Search

To systematize published laboratory methods to inactivate Mycobacterium tuberculosis (MTB) and to describe their effectiveness. We carried out a review of the scientific literature to identify the publications that reported methods for the inactivation of MTB, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The search addressed inactivation methodologies used in Public health laboratories for the treatment of biological material and only included studies reporting the efficacy of the method. The database used were PubMed (National Library of Medicine) and LILACS (Latin American and Caribbean Literature in Health Sciences). We evaluated the quality of the studies with the JBI (Joanna Briggs Institute) Critical Instrument Appraisal Checklist. We included 14 publications meeting the established inclusion and exclusion criteria. These 14 studies actually described a total of 35 inactivation methods. Most of them combined heat treatment with some chemical or enzymatic agent, and there were very few applying a single strategy. Twenty-four (68.57%) methods demonstrated significant efficacy in inactivating MTB. The systematic review identified 35 methods of inactivation of MTB, published in 14 studies. Most of the methods combined physical treatment techniques, especially heat, with chemical and/or enzymatic treatment techniques, obtaining mostly good results in preventing the reproduction of the microorganism. PROSPERO (International Prospective Register of Ongoing Systematic Reviews) (Code CRD42024503621).

ABSTRACT Objective: To describe how smartphone applications can contribute to the management of epilepsy in children and adolescents. Data source: This is an integrative review conducted on the Medline, PubMed, and SciELO databases, based on the descriptors “epilepsy” and “smartphone.” Original studies published between 2017–2023 in Portuguese or English that addressed the research question were included. Theses and dissertations, duplicate studies, literature reviews, and studies that did not answer the research question were excluded. Data synthesis: A total of 178 studies were located, of which six were selected for this review. The sample included 731 participants (631 children and adolescents with epilepsy and 100 caregivers). The applications allow for the collection of seizure frequency; timing and type of crisis; reminders for medication administration; and information about sleep quality. They can store these data for healthcare professionals, caregivers, and users to monitor the progress of the condition. Conclusions: The use of applications in managing seizures in children and adolescents with epilepsy shows promising results by promoting continuous and personalized monitoring. Further studies are needed to optimize beneficial outcomes and overcome challenges.

Manufacturing of adeno-associated viruses (AAV) for gene and cell therapy applications has increased significantly and spurred development of improved mammalian and insect cell-based production systems. We developed a baculovirus-based insect cell production system—the SGMO Helper—with a novel gene architecture and greater flexibility to modulate the expression level and content of individual Rep and Cap proteins. In addition, we incorporated modifications to the AAV6 capsid sequence that improves yield, capsid integrity, and potency. Production of recombinant AAV 6 (rAAV6) using the SGMO Helper had improved yields compared to the Bac-RepCap helper from the Kotin lab. SGMO Helper-derived rAAV6 is resistant to a previously described proteolytic cleavage unique to baculovirus-insect cell production systems and has improved capsid ratios and potency, in vitro and in vivo, compared with rAAV6 produced using Bac-RepCap. Next-generation sequencing sequence analysis demonstrated that the SGMO Helper is stable over six serial passages and rAAV6 capsids contain comparable amounts of non-vector genome DNA as rAAV6 produced using Bac-RepCap. AAV production using the SGMO Helper is scalable using bioreactors and has improved yield, capsid ratio, and in vitro potency. Our studies demonstrate that the SGMO Helper is an improved platform for AAV manufacturing to enable delivery of cutting-edge gene and cell therapies.

The telecommunications sector has experienced exponential growth since the year 2000, reaching 5.31 trillion users by 2022, generating 1.07 trillion in revenue for telecommunications companies. However, this growth leads to intense competition among companies for customer acquisition, often resulting in customer churn or switching between telecommunications providers due to the services or experiences received by users. At the moment, algorithms are being developed for churn prediction to assist in taking actions to prevent customer defection. Nevertheless, there is no comprehensive inventory of churn factors or a list of algorithms that explain the reasons for customer churn, despite the existence of numerous factors influencing user retention or defection. This highlights the importance of our work in allowing us to know in advance which client will be a deserter (churn). The purpose of this research is to identify how factors intervene in the customer churn process in telecommunications companies, as well as to list existing techniques for prediction and finally, to present advances in explainability, using a systematic literature review from 2018 to August 2023 using the Scopus and Wos meta-search engines. Regarding the factors contributing to churn, we identified 19 factors encompassing 87 sub-factors, detailed in 87 out of 112 reviewed articles. In terms of prediction, 26 unique algorithm techniques and 16 combinations were identified, presented in 102 out of 112 reviewed articles. Finally, in the realm of explainability, 4 out of 112 articles were found, detailing 5 techniques that help identify why an algorithm selects a customer as potential defector.

The genus Rhinella corresponds to a group of anurans characterized by numerous taxonomic and systemic challenges, leading to their organization into species complexes. Cytogenetic data for this genus thus far are limited to the diploid number and chromosome morphology, which remain highly conserved among the species. In this study, we analyse the karyotypes of three species of the genus Rhinella (Rhinella granulosa, Rhinella margaritifera, and Rhinella marina) using both classical (conventional staining and C-banding) and molecular (FISH-fluorescence in situ hybridization with 18S rDNA, telomeric sequences, and microsatellite probes) cytogenetic approaches. The aim of this study is to provide data that can reveal variations in the distribution of repetitive sequences that can contribute to understanding karyotypic diversification in these species. The results revealed a conserved karyotype across the species, with 2n = 22 and FN = 44, with metacentric and submetacentric chromosomes. C-banding revealed heterochromatic blocks in the pericentromeric region for all species, with a proximal block on the long arms of pairs 3 and 6 in R. marina and on the short arms of pairs 4 and 6 in R. margaritifera. Additionally, 18S rDNA probes hybridized to pair 5 in R. granulosa, to pair 7 in R. marina, and to pair 10 in R. margaritifera. Telomeric sequence probes displayed signals exclusively in the distal region of the chromosomes, while microsatellite DNA probes showed species-specific patterns. These findings indicate that despite a conserved karyotypical macrostructure, chromosomal differences exist among the species due to the accumulation of repetitive sequences. This variation may be attributed to chromosome rearrangements or differential accumulation of these sequences, highlighting the dynamic role of repetitive sequences in the chromosomal evolution of Rhinella species. Ultimately, this study emphasizes the importance of the role of repetitive DNAs in chromosomal rearrangements to elucidate the evolutionary mechanisms leading to independent diversification in the distinct phylogenetic groups of Rhinella.

5G has been heralded as a critical, decisive technology for verticals’ digital transformation. It targets innovative technical capabilities, allowing dedicated and improved communication mechanisms, going beyond the mere performance increase experienced by past generations’ evolution. Despite the literature already envisaging the application of 5G-enabled solutions in vertical-based deployments, there is still a lack of experimental insights shedding light on the actual feasibility of 5G capabilities in specific vertical deployments. This gap is particularly evident in verticals that did not traditionally rely on mobile network solutions for their communication needs, such as safety-related control signals in railway operations. This paper aims to fill this gap by delivering an extensive empirical analysis performed through a 5G-enabled railway deployment. We designed and implemented a joint testbed, which allows us to faithfully reproduce two important transportation railway use cases that leverage 5G communications involving the vertical, communication service solutions operator, and integration actors. There, we expose the necessary integration engineering behind the enablement of 5G capabilities in such scenarios, considering the highly safety-certified and standardized environment of railway vertical sector regulations (which never considered the utilization of mobile networks in their development). We empirically demonstrate the performance capability achieved by the 5G-enabled network using two different systems, a carrier-grade one and an open-development one, in light of the required key performance indicators. To the best of our knowledge, this is the very first field trial and empirical evaluation of the suitability of 5G with the implementation of a 5G-enabled railway cross-level scenario within the transportation context.

Despite being one of the most speciose fish families in the Mediterranean Sea, knowledge about the diversity of gobies (Actinopterygii: Gobiidae) in this sea is still unsatisfactory, as documented by recent descriptions of a number of new species. Although very common in shallow water, Gobius incognitus Kovačić & Šanda, 2016, had escaped attention until 2016, when it was discovered. Due to its overall superficial morphological similarity, G. incognitus used to be confused with a much rarer species, Gobius bucchichi Steindachner, 1870, which was considered one of the most common shallow-water gobies in the Mediterranean Sea. In this work, we tested the suitability of the genetic data (mitochondrial gene encoding cytochrome b) for identifying and distinguishing between these two goby species, and assessed the congruency between the distribution records based on genetic data and those based on morphological identification. We analysed material of 304 specimens of G. incognitus and G. bucchichi from 49 localities covering a considerable part of the Mediterranean Sea, Black Sea, and the Atlantic Ocean near Gibraltar, representing 19 geographically well-separated areas. We detected 270 sequences of G. incognitus, and only 34 of G. bucchichi. In both species, a high haplotype variability was observed. The sequence species identity matched morphological identification for all specimens for which vouchers were available. The mean uncorrected p-distance between G. incognitus and G. bucchichi was 13%, while the mean intraspecific distances were much lower (0.63% and 0.68%, respectively). We found 79 fixed mutations between these two species. Data on distribution based on genetic identification are completely congruent with published results based on morphological identification. The results of this study support molecular methods as a reliable tool for distinguishing morphologically similar fish species, which is particularly useful when only tissue is available for determination.

Abstract Background Tuberculosis (TB) is a communicable, preventable and curable disease caused by the bacterium Mycobacterium tuberculosis (MTB). Peru is amongst the 30 countries with the highest burden of multidrug-resistant tuberculosis (MDR-TB) worldwide. In the fight against drug-resistant tuberculosis, the UKMYC6 microdilution plate was developed and validated by the CRyPTIC project. The objective of the study was to evaluate the use of the broth microdilution (BMD) plate methodology for susceptibility testing of drug-resistant MTB strains in Peru. Methods MTB strains isolated between 2015 and 2018 in Peru were used. 496 nationally-representative strains determined as drug-resistant by the routine 7H10 Agar Proportion Method (APM) were included in the present study. The Minimum Inhibitory Concentration (MIC) of 13 antituberculosis drugs were determined for each strain using the UKMYC6 microdilution plates. Diagnostic agreement between APM and BMD plate methodology was determined for rifampicin, isoniazid, ethambutol, ethionamide, kanamycin and levofloxacin. Phenotypes were set using binary (or ternary) classification based on Epidemiological cut-off values (ECOFF/ECV) proposed by the CRyPTIC project. Whole Genome Sequencing (WGS) was performed on strains with discrepant results between both methods. Results MIC distributions were determined for 13 first- and second-line anti-TB drugs, including new (bedaquiline, delamanid) and repurposed (clofazimine, linezolid) agents. MIC results were available for 80% (397/496) of the strains at 14 days and the remainder at 21 days. The comparative analysis determined a good agreement (0.64 ≤ k ≤ 0.79) for the drugs rifampicin, ethambutol, ethionamide and kanamycin, and the best agreement (k > 0.8) for isoniazid and levofloxacin. Overall, 12% of MIC values were above the UKMYC6 plate dilution ranges, most notably for the drugs rifampicin and rifabutin. No strain presented MICs higher than the ECOFF/ECV values for the new or repurposed drugs. Discrepant analysis using genotypic susceptibility testing by WGS supported half of the results obtained by APM (52%, 93/179) and half of those obtained by BMD plate methodology (48%, 86/179). Conclusions The BMD methodology using the UKMYC6 plate allows the complete susceptibility characterization, through the determination of MICs, of drug-resistant MTB strains in Peru. This methodology shows good diagnostic performances for rifampicin, isoniazid, ethambutol, ethionamide, kanamycin and levofloxacin. It also allows for the characterization of MICs for other drugs used in previous years against tuberculosis, as well as for new and repurposed drugs recently introduced worldwide.

Pasta, a globally cherished staple food, is consumed on a wide scale. However, conventional wheat-based pasta often lacks nutrients that can be incorporated to add value to the new product. To address this nutritional deficiency and enhance the health benefits for consumers, a promising approach is to incorporate Opuntia ficus-indica flour as a partial substitute for wheat flour. The primary objective of this study was to craft enriched tagliatelle pasta using Opuntia ficus-indica flour. The evaluation encompassed an assessment of physical-chemical attributes, color quality, cooking properties, texture profile analysis (TPA), and the analysis of bioactive compounds within the pasta products. Upon conclusion of the experiments, the F10 formulation, comprising 10% Opuntia ficus-indica flour, emerged as the most favorable pasta option. It exhibited an acceptable acidity level of 3.71% and demonstrated remarkable nutritional characteristics. These findings suggest that this formulation could serve as a promising alternative for the production of health-conscious pasta.

El presente artículo se propone esbozar respuestas que nos permitan dilucidar cuándo y cómo el populismo se constituyó como un concepto político latinoamericano. ¿Quiénes fueron sus productores conceptuales? Y ¿qué revelan dichas conceptualizaciones y sus variados usos respecto a transformaciones sociopolíticas más vastas acontecidas en la región? Se acude a un enfoque histórico conceptual y político intelectual para auscultar conexiones entre problemas y debates en torno a “la cuestión populista” en países como Argentina, Brasil, Colombia y México durante los años setenta. Se rastrean usos diversos del término y modos de producción teórica utilizados por intelectuales y académicos del subcontinente para “fabricar” el concepto. Nuestro análisis muestra que el populismo es un concepto clave en el léxico político de América Latina y que los debates por su definición a escala continental catalizaron representaciones sobre “lo autóctono” y “lo propio” de la política latinoamericana. Concluimos que estamos ante un concepto que hizo posible la invención de esa representación llamada América Latina, una categoría que en los primeros años de la década de 1970 fue dotada de una identidad esencial, articulada a nuevas versiones sobre el autoexotismo y la dimensión negativa de las formas de organización de la vida comunitaria en el subcontinente. El artículo aporta a la comprensión de los debates en torno al populismo a escala nacional y continental, conectando representaciones, problemas y conceptualizaciones que dieron vida a la idea según la cual la esencia de la política latinoamericana del siglo XX es lo opuesto a los horizontes políticos ideales o deseables.

Objective. To determine the genetic structure of drug-resistant strains of Mycobacterium tuberculosis that circulated throughout Peru during the years 2011-2015, by using haplotypes obtained from a line probe assay. Materials and methods. A total of 6589 samples that were admitted to the Instituto Nacional de Salud for routine diagnosis using the GenoType® MTBDRplus v2 assay were analyzed during the study period. Resistant haplotypes were created by concatenating 21 polymorphic sites of the evaluated genes using the line probe assay; and the association analysis was carried out with phenotypes obtained by the 7H10 agar ratio method. Results. The most frequent mutations were: rpoB S531L (55.4%) and rpoB D516V (18.5%) for rifampicin resistance, and katG S315T (59.5%) and inhA c-15t (25.7%) for isoniazid resistance. We obtained 13 representative haplotypes (87.8% of analyzed samples), 6 corresponded to the multidrug-resistant genotype, 4 to the isoniazid mono-resistant genotype and 3 to the rifampicin mono-resistant genotype. Eighteen regions and the province of Callao showed high haplotype diversity; four showed moderate diversity and two showed low diversity. Conclusions. Most regions showed high haplotype diversity; in addition, most drug-resistant strains of Mycobacterium tuberculosis were concentrated in the cities of Lima and Callao. Likewise, drugresistant Mycobacterium tuberculosis strains circulating in Peru mainly contain the genetic markers with the highest prevalence worldwide, which are associated with resistance to rifampicin and isoniazid.

A comparative study of the two recognized subspecies of Alstroemeria garaventae Ehr. Bayer in Chile was conducted using chromosomes and chloroplast DNA as sources of taxonomic evidence. Both characters indicate both subspecies as separate entities, supporting previous taxonomic hypotheses. Yet, nuclear DNA analyses will be necessary to confirm their taxonomic status.

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the deadliest infectious diseases worldwide. Multidrug and extensively drug-resistant strains are making disease control difficult, and exhausting treatment options. New anti-TB drugs bedaquiline (BDQ), delamanid (DLM) and pretomanid (PTM) have been approved for the treatment of multi-drug resistant TB, but there is increasing resistance to them. Nine genetic loci strongly linked to resistance have been identified (mmpR5, atpE, and pepQ for BDQ; ddn, fgd1, fbiA, fbiB, fbiC, and fbiD for DLM/PTM). Here we investigated the genetic diversity of these loci across >33,000 M . tuberculosis isolates. In addition, epistatic mutations in mmpL5-mmpS5 as well as variants in ndh, implicated for DLM/PTM resistance in M. smegmatis, were explored. Our analysis revealed 1,227 variants across the nine genes, with the majority (78%) present in isolates collected prior to the roll-out of BDQ and DLM/PTM. We identified phylogenetically-related mutations, which are unlikely to be resistance associated, but also high-impact variants such as frameshifts (e.g. in mmpR5, ddn) with likely functional effects, as well as non-synonymous mutations predominantly in MDR-/XDR-TB strains with predicted protein destabilising effects. Overall, our work provides a comprehensive mutational catalogue for BDQ and DLM/PTM associated genes, which will assist with establishing associations with phenotypic resistance; thereby, improving the understanding of the causative mechanisms of resistance for these drugs, leading to better treatment outcomes.

El artículo propone enriquecer y ampliar el alcance de los indicadores sobre innovación, vinculados al desarrollo del sistema agroalimentario y al Plan de Soberanía Alimentaria y Educación Nutricional hasta el 2030. Esta mejora se origina mediante el diseño de la propuesta metodológica de la encuesta nacional de innovación para el sector agroalimentario con indicadores específicos, a partir de los resultados de la Tercera Encuesta Nacional de Innovación que contribuyeron al sector agroalimentario. Con esta propuesta, se dispondrá de un conjunto de indicadores para la medición de las capacidades de innovación en el sector agroalimentario; como alternativa para promover el encadenamiento productivo, la toma de decisiones y la elaboración de nuevas políticas públicas. Esta propuesta es coherente con el proceso de transformación del Sistema de ciencia, tecnología e innovación, refrendado en los documentos rectores del Estado y del Gobierno, constituyendo un aporte al modelo de desarrollo económico social del país.

El artículo expone el impacto de la innovación para el desarrollo organizacional con énfasis en el sector agroalimentario. Se presenta una caracterización del sistema de ciencia, tecnología e innovación en Cuba en el que evalúa la incidencia en el desarrollo económico y social. Se analizan las bases metodológicas que facilita la realización del estudio de medición de la cultura y la capacidad innovadora en empresas pertenecientes al sector agroalimentario, a partir de lo cual se analizan los resultados e identifican las principales limitaciones y potencialidades. La investigación denota que en materia de innovación no existe un desarrollo para este sector, lo que requiere a partir de los resultados se diseñen estrategias y políticas conducentes a elevar las capacidades y cultura innovadoras con la premisa de garantizar una seguridad alimentaria, eficiencia económica y productiva de empresas del sector.

Abstract Optical response of crystalline solids is to a large extent driven by excitations that promote electrons among individual bands. This allows one to apply optical and magneto‐optical methods to determine experimentally the energy band gap —a fundamental property crucial to our understanding of any solid—with a great precision. Here it is shown that such conventional methods, applied with great success to many materials in the past, do not work in topological Dirac semimetals with a dispersive nodal line. There, the optically deduced band gap depends on how the magnetic field is oriented with respect to the crystal axes. Such highly unusual behavior is explained in terms of band‐gap renormalization driven by Lorentz boosts which results from the Lorentz‐covariant form of the Dirac Hamiltonian relevant for the nodal line at low energies.

Abstract Peru has the highest burden of multidrug-resistant tuberculosis in the Americas region. Since 1999, the annual number of extensively drug-resistant tuberculosis (XDR-TB) Peruvian cases has been increasing, becoming a public health challenge. The objective of this study was to perform genomic characterization of Mycobacterium tuberculosis strains obtained from Peruvian patients with XDR-TB diagnosed from 2011 to 2015 in Peru. Whole genome sequencing (WGS) was performed on 68 XDR-TB strains from different regions of Peru. 58 (85.3%) strains came from the most populated districts of Lima and Callao. Concerning the lineages, 62 (91.2%) strains belonged to the Euro-American Lineage, while the remaining 6 (8.8%) strains belonged to the East-Asian Lineage. Most strains (90%) had high-confidence resistance mutations according to pre-established WHO-confident grading system. Discordant results between microbiological and molecular methodologies were caused by mutations outside the hotspot regions analysed by commercial molecular assays (rpoB I491F and inhA S94A). Cluster analysis using a cut-off ≤ 10 SNPs revealed that only 23 (34%) strains evidenced recent transmission links. This study highlights the relevance and utility of WGS as a high-resolution approach to predict drug resistance, analyse transmission of strains between groups, and determine evolutionary patterns of circulating XDR-TB strains in the country.

Abstract The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.

Climate change is expected to impact both the population structure and geographic distribution of plants. Species distribution models are widely used to assess range shifts and the vulnerability of plants to climate change. Despite the abundance of modeling studies, little is known about how existing populations respond to climate change. We investigated the demographic structure and vulnerability to climate change in Anemone moorei, a sub-shrub with a highly restricted distribution in a biodiversity hotspot. We improved the distribution knowledge through intensive field work. We conducted a census of stem length as a proxy for age for all known populations. We used ensemble forecasting to project distributions considering 10 future climate scenarios and developed a novel climate change vulnerability index for the species’ distribution. We found that the mean stem length decreases and the proportion of young plants increases, while the size of fruiting plants decreases as A. moorei faces greater climate change vulnerability. We interpret these results as evidence for the onset of recent adaptation to climate change, consisting of reduced adult longevity and an earlier onset of reproduction. As a result of these changes, the proportion of juveniles in the population increases.

This paper presents an automated Non-Destructive Testing (NDT) system for the in-service inspection of orbital welds on tubular components operating at temperatures as high as 200 °C. The combination of two different NDT methods and respective inspection systems is here proposed to cover the detection of all potential defective weld conditions. The proposed NDT system combines ultrasounds and Eddy current techniques with dedicated approaches for dealing with high temperature conditions. Phased array ultrasound was employed, searching for volumetric defects within the weld bead volume while Eddy currents were used to look for surface and sub-surface cracks. The results from the phased array ultrasound results showed the effectiveness of the cooling mechanisms and that temperature effects on sound attenuation can be easily compensated for up to 200 °C. The Eddy current results showed almost no influence when temperatures were raised up to 300 °C.

This article presents a framework for improved and efficient video delivery in scenarios featuring users moving at high speed (e.g., trains), leveraging on dynamic Multi-access Edge Computing (MEC) enabled 5G network capabilities. The framework is location-aware and it allows the content to efficiently follow the users, conserving load usage on network and computational resources, by placing virtualized Content Delivery Network (vCDN) nodes at edge sites. The nodes are controlled by the framework's centralized control unit, which is able to dynamically and preemptively deploy virtulized resources, as the train moves. The framework is capable of segmenting video content and placing the specific portion of content that a user is likely to consume across a set of dynamically deployed vCDN nodes, associated to the coverage section the train is currently passing. A proof of concept was implemented and evaluated, where the benefits of using this framework are assessed. Results showed that the proposed system was able to reduce the load on the core network by 10.9 percent and maximize the cache hit ratio to a value of 99.8 percent.

Objective: To determine whether miR-125b regulates cholesterol efflux in vivo and in vitro through the regulation of scavenger receptor type B1 (SR-B1). Approach and results: We demonstrated that miR-125b is up-regulated in the human aortas of patients with CAD and is located in macrophages and vascular smooth muscle cells (VSMCs). We identified SCARB1 as a direct target of miR-125b by repressing the activity of the SCARB1 3′-untranslated region reporter construct. Moreover, the overexpression of miR-125b in both human and mouse macrophages as well as VSMCs was found to downregulated the expression of the SCARB1 and the SR-B1 protein levels, thereby impairing α-HDL-mediated macrophage cholesterol efflux in vitro. The in vivo reverse cholesterol transport (RCT) rate from non-cholesterol-loaded macrophages transfected with miR-125b to feces was also found to be decreased when compared with that of control mimic-transfected macrophages. Conclusions: Together, these results provide evidence that miR-125b downregulates SCARB1 and SR-B1 in both human and mouse macrophages as well as VSMCs, thereby impairing macrophage cholesterol efflux in vitro and the whole macrophage-specific RCT pathway in vivo.

Objective. To systematize available information regarding mutations that confer resistance to first-line anti-tuberculosis drugs. Materials and Methods. A systematic review of the scientific literature was conducted to identify articles that reported mutations conferring resistance to first-line anti-tuberculosis drugs. This search emphasized resistance to isoniazid and rifampicin drugs in M. tuberculosis strains of Peruvian patients. The search was performed on PubMed and LILACS (Latin American and Caribbean Health Sciences Literature). Results. Fourteen (14) articles were included, of which three reported mutations associated with resistance to isoniazid, six to rifampicin, eight to pyrazinamide and one to ethambutol. All mutations to isoniazid or rifampicin were identified directly or indirectly by the molecular diagnostic test GenoType MTBDRplus® v2.0. The greatest variability of mutations was determined in resistance to pyrazinamide. Conclusions. There is a great variability of mutations associated with resistance to anti-tuberculosis drugs that have been reported in Peru, and they are systematized in this report. These mutations must be taken into account for the development of diagnostic devices or selection of diagnostic tests to be applied in our country.

Abstract Background Müllerian adenosarcoma is a rare malignancy. These tumors occur mainly in the uterus, but also in extrauterine locations, usually related to endometriosis. Because of their rarity, there is limited data on optimal management strategies. Case presentation We present a 44-year-old woman with a history of endometriosis who consults for chronic pelvic pain. In the imaging tests, a heterogeneous mass is observed that impresses endometriosis, encompassing the uterus and left appendage. Surgery is performed by finding an extrauterine adenosarcoma that affected the uterus, ovary and bladder wall. Conclusion This is a rare case but should be considered in a patient with atypical clinical characteristics or preoperative pathology, so we show the diagnostic and therapeutic strategies carried out for the resolution of the case.

The present research examined how individuals' thinking style (holistic vs. analytic) is associated with the way they deal with contradictory information and whether experiencing mixed emotions can mediate this relationship. Participants first completed the thinking style measure and then were exposed to two contradictory pieces of information (Studies 1 and 2). In study 2, we also measured the experience of mixed emotions to test the mediating role of this variable. Across two studies, we found that individuals with a holistic thinking style were more able to reconcile contradictory information compared to individuals with an analytic thinking style. Study 2 showed that the relationship between thinking style and dealing with contradiction was mediated by the experience of mixed emotions. This research extends previous findings on confrontation of contradiction and mixed emotions by using an individual-differences rather than a cultural-differences approach, and establishes mixed emotions as a plausible mediating variable.

Background Early cholecystectomy (EC) for acute cholecystitis (AC) is standard. Often patients with cancer are not EC candidates and require non-surgical treatments. We analyzed factors associated with non-surgical treatments and progression to interval cholecystectomy (IC).Materials and methods We performed a case–control study reviewing consults for AC from 2001 to 2017 in a tertiary cancer center. Study patients had cancer, abdominal pain, and positive imaging studies. Univariate analysis and regression modeling evaluated associations between non-surgical management, resolution of AC, and IC.Results 206 patients met the criteria. 20 underwent EC, 132 took antibiotics (ABX), and were treated with 54 percutaneous cholecystostomy tubes (PCTs). AC resolution was higher with PCT versus ABX (94% vs. 80%, p=0.02). Univariate analysis revealed higher absolute neutrophil counts (ANCs) and longer length of stay in PCT, and logistic regression revealed independent associations of abdominal malignancy (OR=6.66, 95% CI 1.36 to 32.6, p=0.09), abdominal radiation (OR=0.09, 95% CI 0.02 to 0.53, p

The bioeconomic efficiency of cow-calf systems was compared by a deterministic dynamic simulation. The simulation model considered stable cow-calf systems differentiated by the maximum age for culling cows, lifetime, culled at 4–13 years old. The necessary supply of metabolizable energy for the herd was established as natural grasslands, cultivated pasture in the winter/spring, and pre-dried pasture produced by the system. The biological efficiency of the systems was considered the ratio between the production of total live weight and the metabolizable energy consumed over one production cycle. Economic efficiency was determined by the ratio between gross margin and production area and the ratio between gross margin and number of cows. Bioeconomic efficiency was determined by a simple linear regression between biological efficiency, economic efficiency per area, and economic efficiency per cow. The efficiency of the animal unit, considering biological efficiency and economic efficiency per area were better in the system that culled cows at 4 years old, while economic efficiency per cow was better in the system that culled cows at 13 years old. In determining the bioeconomic efficiency of the systems, the best results were found in the system that culled cows at 6 years old, which suggests that the best efficiency of a cow-calf herd is reached when the adult age and mature weight of the cow are reached, and there is no more energy used for growing. The results indicate that stable cow-calf herds express their best biological efficiency and economic efficiency per area when the cow culling age is lower. However, economic efficiency per cow depends on cows that remain in the herd as long as possible. The culling age of cow that balances these biological and economic indicators is reached around 5 and half years.

La preocupación por el Bienestar animal ha evolucionado en la sociedad actual de una forma tan evidente que hoy en día se considera uno de los pilares de la ganadería europea junto con la sanidad, la sustentabilidad y la seguridad alimentaria. Aunque existe una obligación lícita y moral de promover un buen trato a los animales al considerarlos seres que sienten y padecen, excepcionalmente surgen situaciones puntuales y mediáticas que presentan una difícil solución al carecer de un encaje legal claro y de procedimientos específicos de actuación que limitan la eficacia de la actuación en estos casos. En este artículo se analizan los supuestos especiales más comunes que aparecen en las explotaciones ganaderas y que presentan dificultades de intervención administrativa desde una perspectiva legal y del bienestar animal.

Agricultural landscapes sometimes include natural habitats which can support the ecosystem by enhancing the pollination of crops, thus boosting the productivity. This research was conducted between May and July 2017, in the municipality of Tangará da Serra, Mato Grosso, Brazil, to assess the Cerrado from the perspective of it being a crucial habitat to sustain the sunflower-pollinating bees (Helianthus annuus L.). The bees were sampled using entomological nets and pan traps, in specifically marked out plots (20 m x 150 m), in the Cerrado, and in a sunflower crop, at different distances from the Cerrado border. The assessment was done in terms of the composion and species richness, abundance of individuals and the mass (g) of the sunflower chapters exposed and isolated from the floral visitors. While species richness showed no differences between the Cerrado and sunflower crop, a difference was observed for abundance, with more numbers of individuals in the sunflower crop, most likely because of the food source supply. In the sunflower crop, the bee diversity decreased proportionally as the distance from the border increased. The seed mass of the sunfl ower chapters was significantly higher in the flowers open to visitors than in those of the isolated chapters open for visitation. From the results, it was evident that the bees presente in the Cerrado visit the sunflower crop to gather pollen and nectar, and thus assist in cross-pollinating them and raising the productivity.

Power reserves are usually scheduled in day-ahead unit commitment (UC) to minimize operating costs while maintaining system security. In applying basic UC (bUC) after a contingency, the system frequency may fall upon the activation of the load-shedding global control (under-frequency load-shedding or UFLS) limits. Small isolated microgrids are more sensitive to this issue due to their lack of inertia. Including dynamic considerations into the bUC problem can minimize UFLS activation and also avoid the need for the operator to later check the short-term feasibility of a bUC solution. These proposals are known as Frequency-Constrained UC (FCUC), although the implementation are very time-consuming. FCUC implementation will increase the system’s operational costs, which should be calculated to estimate remuneration to the safety service based on the additional reserve provision. The electrical system of Gran Canaria island has suffered several episodes of greater blackouts in recent years. Shortly, there will be 242 MW of wind generation installed (26% of the thermal power installed on Gran Canaria). The main objective of this work is to improve the island system reliability by means of an FCUC formulation applied by the system operator in practice, including renewable sources. The results show that the frequency values remained within the admissible boundaries, but the system’s operational costs increased by around 13%.

Impaired HDL-mediated macrophage cholesterol efflux and higher circulating concentrations of trimethylamine N-oxide (TMAO) levels are independent risk factors for cardiovascular mortality. The TMAO precursors, γ-butyrobetaine (γBB) and Trimethyllysine (TML), have also been recently associated with cardiovascular death, but their interactions with HDL-mediated cholesterol efflux remain unclear. We aimed to determine the associations between APOB depleted plasma-mediated macrophage cholesterol efflux and plasma TMAO, γBB, and TML concentrations and explore their association with two-year follow-up mortality in patients with acute ST-elevation myocardial infarction (STEMI) and unstable angina (UA). Baseline and ATP-binding cassette transporter ABCA1 and ABCG1 (ABCA1/G1)-mediated macrophage cholesterol efflux to APOB-depleted plasma was decreased in patients with STEMI, and the latter was further impaired in those who died during follow-up. Moreover, the circulating concentrations of TMAO, γBB, and TML were higher in the deceased STEMI patients when compared with the STEMI survivors or UA patients. However, after statistical adjustment, only ABCA1/G1-mediated macrophage cholesterol efflux remained significantly associated with mortality. Furthermore, neither the TMAO, γBB, nor TML levels altered the HDL-mediated macrophage cholesterol efflux in vitro. We conclude that impaired ABCA1/G1-mediated macrophage cholesterol efflux is independently associated with mortality at follow-up in STEMI patients.

Abstract Background Breast cancer is the most common among women worldwide, and ovarian cancer is the most difficult gynecological tumor to diagnose and with the lowest chance of cure. Mutations in BRCA1 and BRCA2 genes increase the risk of ovarian cancer by 60% and breast cancer by up to 80% in women. Molecular tests allow a better orientation for patients carrying these mutations, affecting prophylaxis, treatment, and genetic counseling. Results Here, we evaluated the performance of a panel for BRCA1 and BRCA2, using the Ion Torrent PGM (Life Technologies) platform in a customized workflow and multiplex ligation-dependent probe amplification for detection of mutations, insertions, and deletions in these genes. We validated the panel with 26 samples previously analyzed by Myriad Genetics Laboratory, and our workflow showed 95.6% sensitivity and 100% agreement with Myriad reports, with 85% sensitivity on the positive control sample from NIST. We also screened 68 clinical samples and found 22 distinct mutations. Conclusions The selection of a robust methodology for sample preparation and sequencing, together with bioinformatics tools optimized for the data analysis, enabled the development of a very sensitive test with high reproducibility. We also highlight the need to explore the limitations of the NGS technique and the strategies to overcome them in a clinically confident manner.

Canine leishmaniosis (CanL) caused by Leishmania infantum is a zoonotic disease of global concern. Antileishmanial drug therapies commonly used to treat sick dogs improve their clinical condition, although when discontinued relapses can occur. Thus, the current study aims to evaluate the effect of CanL treatments in peripheral blood, lymph node, and bone marrow cytokine profile associated with clinical recovery. Two groups of six dogs diagnosed with CanL were treated with miltefosine combined with allopurinol and meglumine antimoniate combined with allopurinol (MT+A and MG+A), respectively. At diagnosis and after treatment, during a 3-month follow-up, clinical signs, hematological and biochemical parameters, urinalysis results and antileishmanial antibody titers were registered. Furthermore, peripheral blood, popliteal lymph node, and bone marrow samples were collected to assess the gene expression of IL-2, IL-4, IL-5, IL-10, IL-12, TNF-α, TGF-β, and IFN-γ by qPCR. In parallel, were also evaluated samples obtained from five healthy dogs. Both treatment protocols promoted the remission of clinical signs as well as normalization of hematological and biochemical parameters and urinalysis values. Antileishmanial antibodies returned to non-significant titers in all dogs. Sick dogs showed a generalized upregulation of IFN-γ and downregulation of IL-2, IL-4, and TGF-β, while gene expression of IL-12, TNF-α, IL-5, and IL-10 varied between groups and according to evaluated tissue. A trend to the normalization of cytokine gene expression was induced by both miltefosine and meglumine antimoniate combined therapies. However, IFN-γ gene expression was still up-regulated in the three evaluated tissues. Furthermore, the effect of treatment in the gene expression of cytokines that were not significantly changed by infection, indicates that miltefosine and meglumine antimoniate combined therapy directly affects cytokine generation. Both combined therapies are effective in CanL treatment, leading to sustained pro-inflammatory immune environments that can compromise parasite survival and favor dogs' clinical cure. In the current study, anti-inflammatory and regulatory cytokines do not seem to play a prominent role in CanL or during clinical recovery.

This article deals with the problem of joint representation of mechanical and motion control information of machines with servo axes. A new conceptual model is proposed for the graphical representation of industrial mechatronic systems covering the minimum information requirements from both mechanical and motion automation points of view. The model also takes into account new electronic motion control concepts such as virtual axes and temporary electronic coordination relationships between axes (e-gears). The objective is to support more integrated and collaborative work between mechanical designers and automation developers when implementing complex machines and industrial mechatronic systems. Schemes graphically representing the relevant common information are obtained from the information model, which may simplify the exchange of information between the mechanical and the motion control fields, not only at conceptualization and design stages, but also throughout the rest of the implementation process of industrial mechatronic systems.

In this review, the state of the art of 23 distributed generation and microgrids standards has been analyzed. Among these standards, 18 correspond mainly to distributed generation while five of them introduce the concept of microgrid. The following topics have been considered: interconnection criteria, operating conditions, control capabilities, power quality, protection functions and reference variables. The revised national standards cover ten countries on four continents, which represents 80% of the countries with the largest installed renewable capacities. In addition, eight other relevant international standards have been analyzed, finding IEEE 1547 as the most comprehensive standard. It is identified a clear need to define a common framework for distributed energy resources (DERs) and microgrid standards in the future, wherein topics, terminology, and values are expressed in a manner that may widely cover the entire diversity in a way similar to how it has already been expressed at the network transport level by the ENTSO-E codes.

The application of innovative three-dimensional (3D) spheroids cell culture strategy to Parasitology offers the opportunity to closely explore host–parasite interactions. Here we present a first report on the application of 3D hepatic spheroids to unravel the immune response of canine hepatocytes exposed to Leishmania infantum. The liver, usually considered a major metabolic organ, also performs several important immunological functions and constitutes a target organ for L. infantum infection, the etiological agent of canine leishmaniasis (CanL), and a parasitic disease of major veterinary and public health concern. 3D hepatic spheroids were able to sense and immunologically react to L. infantum parasites, generating an innate immune response by increasing nitric oxide (NO) production and enhancing toll-like receptor (TLR) 2 and interleukin-10 gene expression. The immune response orchestrated by canine hepatocytes also lead to the impairment of several cytochrome P450 (CYP450) with possible implications for liver natural xenobiotic metabolization capacity. The application of meglumine antimoniate (MgA) increased the inflammatory response of 3D hepatic spheroids by inducing the expression of Nucleotide oligomerization domain (NOD) -like receptors 1 and NOD2 and TLR2, TLR4, and TLR9 and enhancing gene expression of tumour necrosis factor α. It is therefore suggested that hepatocytes are key effector cells and can activate and orchestrate the immune response to L. infantum parasites.

Future spintronic devices may exploit spin-orbit interactions, which often emerge from broken symmetries and strongly influence electronic behaviour. Here, the authors evidence the amplification of Rashba coupling by a crystal field that breaks the local inversion symmetry at the Ni site in BaNiS2.

The potential of nicotinamide (NAM) to prevent atherosclerosis has not yet been examined. This study investigated the effect of NAM supplementation on the development of atherosclerosis in a mouse model of the disease. The development of aortic atherosclerosis was significantly reduced (NAM low dose: 45%; NAM high dose: 55%) in NAM-treated, apolipoprotein (Apo)E-deficient mice challenged with a Western diet for 4 weeks. NAM administration significantly increased (1.8-fold) the plasma concentration of proatherogenic ApoB-containing lipoproteins in NAM high-dose (HD)-treated mice compared with untreated mice. However, isolated ApoB-containing lipoproteins from NAM HD mice were less prone to oxidation than those of untreated mice. This result was consistent with the decreased (1.5-fold) concentration of oxidized low-density lipoproteins in this group. Immunohistochemical staining of aortas from NAM-treated mice showed significantly increased levels of IL-10 (NAM low-dose (LD): 1.3-fold; NAM HD: 1.2-fold), concomitant with a significant decrease in the relative expression of TNFα (NAM LD: −44%; NAM HD: −57%). An improved anti-inflammatory pattern was reproduced in macrophages cultured in the presence of NAM. Thus, dietary NAM supplementation in ApoE-deficient mice prevented the development of atherosclerosis and improved protection against ApoB-containing lipoprotein oxidation and aortic inflammation.

The clinical manifestation of leishmaniases depends on parasite species, host genetic background, and immune response. Manifestations of human leishmaniases are highly variable, ranging from self-healing skin lesions to fatal visceral disease. The scope of standard model hosts is insufficient to mimic well the wide disease spectrum, which compels the introduction of new model animals for leishmaniasis research. In this article, we study the susceptibility of three Asian rodent species (Cricetulus griseus, Lagurus lagurus, and Phodopus sungorus) to Leishmania major and L. donovani. The external manifestation of the disease, distribution, as well as load of parasites and infectiousness to natural sand fly vectors, were compared with standard models, BALB/c mice and Mesocricetus auratus. No significant differences were found in disease outcomes in animals inoculated with sand fly- or culture-derived parasites. All Asian rodent species were highly susceptible to L. major. Phodopus sungorus showed the non-healing phenotype with the progressive growth of ulcerative lesions and massive parasite loads. Lagurus lagurus and C. griseus represented the healing phenotype, the latter with high infectiousness to vectors, mimicking best the character of natural reservoir hosts. Both, L. lagurus and C. griseus were also highly susceptible to L. donovani, having wider parasite distribution and higher parasite loads and infectiousness than standard model animals.

The intake of olive oil (OO) enriched with phenolic compounds (PCs) promotes ex vivo HDL-mediated macrophage cholesterol efflux in humans. We aimed to determine the effects of PC-enriched virgin OO on reverse cholesterol transport (RevCT) from macrophages to feces in vivo. Female C57BL/6 mice were given intragastric doses of refined OO (ROO) and a functional unrefined virgin OO enriched with its own PC (FVOO) for 14 days. Our experiments included two independent groups of mice that received intragastric doses of the phenolic extract (PE) used to prepare the FVOO and the vehicle solution (saline), as control, for 14 days. FVOO intake led to a significant increase in serum HDL cholesterol and its ability to induce macrophage cholesterol efflux in vitro when compared with ROO group. This was concomitant with the enhanced macrophage-derived [3H]cholesterol transport to feces in vivo. PE intake per se also increased HDL cholesterol levels and significantly promoted in vivo macrophage-to-feces RevCT rate when compared with saline group. PE upregulated the expression of the main macrophage transporter involved in macrophage cholesterol efflux, the ATP binding cassettea1. Our data provide direct evidence of the crucial role of OO PCs in the induction of macrophage-specific RevCT in vivo.

Mimetic peptides are potential therapeutic agents for atherosclerosis. d-[113–122]apolipoprotein (apo) J (d-[113–122]apoJ) is a 10-residue peptide that is predicted to form a class G* amphipathic helix 6 from apoJ; it shows anti-inflammatory and anti-atherogenic properties. In the present study, we analyzed the effect of d-[113–122]apoJ in low-density lipoprotein receptor knockout mice(LDLR-KO) on the development of atherosclerosis and lipoprotein function. Fifteen-week-old female LDLR-KO mice fed an atherogenic Western-type diet were treated for eight weeks with d-[113–122]apoJ peptide, a scrambled peptide, or vehicle. Peptides were administered subcutaneously three days per week (200 µg in 100 µL of saline). After euthanasia, blood and hearts were collected and the aortic arch was analyzed for the presence of atherosclerotic lesions. Lipoproteins were isolated and their composition and functionality were studied. The extent of atherosclerotic lesions was 43% lower with d-[113–122]apoJ treatment than with the vehicle or scramble. The lipid profile was similar between groups, but the high-density lipoprotein (HDL) of d-[113–122]apoJ-treated mice had a higher antioxidant capacity and increased ability to promote cholesterol efflux than the control group. In addition, low-density lipoprotein (LDL) from d-[113–122]apoJ-treated mice was more resistant to induced aggregation and presented lower electronegativity than in mice treated with d-[113–122]apoJ. Our results demonstrate that the d-[113–122]apoJ peptide prevents the extent of atherosclerotic lesions, which could be partially explained by the improvement of lipoprotein functionality.

Recent studies have raised the possibility of a role for lipoproteins, including high-density lipoprotein cholesterol (HDLc), in abdominal aortic aneurysm (AAA). The study was conducted in plasmas from 39 large size AAA patients (aortic diameter > 50 mm), 81 small/medium size AAA patients (aortic diameter between 30 and 50 mm) and 38 control subjects (aortic diameter < 30 mm). We evaluated the potential of HDL-mediated macrophage cholesterol efflux (MCE) to predict AAA growth and/or the need for surgery. MCE was impaired in the large aortic diameter AAA group as compared with that in the small/medium size AAA group and the control group. However, no significant difference in HDL-mediated MCE capacity was observed in 3 different progression subgroups (classified according to growth rate < 1 mm per year, between 1 and 5 mm per year or >5 mm per year) in patients with small/medium size AAA. Moreover, no correlation was found between MCE capacity and the aneurysm growth rate. A multivariate Cox regression analysis revealed a significant association between lower MCE capacity with the need for surgery in all AAA patients. Nevertheless, the significance was lost when only small/medium size AAA patients were included. Our results suggest that MCE, a major HDL functional activity, is not involved in AAA progression.

The ST2 receptor plays an important role in the gut such as permeability regulation, epithelium regeneration, and promoting intestinal immune modulation. Here, we studied the role of ST2 receptor in a murine model of oral infection with Brucella abortus, its influence on gut homeostasis and control of bacterial replication. Balb/c (wild-type, WT) and ST2 deficient mice (ST2−/−) were infected by oral gavage and the results were obtained at 3 and 14 days post infection (dpi). Our results suggest that ST2−/− are more resistant to B. abortus infection, as a lower bacterial colony-forming unit (CFU) was detected in the livers and spleens of knockout mice, when compared to WT. Additionally, we observed an increase in intestinal permeability in WT-infected mice, compared to ST2−/− animals. Breakage of the intestinal epithelial barrier and bacterial dissemination might be associated with the presence of the ST2 receptor; since, in the knockout mice no change in intestinal permeability was observed after infection. Together with enhanced resistance to infection, ST2−/− produced greater levels of IFN-γ and TNF-α in the small intestine, compared to WT mice. Nevertheless, in the systemic model of infection ST2 plays no role in controlling Brucella replication in vivo. Our results suggest that the ST2 receptor is involved in the invasion process of B. abortus by the mucosa in the oral infection model.

ABSTRACT This study assessed the risks of different management practices to increase pregnancy rate in beef cow-calf systems, aiming at assisting decision-making. The perception of 18 experts on animal sciences regarding the risks of 32 nutritional, breeding, and general management practices applied to increase pregnancy rate were evaluated through questionnaires. The experts were selected by a non-probability sampling of researchers on veterinary and animal sciences. In addition, five farmers and eight technical consultants were also selected. The questionnaire was applied during a face-to-face meeting. The risk of each practice was assessed according to four factors, namely, cost, technical knowledge, operational complexity, and flexibility, and an equation was developed to calculate this risk. The applied method allowed to determine the risk of each practice, obtaining results similar to those previously perceived by the experts. Operational complexity and cost had greater influence on the estimated risks compared with the other factors. Moreover, the increase of one unit in operational complexity and cost increased the perceived risk and the estimated risk scores in 0.43 and 0.28 points, respectively. Overall, the application of general management practices presented lower risk score compared with nutritional and breeding practices, which were not different from which other. Equations to estimate the risks of farm managers should routinely apply management practices to increase the efficiency of cow-calf production systems.

The antinociceptive effects of the carbon monoxide-releasing molecule tricarbonyldichlororuthenium (II) dimer (CORM-2) during chronic pain are well documented, but most of its possible side-effects remain poorly understood. In this work, we examine the impact of CORM-2 treatment on the lipoprotein profile and two main atheroprotective functions attributed to high-density lipoprotein (HDL) in a mouse model of type 1 diabetes while analyzing the effect of this drug on diabetic neuropathy. Streptozotocin (Stz)-induced diabetic mice treated with CORM-2 (Stz-CORM-2) or vehicle (Stz-vehicle) were used to evaluate the effect of this drug on the modulation of painful diabetic neuropathy using nociceptive behavioral tests. Plasma and tissue samples were used for chemical and functional analyses, as appropriate. Two main antiatherogenic properties of HDL, i.e., the ability of HDL to protect low-density lipoprotein (LDL) from oxidation and to promote reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT), were also assessed. Stz-induced diabetic mice displayed hyperglycemia, dyslipidemia and pain hypersensitivity. The administration of 10 mg/kg CORM-2 during five consecutive days inhibited allodynia and hyperalgesia and significantly ameliorated spinal cord markers (Cybb and Bdkrb1expression) of neuropathic pain in Stz mice, but it did not reduce the combined dyslipidemia shown in Stz-treated mice. Its administration to Stz-treated mice led to a significant increase in the plasma levels of cholesterol (∼ 1.4-fold vs. Ctrl, ∼ 1.3- fold vs. Stz-vehicle; p < 0.05) and was attributed to significant elevations in both non-HDL (∼ 1.8-fold vs. Ctrl; ∼ 1.6-fold vs. Stz-vehicle; p < 0.05) and HDL cholesterol (∼ 1.3-fold vs. Ctrl, ∼ 1.2-fold vs. Stz-vehicle; p < 0.05). The increased HDL in plasma was not accompanied by a commensurate elevation in m-RCT in Stz-CORM-2 compared to Stz-vehicle mice; instead, it was worsened as revealed by decreased [3H]-tracer trafficking into the feces in vivo. Furthermore, the HDL-mediated protection against LDL oxidation ex vivo shown by the HDL isolated from Stz-CORM-2 mice did not differ from that obtained in Stz-vehicle mice. In conclusion, the antinociceptive effects produced by a high dose of CORM-2 were accompanied by antioxidative effects but were without favorable effects on the dyslipidemia manifested in diabetic mice.

The CRISPR-Cas9 system has the potential to revolutionize genome editing in human pluripotent stem cells (hPSCs), but its advantages and pitfalls are still poorly understood. We systematically tested the ability of CRISPR-Cas9 to mediate reporter gene knockin at 16 distinct genomic sites in hPSCs. We observed efficient gene targeting but found that targeted clones carried an unexpectedly high frequency of insertion and deletion (indel) mutations at both alleles of the targeted gene. These indels were induced by Cas9 nuclease, as well as Cas9-D10A single or dual nickases, and often disrupted gene function. To overcome this problem, we designed strategies to physically destroy or separate CRISPR target sites at the targeted allele and developed a bioinformatic pipeline to identify and eliminate clones harboring deleterious indels at the other allele. This two-pronged approach enables the reliable generation of knockin hPSC reporter cell lines free of unwanted mutations at the targeted locus.

En este artículo se realiza una contribución al desarrollo y la implantación de la educación cívica en el currículum escolar como un instrumento para abordar la exclusión social. Para ello, se analiza la importancia que tiene la participación de los niños en el proceso de toma de decisiones para su salud y para su desarrollo. Además, también se aborda el rol que tiene la participación (p.ej., actividades de voluntariado, uso de las redes sociales, e Internet, etc.) tanto en su bienestar como en romper el ciclo de la pobreza y la exclusión social. Después se proporciona un repaso sobre los antecedentes habituales de la participación y los factores asociados a ésta. Finalmente,se analiza la situación de la participación en los países de la Unión Europea como un ejemplo para realizar propuestas aplicables al caso de los países iberoamericanos.