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Abstract Background The emergence of new SARS-CoV-2 variants and the waning of immunity raise concerns about vaccine effectiveness and protection against COVID-19. While antibody response has been shown to correlate with the risk of infection with the original variant and earlier variants of concern, the effectiveness of antibody-mediated protection against Omicron and the factors associated with protection remain uncertain. Methods We evaluated antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from Wuhan and variants of concern by Luminex and their role in preventing breakthrough infections 1 year after a third dose of mRNA vaccination, in a cohort of health care workers followed since the pandemic onset in Spain (N = 393). Data were analyzed in relation to COVID-19 history, demographic factors, comorbidities, vaccine doses, brand, and adverse events. Results Higher levels of anti-S IgG and IgA to Wuhan, Delta, and Omicron were associated with protection against vaccine breakthroughs (IgG against Omicron S antigen HR, 0.06, 95%CI, 0.26–0.01). Previous SARS-CoV-2 infection was positively associated with antibody levels and protection against breakthroughs, and a longer time since last infection was associated with lower protection. In addition, priming with BNT162b2 followed by mRNA-1273 booster was associated with higher antibody responses than homologous mRNA-1273 vaccination. Conclusions Data show that IgG and IgA induced by vaccines against the original strain or by hybrid immunization are valid correlates of protection against Omicron BA.1 despite immune escape and support the benefits of heterologous vaccination regimens to enhance antibodies and the prioritization of booster vaccination in individuals without recent infections.

Metastasis is the leading cause of cancer-related deaths, making the development of novel, more effective therapies imperative to alleviate patient suffering. Metabolic switching is a hallmark of cancer cells that facilitates metastasis. Cancer cells obtain most of their energy and intermediate metabolites, which are required to proliferate and metastasize, through aerobic glycolysis. Previous work from our laboratory has shown that Caveolin-1 (CAV1) expression in cancer cells promotes glycolysis and metastasis. Here, we sought to determine if limiting glycolysis reduced CAV1-enhanced metastasis and to identify the mechanism(s) involved. We evaluated the effects of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) in metastatic melanoma and breast cancer cell lines expressing or not CAV1. Non-cytotoxic concentrations of 2-DG (1 mM) inhibited the migration of B16-F10 melanoma and MDA-MB-231 breast cancer cells. CAV1-mediated activation of Src/Akt signaling was required for CAV1-enhanced migration and was blocked in the presence of 2-DG. Moreover, inhibition of Akt reduced CAV1-enhanced lung metastasis of B16-F10 cells. Collectively, these findings highlight the importance of CAV1-induced metabolic reprogramming for metastasis and point towards possible therapeutic approaches to prevent metastatic disease by inhibiting glycolysis and Src/Akt signaling.

Background The Atlantic mackerel, Scomber scombrus (Linnaeus, 1758) is a commercially valuable migratory pelagic fish inhabiting the northern Atlantic Ocean and the Mediterranean Sea. Given its highly migratory behaviour for feeding and spawning, several studies have been conducted to assess differentiation among spawning components to better define management units, as well as to investigate possible adaptations to comprehend and predict recent range expansion northwards. Methods Here, a high-quality genome of S. scombrus was sequenced and annotated, as an increasing number of population genetic studies have proven the relevance of reference genomes to investigate genomic markers/regions potentially linked to differences at finer scale. Such reference genome was used to map Restriction-site-associated sequencing (RAD-seq) reads for SNP discovery and genotyping in more than 500 samples distributed along the species range. The resulting genotyping tables have been used to perform connectivity and adaptation analyses. Results The assembly of the reference genome for S. scombrus resulted in a high-quality genome of 741 Mb. Our population genetic results show that the Atlantic mackerel consist of three previously known genetically isolated units (Northwest Atlantic, Northeast Atlantic, Mediterranean), and provide no evidence for genetically distinct spawning components within the Northwest or Northeast Atlantic. Conclusions Therefore, our findings resolved previous uncertainties by confirming the absence of genetically isolated spawning components in each side of the northern Atlantic, thus rejecting homing behaviour and the need to redefine management boundaries in this species. In addition, no further genetic signs of ongoing adaptation were detected in this species.

Salinity is a very important parameter from an environmental perspective, and therefore, efficient and accurate systems are required for marine environmental monitoring and productive industries. A plasmonic sensor based on doubly deposited tapered optical fibers (DLUWTs—double-layer uniform-waist tapers) for the measurement of salinity is presented. The physical principle of the sensor, as well as its structure, is discussed, and its performance is experimentally demonstrated, obtaining very good sensitivities. The possibility of shifting towards higher wavelength measuring ranges associated with DLUWTs is also exploited. At the same time, we have considered the necessity of an extensive characterization of the behavior of the refractive index of salty water, both with variations in temperature and the composition of the salts dissolved. This is important due to the somehow changing reality of salinity measurements and the possibility of establishing new approaches for the determination of absolute salinity as opposed to practical salinity based on electrical conductivity measurements. The results obtained, which show high sensitivity and a good performance in general without the need for the use of semi-empirical algorithms, permit, in our opinion, an advance in the tendency towards refractometric determination of salinity with optical sensors apt for in situ, real-time, accurate measurements in realistic measuring conditions.

Background: Muscle Tension Dysphonia is a relatively new clinical entity that, despite being one of the most frequent causes of functional dysphonia, is little-known by many otorhinolaryngologists. Objective: The objective of the current work is to describe the evolution of Muscle Tension Dysphonia—the concepts and the ways it has been diagnosed and treated—from its first descriptions to our current knowledge. Design: A scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. A search of three bibliographic databases was performed to identify original articles on Muscle Tension Dysphonia. Study selection and characterization was conducted by three independent reviewers and was further reviewed by a fourth individual. In case of relocating any of the studies, it was performed by agreement of two reviewers. We excluded articles not written in English or Spanish, letters to the editor, review articles, studies of the pediatric population, articles related to dysphagia, and other publications that were not relevant. Results: The search identified 1144 articles published from 1983 to December 2022. A total of 581 studies were repeated and another 462 were excluded because they were not written in English or Spanish, were not original articles, or were not relevant to the objective of the study. Finally, 101 articles were included in the review. The articles included in the review were divided into three groups considering the objective and conclusions of each study: 21 articles were classified as “Etiology and Physiopathology”, 29 articles as “Diagnosis”, and 51 articles were included in the “Treatment” group. Conclusions: The concept of Muscle Tension Dysphonia has been developed during the last forty years. For its diagnosis, endoscopic visualization of the larynx is crucial, but must be combined with the patient’s clinical history and other methods can also be useful. This entity should be addressed in a multidisciplinary approach, with the active participation of speech therapists. Most therapeutic options include voice education, vocal hygiene, and rehabilitation of the voice.

Thyme oil (THO) possesses excellent antibacterial and antioxidant properties which are suitable for skin inflammatory disorders such as acne vulgaris. However, THO is insoluble in water and its components are highly volatile. Therefore, these drawbacks may be overcome by its encapsulation in biodegradable PLGA nanoparticles (THO-NPs) that had been functionalized using several strategies. Moreover, cell viability was studied in HaCat cells, confirming their safety. In order to assess therapeutic efficacy against acne, bacterial reduction capacity and antioxidant properties were assessed. Moreover, the anti-inflammatory and wound-healing abilities of THO-NPs were also confirmed. Additionally, ex vivo antioxidant assessment was carried out using pig skin, demonstrating the suitable antioxidant properties of THO-NPs. Moreover, THO and THO-NPs were dispersed in a gelling system, and stability, rheological properties, and extensibility were assessed. Finally, the biomechanical properties of THO-hydrogel and THO-NP-hydrogel were studied in human volunteers, confirming the suitable activity for the treatment of acne. As a conclusion, THO has been encapsulated into PLGA NPs, and in vitro, ex vivo, and in vivo assessments had been carried out, demonstrating excellent properties for the treatment of inflammatory skin disorders.

El artículo expone las principales fortalezas, limitaciones y desafíos de la escuela multinivel en contexto indígena, desde las voces de los profesores en La Araucanía (Chile). La metodología es cualitativa, se aplicaron seis entrevistas semiestructuradas a profesores; la técnica de análisis de la información es el análisis de contenido en complementariedad con la teoría fundamentada. Los resultados revelan la persistencia de prejuicios hacia la familia indígena, el desconocimiento de los profesores sobre los saberes locales y la carencia de competencias para desarrollar una educación en perspectiva intercultural. Se concluye la necesidad de vinculación y diálogo entre escuela-familia-comunidad, lo que permita la revitalización de la identidad sociocultural en los procesos de enseñanza y aprendizaje.

Caveolin-1 (CAV1) is a membrane-bound protein that suppresses tumor development yet also promotes metastasis. E-cadherin is important in CAV1-dependent tumor suppression and prevents CAV1-enhanced lung metastasis. Here, we used murine B16F10 and human A375 melanoma cells with low levels of endogenous CAV1 and E-cadherin to unravel how co-expression of E-cadherin modulates CAV1 function in vitro and in vivo in WT C57BL/6 or Rag−/− immunodeficient mice and how a pro-inflammatory environment generated by treating cells with prostaglandin E2 (PGE2) alters CAV1 function in the presence of E-cadherin. CAV1 expression augmented migration, invasion, and metastasis of melanoma cells, and these effects were abolished via transient co-expression of E-cadherin. Importantly, exposure of cells to PGE2 reverted the effects of E-cadherin expression and increased CAV1 phosphorylation on tyrosine-14 and metastasis. Moreover, PGE2 administration blocked the ability of the CAV1/E-cadherin complex to prevent tumor formation. Therefore, our results support the notion that PGE2 can override the tumor suppressor potential of the E-cadherin/CAV1 complex and that CAV1 released from the complex is phosphorylated on tyrosine-14 and promotes migration/invasion/metastasis. These observations provide direct evidence showing how a pro-inflammatory environment caused here via PGE2 administration can convert a potent tumor suppressor complex into a promoter of malignant cell behavior.

Abstract Background Acne is a common skin disorder that involves an infection inside the hair follicle, which is usually treated with antibiotics, resulting in unbalanced skin microbiota and microbial resistance. For this reason, we developed polymeric nanoparticles encapsulating thymol, a natural active compound with antimicrobial and antioxidant properties. In this work, optimization physicochemical characterization, biopharmaceutical behavior and therapeutic efficacy of this novel nanostructured system were assessed. Results Thymol NPs (TH-NP) resulted on suitable average particle size below 200 nm with a surface charge around − 28 mV and high encapsulation efficiency (80%). TH-NP released TH in a sustained manner and provide a slow-rate penetration into the hair follicle, being highly retained inside the skin. TH-NP possess a potent antimicrobial activity against Cutibacterium acnes and minor effect towards Staphylococcus epidermis, the major resident of the healthy skin microbiota. Additionally, the stability and sterility of developed NPs were maintained along storage. Conclusion TH-NP showed a promising and efficient alternative for the treatment of skin acne infection, avoiding antibiotic administration, reducing side effects, and preventing microbial drug resistance, without altering the healthy skin microbiota. Additionally, TH-NP enhanced TH antioxidant activity, constituting a natural, preservative-free, approach for acne treatment. Graphical Abstract

Abstract Understanding population connectivity within a species as well as potential interactions with its close relatives is crucial to define management units and to derive efficient management actions. However, although genetics can reveal mismatches between biological and management units and other relevant but hidden information such as species misidentification or hybridization, the uptake of genetic methods by the fisheries management process is far from having been consolidated. Here, we have assessed the power of genetics to better understand the population connectivity of white (Lophius piscatorius) and its interaction with its sister species, the black anglerfish (Lophius budegassa). Our analyses, based on thousands of genome‐wide single nucleotide polymorphisms, show three findings that are crucial for white anglerfish management. We found (i) that white anglerfish is likely composed of a single panmictic population throughout the Northeast Atlantic, challenging the three‐stock based management, (ii) that a fraction of specimens classified as white anglerfish using morphological characteristics are genetically identified as black anglerfish (L. budegassa), and iii) that the two Lophius species naturally hybridize leading to a population of hybrids of up to 20% in certain areas. Our results set the basics for a genetics‐informed white anglerfish assessment framework that accounts for stock connectivity, revises and establishes new diagnostic characters for Lophius species identification, and evaluates the effect of hybrids in the current and future assessments of the white anglerfish. Furthermore, our study contributes to provide additional evidence of the potentially negative consequences of ignoring genetic data for assessing fisheries resources.

Objetivo. Este artículo presenta los resultados de investigación en cuanto a los factores asociados a la satisfacción laboral del personal administrativo de una universidad pública, teniendo en cuenta los aspectos sociodemográficos y las condiciones de contratación y demás factores laborales que caracterizan a este tipo de empleados, por medio de la identificación de asociaciones entre variables sociodemográficas y variables propias de la institución y del puesto de trabajo. Métodos y datos. Estudio cuantitativo de alcance descriptivo y basado en datos de corte transversal con cálculo de muestra para población finita y variables de naturaleza cualitativa. Resultados. Se realiza un análisis descriptivo de las variables incluidas en el instrumento de la mano de tablas de contingencia para identificar la presencia de asociación entre estas. Conclusiones. Los factores asociados a la satisfacción laboral corresponden a sexo, edad, tipo de vinculación y antigüedad. De igual forma, se destacan los niveles altos de satisfacción que presenta el personal administrativo con el tipo de tareas que desarrollan, el modo de ser y estilo de dirección de los superiores, el modo de ser y comportamiento de los colegas y el trabajo en general, lo cual no es tan representativo con el salario ni con la promoción u oportunidad de ascenso.

Abstract Although the commensal Streptococcus sanguinis [ S. sanguinis] is isolated from caries-free people, it can ferment carbohydrates producing acids. We aimed to characterize S. sanguinis cariogenic potential as a function of different enamel biofilm formation periods, in vitro. Saliva-coated enamel slabs were inoculated with S. sanguinis to form initial biofilms for 8, 12 or 16 h in presence of sucrose and followed by a period in medium with glucose for 16, 12 or 8 h, respectively, until completion of 24 h. To simulate cariogenic challenges, S. sanguinis biofilms were exposed to 10% sucrose for 5 minutes, 3x/day for 5 days. Biofilm biomass, viable cells, total proteins, intracellular and extracellular polysaccharides production, acidogenicity and enamel demineralization were determined. Biofilms of Streptococcus mutans [ S. mutans ] served as caries-positive control. Biofilms of S. sanguinis forming on enamel for 12 and 16 h showed higher demineralization than those formed during 8 h, but lower than S. mutans biofilms, regardless of the initial biofilm formation time. No differences were detected in the biofilm properties among the different biofilm formation times tested for S. sanguinis . Increased enamel initial biofilm formation time by S. sanguinis appears to induce a cariogenic potential, but lower than S. mutans .

Objective. Whether a minimum quantity of saliva inhibit the caries process remains uncertain. This study aimed to investigate the impact of saliva dilutions on an in vitro caries model using Streptococcus mutans (S. mutans) biofilms. Methods. S. mutans biofilms were cultivated on enamel and root dentin slabs, in culture media containing different proportions of saliva (v/v): 0%, 5%, 10%, 25%, 50%, 75%, and 100% saliva, and exposed to a 10% sucrose solution (5 min, 3x/day), with appropriate controls. After 5 (enamel) and 4 (dentin) days, demineralization, biomass, viable bacteria, and polysaccharide formation were analyzed. The acidogenicity of the spent media was monitored overtime. Each assay was performed in triplicate across two independent experiments (n = 6). Results. In both enamel and dentin, an inverse relationship was observed between acidogenicity, demineralization, and the proportion of saliva. Even small quantities of saliva incorporated into the media led to a noticeable reduction in enamel and dentin demineralization. Saliva presence resulted in significant reductions in biomass, viable S. mutans cells, and polysaccharides, with the effects being concentration-dependent for both tissues. Conclusions. High quantities of saliva can almost completely inhibit sucrose-induced cariogenicity, while even small amounts exhibit a dose-dependent caries-protective effect.

Graphene-based materials have been increasingly incorporated to optical fiber plasmonic sensors due to the peculiar physical and chemical properties of these materials (hardness and flexibility, high electrical and thermal conductivity, and very good adsorption for many substances, etc.). In this paper, we theoretically and experimentally showed how the addition of graphene oxide (GO) to optical fiber refractometers permits the development of surface plasmon resonance (SPR) sensors with very good characteristics. We used doubly deposited uniform-waist tapered optical fibers (DLUWTs) as supporting structures because of their already proven good performance. The presence of GO as an effective third layer is useful to tune the wavelength of the resonances. In addition, the sensitivity was improved. We depict the procedures for the production of the devices and characterize the GO+DLUWTs produced in this way. We also showed how the experimental results are in agreement with the theoretical predictions and used these to estimate the thickness of deposited GO. Finally, we compared the performance of our sensors with other ones that have been recently reported, showing that our results are among the best reported. Using GO as the medium in contact with the analyte, in addition to the good overall performance of devices, permit consideration of this option as an interesting possibility for the future development of SPR-based fiber sensors.

The southern king crab Lithodes santolla experiences low temperatures and unpredictable food conditions, and is under variable fishing pressure. To compare the reproductive investment of females, crabs were captured from three sites (Beagle Channel 55°S, Tierra del Fuego Atlantic coast 52-54°S and San Jorge Gulf 45-47°S). Fecundity, water and lipid contents were measured in midgut gland, ovary and muscle. To assess the maternal investment in the offspring, egg masses were analysed on lipid, protein, water and inorganic matter contents, egg volume and embryo size. Although fecundity was similar among sites, San Jorge Gulf females showed higher water and lower lipid contents in somatic and reproductive organs. The egg mass energy reserves varied among sites, showing the highest lipid values in the Beagle Channel, and the highest protein and inorganic matter content in San Jorge Gulf. Though water content was similar, egg volume and embryo size were higher in San Jorge Gulf. Moreover, maternal size did not correlate with egg volume, embryo size or lipid, protein and inorganic matter content of the eggs. This study suggests that reproductive investment of L. santolla varies among regions exposed to different environmental conditions, such as the quality of food available, denoting a female compensatory mechanism.

Extracellular matrix components of bacterial biofilms include biopolymers such as polysaccharides, nucleic acids and proteins. Similar to polysaccharides, the secretion of adhesins and other matrix proteins can be regulated by the second messenger cyclic diguanylate (cdG). We have performed quantitative proteomics to determine the extracellular protein contents of a Rhizobium etli strain expressing high cdG intracellular levels. cdG promoted the exportation of proteins that likely participate in adhesion and biofilm formation: the rhizobial adhesion protein RapA and two previously undescribed likely adhesins, along with flagellins. Unexpectedly, cdG also promoted the selective exportation of cytoplasmic proteins. Nearly 50% of these cytoplasmic proteins have been previously described as moonlighting or candidate moonlighting proteins in other organisms, often found extracellularly. Western blot assays confirmed cdG-promoted export of two of these cytoplasmic proteins, the translation elongation factor (EF-Tu) and glyceraldehyde 3-phosphate dehydrogenase (Gap). Transmission Electron Microscopy immunolabeling located the Gap protein in the cytoplasm but was also associated with cell membranes and extracellularly, indicative of an active process of exportation that would be enhanced by cdG. We also obtained evidence that cdG increases the number of extracellular Gap proteoforms, suggesting a link between cdG, the post-translational modification and the export of cytoplasmic proteins.

Abstract The intestine is fundamental in controlling human health. Intestinal epithelial and immune cells are continuously exposed to millions of microbes that greatly impact on intestinal epithelial barrier and immune function. This microbial community, known as gut microbiota, is now recognized as an important partner of the human being that actively contribute to essential functions of the intestine but also of distal organs. In the gut ecosystem, bidirectional microbiota‐host communication does not involve direct cell contacts. Both microbiota and host‐derived extracellular vesicles (EVs) are key players of such interkingdom crosstalk. There is now accumulating body of evidence that bacterial secreted vesicles mediate microbiota functions by transporting and delivering into host cells effector molecules that modulate host signalling pathways and cell processes. Consequently, vesicles released by the gut microbiota may have great influence on health and disease. Here we review current knowledge on microbiota EVs and specifically highlight their role in controlling host metabolism, intestinal barrier integrity and immune training.

Abstract Background Enteric pathogens have developed mechanisms to disrupt tight junctions and increase gut permeability. Many studies have analysed the ability of live probiotics to protect intestinal epithelial cells against tight junction damage caused by bacterial pathogens. Escherichia coli Nissle 1917 (EcN) is among the probiotics that positively modulates the intestinal epithelial barrier by regulating expression and distribution of tight junction proteins. We previously reported that regulation of ZO-1, claudin-14 and claudin-2 is mediated by EcN secreted factors, either free-released or associated with outer membrane vesicles (OMVs). Factors secreted by commensal ECOR63 elicited comparable effects in intact epithelial T-84 and Caco-2 cell monolayers. Results Here we analyse the ability of OMVs and soluble secreted factors to protect epithelial barrier function in polarized T-84 and Caco-2 cells infected with enteropathogenic Escherichia coli (EPEC). Transepithelial electrical resistance, paracellular permeability, mRNA levels and subcellular distribution of tight junction proteins were monitored in the absence or presence of EcN and ECOR63 extracellular fractions. EPEC downregulated expression of ZO-1 ZO-2, occludin and claudin-14 and altered the subcellular localization of ZO-1, occludin and F-actin cytoskeleton. OMVs and soluble factors secreted by EcN and ECOR63 counteracted EPEC-altered transepithelial resistance and paracellular permeability, preserved occludin and claudin-14 mRNA levels, retained ZO-1 and occludin at tight junctions in the cell boundaries and ameliorated F-actin disorganization. Redistribution of ZO-1 was not accompanied by changes at mRNA level. Conclusion This study provides new insights on the role of microbiota secreted factors on the modulation of intestinal tight junctions, expanding their barrier-protective effects against pathogen-induced disruption.

Debido a los avances en las neurociencias, la evolución y accesibilidad a dispositivos biométricos, que permiten la captura de respuestas fisiológicas ante estímulos externos, se ha presentado una forma diferente de conocer al consumidor y poder adaptar todas las estrategias de mercadeo lo más personalizado posible en una disciplina llamada Neuromarketing. Atendiendo a esta realidad, el objetivo de la presente investigación es analizar de forma experimental la percepción frente a ciertos estímulos sensoriales derivados de cinco sabores (vainilla, fresa, chocolate, chicle y cookies and cream) de malteadas pertenecientes a la industria de helados y postres. Se realizó una muestra de 20 sujetos, seleccionados mediante una entrevista semiestructurada para garantizar que no habían consumido los sabores de esas malteadas. Posteriormente, fueron expuestos a los cinco sabores en tres momentos diferentes, sólo con el olfato como primer momento, sólo con el canal sensorial del gusto y, por último, sólo con el canal sensorial de la vista. Esto nos permitió capturar la actividad cerebral de ondas (theta, alpha, beta y hi-beta), y también la actividad galvánica, mediante un electroencefalograma (EEG) y un medidor (GSR). Los resultados permitieron observar que los sabores de chocolate y fresa son los que mostraron más cambios y diferencias de género, así mismo, el canal del olfato es el que mayor incidencia tiene en la forma como se perciben los sabores.

The poor water solubility of apremilast (APR) is the main impediment to the penetration of the drug through the skin barrier. The objective of this study was to evaluate the permeability of APR in different solutions enriched with penetration promoters in ex vivo samples of human skin, and additionally assess its tolerance in vivo. To this end, APR solutions with 5% promoter were developed, and the drug’s ability to penetrate human abdominal skin samples was evaluated; the coefficients of permeability, cumulated amounts permeated, and flow were some of the parameters evaluated; likewise, the in vitro and in vivo tolerance of the solutions was evaluated. The results obtained showed that the solutions containing squalene as a promoter improved the penetration of APR compared to the other promoters evaluated; in the same way, on an in vitro scale in HaCaT cells, the promoters were not toxic, finding a cell viability greater than 80% at the different dilutions evaluated. In the in vivo tests carried out with the solution that presented the best results (APR-Squalene solution), it was observed that it does not cause irritation or erythema on the skin after its colorimetric and histological evaluation of the dorsal region of rats after its application. Squalene becomes an excellent candidate to improve the permeability of the drug in the case of the development of a topical formulation; in addition, it was confirmed that this penetration enhancer is neither toxic nor irritating when in contact with the skin in in vivo tests.

The use of artificial intelligence (AI) in a variety of research fields is speeding up multiple digital revolutions, from shifting paradigms in healthcare, precision medicine and wearable sensing, to public services and education offered to the masses around the world, to future cities made optimally efficient by autonomous driving. When a revolution happens, the consequences are not obvious straight away, and to date, there is no uniformly adapted framework to guide AI research to ensure a sustainable societal transition. To answer this need, here we analyze three key challenges to interdisciplinary AI research, and deliver three broad conclusions: 1) future development of AI should not only impact other scientific domains but should also take inspiration and benefit from other fields of science, 2) AI research must be accompanied by decision explainability, dataset bias transparency as well as development of evaluation methodologies and creation of regulatory agencies to ensure responsibility, and 3) AI education should receive more attention, efforts and innovation from the educational and scientific communities. Our analysis is of interest not only to AI practitioners but also to other researchers and the general public as it offers ways to guide the emerging collaborations and interactions toward the most fruitful outcomes.

El presente artículo expone los resultados del análisis de las fichas clínicas de un consultorio infanto juvenil de la región de Valparaíso, Chile. para indagar y conocer de qué sufren los niños, niñas y adolescentes en el contexto local. Este es un estudio enmarcado en una investigación de carácter cuantitativo descriptivo, por frecuencias de presentación de las temáticas. En los resultados existe una mayor proporción de niños respecto de las niñas. Así como también, que la mayor frecuencia de demanda aparece en la educación inicial, decreciendo de manera constante hacia el final de la escolaridad obligatoria. Las problemáticas asociadas a la escuela que aparecen en las demandas clínicas, como lo son la “agresividad”, “problemas conductuales” y de “rendimiento” predominan dentro de las problemáticas encontradas. Se concluye la relevancia de pensar la infancia como una construcción cambiante a cada época. Junto a ello, la necesidad de un diálogo comprensivo entre clínica y escuela.

The higher molecular weight and low solubility of amphotericin B (AmB) hinders its topical administration. The aim of this study was to incorporate Bursera graveolens essential oil into an AmB topical gel (AmB + BGEO gel) in order to promote the diffusion of the drug through the skin in the treatment of cutaneous candidiasis. AmB + BGEO gel formulation was determined using a factorial experiment. Physical and chemical parameters, stability, in vitro release profile and ex vivo permeation in human skin were evaluated. In vitro antimicrobial activity was studied using strains of C. albicans, C. glabrata and C. parapsilosis. The tolerability was evaluated using in vitro and in vivo models. AmB + BGEO gel presented appropriate characteristics for topical administration, including pH of 5.85, pseudoplastic behavior, optimal extensibility, as well as high stability and acceptable tolerability. In vitro release studies showed that the formulation releases the drug following a Boltzmann sigmoidal model. Finally, AmB + BGEO gel exhibited higher amount of drug retained inside the skin and lower Minimum Inhibitory Concentration than a formulation sans essential oil. Therefore, these results suggest that the incorporation of B. graveolens essential oil in the formulation could be used as strategy to promote a local effect in the treatment of cutaneous candidiasis.

Dry eye disease (DED) is a high prevalent multifactorial disease characterized by a lack of homeostasis of the tear film which causes ocular surface inflammation, soreness, and visual disturbance. Conventional ophthalmic treatments present limitations such as low bioavailability and side effects. Lactoferrin (LF) constitutes a promising therapeutic tool, but its poor aqueous stability and high nasolacrimal duct drainage hinder its potential efficacy. In this study, we incorporate lactoferrin into hyaluronic acid coated liposomes by the lipid film method, followed by high pressure homogenization. Pharmacokinetic and pharmacodynamic profiles were evaluated in vitro and ex vivo. Cytotoxicity and ocular tolerance were assayed both in vitro and in vivo using New Zealand rabbits, as well as dry eye and anti-inflammatory treatments. LF loaded liposomes showed an average size of 90 nm, monomodal population, positive surface charge and a high molecular weight protein encapsulation of 53%. Biopharmaceutical behaviour was enhanced by the nanocarrier, and any cytotoxic effect was studied in human corneal epithelial cells. Developed liposomes revealed the ability to reverse dry eye symptoms and possess anti-inflammatory efficacy, without inducing ocular irritation. Hence, lactoferrin loaded liposomes could offer an innovative nanotechnological tool as suitable approach in the treatment of DED.

The present work is focused on the development of novel surface-functionalized poly(lactic-co-glycolic acid) nanoparticles loaded with thymol (TH-NPs) for topical administration enhancing thymol anti-inflammatory, antioxidant and wound healing activities against acne. TH-NPs were prepared by solvent evaporation method using different surface functionalization strategies and obtaining suitable physicochemical parameters and a good short-term stability at 4 °C. Moreover, TH-NPs skin penetration and antioxidant activity were assessed in ex vivo pig skin models. Skin penetration of TH-NPs followed the follicular route, independently of the surface charge and they were able to enhance antioxidant capacity. Furthermore, antimicrobial activity against Cutibacterium acnes was evaluated in vitro by the suspension test showing improved antibacterial performance. Using human keratinocyte cells (HaCat), cytotoxicity, cellular uptake, antioxidant, anti-inflammatory and wound healing activities were studied. TH-NPs were non-toxic and efficiently internalized inside the cells. In addition, TH-NPs displayed significant anti-inflammatory, antioxidant and wound healing activities, which were highly influenced by TH-NPs surface modifications. Moreover, a synergic activity between TH-NPs and their surface functionalization was demonstrated. To conclude, surface-modified TH-NPs had proven to be suitable to be used as anti-inflammatory, antioxidant and wound healing agents, constituting a promising therapy for treating acne infection and associated inflammation.

There are a large number of remedies in traditional medicine focused on relieving pain and inflammation. Flavanones have been a potential source in the search for leading compounds and biologically active components, and they have been the focus of much research and development in recent years. Eysenhardtia platycarpa is used in traditional medicine for the treatment of kidney diseases, bladder infections, and diabetes mellitus. Many compounds have been isolated from this plant, such as flavones, flavanones, phenolic compounds, triterpenoid acids, chalcones, sugars, and fatty acids, among others. In this paper, natural flavanone 1 (extracted from Eysenhardtia platycarpa) as lead compound and flavanones 1a–1d as its structural analogues were screened for anti-inflammatory activity using Molinspiration® and PASS Online in a computational study. The hydro alcoholic solutions (FS) of flavanones 1, 1a–1d (FS1, FS1a–FS1d) were also assayed to investigate their in vivo anti-inflammatory cutaneous effect using two experimental models, a rat ear edema induced by arachidonic acid (AA) and a mouse ear edema induced by 12-O-tetradecanoylphorbol acetate (TPA). Histological studies and analysis of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were also assessed in AA-inflamed rat ear tissue. The results showed that the flavanone hydro alcoholic solutions (FS) caused edema inhibition in both evaluated models. This study suggests that the evaluated flavanones will be effective when used in the future in skin pathologies with inflammation, with the results showing 1b and 1d to be the best.

Abstract Background Self-quantification of health parameters is becoming more popular; thus, the validity of the devices requires assessments. The aim of this study was to evaluate the validity of Fitbit One step counts (Fitbit Inc., San Francisco, CA, USA) against Actigraph wActisleep-BT step counts (ActiGraph, LLC, Pensacola, FL, USA) for measuring habitual physical activity among children. Design The study was implemented as a cross-sectional experimental design in which participants carried two waist-worn activity monitors for five consecutive days. Methods The participants were chosen with a purposive sampling from three fourth grade classes (9–10 year olds) in two comprehensive schools. Altogether, there were 34 participants in the study. From these, eight participants were excluded from the analysis due to erroneous data. Primary outcome measures for step counts were Fitbit One and Actigraph wActisleep-BT. The supporting outcome measures were based on activity diaries and initial information sheets. Classical Bland–Altman plots were used for reporting the results. Results The average per-participant daily difference between the step counts from the two devices was 1937. The range was [116, 5052]. Fitbit One gave higher step counts for all but the least active participant. According to a Bland–Altman plot, the hourly step counts had a relative large mean bias across participants (161 step counts). The differences were partially explained by activity intensity: higher intensity denoted higher differences, and light intensity denoted lower differences. Conclusions Fitbit One step counts are comparable to Actigraph step counts in a sample of 9–10-year-old children engaged in habitual physical activity in sedentary and light physical activity intensities. However, in moderate-to-vigorous physical activity, Fitbit One gives higher step counts when compared to Actigraph.

Restriction site-associated DNA sequencing (RAD-seq) has become a powerful and widely used tool in molecular ecology studies as it allows to cost-effectively recover thousands of polymorphic sites across individuals of non-model organisms. However, its successful implementation in population genetics relies on correct data processing that would minimize potential loci-assembly biases and consequent genotyping error rates. RAD-seq data processing when no reference genome is available involves the assembly of hundreds of thousands high-throughput sequencing reads into orthologous loci, for which various key parameter values need to be selected by the researcher. Previous studies exploring the effect of these parameter values found or assumed that a larger number of recovered polymorphic loci is associated with a better assembly. Here, using three RAD-seq datasets from different species, we explore the effect of read filtering, loci assembly and polymorphic site selection on number of markers obtained and genetic differentiation inferred using the Stacks software. We find (i) that recovery of higher numbers of polymorphic loci is not necessarily associated with higher genetic differentiation, (ii) that the presence of PCR duplicates, selected loci assembly parameters and selected SNP filtering parameters affect the number of recovered polymorphic loci and degree of genetic differentiation, and (iii) that this effect is different in each dataset, meaning that defining a systematic universal protocol for RAD-seq data analysis may lead to missing relevant information about population differentiation.

This paper reviews the literature concerning technology used for creating and delivering accessible museum and cultural heritage sites experiences. It highlights the importance of the delivery suited for everyone from different areas of expertise, namely interaction design, pedagogical and participatory design, and it presents how recent and future artificial intelligence (AI) developments can be used for this aim, i.e.,improving and widening online and in situ accessibility. From the literature review analysis, we articulate a conceptual framework that incorporates key elements that constitute museum and cultural heritage online experiences and how these elements are related to each other. Concrete opportunities for future directions empirical research for accessibility of cultural heritage contents are suggested and further discussed.

Apremilast (APR) is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. The low solubility and permeability of this drug hinder its dermal administration. The purpose of this study was to design and characterize an apremilast-loaded microemulsion (APR-ME) as topical therapy for local skin inflammation. Its composition was determined using pseudo-ternary diagrams. Physical, chemical and biopharmaceutical characterization were performed. Stability of this formulation was studied for 90 days. Tolerability of APR-ME was evaluated in healthy volunteers while its anti-inflammatory potential was studied using in vitro and in vivo models. A homogeneous formulation with Newtonian behavior and droplets of nanometric size and spherical shape was obtained. APR-ME released the incorporated drug following a first-order kinetic and facilitated drug retention into the skin, ensuring a local effect. Anti-inflammatory potential was observed for its ability to decrease the production of IL-6 and IL-8 in the in vitro model. This effect was confirmed in the in vivo model histologically by reduction in infiltration of inflammatory cells and immunologically by decrease of inflammatory cytokines IL-8, IL-17A and TNFα. Consequently, these results suggest that this formulation could be used as an attractive topical treatment for skin inflammation.

The interconnection between nutrients, metabolites and microbes is a key factor governing the healthy/pathological status of an individual. Thus, microbiota-based research is essential in order to better understand human health and nutrition. Gut bacteria release membrane vesicles (MVs) as an intercellular communication mechanism that allows the direct delivery of factors that prime the host’s innate immune system. We have previously shown that MVs from intestinal E. coli activate dendritic cells (DCs) in a strain-specific manner. To gain insights into the regulatory mechanisms involved, here, we have used an RNA deep sequencing approach to identify differentially expressed miRNAs (microRNAs) in DCs which are challenged by the MVs of the probiotic Nissle 1917 (EcN) or the commensal ECOR12. MicroRNAs are post-transcriptional regulatory mediators that permit the fine tuning of signaling pathways. This approach allowed the identification of a common set of miRNAs which are modulated by MVs from both strains and miRNAs which are differentially expressed in response to EcN or ECOR12 MVs. Based on the differential expression of the target genes and subsequent validation experiments, we correlated some of the selected miRNAs with the reported cytokine profile and specific T cell responses. As far as we know, this is the first study to analyze the regulation of miRNAs in DCs by MVs released by gut microbiota.

Reinforcement learning (RL) aims at building a policy that maximizes a task-related reward within a given domain. When the domain is known, i.e., when its states, actions and reward are defined, Markov Decision Processes (MDPs) provide a convenient theoretical framework to formalize RL. But in an open-ended learning process, an agent or robot must solve an unbounded sequence of tasks that are not known in advance and the corresponding MDPs cannot be built at design time. This defines the main challenges of open-ended learning: how can the agent learn how to behave appropriately when the adequate states, actions and rewards representations are not given? In this paper, we propose a conceptual framework to address this question. We assume an agent endowed with low-level perception and action capabilities. This agent receives an external reward when it faces a task. It must discover the state and action representations that will let it cast the tasks as MDPs in order to solve them by RL. The relevance of the action or state representation is critical for the agent to learn efficiently. Considering that the agent starts with a low level, task-agnostic state and action spaces based on its low-level perception and action capabilities, we describe open-ended learning as the challenge of building the adequate representation of states and actions, i.e., of redescribing available representations. We suggest an iterative approach to this problem based on several successive Representational Redescription processes, and highlight the corresponding challenges in which intrinsic motivations play a key role.

Human activity recognition is a key task in ambient intelligence applications to achieve proper ambient assisted living. There has been remarkable progress in this domain, but some challenges still remain to obtain robust methods. Our goal in this work is to provide a system that allows the modeling and recognition of a set of complex activities in real life scenarios involving interaction with the environment. The proposed framework is a hybrid model that comprises two main modules: a low level sub-activity recognizer, based on data-driven methods, and a high-level activity recognizer, implemented with a fuzzy ontology to include the semantic interpretation of actions performed by users. The fuzzy ontology is fed by the sub-activities recognized by the low level data-driven component and provides fuzzy ontological reasoning to recognize both the activities and their influence in the environment with semantics. An additional benefit of the approach is the ability to handle vagueness and uncertainty in the knowledge-based module, which substantially outperforms the treatment of incomplete and/or imprecise data with respect to classic crisp ontologies. We validate these advantages with the public CAD-120 dataset (Cornell Activity Dataset), achieving an accuracy of 90.1% and 91.07% for low-level and high-level activities, respectively. This entails an improvement over fully data-driven or ontology-based approaches.

La automedicación es un fenómeno global creciente que tradicionalmente se ha definido como la acción individual de consumir un medicamento o seguir un tratamiento sin prescripción médica. Sin embargo, esta visión se ha quedado corta ante las manifestaciones contemporáneas del fenómeno que van más allá del autocuidado y se asocia cada vez más al consumo masivo de medicamentos inducido por la publicidad. En ese sentido, este artículo presenta las definiciones y las teorías explicativas de la automedicación ofrecidas por la literatura científica, especialmente aquellas que enfatizan en la dimensión del autocuidado (por ejemplo, el concepto de la Zoofarmacognosia) y desarrolla una nueva hipótesis sobre la automedicación, como comportamiento individual de consumo, explicada por un posicionamiento cognitivo causal simple acerca de la acción de los medicamentos, facilitado por la publicidad y el mercadeo de estos. Se concluye al mostrar la importancia de contrarrestar el efecto de la publicidad mediante la educación del consumidor acerca del riesgo que implica la complejidad de la automedicación a partir de la acción de los medicamentos en el organismo.

A review of the surface plasmon resonance (SPR) transducers based on tapered fibers that have been developed in the last years is presented. The devices have proved their good performance (specifically, in terms of sensitivity) and their versatility and they are a very good option to be considered as basis for any kind of chemical and biological sensor. The technology has now reached its maturity and here we summarize some of the characteristics of the devices produced.

To complete the master’s program in Teaching English as a Foreign Language at the University of Costa Rica, the teachers designed and taught an ESP course for ten students enrolled in a master’s program in Disability Studies. Three learners have visual impairments, and one has hypoacusis. Different curricular accommodations were made for them to work autonomously, but the results show that some could not always do so. However, their attitude towards learning English improved. This paper presents the challenges and outcomes of the lessons and materials used to raise awareness about the importance of inclusive classes, as well as recommendations to work with this population.

The spectacled caiman, Caiman crocodilus, has a significant population in the Caño Negro Wildlife Refuge, Costa Rica, and some fishermen consider them a cause for the decline of sh stocks. We did semi-structured and open interviews with fishermen in central Caño Negro, Las Cubas and Veracruz on: 1) impact on the eco- system and interactions with humans; and 2) beliefs and traditions. All respondents felt that stocks have decreased in both abundance and diversity, in the river and ponds, and 38% of the community interacts little with these reptiles and do not consider them a problem for sh- ing activities. There is interest in a management that includes leverage reptile skin and flesh.

En este artículo hemos puesto de manifiesto que el aprendizaje utilizando estrategias lúdicas mejora la adquisición de competencias y estrategias deseadas para educar y alcanzar los objetivos de aprendizaje previstos por la escuela. Señalaremos la motivación como la característica básica para avanzar en el juego y para determinar el grado de éxito de nuestro sistema. Además las características propias del juego, las competencias y estrategias que se dan al jugar y su posible aplicación en las aulas en un sistema gamificado. Partiendo de la observación a jugadores, reseñaremos estrategias de juego tales como la preparación previa, la búsqueda del detalle, la colaboración o la creación, que se revelan como los fundamentos del juego y también del aprendizaje. Para llegar a ellas el diseño de nuestro sistema debe tener en cuenta el por qué, el qué, para quiénes y el cómo. Y cuando todo ello está encauzado se produce la práctica, juegos en el aula, elementos de juegos para aprender, reflexión sobre el juego...

This paper aims to discover suspected differences in the interpretative quality during a performance with a Spanish guitar of a musical piece using two different performance techniques by pressing the strings or not. Fourteen students from different levels of guitar lessons were distributed in two student groups and put in the same leve! after a pre-test measure. Once the acquisition stage ended, it was made post-test measure, a withholding measure and transfer. The final results suggested a better sound quality when playing a melody by pressing the strings, both at the end of the leaming process (post-test) and during learning transfer and withholding processes.

Caveolin-1 is known to promote cell migration, and increased caveolin-1 expression is associated with tumor progression and metastasis. In fibroblasts, caveolin-1 polarization and phosphorylation of tyrosine-14 are essential to promote migration. However, the role of caveolin-1 in migration of metastatic cells remains poorly defined. Here, caveolin-1 participation in metastatic cell migration was evaluated by shRNA targeting of endogenous caveolin-1 in MDA-MB-231 human breast cancer cells and ectopic expression in B16-F10 mouse melanoma cells. Depletion of caveolin-1 in MDA-MB-231 cells reduced, while expression in B16-F10 cells promoted migration, polarization and focal adhesion turnover in a sequence of events that involved phosphorylation of tyrosine-14 and Rac-1 activation. In B16-F10 cells, expression of a non-phosphorylatable tyrosine-14 to phenylalanine mutant failed to recapitulate the effects observed with wild-type caveolin-1. Alternatively, treatment of MDA-MB-231 cells with the Src family kinase inhibitor PP2 reduced caveolin-1 phosphorylation on tyrosine-14 and cell migration. Surprisingly, unlike for fibroblasts, caveolin-1 polarization and re-localization to the trailing edge were not observed in migrating metastatic cells. Thus, expression and phosphorylation, but not polarization of caveolin-1 favor the highly mobile phenotype of metastatic cells.