densities. For all monoculture trials, total pot biomass increased as density increased. Monoculture plantings of brassica were associated with the bacteria Azospirillum spp., fescue with Ensifer adhaerens, and alfalfa with both bacterial taxa. In the polycultures of cover crops, for all plant mixtures, total above-ground alfalfa biomass increased with density, and total above ground brassica biomass remained unchanged. For each plant mixture, differential abundances highlighted bacterial taxa which had not been previously identified in monocultures. For instance, mixtures of all three plants showed an increase in abundance of Planctomyces sp. SH-PL14 and Sandaracinus amylolyticus which were not represented in the monocultures. Facilitation was best supported for the alfalfa-fescue interaction as the total above ground biomass was the highest of any mixture. Additionally, the bulk soil microbiome that correlated with increasing plant densities showed increases in plant growth-promoting rhizobacteria such as Achromobacter xylosoxidans, Stentotrophomonas spp., and Azospirillum sp. In contrast, Agrobacterium tumefaciens, a previously known generalist phytopathogen, also increased with alfalfa-fescue plant densities. This could suggest a strategy by which, after facilitation, a plant neighbor could culture a pathogen that could be more detrimental to the other.

Resumen: Introducción: Para el manejo del síndrome de distrés respiratorio agudo (SDRA) moderado a severo por COVID-19 se recomendó el uso de ventilación mecánica protectora y decúbito prono debido a la gran utilidad reportada sobre la oxigenación y mortalidad. Nuestro objetivo es describir el comportamiento gasométrico y mecánico en sujetos con SDRA por COVID-19 manejados con ventilación mecánica protectora y decúbito prono en un hospital de alta complejidad. Método: Estudio observacional. Se incluyeron sujetos ≥ 18 años con SDRA por COVID-19. Se inició ventilación mecánica protectora desde la primera conexión a ventilación invasiva, mientras que el decúbito prono inició con PaO2/FIO2 150. Se realizó un seguimiento durante y posterior al decúbito prono. Se realizó un análisis descriptivo de las características basales y comparación de medias entre grupos mediante prueba de Dunn y Friedman. La significación estadística se estableció en p 0,05 a dos colas en todos los análisis. Resultados: Se estudiaron 74 sujetos, 58% corresponden a hombres con media de 60 años. La oxigenación valorada mediante PaO2 (76 a 98 mmHg, p 0,05) y PaO2/FIO2 (100 a 161, p 0,05) muestra un incremento significativo durante la primera hora de tratamiento con estabilidad de los valores más allá de las 48 horas posteriores al prono. Los parámetros de mecánica pulmonar se mantienen constantes y dentro de rangos protectores (p = 0,18). Conclusión: La estrategia de ventilación mecánica protectora y decúbito prono igual o mayor a 48 horas, en sujetos con SDRA moderado a severo secundario a COVID-19, mejora y mantiene la oxigenación hasta 48 horas después de la supinación. Abstract: Introduction: The use of protective mechanical ventilation and prone position was recommended for the management of moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19, as a result of its reported utility on oxygenation and mortality. Our objective is to describe gasometric and mechanical behavior in subjects with ARDS due to COVID-19 managed with protective mechanical ventilation and prone position in a high complexity hospital. Method: Observational study. Subjects ≥18 years of age with ARDS due to COVID-19 were included. Protective mechanical ventilation was started from the first connection to invasive ventilation, while the prone position started with PaO2/FIO2 150. Follow-up was performed during and after the prone position. A descriptive analysis of baseline characteristics and comparison of means between groups was performed using the Dunn and Friedman test. Statistical significance corresponds to p 0.05 in all analyses. Results: 74 subjects were studied, 58% correspond to men with a mean age of 60 years. There is evidence of a significant increase in arterial oxygenation assessed by PaO2 (76 to 98 mmHg, p 0.05) and PaO2/FIO2 (100 to 161, p 0.05) during the first hour of treatment, with stability of values beyond 48 hours after supination. Pulmonary mechanics values remain constant within the established protection range (p = 0,18). Conclusion: The strategy of protective mechanical ventilation and prone position for 48 or more hours, in subjects with moderate to severe ARDS due to COVID-19, improves and maintains arterial oxygenation up to 48 hours after supination.

Abstract Low phosphorus (P) availability in soils is a major challenge for sustainable food production, as most soil P is often unavailable for plant uptake and effective strategies to access this P are limited. Certain soil occurring bacteria and root exudate-derived compounds that release P are in combination promising tools to develop applications that increase phosphorus use efficiency in crops. Here, we studied the ability of root exudate compounds (galactinol, threonine, and 4-hydroxybutyric acid) induced under low P conditions to stimulate the ability of bacteria to solubilize P. Galactinol, threonine, and 4-hydroxybutyric acid were incubated with the P solubilizing bacterial strains Enterobacter cloacae, Pseudomonas pseudoalcaligenes, and Bacillus thuringiensis under either inorganic (calcium phosphate) or organic (phytin) forms of plant-unavailable P. Overall, we found that the addition of individual root exudate compounds did not support bacterial growth rates. However, root exudates supplemented to the different bacterial appeared to enhance P solubilizing activity and overall P availability. Threonine and 4-hydroxybutyric acid induced P solubilization in all three bacterial strains. Subsequent exogenous application of threonine to soils improved the root growth of corn, enhanced nitrogen and P concentrations in roots and increased available levels of potassium, calcium and magnesium in soils. Thus, it appears that threonine might promote the bacterial solubilization and plant-uptake of a variety of nutrients. Altogether, these findings expand on the function of exuded specialized compounds and propose alternative approaches to unlock existing phosphorus reservoirs of P in crop lands.

Introduction The expansion of higher education is a worldwide phenomenon. To our knowledge, there are no studies analyzing the trends in demands of enrollment in health-related studies in Spain. Therefore, the objective was to analyze the change in demand (the number of requests for enrollment divided by the number of offered places) for undergraduate health-related studies in Spain during the period 2015–2021 as well as compare the change by region in the pre (2015–2019) and pandemic (2020–2021) period. Methods This is an observational (ecological type) study with temporal series analyses using data from public (non-for-profit) higher education institutions from the Integrated University Information System. For the analysis by region, we calculated the demand of all twelve undergraduate health-related degrees and the percentages of change between both periods using the Wilcoxon test. The Joinpoint Regression program was used to analyze the trends in demand for each degree during the 7-year period. Results Significant (p < 0.001) increases in demand during the pandemic period were observed in all regions. During the pandemic, medicine, biomedicine, nursing, odontology and pharmacy presented a higher demand in comparison with data collected before the pandemic started. In contrast, this pattern was not confirmed in the following cases: physiotherapy, occupational therapy, podiatry, psychology, social work, human nutrition and dietetics. By regions, Navarra, Asturias, and La Rioja presented the most drastic changes. In regions with the biggest number of universities, such as Catalonia, Andalusia and Madrid, the change observed was smaller.

Abstract Cell mechanical properties have been proposed as label free markers for diagnostic purposes in diseases such as cancer. Cancer cells show altered mechanical phenotypes compared to their healthy counterparts. Atomic Force Microscopy (AFM) is a widely utilized tool to study cell mechanics. These measurements often need skilful users, physical modelling of mechanical properties and expertise in data interpretation. Together with the need to perform many measurements for statistical significance and to probe wide enough areas in tissue structures, the application of machine learning and artificial neural network techniques to automatically classify AFM datasets has received interest recently. We propose the use of self-organizing maps (SOMs) as unsupervised artificial neural network applied to mechanical measurements performed via AFM on epithelial breast cancer cells treated with different substances that affect estrogen receptor signalling. We show changes in mechanical properties due to treatments, as estrogen softened the cells, while resveratrol led to an increase in cell stiffness and viscosity. These data were then used as input for SOMs. Our approach was able to distinguish between estrogen treated, control and resveratrol treated cells in an unsupervised manner. In addition, the maps enabled investigation of the relationship of the input variables.

Abstract The exposure to environmental variations in pH and temperature has proven impacts on benthic ectotherms calcifiers, as evidenced by tradeoffs between physiological processes. However, how these stressors affect structure and functionality of mollusk shells has received less attention. Episodic events of upwelling of deep cold and low pH waters are well documented in eastern boundary systems and may be stressful to mollusks, impairing both physiological and biomechanical performance. These events are projected to become more intense, and extensive in time with ongoing global warming. In this study, we evaluate the independent and interactive effects of temperature and pH on the biomineral and biomechanical properties of Argopecten purpuratus scallop shells. Total organic matter in the shell mineral increased under reduced pH (~ 7.7) and control conditions (pH ~ 8.0). The periostracum layer coating the outer shell surface showed increased protein content under low pH conditions but decreasing sulfate and polysaccharides content. Reduced pH negatively impacts shell density and increases the disorder in the orientation of calcite crystals. At elevated temperatures (18 °C), shell microhardness increased. Other biomechanical properties were not affected by pH/temperature treatments. Thus, under a reduction of 0.3 pH units and low temperature, the response of A. purpuratus was a tradeoff among organic compounds (biopolymer plasticity), density, and crystal organization (mineral plasticity) to maintain shell biomechanical performance, while increased temperature ameliorated the impacts on shell hardness. Biopolymer plasticity was associated with ecophysiological performance, indicating that, under the influence of natural fluctuations in pH and temperature, energetic constraints might be critical in modulating the long-term sustainability of this compensatory mechanism.

Abstract Logging causes changes in habitat structure, which can potentially lead to variations in taxonomic and functional richness of biodiversity. Studies on how functional traits in birds are affected by logging operations can provide an important element for the understanding of ecosystem processes. In this paper, we examined how logging in subtropical Andean forests influenced taxonomic and functional diversity of cavity-nesting birds. We used these results to compare how logging affected ecosystem functions in temperate and subtropical forests of the Americas. We used point-counts to examine the effects of logging on taxonomic and functional traits in avian communities (Functional Richness, Functional evenness, Functional Divergence, and Community-weighted mean). We found that logging changed bird richness and abundance, although it had no effect on the functional response to the measured traits. The comparison of our results with those of temperate forests of Canada and Chile reveals differences in the functional richness of birds in these habitats, with a lower impact of logging on functional traits. We highlight the importance of including functional traits in the analyses, since the reduction in the species richness and abundance may not be translated into functional changes within the ecosystem.

Abstract Rhizobacterial communities can contribute to plant trait expression and performance, including plant tolerance against abiotic stresses such as drought. The conditioning of microbial communities related to disease resistance over generations has been shown to develop suppressive soils which aid in plant defense responses. Here, we applied this concept for the development of drought resistant soils. We hypothesized that soils conditioned under severe drought stress and tomato cultivation over two generations, will allow for plant selection of rhizobacterial communities that provide plants with improved drought resistant traits. Surprisingly, the plants treated with a drought-conditioned microbial inoculant showed significantly decreased plant biomass in two generations of growth. Microbial community composition was significantly different between the inoculated and control soils within each generation (i.e., microbial history effect) and for the inoculated soils between generations (i.e., conditioning effect). These findings indicate a substantial effect of conditioning soils on the abiotic stress response and microbial recruitment of tomato plants undergoing drought stress.

Abstract Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses ( 800 mg), either at the viral (1–7 days post-symptom onset), early inflammatory (8–15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37–4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4–15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400–800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Abstract Exposure to air particulate matter has been linked with hypertension and blood pressure levels. The metabolic risks of air pollution could vary according to the specific characteristics of each area, and has not been sufficiently evaluated in Spain. We analyzed 1103 individuals, participants in a Spanish nationwide population based cohort study (di@bet.es), who were free of hypertension at baseline (2008–2010) and completed a follow-up exam of the cohort (2016–2017). Cohort participants were assigned air pollution concentrations for particulate matter

BackgroundHealth technology assessment (HTA) is one of the main tools that health systems have to appraise evidence and determine the value of a given health technology. Although the existing HTA frameworks are useful tools for the evaluation of a wide range of health technologies, more and more experts, organizations across the world, and HTA agencies are highlighting the need to update or develop specific methodological frameworks for the evaluation of digital health technologies in order to take into account additional domains that cover these technologies’ intrinsic characteristics. ObjectiveThe purpose of our scoping review is to identify the methodological frameworks that are used worldwide for the assessment of digital health technologies; determine what dimensions and aspects are being considered; and generate, through a thematic analysis, a proposal for a methodological framework that is based on the most frequently described dimensions in the literature. MethodsThe scoping review will be performed in accordance with the guidelines established in the updated statement of the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). We will search for peer-reviewed and grey literature published between 2011 and the date of the search execution. The retrieved references will be reviewed in a single-blind manner by 2 independent authors, and their quality will be assessed by using the Critical Appraisal Skills Program tool. The ATLAS.ti software (Scientific Software Development GmbH) will be used for data extraction and to perform the thematic analysis. ResultsThe scoping review is currently (May 2022) in progress. It is expected to be completed in October 2022, and the final results of the research will be presented and published by November 2022. ConclusionsTo our knowledge, no studies have been published to date that identify the existing methodological frameworks for digital HTA, determine which dimensions must be evaluated for correct decision-making, and serve as a basis for the development of a methodological framework of reference that health care systems can use to carry out this kind of assessment. This work is intended to address this knowledge gap of key relevance for the field of HTA. International Registered Report Identifier (IRRID)DERR1-10.2196/39905

Objetivo: Describir una experiencia de vinculación con el medio entre la comunidad educativa perteneciente a establecimientos educacionales de la región de Coquimbo y la carrera de enfermería de la Universidad Católica del Norte (UCN) a través de capacitación surgida en tiempos de pandemia en el año 2020. Metodología: Artículo descriptivo que da cuenta de la ejecución de un proceso de capacitación e-learning a establecimientos educacionales con nexo con la Facultad de Medicina de la UCN, para posteriormente incluir establecimientos educacionales Programa de Acceso a la Educación Superior. Para el desarrollo del programa educativo se utilizaron las plataformas virtuales Classroom y Zoom. Resultados: Este programa ha contado con gran interés por parte tanto de los directivos como de los participantes. Se contó con 911 inscritos, de los cuales 661 finalizan la actividad, correspondiente a un 72% y 587 la aprueban, lo cual corresponde al 94% de las personas que finalizaron el programa educativo. La capacitación cuenta con dos actividades de evaluación, distribuidas en foro y evaluación de contenidos. El foro equivale a un 30% de la nota y la evaluación de contenidos a un 70%. Conclusiones: Durante la contingencia sanitaria por COVID.19 se vio la necesidad de implementar este programa educativo de vinculación para dar respuesta a la situación sanitaria del país. Esta experiencia permitió desarrollar educación para la salud a distancia, utilizando tecnología digital e innovación. El compromiso y la colaboración de las partes interesadas logró favorecer la prevención de la infección por SARS-CoV-2 y fomentar la promoción dela salud.

El manejo especializado de la vía aérea (VA) es fundamental en las unidades de urgencia donde la intubación orotraqueal ha sido la técnica de elección para lograrlo. Una VA difícil se define como una situación clínica en la cual un equipo médico entrenado experimenta dificultades en la ventilación y/o en intubación. La obstrucción aguda de la VA constituye una de las emergencias médicas más extremas, requiriendo intervención inmediata. Se presenta el caso de un paciente con estridor inspiratorio con criterios inmediatos de intubación donde se evidencia un tumor en cuerdas vocales con obstrucción de la vía aérea.

La mordedura de la araña de rincón es un motivo de consulta frecuente en los servicios de urgencia de Chile, que puede producir un cuadro severo con manifestaciones cutáneas y sistémicas. En Chile, Loxocelles laeta se ubica principalmente desde la I a la VIII región, aunque se han reportado casos de loxocelismo en todo el país. El veneno de esta araña tiene efecto cutáneo-necrosante, hemolítico, vasculítico y coagulante. Podemos identificar 3 tipos de loxocelismo: cutáneo necrótico (80% de los casos), cutáneo edematoso (5%) y cutáneo visceral (10-15%). Este último tiene una letalidad entre 1 y 3% del total de casos de loxocelismo, la cual depende en gran parte de la precocidad de su diagnóstico y manejo oportuno. Se debe controlar cualquier tipo de loxocelismo durante las primeras 24 a 48 horas y vigilar la aparición de síntomas y signos sugerentes del cuadro visceral. No existe ningún examen de laboratorio que confirme el diagnóstico, los cuales sólo se alteran de modo marcado en los casos viscerales. El manejo de las lesiones cutáneas es con hielo local, antiinflamatorios, antihistamínicos y curaciones seriadas. En caso del loxocelismo visceral, el tratamiento principal es de soporte. La dapsona fue una indicación frecuente en el pasado y se asocia a efectos adversos graves, siendo el principal la exacerbación de la hemólisis, por lo que actualmente su uso no está recomendado. El suero anti-loxoceles no tiene evidencia que avale menor severidad ni mortalidad del cuadro.

El enfisema subcutáneo se produce como complicación frecuente en intervenciones quirúrgicas, técnicas invasivas, ventilación mecánica, lesiones traqueales y neumotórax. La progresión fuera del tórax con afectación facial, abdominal e incluso inguinal puede producir un síndrome compartimental con compresión de estructuras aledañas como la tráquea y vasos del cuello, tal situación se ha denominado enfisema subcutáneo masivo. En este documento se reporta el caso de un paciente que desarrolló un enfisema subcutáneo masivo como signo precoz de lesión traqueal asociada a la intubación y ventilación a presión positiva.

Abstract Insects are known plant pests, and some of them such as Trichoplusia ni feed on a variety of crops. In this study, Trichoplusia ni was fed distinct diets of leaves of Arabidopsis thaliana or Solanum lycopersicum as well as an artificial diet. After four generations, the microbial composition of the insect gut was evaluated to determine if the diet influenced the structure and function of the microbial communities. The population fed with A. thaliana had higher proportions of Shinella, Terribacillus and Propionibacterium, and these genera are known to have tolerance to glucosinolate activity, which is produced by A. thaliana to deter insects. The population fed with S. lycopersicum expressed increased relative abundances of the Agrobacterium and Rhizobium genera. These microbial members can degrade alkaloids, which are produced by S. lycopersicum. All five of these genera were also present in the respective leaves of either A. thaliana or S. lycopersicum, suggesting that these microbes are acquired by the insects from the diet itself. This study describes a potential mechanism used by generalist insects to become habituated to their available diet based on acquisition of phytochemical degrading gut bacteria.

Abstract Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.

Soil microbiome disruption methods are regularly used to reduce populations of microbial pathogens, often resulting in increased crop growth. However, little is known about the effect of soil microbiome disruption on non-pathogenic members of the soil microbiome. Here, we applied soil microbiome disruption in the form of moist-heat sterilization (autoclaving) to reduce populations of naturally occurring soil microbiota. The disruption was applied to analyze bacterial community rearrangement mediated by four crops (corn, beet, lettuce, and tomato) grown in three historically distinct agroecosystem soils (conventional, organic, and diseased). Applying the soil disruption enhanced plant influence on rhizosphere bacterial colonization, and significantly different bacterial communities were detected between the tested crops. Furthermore, bacterial genera showed significant abundance increases in ways both unique-to and shared-by each tested crop. As an example, corn uniquely promoted abundances of Pseudomonas and Sporocytophaga, regardless of the disrupted soil in which it was grown. Whereas the promotion of Bosea, Dyadobacter and Luteoliobacter was shared by all four crops when grown in disrupted soils. In summary, soil disruption followed by crop introduction amplified the plant colonization of potential beneficial bacterial genera in the rhizosphere.

La trombosis arterial cerebral podría ser una complicación del cáncer, aumentando la morbi-mortalidad. A continuación, se presente el caso clínico de una mujer de 61 años, que debuta con cefalea, hematemesis y focalidad neurológica, se realiza estudios complementarios llegando al diagnóstico de evento vascular cerebral de tipo isquémico asociado a adenocarcinoma gástrico. La enfermedad cardiovascular es multicausal, por lo que se debe pensar en otras enfermedades como las neoplasias, que pudieran debutar como un evento vascular cerebral. Por lo tanto, el diagnóstico oportuno y tratamiento precoz son importantes.

Objective. To determine the reliability of a non-laboratorial questionnaire, the Encuesta de Identificación de Sujetos Metabólicamente Comprometidos en Fase-I (ESF-I) for identifying Metabolic Syndrome among a population in central Mexico. Methods. Clinical and biochemical parameters were collected for 232 participants from 1 June 2012 – 31 August 2013. Three definitions of Metabolic Syndrome (Harmonizing, National Cholesterol Education Program Expert Panel and Adult Treatment Panel III [ATPIII], and International Diabetes Federation [IDF]) were used to allocate subjects to either the normal or Metabolic Syndrome positive (MetS+) group. The predictability of the questionnaire was determined by the Area-Under-the-Receiver-Operating Characteristic curve (AUC). Youden's index was calculated and the highest score was considered the optimal cutoff value. Cohen´s kappa (κ) was calculated to determine the level of agreement between the ESF-I questionnaire (max score: 15 based on 15 items) and Metabolic Syndrome. Results. From 53.8% – 60.7% of the participants were determined to be MetS+. The average questionnaire score was significantly higher in the MetS+ group for each definition (4.0 vs. 8.0, P < 0.05). The ESF-I questionnaire was predictive for the Harmonizing definition (AUC = 0.841, 95%CI: 0.790 – 0.892), the ATPIII definition (AUC = 0.827, 95%CI: 0.774 – 0.880), and the IDF definition (AUC = 0.836, 95%CI: 0.785 – 0.887). A cutoff value of 7 was determined for each definition; therefore, the cohort was re-categorized based on questionnaire results. There was a strong agreement between the ESF-I questionnaire and MetS (Harmonizing: accuracy = 77.6%, κ = 0.554; ATPIII: accuracy = 74.1%, κ = 0.489; IDF: accuracy = 74.6%, κ = 0.495, P < 0.001). Conclusion. The ESF-I questionnaire can identify MetS+ patients, and therefore, lead to earlier diagnoses, reduced number of consultations, and lower costs with easier application.

SOX11 is an embryonic mammary epithelial marker that is normally silenced prior to birth. High SOX11 levels in breast tumours are significantly associated with distant metastasis and poor outcome in breast cancer patients. Here, we show that SOX11 confers distinct features to ER-negative DCIS.com breast cancer cells, leading to populations enriched with highly plastic hybrid epithelial/mesenchymal cells, which display invasive features and alterations in metastatic tropism when xenografted into mice. We found that SOX11+DCIS tumour cells metastasize to brain and bone at greater frequency and to lungs at lower frequency compared to cells with lower SOX11 levels. High levels of SOX11 leads to the expression of markers associated with mesenchymal state and embryonic cellular phenotypes. Our results suggest that SOX11 may be a potential biomarker for breast tumours with elevated risk of developing metastases and may require more aggressive therapies.

The role of root exudates has long been recognized for its potential to improve nutrient use efficiency in cropping systems. However, studies addressing the variability of root exudates involved in phosphorus solubilization across plant developmental stages remain scarce. Here, we grew Arabidopsis thaliana seedlings in sterile liquid culture with a low, medium, or high concentration of phosphate and measured the composition of the root exudate at seedling, vegetative, and bolting stages. The exudates changed in response to the incremental addition of phosphorus, starting from the vegetative stage. Specific metabolites decreased in relation to phosphate concentration supplementation at specific stages of development. Some of those metabolites were tested for their phosphate solubilizing activity, and 3-hydroxypropionic acid, malic acid, and nicotinic acid were able to solubilize calcium phosphate from both solid and liquid media. In summary, our data suggest that plants can release distinct compounds to deal with phosphorus deficiency needs influenced by the phosphorus nutritional status at varying developmental stages.

This study aimed to assess agreement between antenatal estimates of gestational age by ultrasound and clinical records at birth in the Brazilian Amazon. Ultrasound examinations were scheduled during the second trimester for 578 pregnant women prospectively screened at primary health care units, following a standardized protocol for image quality control. A multistage algorithm was used to assess the best estimate of gestational age during the antenatal period, considering reliability of last menstrual period (LMP) and acceptable differences in relation to ultrasound estimates derived from fetal biparietal diameter and femur length. Agreement of antenatal estimates of gestational age confirmed by ultrasound and clinical records at birth was analyzed with Bland-Altman plots and kappa coefficients (preterm and postterm births). Overall, ultrasound examinations presented high quality (>90% of satisfactory images), and were adopted as the best estimate of gestational age among 83.4% of pregnant women, confirming reliable LMP in the remaining proportion. On average, difference in gestational age between antenatal estimates and clinical records was 0.43 week (95% CI: 0.32, 0.53). Classification of preterm births had a good agreement (kappa: 0.82, p11 years of education and cases of caesarean deliveries. In conclusion, high-quality ultrasound images from the second trimester of pregnancy based the assessment of gestational age, while reliability of LMP was limited. Information from clinical records at birth presented an acceptable agreement on average and for classification of preterm births, which is relevant for properly interpreting perinatal outcomes. Discrepancies in caesarean deliveries may warrant further investigation.

BackgroundViral hepatitis (hepatitis A, B, C, D and E) remains a public health problem in Peru, with a high disease burden. There are limited data on the prevalence of viral hepatitis at a national level, and none reported for over two decades. In this study, the prevalence rates of hepatitis A (HAV), B (HBV), C (HCV), D (HDV) and E virus (HEV) infections in the Peruvian population were determined to provide updated baseline data that would help guide the development of strategies aimed at reducing the transmission of viral hepatitis in Peru.MethodsWe conducted a cross-sectional, population-based study in the 25 regions of Peru. The study included participants of both sexes, aged 15-69 years, who had lived for >6 months in a specific region of Peru. Serum samples were analyzed by ELISA for anti-HAV (IgG), anti-HBs ≥10 mUI/ml, anti-HCV, anti-HDV and anti-HEV (IgG) antibodies, and by chemiluminescence for the HBV surface antigen (HBsAg) and antibodies against the core HBV antigen (anti-HBc IgM and IgG).ResultsIn a total of 5183 study participants, the prevalence rates of anti-HAV (IgG), HBsAg, total anti-HBc IgG, anti-HBs ≥10 mUI/ml, anti-HCV and anti-HEV (IgG) were 98.4% [95% confidence interval (CI) 98.0-98.7), 0.4% (95% CI 0.21-0.55), 10.1% (95% CI 9.4-11.0), 60% (95% CI 58.5-61.2), 0.1% (95% CI 0.02-0.25), and 14% (95% CI 13.1-15.0%), respectively. The prevalence of anti-HDV among HBsAg carriers was 15% (3/20).ConclusionsThe prevalence of HAV and HEV in the population aged 15-69 years in Peru is high, while the prevalence of HBV and HDV has changed from intermediate to low endemicity level and the prevalence of HCV is low. These findings would prove useful in the development of new strategies aimed at reducing the transmission of viral hepatitis in Peru, with a view to ultimately eliminating these infections in the future.

Abstract Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria development: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Quantitative analysis was performed in a first discovery cohort by isobaric labeling methodology. Alterations of proteins of interest were confirmed by target mass spectrometry analysis in an independent cohort. A total of 2416 proteins and 1223 functional categories (coordinated protein responses) were identified. Immune response, adhesion of immune and blood cells, and phagocytosis were found significantly altered in patients with albuminuria compared to normoalbuminuric individuals. The complement system C3 increases, while Annexin A1, CD44, S100A8 and S100A9 proteins showed significant diminishment in their urinary levels when albuminuria is present. This study reveals specific links between immune response and controlled hypertension in patients who develop albuminuria, pointing to potential protein targets for novel and future therapeutic interventions.

Abstract Candida albicans is an opportunistic pathogen, typically found as a benign commensal yeast living on skin and mucosa, but poised to invade injured tissue to cause local infections. In debilitated and immunocompromised individuals, C. albicans may spread to cause life-threatening systemic infections. Upon contact with serum and at body temperature, C. albicans performs a regulated switch to filamentous morphology, characterized by emergence of a germ tube from the yeast cell followed by mold-like growth of branching hyphae. The ability to switch between growth morphologies is an important virulence factor of C. albicans. To identify compounds able to inhibit hyphal morphogenesis, we screened libraries of existing drugs for inhibition of the hyphal switch under stringent conditions. Several compounds that specifically inhibited hyphal morphogenesis were identified. Chemogenomic analysis suggested an interaction with the endocytic pathway, which was confirmed by direct measurement of fluid-phase endocytosis in the presence of these compounds. These results suggest that the activity of the endocytic pathway, which is known to be particularly important for hyphal growth, represents an effective target for hyphae-inhibiting drugs.

Background. Intestinal-type adenocarcinoma (ITAC) is a rare tumour occurring in the ethmoid sinus. Recent years have brought advances in endoscopic surgery and precision radiotherapy; however, five-year overall survival has not improved and remains at 35–80%, depending on tumour stage and histology. Therefore, there is a need for new therapeutic options. Methods. We evaluated CD8+ tumour-infiltrating lymphocytes (TILs) and tumour microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) as predictive biomarkers for immunotherapy in a series of 133 ITAC. All results were correlated to clinical and follow-up data. Results. The presence of intratumoural CD8+ TILs was low in 57% of cases and high in 8% of cases. Tumoural PD-L1 positivity was observed in 26% of cases. CD8+ TILs and TMIT correlated with the histological subtype of ITAC and with better overall survival. The presence of stromal PD-L1-positive macrophages was related to intratumoural CD8+ TILs. PD-L1 expression on tumour cells or macrophages did not show prognostic value. Conclusions. TMIT classification did not have additional prognostic value over CD8+ TILs alone. The modest percentage of CD8high/PD-L1pos cases indicates that ITAC is a lowly immunogenic tumour type. Nevertheless, a proportion of ITAC, especially the papillary and colonic subtypes, could benefit from therapy with immune checkpoint inhibitors.

The global incidence of calcific aortic stenosis (CAS) is increasing owing, in part, to a growing elderly population. The condition poses a great challenge to public health, because of the multiple comorbidities of these older patients. Using a rabbit model of CAS, we sought to characterize protein alterations associated with calcified valve tissue that can be ultimately measured in plasma as non-invasive biomarkers of CAS. Aortic valves from healthy and mild stenotic rabbits were analyzed by two-dimensional difference gel electrophoresis, and selected reaction monitoring was used to directly measure the differentially expressed proteins in plasma from the same rabbits to corroborate their potential as diagnostic indicators. Similar analyses were performed in plasma from human subjects, to examine the suitability of these diagnostic indicators for transfer to the clinical setting. Eight proteins were found to be differentially expressed in CAS tissue, but only three were also altered in plasma samples from rabbits and humans: transitional endoplasmic reticulum ATPase, tropomyosin α-1 chain and L-lactate dehydrogenase B chain. Results of receiver operating characteristic curves showed the discriminative power of the scores, which increased when the three proteins were analyzed as a panel. Our study shows that a molecular panel comprising three proteins related to osteoblastic differentiation could have utility as a serum CAS indicator and/or therapeutic target.

Plant–microbial interactions in the litter layer represent one of the most relevant interactions for biogeochemical cycling as litter decomposition is a key first step in carbon and nitrogen turnover. However, our understanding of these interactions in the litter layer remains elusive. In an old-growth mixed Nothofagus forest in Patagonia, we studied the effects of single tree species identity and the mixture of three tree species on the fungal and bacterial composition in the litter layer. We also evaluated the effects of nitrogen (N) addition on these plant–microbial interactions. In addition, we compared the magnitude of stimulation of litter decomposition due to home field advantage (HFA, decomposition occurs more rapidly when litter is placed beneath the plant species from which it had been derived than beneath a different plant species) and N addition that we previously demonstrated in this same forest, and used microbial information to interpret these results. Tree species identity had a strong and significant effect on the composition of fungal communities but not on the bacterial community of the litter layer. The microbial composition of the litter layer under the tree species mixture show an averaged contribution of each single tree species. N addition did not erase the plant species footprint on the fungal community, and neither altered the bacterial community. N addition stimulated litter decomposition as much as HFA for certain tree species, but the mechanisms behind N and HFA stimulation may have differed. Our results suggest that stimulation of decomposition from N addition might have occurred due to increased microbial activity without large changes in microbial community composition, while HFA may have resulted principally from plant species’ effects on the litter fungal community. Together, our results suggest that plant–microbial interactions can be an unconsidered driver of litter decomposition in temperate forests.

The study of binding site similarities can be relevant to understand the interaction of different drugs at several molecular targets. The increasing availability of protein crystal structures and the development of novel algorithms designed to evaluate three-dimensional similarities, represent a great opportunity to explore the existence of electronic and shape features shared by clinically relevant proteins, which could assist drug design and discovery. Proteins involved in the recognition of monoaminergic neurotransmitters, such as monoamine transporters or monoamine oxidases (MAO) have been related to several psychiatric and neurological disorders such as depression or Parkinson's disease. In this work, we evaluated the possible existence of similarities among the binding sites of the serotonin transporter (SERT), the dopamine transporter (DAT), MAO-A and MAO-B. This study was carried out using molecular simulation methodologies linked to the statistical algorithm PocketMatch, which was modified in order to obtain similarities profiles. Our results show that DAT and SERT exhibit a high degree of 3-D similarities all along the pathway that is presumably involved in the substrate transport process. Distinct differences, on the other hand, were found both at the extracellular and the intracellular ends of the transporters, which might be involved in the selective initial recognition of the corresponding substrate. Similarities were also found between the active (catalytic) site of MAO-A and the extracellular vestibule of SERT (the S2 binding site). These results suggest some degree of structural convergence for these proteins, which have different functions, tissue distribution and genetic origin, but which share the same endogenous ligand (serotonin). Beyond the functional implications, these findings are valuable for the design of both selective and non-selective ligands.

Fundamentos: La carga económica de la asistencia sanitaria del cáncer de mama es importante. En el contexto de la evaluación del programa de cribado de cáncer de mama del País Vasco es importante conocer los costes unitarios actuales del diagnóstico y el coste de los tratamientos desagregados por el estadío clínico de detección. El objetivo de este estudio fue calcular los costes total y desagregado por componentes del tratamiento del cáncer de mama (CM) según estadío clínico en el año 2011. Métodos: Los costes sanitarios se estimaron desde el diagnóstico hasta la finalización de los tratamientos y seguimiento a partir del consumo de recursos y los costes unitarios del Sistema Vasco de Salud. La técnica aplicada fue el método de micro-costes a partir de las guías de práctica clínica. Resultados: El coste inicial fue de 9.838 € en el estadío 0, de 17.273€ en el I, de 22.145 € en el II y de 28.776 € en el III. El coste del seguimiento anual fue de 172 € en el estadío 0, de 908 € en el I, de 994 € en el II y de 1.166€ en el III. El coste anual del estadío IV fue de 17.879 €. Conclusiones: El componente de mayor coste es la quimioterapia. Los dos determinantes principales del coste total del cáncer de mama son el tratamiento inicial de los estadíos I a III y el coste del estadío IV alcanzando este último los 50.061 € por paciente.

B-1 lymphocytes are known to increase the metastatic potential of B16F10 melanoma cells via the extracellular signal-regulated kinase (ERK) pathway. Since IL-10 is associated with B-1 cells performance, we hypothesized that IL-10 could be implicated in the progression of melanoma. In the present work, we found that the C57BL/6 mice, inoculated with B16F10 cells that were co-cultivated with B-1 lymphocytes from IL-10 knockout mice, developed fewer metastatic nodules than the ones which were injected with the melanoma cells that were cultivated in the presence of wild-type B-1 cells. The impairment of metastatic potential of the B16F10 cells was correlated with low activation of the ERK signaling pathway, supporting the idea that the production of IL-10 by B-1 cells influences the behavior of the tumor. A microarray analysis of the B-1 lymphocytes revealed that IL-10 deficiency is associated with down-regulation of the genes that code for claudin-10, a protein that is involved in cell-to-cell contact and that has been linked to lung adenocarcinoma. In order to determine the impact of claudin-10 in the cross-talk between B-1 lymphocytes and the B16F10 tumor cells, we took advantage of small interfering RNA. The silencing of claudin-10 gene in B-1 lymphocytes inhibited activation of the ERK pathway and abrogated the B-1-induced aggressive behavior of the B16F10 cells. Thus, our findings suggest that the axis IL-10/claudin-10 is a promising target for the development of therapeutic agents against aggressive melanoma.

Interneurons are critical for proper neural network function and can activate Ca2+ signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAA receptors, potentiation involved astrocyte GABAB receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABAB receptor (Gabbr1) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.

El sobrepeso y la obesidad en niños y adolescentes representa un serio problema de salud pública en el Perú, con elevados costos para la sociedad, esto hace necesaria la implementación de un conjunto de políticas públicas dirigidas hacia el control de dicho inconveniente. Así, se han propuesto intervenciones como la regulación de la publicidad de alimentos no saludables, su autorregulación, la implementación de quioscos saludables y el etiquetado nutricional. Desde el análisis de la problemática del sobrepeso y obesidad en niños y adolescentes en el Perú, el presente artículo hace una revisión narrativa de dichas intervenciones.

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La formación de estudiantes de enfermería debe potenciar sus habilidades para brindar cuidados adecuados, vinculando experiencias propias, conocimientos científicos, habilidades técnicas, valores y motivación para trabajar por y para otros. Existe riesgo de deshumanización debido a los modelos institucionales administrativos y técnicos de los centros de salud. El cuidado humanizado propende al desarrollo de una relación transpersonal, considera valores y necesidades superiores de personas que vivencian el proceso de salud, enfermedad y el bien morir. El objetivo de este trabajo fue identificar habilidades para brindar cuidado humanizado desde la perspectiva de estudiantes. Se trata de un estudio descriptivo y transversal con una población de 98 estudiantes de enfermería de 3° y 4° año (n = 57; 3° = 20; 4° = 37) a los que se les solicitó consentimiento informado así como también autorización a la coordinación de la carrera. Se utilizó como instrumento el Inventario de habilidades del cuidado, el cual mide las áreas de Conocimiento, Valor o Coraje y Paciencia correspondientes a un valor α de Cronbach de 0.74. Se utilizaron estadígrafos de distribución de frecuencias, media de datos agrupados, promedios y porcentajes (Software SPSS-15). Los resultados muestran que se obtuvo un resultado de 63% en Paciencia, un 35% en Conocimiento y sólo un 2% en Valor-Coraje. La Paciencia requiere del ejercicio de tolerancia, respeto y adaptación frente a la incertidumbre situacional, generándose un vínculo estrecho entre la persona y el estudiante; fue la habilidad mejor evaluada. El Conocimiento incluye autoconocimiento y conocimiento del otro; está menos desarrollado, provocando una brecha en el acto de cuidar. El bajo resultado en Valor-Coraje señala la dificultad para enfrentarse a lo desconocido y en la propia capacidad de cuidar, influyendo negativamente en el desarrollo de la fuerza necesaria para afrontar el cuidado adecuado. Estos resultados muestran la necesidad de fortalecer en estudiantes de enfermería habilidades de afrontamiento ante situaciones cotidianas emergentes, especialmente las dimensiones de Conocimiento y de Valor.

Objetivo: Determinar el nivel de actividad física global de los pacientes con factores de riesgo cardiovascular, mediante el cuestionario IPAQ. Material y métodos: Estudio tipo serie de casos. La población estuvo compuesta por pacientes con hipertensión arterial, obesidad y diabetes mellitus entre 35 y 69 años de edad. Se utilizó el IPAQ para medir el nivel de actividad física. Resultados: De 180 entrevistados, 122 (67,8%) fueron del sexo femenino. La edad media fue 56,9 ± 8,8 años, el IMC promedio fue 29,0 ± 5,2 (18,6 - 48,5). Ciento nueve (60,5%) pacientes tenían un solo factor de riesgo cardiovascular modificable por medio de actividad física, 59 (32,8%) dos factores y 12 (6,7%) tres factores. El tiempo promedio de diagnóstico en meses fue 34,6 (hipertensos) y 51,1 (diabéticos). El nivel de actividad física fue trabajo en 30 (16,7%) pacientes, en 80 (44,4%) moderado y en 70 (38,9%) alto. No hubo diferencias en el nivel de actividad física según la edad y sexo. Se encontró diferencia significativa en los pacientes con hipertensión quienes tenían actividad moderada (p=0,02) en los hipertensos obesos quienes tenían actividad físca alta (p=0,07). Conclusión: El nivel de actividad física global de los pacientes con factores de riesgo cardiovascular seleccionados fue predominantemente moderado y alto.(Rev Med Hered 2011;22:115-120).

Background: There is a frequent association between renal insufficiency and cardiovascular disease in patients with essential hypertension (HTN). The aim of this study was to analyze the relationship between ECG parameters and the progress of renal damage in patients with treated HTN. Methods: 109 patients with HTN had their microalbuminuria monitored over a 3-year time frame. During the last 3 months of follow-up, an ECG was recorded. Patients were divided into 3 groups according to the deterioration of their renal function: normoalbuminuria during the study period (normo–normo; n = 51); normoalbuminuria developing microalbuminuria (normo–micro; n = 29); and microalbuminuria at baseline (micro–micro; n = 29). Results: There were no differences in presence of left ventricular hypertrophy between the 3 groups. RV6/RV5 >1 was observed more frequently as renal function declined (p = 0.025). The 12-lead QRS-complex voltage-duration product was significantly increased in patients without microalbuminuria at baseline who went on to develop microalbuminuria (p = 0.006). Patients who developed microalbuminuria during follow-up, with positive Cornell voltage criteria, showed a lesser degree of progression of microalbuminuria when compared with the rest of the subgroups (p = 0.044). Furthermore, patients with microalbuminuria at baseline treated with angiotensin receptor blockers and diuretics, and positive Cornell voltage criteria, showed a higher degree of microalbuminuria compared to those with negative Cornell voltage criteria (p = 0.016). Conclusions: In patients with HTN, we identified some ECG parameters, which predict renal disease progression in patients with HTN, which may permit the identification of patients who are at risk of renal disease progression, despite optimal antihypertensive pharmacotherapy.

HGF/Met signaling has recently been associated with basal-type breast cancers, which are thought to originate from progenitor cells residing in the luminal compartment of the mammary epithelium. We found that ICAM-1 efficiently marks mammary luminal progenitors comprising hormone receptor-positive and receptor-negative cells, presumably ductal and alveolar progenitors. Both cell populations strongly express Met, while HGF is produced by stromal and basal myoepithelial cells. We show that persistent HGF treatment stimulates the clonogenic activity of ICAM1-positive luminal progenitors, controlling their survival and proliferation, and leads to the expression of basal cell characteristics, including stem cell potential. This is accompanied by the induction of Snai1 and Snai2, two major transcription factors triggering epithelial–mesenchymal transition, the repression of the luminal-regulatory genes Elf5 and Hey1, and claudin down-regulation. Our data strongly indicate that paracrine Met signaling can control the function of luminal progenitors and modulate their fate during mammary development and tumorigenesis.

Evidence from systems biology indicates that promiscuous drugs, i.e. those that act simultaneously at various protein targets, are clinically better in terms of efficacy, than those that act in a more selective fashion. This has generated a new trend in drug development called polypharmacology. However, the rational design of promiscuous compounds is a difficult task, particularly when the drugs are aimed to act at receptors with diverse structure, function and endogenous ligand. In the present work, using docking and molecular dynamics methodologies, we established the most probable binding sites of SB-206553, a drug originally described as a competitive antagonist of serotonin type 2B/2C metabotropic receptors (5-HT2B/2CRs) and more recently as a positive allosteric modulator of the ionotropic α7 nicotinic acetylcholine receptor (nAChR). To this end, we employed the crystal structures of the 5-HT2BR and acetylcholine binding protein as templates to build homology models of the 5-HT2CR and α7 nAChR, respectively. Then, using a statistical algorithm, the similarity between these binding sites was determined. Our analysis showed that the most plausible binding sites for SB-206553 at 5-HT2Rs and α7 nAChR are remarkably similar, both in size and chemical nature of the amino acid residues lining these pockets, thus providing a rationale to explain its affinity towards both receptor types. Finally, using a computational tool for multiple binding site alignment, we determined a consensus binding site, which should be useful for the rational design of novel compounds acting simultaneously at these two types of highly different protein targets.

The serine–threonine kinase AKT regulates proliferation and survival by phosphorylating a network of protein substrates. In this study, we describe a kinase-independent function of AKT. In cancer cells harboring gain-of-function alterations in MET, HER2, or Phosphatidyl-Inositol-3-Kinase (PI3K), catalytically inactive AKT (K179M) protected from drug induced cell death in a PH-domain dependent manner. An AKT kinase domain mutant found in human melanoma (G161V) lacked enzymatic activity in vitro and in AKT1/AKT2 double knockout cells, but promoted growth factor independent survival of primary human melanocytes. ATP-competitive AKT inhibitors failed to block the kinase-independent function of AKT, a liability that limits their effectiveness compared to allosteric AKT inhibitors. Our results broaden the current view of AKT function and have important implications for the development of AKT inhibitors for cancer.