ERK5 signalling pathway is a novel target of sorafenib: Implication in EGF biology.

Sorafenib is a multikinase inhibitor widely used in cancer therapy with an antitumour effect related to biological processes as proliferation, migration or invasion, among others. Initially designed as a Raf inhibitor, Sorafenib was later shown to also block key molecules in tumour progression such as VEGFR and PDGFR. In addition, sorafenib has been connected with key signalling pathways in cancer such as EGFR/EGF. However, no definitive clue about the molecular mechanism linking sorafenib and EGF signalling pathway has been established so far. Our data in HeLa, U2OS, A549 and HEK293T cells, based on in silico, chemical and genetic approaches demonstrate that the MEK5/ERK5 signalling pathway is a novel target of sorafenib. In addition, our data show how sorafenib is able to block MEK5-dependent phosphorylation of ERK5 in the Ser218/Tyr220, affecting the transcriptional activation associated with ERK5. Moreover, we demonstrate that some of the effects of this kinase inhibitor onto EGF biological responses, such as progression through cell cycle or migration, are mediated through the effect exerted onto ERK5 signalling pathway. Therefore, our observations describe a novel target of sorafenib, the ERK5 signalling pathway, and establish new mechanistic insights for the antitumour effect of this multikinase inhibitor.

Time and energy reduction on grape dehydration by applying dipping solution on freeze drying process.

To preserve freshness and nutritional quality of fruits and vegetables is required large energy expenditure due to most storage techniques require low temperatures, making the product difficult to transport and store. PURPOSE: To reduce energy expenditure, dehydration processes are being improving by pretreatments and changing frozen stage. METHOD: Alkaline emulsion pretreatment was introduced to freeze-drying method to reduce the drying time of grapes and obtain significant energy savings. RESULTS: Dehydration process for untreated fresh grape samples was 22 hours, using industrial freeze-drying equipment. It was obtained a high quality product with range 3 % to 7% of final humidity, without losing natural characteristics and organoleptic properties of the grapes. CONCLUSIONS: it was found by modifying standard equipment frozen method, using dry ice (CO2) and applied coconut oil alkaline emulsion pretreatment, a 54% energy saving. Even more the dehydration process decreased the microbial load in the fruit. A product with low number of microorganisms may be consumed by patients with low defenses as cereals, nutritional bars, salads, yogurts, etc. Finally, if all enterprises involved in this field take into account these findings and improve constantly their process they will stop emitting several kg of CO2 into the atmosphere.

The Population Education Transition Curve: Education Gradients Across Population Exposure to New Health Risks.

The salutary effect of formal education on health-risk behaviors and mortality is extensively documented: ceteris paribus, greater educational attainment leads to healthier lives and longevity. Even though the epidemiological evidence has strongly indicated formal education as a leading "social vaccine," there is intermittent reporting of counter-education gradients for health-risk behavior and associated outcomes for certain populations during specific periods. How can education have both beneficial and harmful effects on health, and under which contexts do particular effects emerge? It is useful to conceptualize the influence of education as a process sensitive to the nature, timing of entry, and uniqueness of a new pleasurable and desirable lifestyle and/or product (such as smoking) with initially unclear health risks for populations. Developed herein is a hypothesis that the education gradient comprises multiple potent pathways (material, psychological, cognitive) by which health-risk behaviors are influenced, and that there can be circumstances under which pathways act in opposite directions or are differentially suppressed and enhanced. We propose the population education transition (PET) curve as a unifying functional form to predict shifting education gradients across the onset and course of a population's exposure to new health risks and their associated consequences. Then, we estimate PET curves for cases with prior epidemiological evidence of heterogeneous education gradients with health-risk behaviors related to mass-produced cigarettes in China and the United States; saturated fats, sugar, and processed food diets in Latin America; and HIV infection in sub-Saharan Africa. Each offers speculation on interactions between environmental factors during population exposure and education pathways to health-risk behaviors that could be responsible for the temporal dynamics of PET curves. Past epidemiological studies reporting either negative or positive education gradients may not represent contradictory findings as much as come from analyses unintentionally limited to just one part of the PET process. Last, the PET curve formulation offers richer nuances about educational pathways, macro-historical population dynamics, and the fundamental cause of disease paradigm.

A Review of Natural Fiber-Reinforced Composites for Lower-Limb Prosthetic Designs.

This paper presents a comprehensive review of natural fiber-reinforced composites (NFRCs) for lower-limb prosthetic designs. It covers the characteristics, types, and properties of natural fiber-reinforced composites as well as their advantages and drawbacks in prosthetic designs. This review also discusses successful prosthetic designs that incorporate NFRCs and the factors that make them effective. Additionally, this study explores the use of computational biomechanical models to evaluate the effectiveness of prosthetic devices and the key factors that are considered. Overall, this document provides a valuable resource for anyone interested in using NFRCs for lower-limb prosthetic designs.

A self-driven approach for multi-class discrimination in Alzheimer's disease based on wearable EEG.

Early detection is critical to control Alzheimer's disease (AD) progression and postpone cognitive decline. Traditional medical procedures such as magnetic resonance imaging are costly, involve long waiting lists, and require complex analysis. Alternatively, for the past years, researchers have successfully evaluated AD detection approaches based on machine learning and electroencephalography (EEG). Nonetheless, these approaches frequently rely upon manual processing or involve non-portable EEG hardware. These aspects are suboptimal regarding automated diagnosis, since they require additional personnel and hinder portability. In this work, we report the preliminary evaluation of a self-driven AD multi-class discrimination approach based on a commercial EEG acquisition system using sixteen channels. For this purpose, we recorded the EEG of three groups of participants: mild AD, mild cognitive impairment (MCI) non-AD, and controls, and we implemented a self-driven analysis pipeline to discriminate the three groups. First, we applied automated artifact rejection algorithms to the EEG recordings. Then, we extracted power, entropy, and complexity features from the preprocessed epochs. Finally, we evaluated a multi-class classification problem using a multi-layer perceptron through leave-one-subject-out cross-validation. The preliminary results that we obtained are comparable to the best in literature (0.88 F1-score), what suggests that AD can potentially be detected through a self-driven approach based on commercial EEG and machine learning. We believe this work and further research could contribute to opening the door for the detection of AD in a single consultation session, therefore reducing the costs associated to AD screening and potentially advancing medical treatment.

An Automated Approach for the Detection of Alzheimer's Disease From Resting State Electroencephalography.

Early detection is crucial to control the progression of Alzheimer's disease and to postpone intellectual decline. Most current detection techniques are costly, inaccessible, or invasive. Furthermore, they require laborious analysis, what delays the start of medical treatment. To overcome this, researchers have recently investigated AD detection based on electroencephalography, a non-invasive neurophysiology technique, and machine learning algorithms. However, these approaches typically rely on manual procedures such as visual inspection, that requires additional personnel for the analysis, or on cumbersome EEG acquisition systems. In this paper, we performed a preliminary evaluation of a fully-automated approach for AD detection based on a commercial EEG acquisition system and an automated classification pipeline. For this purpose, we recorded the resting state brain activity of 26 participants from three groups: mild AD, mild cognitive impairment (MCI-non-AD), and healthy controls. First, we applied automated data-driven algorithms to reject EEG artifacts. Then, we obtained spectral, complexity, and entropy features from the preprocessed EEG segments. Finally, we assessed two binary classification problems: mild AD vs. controls, and MCI-non-AD vs. controls, through leave-one-subject-out cross-validation. The preliminary results that we obtained are comparable to the best reported in literature, what suggests that AD detection could be automatically detected through automated processing and commercial EEG systems. This is promising, since it may potentially contribute to reducing costs related to AD screening, and to shortening detection times, what may help to advance medical treatment.

The cognitive and psychiatric subacute impairment in severe Covid-19.

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.

Educational Attainment and Psychological Distress Among Working-Age Adults in the United States.

This study builds on a growing body of literature analyzing the education-health gradient across detailed educational categories, which documents that US working-age adults who attended college but did not earn a bachelor's degree report equal or worse health than adults with a high school diploma. This is known as the "anomaly" in the education-health gradient. The purpose of this study is to test whether this pattern extends to measures of serious psychological distress (SPD) and individual symptoms by using data from the National Health Interview Survey (NHIS, 1997-2018) and a series of logistic regression models. We find that the anomaly in the education-health gradient is present for a summary measure of SPD as well as for five of the six symptoms that make up this measure. The exception was reporting feeling sad most or all the time during the last month, where adults with "some college" were found to have lower odds than those with a high school diploma. Further stratified analysis by sex revealed that this result for feeling sad was driven by women. In terms of associate degrees, our models show that adults with a vocational/technical associate degree have statically similar odds of SPD and reporting four out of six symptoms (exceptions were feeling hopeless and sadness), while those with an academic associate degree have significantly lower odds in all outcomes. The robustness of the models used is supported by an extensive sensitivity analysis. Overall, we find evidence of the anomaly in the education-health gradient in SPD and individual symptoms of psychological distress at the sub-baccalaureate level, adding to previous studies that document the anomaly in markers of physiological dysregulation, health conditions, vision problems, functional limitations, and pain.

A Symbiosis of Access: Proliferating STEM PhD Training in the U.S. from 1920-2010.

Over the course of the 20th century, unprecedented growth in scientific discovery was fueled by broad growth in the number of university-based scientists. During this period the American undergraduate enrollment rate and number of universities with STEM graduate programs each doubled three times and the annual volume of new PhDs doubled six times. This generated the research capacity that allowed the United States to surpass early European-dominated science production and lead for the rest of the century. Here, we focus on origins in the organizational environment and institutional dynamics instead of conventional economic factors. We argue that three trends of such dynamics in the development of American higher education not often considered together-mass undergraduate education, decentralized founding of universities, and flexible mission charters for PhD training-form a process characterized by a term coined here: access symbiosis. Then using a 90-year data series on STEM PhD production and institutional development, we demonstrate the historical progression of these mutually beneficial trends. This access symbiosis in the U.S., and perhaps versions of it in other nations, is likely one critical component of the integration of higher education development with the growing global capacity for scientific discovery. These results are discussed in terms of the contributions of American universities to the Century of Science, recent international trends, and its future viability.

Explaining the Education-Health Gradient in Preventing STIs in Andean Peru: Cognitive Executive Functioning, Awareness and Health Knowledge.

CONTEXT: Little is known about the pathways mediating the relationship between education and health. It is widely assumed that formal schooling leads to awareness of health risks (e.g., STIs) and, in turn, to adoption of preventive behavior (e.g., condom use); however, evidence supporting this mechanism has been limited. METHODS: Survey data were collected in 2010 from a sample of 247 adults aged 30-62 living in an isolated Andean district of Peru; these individuals had widely varying exposure to schooling, and their community had recently experienced elevated risks of STIs. Structural equation modeling was used to estimate the degree to which schooling is associated with cognitive resources, STI awareness and sexual health knowledge, and how these jointly are associated with ever-use of condoms. RESULTS: Thirty-two percent of respondents reported ever-use of condoms. One additional year of schooling was associated with a 2.7-percentage-point increase in the probability of condom use, after adjustment for covariates. The pathway between education and condom use was mediated by cognitive executive functioning (CEF) skills (0.26 standard deviations), STI awareness (0.09) and sexual health knowledge (0.10); CEF skills were associated with condom use both directly and indirectly, through STI awareness and sexual health knowledge, and accounted for two-thirds of the education-condom use gradient. CONCLUSIONS: The relationship between education and STI prevention may be more complex than is often assumed and is mediated by CEF skills, STI awareness and sexual health knowledge. Studies should examine whether STI prevention interventions are more effective if they enhance cognitive skills used to translate information into protective behaviors.

RESUMEN Contexto: Se sabe poco acerca de las vías que median la relación entre el nivel educativo y la salud. Generalmente se supone que la escolaridad formal conduce a la conciencia de los riesgos para la salud (por ejemplo, las ITS) y, a su vez, a la adopción de un comportamiento preventivo (por ejemplo, el uso del condón); sin embargo, la evidencia que apoya este mecanismo ha sido limitada. Métodos: Los datos de la encuesta se obtuvieron en 2010 de una muestra de 247 adultos de 30 a 62 años que vivían en un distrito andino aislado de Perú; estas personas tenían una exposición muy variable a la escolaridad y su comunidad había experimentado recientemente riesgos elevados de ITS. Se usó el modelo de ecuaciones estructurales para estimar el grado en que la escolaridad se asociaba con los recursos cognitivos, la conciencia de las ITS y el conocimiento de la salud sexual y cómo estos se asocian conjuntamente con el haber usado alguna vez condones. Resultados: El treinta y dos por ciento de los encuestados informaron que alguna vez usaron condones. Un año adicional de escolaridad se asoció con un aumento de 2.7 puntos porcentuales en la probabilidad de uso del condón, después del ajuste por covariables. La vía entre el nivel educativo y el uso del condón estuvo mediada por las habilidades de funcionamiento cognitivo ejecutivo (FCE) (0.26 desviaciones estándar), conciencia de las ITS (0.09) y conocimiento de salud sexual (0.10); Las habilidades de FCE se asociaron con el uso del condón tanto directa como indirectamente, a través de la conciencia de las ITS y los conocimientos sobre salud sexual y representaron dos tercios del gradiente educativo del uso del condón. Conclusiones: La relación entre el nivel educativo y la prevención de las ITS podría ser más compleja de lo que a menudo se supone y está mediada por las habilidades de FCE, la conciencia de las ITS y el conocimiento de la salud sexual. Los estudios deben examinar si las intervenciones de prevención de ITS son más efectivas si mejoran las habilidades cognitivas utilizadas para traducir la información en comportamientos protectores.

RÉSUMÉ Contexte: Les voies de médiation de la relation entre l'éducation et la santé ne sont guère documentées. Il est généralement présumé que la scolarité mène à la conscience des risques de santé (par ex., les IST), qui conduit à son tour à l'adoption d'un comportement préventif (par ex., l'utilisation du préservatif). Les données qui appuient ce mécanisme sont cependant limitées. Méthodes: Des données d'enquête ont été collectées en 2010 auprès d'un échantillon de 247 adultes de 30 à 62 ans vivant dans un district andin isolé du Pérou. Ces personnes présentaient une exposition fort variable à la scolarité et leur communauté était depuis peu confrontée à un risque élevé d'IST. La modélisation par équation structurelle a permis d'estimer le degré d'association entre, d'une part, la scolarité et, d'autre part, les ressources cognitives, la conscience des IST et la connaissance en matière de santé sexuelle, ainsi que de déterminer l'association globale de ces éléments avec le fait d'avoir déjà utilisé le préservatif. Résultats: Trente-deux pour cent des répondants ont déclaré avoir utilisé le préservatif. Chaque année supplémentaire de scolarité s'est avérée associée à une augmentation de 2,7 points de pourcentage de la probabilité d'usage du préservatif, sous correction des covariables. Le lien entre l'éducation et l'utilisation du préservatif était induit par les compétences de fonctionnement exécutif cognitif (FEC) (écarts types de 0,26), la conscience des IST (0,09) et la connaissance en matière de santé sexuelle (0,10). Les compétences FEC étaient associées à l'utilisation du préservatif de façon directe et indirecte, du fait de la conscience des IST et de la connaissance en matière de santé sexuelle; elles représentaient deux tiers du gradient éducation-utilisation du préservatif. Conclusions: La relation entre l'éducation et la prévention des IST peut être plus complexe qu'on ne le pense souvent. Elle est induite par les compétences FEC, la conscience des IST et la connaissance en matière de santé sexuelle. Il serait utile d'examiner si les interventions de prévention des IST sont plus efficaces quand elles améliorent les compétences cognitives qui traduisent l'information en comportements de protection.

PET-Amyloid After Inconclusive Cerebrospinal Fluid Biomarkers in Clinical Practice. Is it Necessary to Duplicate Procedures?

INTRODUCTION: In the absence of a gold standard for in vivo Alzheimer disease (AD) diagnosis, AD biomarkers such as cerebrospinal fluid biomarkers (CSF-B) and PET-Amyloid are considered diagnostically useful in clinical practice guidelines and have consensual appropriate use criteria (AUC). However, little evidence has been published on their utilization in the clinical setting or on approaches to mismatched results. The objective of this work was to evaluate the use of AD biomarkers in clinical practice, focusing on the implementation of PET-Amyloid in cases of inconclusive CSF-B. METHODS: This naturalistic, ambispective case series included patients fulfilling AUC for CSF-B and PET-Amyloid whose CSF-B results were non-diagnostic (target population), analyzing the diagnostic certainty, the treatment approach, and the relationship between CSF-B and PET-Amyloid results. RESULTS: Out of 2373 eligible patients, AD biomarkers were studied in 417 (17.6%), most frequently due to cognitive impairment in under 65-year-olds, using CSF-B in 311 patients and PET-Amyloid in 150. CSF-B results were non-diagnostic for 44 patients (52.3% male; aged 60.9±6.6 years), who then underwent PET-Amyloid study, which was positive in 31. A 'k' coefficient of 0.108 was obtained between CSF-B and PET-amyloid (54.5% concordance). In multivariate regression analysis, Aß42 was the only significant predictor (p= 0.018) of a positive PET-Amyloid result. In the target population, PETAmyloid increased diagnostic confidence by 53.7% (p <0.001) and modified the therapeutic approach in 36.4% of cases. CONCLUSION: These findings support the duplication of AD biomarkers and demonstrate that the implementation of PET-Amyloid provides an early and certain diagnosis to guide appropriate treatment.

Inestabilidad atlantoaxial: fijación transarticular con tornillos / Atlantoaxial instability: screw fixation technique

Introducción: los cerclajes de alambre para la estabilización atlantoaxial no controlan las fuerzas de carga axial, rotación o extensión. Magerl y Seemann (1979) reportaron la fijación transarticular con buenos resultados. En la literatura nacional no se han reportado experiencias con dicha técnica. El objetivo de este estudio fue revisar la experiencia en el manejo de inestabilidades atlantoaxiales mediante fijación transarticular con tornillos. Materiales y métodos: se diseñó un estudio observacional descriptivo, tipo serie de casos. 25 pacientes fueron intervenidos entre marzo de 1993 y junio del 2004. Los casos se tabularon según edad, sexo, etiología, déficit neurológico y complicaciones. La patología traumática se analizó según diagnóstico, mecanismos de trauma, compromiso neurológico y lesiones asociadas. Resultados: se incluyeron 25 pacientes, 8 mujeres (32%) y 17 hombres (62%) con una edad promedio de 40 años (15-83) y un promedio de seguimiento de 73 meses (30-165 meses). Se encontró etiología traumática en 18 casos (64%), inflamatoria en 6 (24%) y congénita en uno (4%). La lesión traumática más frecuente fue subluxación rotatoria fija de C1-C2 en 6 casos (33%). El mecanismo de producción más frecuente fue el accidente de tránsito en 8 casos (32%). Se encontró déficit neurológico preoperatorio en 2 pacientes (11%). En cuanto a las complicaciones, hubo infección superficial en 2 casos (8%) y se presentaron dos fallas de material y una inestabilidad subaxial en el seguimiento tardío. No se documentaron pseudoartrosis sintomáticas ni complicaciones vasculares o neurológicas. Discusión: la técnica de fijación atlantoaxial transarticular es segura y proporciona estabilidad biomecánica inmediata, facilitando la rehabilitación.

[Repercussion on the hemodynamic measurements across a Swan-Ganz catheter with the postural changes]. / Repercusión en las mediciones hemodinámicas a través de un Swan-Ganz con los cambios posturales.

AIM: Usually hemodynamic measures are done with the patient in dorsal decubitus and the bedside at 0 degrees. Our aim has been to evaluate the influence that postural changes has in the hemodynamic measures which were carried out with a pulmonary artery catheter, so as called Swan-Ganz. MATERIAL AND METHOD: It's a prospective study. The same patient is control group and study group. There were done tree consecutive measures in each patient. Firstly in dorsal decubitus, then right lateral decubitus and finally in left lateral decubitus. Before doing the measures after change of posture a thirty minutes period was left in order to stabilise the hemodynamical flow. The items of study were, a part of demographic ones, cardiac index, pulmonary artery systolic pressure, pulmonary artery diastolic pressure, pulmonary artery mean pressure, pulmonary artery occlusion pressure, right atrial pressure, systolic arterial pressure, diastolic arterial pressure, mean arterial pressure and heart rate. 28 patients were included in the study. RESULTS: The age average was 62.5 years (27.05-67.05); a 78.6% were male. Who had a NEMS average of 42.4 (39.9-44.9). No difference was found between hemodynamic measures in the different postures. CONCLUSIONS: Postural changes in stable patients have no influence in pressures and other hemodynamic variables measures.