Diabetes mellitus entails increased atherosclerotic burden and medial arterial calcification but the precise mechanisms are not fully elucidated. Our aim was to investigate the implication of CD36 in inflammation and calcification processes orchestrated by vascular smooth muscle cells (VSMCs) under hyperglycemic and atherogenic conditions. We examined the expression of CD36, pro-inflammatory cytokines, endoplasmic reticulum (ER) stress markers and mineralization-regulating enzymes by RT-PCR in human VSMCs, cultured in medium containing normal (5 mM) or high glucose (22 mM) for 72 h with or without oxLDL (24 h). The uptake of DiI-labelled oxLDL was quantified by flow citometry and fluorimetry and calcification assays were performed in VSMC cultured in osteogenic medium and stained by alizarin red. We observed an induction in the expression of CD36, cytokines, calcification markers and ER stress markers under high glucose that was exacerbated by oxLDL. These results were confirmed in carotid plaques from subjects with diabetes versus non-diabetic subjects. Accordingly, the uptake of DiI-labelled oxLDL was increased after exposure to high glucose. Silencing of CD36 abolished the induction of CD36 and reduced the expression of calcification enzymes and mineralization of VSMC. Our results indicate that CD36 signaling is involved in hyperglycemia and oxLDL-induced vascular calcification in diabetes.

Compared to other 2D materials, MBenes are at an early stage in both experimental and theoretical approaches. However, the wide range of possible 2D structures leads to novel and challenging properties and their consequent applications. From all the possible stoichiometries, we have performed a theoretical study of orthorhombic and hexagonal M2B2 MBenes in the framework of the Density Functional Theory. We have found that both symmetries of Cr2B2, Fe2B2, and Zr2B2 show a metallic behavior and could be grown under certain conditions, as they are demonstrated to be dynamically stable. Moreover, the values of the magnetic moment, in specific ferromagnetic cases exceeding 2.5 μB/M2B2, make them suitable as robust 2D magnets. All our findings represent an important step in the understanding of MBenes and open several windows to future research in fields like energy conversion and storage, sensing, catalysis, biochemistry, or nanotechnology, among others.

Generation of unique identifiers extracted from the physical characteristics of the underlying hardware ensures the protection of electronic devices against counterfeiting and provides security to the data they store and process. This work describes the design of an efficient Physical Unclonable Function (PUF) based on the differences in the frequency of Ring Oscillators (ROs) with identical layout due to variations in technological processes involved in the manufacture of the integrated circuit. The logic resources available in the Xilinx Series-7 programmable devices are exploited in the design to make it more compact and achieve an optimal bit-per-area rate. On the other hand, the design parameters can also be adjusted to provide a high bit-per-time rate for a particular target device. The PUF has been encapsulated as a configurable Intellectual Property (IP) module, providing it with an AXI4-Lite interface to ease its incorporation into embedded systems in combination with soft- or hard-core implementations of general-purpose processors. The capability of the proposed RO-PUF to generate implementation-dependent identifiers has been extensively tested, using a series of metrics to evaluate its reliability and robustness for different configuration options. Finally, in order to demonstrate its utility to improve system security, the identifiers provided by RO-PUFs implemented on different devices have been used in a Helper Data Algorithm (HDA) to obfuscate and retrieve a secret key.

Pterygium is a common ocular disease caused by abnormal cellular proliferation leading to abnormal fibrovascular growth of the conjunctiva. The main treatment is surgical removal; however, despite the improvement of surgical techniques and development of adjuvant therapies, postoperative recurrence, which can be as high as 89%, remains a challenge. Currently, pterygium excision with conjunctival autograft remains the preferred surgical technique to decrease recurrence, especially when combined with ciclosporin eye drops. Nevertheless, there is no gold standard surgical technique to prevent pterygium recurrence. Therefore, this review aims to assess the safety, effectiveness and, applicability of platelet-rich fibrin membrane for primary pterygium surgery and assess its possible benefits in resource-limited settings.

This study analyzes the academic performance of students from an official school in Bogotá (Colombia) who had asymmetric access to Information and Communication Technologies during the first year of the Covid-19 pandemic. The Classical Linear Regression Model is employed using data from a survey of a representative group of students in the year 2020. Results show technological gaps between students that are associated with asymmetric academic performance against students with limited or null access to the Internet and electronic devices. Results also show that, among students with permanent access to the Internet, women have better scores compared to men’s scores, which implies that women can achieve better academic results than men in virtual education. It is also noted that the sole access to an electronic device does not guarantee good academic achievements if there is no full access to the Internet, and if ICT-use skills have not been developed.

Tanning, crucial for leather production, relies heavily on chromium yet poses risks due to chromium's oxidative conversion, leading to significant wastewater and solid waste generation. Physico-chemical methods are typically used for heavy metal removal, but they have drawbacks, prompting interest in eco-friendly biological remediation techniques like biosorption, bioaccumulation, and biotransformation. The EU Directive (2018/850) mandates alternatives to landfilling or incineration for industrial textile waste management, highlighting the importance of environmentally conscious practices for leather products' end-of-life management, with com-posting being the most researched and viable option. This study aimed to isolate microorganisms from tannery wastewater and identify those responsible for different types of tanned leather biodegradation. Using a leather biodegradation assay (ISO 20136) with tannery and municipal wastewaters as inoculum, bacterial shifts during leather biodegradation were observed. Over 10,000 bacterial species were identified in all analyzed samples, with 8 bacterial strains isolated from tannery wastewater. Identification of bacterial genera like Acinetobacter, Brevundimo-nas, and Mycolicibacterium provides insights into potential microbial candidates for enhancing leather biodegradability, wastewater treatment, and heavy metal bioremediation in industrial applications.

Bartonella spp. bacteria can be found around the globe and are the causative agents of multiple human diseases. The most well-known infection is called cat-scratch disease, which causes mild lymphadenopathy and fever. As our knowledge of these bacteria grows, new presentations of disease have been recognized with serious manifestations. Not only has more severe disease been associated with these bacteria, but Bartonella species have also been discovered in a wide range of mammals and the pathogens’ DNA can be found in multiple vectors. This review will focus on some common mammalian reservoirs as well as the suspected vectors in relation to disease transmission and prevalence. Understanding the complex interactions between these bacteria, their vectors, and reservoirs as well as the breadth of infection by Bartonella around the world will help toassess the impact of Bartonellosis on public health.

Here we analyze three well-known conjectures: (i) the existence of infinitely-many twin primes, (ii) Goldbach’s strong conjecture, and (iii) Polignac’s conjecture. We show that the three conjectures are related to each other. In particular, we see that in analysing the validity of the Goldbach’s strong conjecture, one must consider also the existence of an infinite number of twin primes. As a consequence of how we approach this analysis, we also observe that if this conjecture is true, then so is Polignac’s conjecture. Our first step is an analysis of the existence of infinitely-many twin primes numbers. For this, using the formula 4((n−1)!+1) ≡ −n (mod n(n + 2)) – satisfied if and only if (n, n + 2) are twin primes –, together with Wilson’s theorem, we obtain conditions that must be met for two numbers to be twin primes. Our results, obtained from an analytic and functional study, lead us to conclude that there may exist infinitely-many twin primes. Next, we consider the validity of the Goldbach’s strong conjecture. After showing that the conjecture is true for the first even numbers, we notice a pattern that we analyze for any even number, reducing it to three cases: (i) when the even number 2n is two times a prime number n; (ii) when the even number 2n is such that n = 2m, with 2m − 1 and 2m + 1 twin primes; (iii) all other cases, i.e., for any 2n even number ∀n ∈ N with n > 1, n prime or not, with independence of n = 2m being 2m−1 and 2m+1 twin primes or not. In this last case we show that one can always find a certain r ∈ N such that 1 < r < n satisfying that n−r and n+r are primes, so that their sum is 2n. In this case we use the reduction to absurd method, and our results lead us to conclude that Goldbach’s strong conjecture is true to the best of our calculations, as well as the Polignac’s conjecture.

In this paper, we demonstrate the Collatz conjecture using the mathematical complete induction method. We show that this conjecture is satisfied for the first values of natural numbers, and in analyzing the sequence generated by odd numbers, we can deduce a formula for the general term of the Collatz sequence for any odd natural number n after several iterations. This formula is used in one case that we analyze using the mathematical complete induction method in the process of demonstrating the conjecture.

Agavins consumption has lead to accelerate body weight loss in mice. We investigated the changes on cecal microbiota and short chain fatty acids (SCFA) associated to body weight loss in overweight mice. Firstly, mice were fed with standard (ST5) or high fat (HF5) diet for 5 weeks. Secondly, overweight mice were shifted to standard diet alone (HF-ST10) or supplemented with agavins (HF-ST+A10) or oligofructose (HF-ST+O10), five more weeks. Cecal contents were collected before and after supplementation to determine microbiota and SCFA concentrations. At the end of first phase, HF5 mice showed a significant increase of body weight, which was associated with reduction of cecal microbiota diversity (PD whole tree; non-parametric t-test, P < 0.05), increased Firmicutes/Bacteroidetes ratio and reduced SCFA concentrations (t-test, P < 0.05). After diet shifted, HF-ST10 normalized its microbiota, increase its diversity and SCFA levels, whereas agavins (HF-ST+A10) or oligofructose (HF-ST+O10) led to partial microbiota restoration, with normalization of the Firmicutes/Bacteroides ratio as well as higher SCFA levels (P < 0.1). Moreover, agavins noticeably enriched Klebsiella and Citrobacter (LDA > 3.0); this enrichment has not been reported previously under a prebiotic treatment. In conclusion, agavins or oligofructose modulated cecal microbiota composition, reduced extent of diversity and increased SCFA. Furthermore, identification of bacteria enriched by agavins, opens opportunities to explore new probiotics.

A Global Historical Megatsunami Catalog (GHMCat) is presented, including all the events documented to date. The oldest event is from 1674 the Santorini event, ~3600 BP, is considered a particular case, and the most recent is from 2020. Although there is no formal definition of the term megatsunami, it is usually associated to the maximum height or runup reached by the waves when hitting the coast. Here we adopt this criterion and define a megatsunami when the wave reaches a height of 40 m or more. The catalog is initially based on tsunamis that meet this condition from the two existing Global Historical Tsunami Databases (GHTDs). Then, each of the events have been researched for its available references including earliest in order to verify the data, mainly on the maximum height of the waves and their causes. After a comprehensive review of published or on-line literature on historical tsunamis, including regional and local catalogs, papers, books, studies, reports and other available references, some of the oldest events have been ruled out. On the other hand, the literature review has also led to include in the catalog some new megatsunamis not included in the GHTDs. The global catalog contains 37 events from 1674 to 2023, 11 of which are either not included in the GHTDs or included with (erroneous) wave heights &lt;40 m. All of them are described and characterized as far as can be gathered within the limitations of the scope of a global catalog and the available information on each historical case. The analysis of recorded historical megatsunamis shows that virtually all have been originated by large landslides, most of them subaerial landslides, with an unusual frequency of events in certain glaciated areas of Alaska and Norway, mainly in the first decades of the 20th century. In contrast, it is worth noting the small number of megatsunamis caused by submarine landslides or associated with volcanic explosions.

The hypothesis posed was whether participation in LaLiga Genuine Santander (competitive football) influenced the quality of life (QL) of the people who participated in it, since their perception of themselves is enhanced by all the aformentioned factors (self-determination, social inclusion, emotional well-being, physical well-being, material well-being, rights, personal development, interpersonal relationships). The objective was to evaluate the QL of people with Down's Syndrome (DS) using their self-perception (n=39) and the perception of the informants (family members, teachers) (n=39). The KidsLife-Down Scale, with a few modifications was used. In general, differences of opinion between the subgroups of participants with DS and informants showed that results were higher in terms of perception for participants in the DS subgroup. Scores for all variables were higher for those participants with DS who said they did engage in practicing competitive football. Despite the perception of informants provides a great deal of information regarding the QL of participants with DS, the latter should be involved in the evaluation process and their self perceptions taken into account. Our research shows that participation in the league modifies the perceptions of the participants with Down's Syndrome regarding their quality of life. However, these perceptions are not shared by the informants.

This study aimed to evaluate the biological activities of two Allium species (Garlic and onion) as well as diallyl disulphide (DADS) and dipropyl disulphide (DPDS) as their representative bioactive compounds in a multi-assay experimental design. The genotoxic, antigenotoxic and lifespan effects of garlic, onion, DADS and DPDS were checked in Drosophila melanogaster and their cytotoxic, pro-apoptotic and DNA-clastogenic activities were analysed using HL60 tumoral cells. All compounds were non-genotoxic and antigenotoxic against H2O2-induced DNA damage with a positive dose-response effect and different inhibition percentages (the highest value: 95% for DADS) at all tested concentrations. Daily intake of Allium vegetables, DADS or DPDS had no positive effects on flies’ lifespan and healthspan. Garlic and DADS exerted the highest cytotoxic effects in a positive dose-dependent manner. Garlic and DADS exerted a DNA-internucleosomal fragmentation as an index of induced proapoptotic activity on HL60 cells. Allium vegetables and DADS were able to induce clastogenic strand breaks in the DNA of HL60 cells. This study showed the genomic safety of the assayed substances and their protective genetic effects against the hydrogen peroxide genotoxine. Long-term treatments during the whole life of Drosophila genetic model were beneficial only at low-median concentrations. The chemopreventive activity of garlic could be associated to its distinctive organosulphur DADS. We suggest that supplementary studies are needed to clarify the cell death pathway against garlic and DADS.

Evolutionary ecologists seek to understand how phenotypic evolution relates to population level traits. To document that, we quantified functional traits (escape strategy, sprint speed and predatory performance) and population density across 10 lizard species representing the acquisition of burrowing snake-like morphs (BSLM), from Brazil. We used phylogenetic mixed models to test if: a) morph and substrate affects lizards’ flight strategy and speed, b) BSLM species get more access to different potential prey types than lacertoid ones, when in syntopy, and d) morph is correlated with population abundance and habitat use in a way expected from the output of the previous experiments. We found that BSLM rigidly relied on burrowing as flight strategy, while syntopic lacertoid species changed their strategy according to the substrate. Also, sand has opposite effects on sprint speed depending on morph, making lacertoids run slower and BSLM faster. Despite BSLM were overall slower than lacertoids, they were as good hunters of challengingly fast prey, and better hunters of underground prey. Further, in the sandy habitats where these morphs are syntopic, prey is most available at superficial leaf litter under vegetation, although there is a large stock of underground prey, under the vegetation, too. These results support our observed higher importance of sand for BSLM’s populations and the higher importance of vegetation for lacertoids’ population density. Finally, although BSLM species reached the highest populational densities among the studied species, a systematic effect of morphological evolution on abundance remains elusive.

Selection of the most suitable material is one of the key decisions to be taken at the design stage of a manufacturing process. Traditional approaches as Ashby maps based on material properties are widely used in the industry. However, in the production of multimaterial components, the criteria for the selection can include antagonistic approaches. The aim of this work is the implementation of a methodology based on the results of process simulations for several materials and classify them by applying an advanced data analytics method based on Machine Learning (ML), in this case the Support Vector Regression (SVR) and Multi-Criteria Decision Making (MCDM) methodolo-gies, in this case Multi-criteria Optimization and Compromise Solution (VIKOR) combined with Entropy weighting methods. In order to do this, a Finite Element Model (FEM) has been built to evaluate the extrusion force and the die wear in a multi-material co-extrusion process of bimetallic Ti6Al4V-AZ31B billets. After applying SVR and VIKOR combined with Entropy weighting methodologies, a comparison has been established based on the material selection and complexity of the methodology used, resulting that material chosen in both methodologies is very similar and MCDM method is easier to implement because there is no need of evaluate the error of the pre-diction model and the time for data preprocessing is less than the time needed in SVR.

The cancer stem cell hypothesis suggests that neoplastic cells with stem characteristics hierarchically regulate tumor generation and its high cellular heterogeneity. These cells have been detected in all cancer types, and specific signaling pathways give the regulation of self-renewal and differentiation. In prostate cancer, androgen receptor signaling has been extensively studied, and in non-stem cells, it promotes cell proliferation and tumor progression, but in the cancer stem cell population, it negatively regulates processes such as self-renewal. However, in other types of cancer, such as breast and glioblastoma, the androgen receptor seems to favor the maintenance of cancer stem cells, suggesting that androgen signaling has different effects depending on the tumor context. This review discusses the role of androgen receptor in maintaining cancer stem cells by regulating proliferation, self-renewal, and differentiation, as well as the possible signaling pathways involved in these processes.

Genes coding for enzymes of the denitrification pathway appear randomly distributed among isolates of the ancestral genus Thermus, but only in few strains of the species T. thermophilus the pathway has been studied to a certain detail. Here, we review the enzymes involved in this pathway present in T. thermophilus NAR1, a strain extensively employed as a model for nitrate respiration, on the light of its full sequence recently assembled through a combination of PacBio and Illumina technologies in order to counteract the systematic errors introduced by the former technique. The genome of this strain is divided in four replicons, a chromosome of 2,021,843 pb, two megaplasmids of 370,865 and 77,135 bp and a small plasmid of 9,799 pb. Nitrate respiration is encoded in the largest megaplasmid, pTTHNP4, within a region that includes operons for O2 and nitrate sensory systems, a nitrate reductase, nitrate and nitrite transporters and a nitrate specific NADH dehydrogenase, in addition to multiple insertion sequences (IS), suggesting its mobility-prone nature. Despite nitrite is the final product of nitrate respiration in this strain, the megaplasmid encodes two putative nitrite reductases of the cd1 and Cu-containing types, apparently inactivated by IS. No nitric oxide reductase genes have been found within this region, although the NorR sensory gene, needed for its expression, is found near the inactive nitrite respiration system. These data clearly support that partial denitrification in this strain is the consequence of recent deletions and IS insertions in genes involved in nitrite respiration. Based on these data, the capability of this strain to transfer or acquire denitrification clusters by horizontal gene transfer is discussed.

This paper analyzes if the Financial Fair Play (FFP) regulations set by UEFA have influenced the auditing fees charged to the football clubs. In addition, it explores the determinants of audit fees. We use a two-sample t test with equal variances to determine whether differences are present. After this, we carry out a panel data regression with clubs fix effect to estimate the determinants of audit fees in football clubs. Our findings reveal an increase of audit fees after the implementation of FFP regulations. On top of that, audit fees are explained by the presence of foreign investors if the audit firm is one of the Big4 and if the auditor is a woman. The regulation change has an impact on the audit fees charged by auditors for their services. However, this increase can be compensated across future years given the improving financial situation of clubs; therefore, the auditors’ risk diminishes and subsequent audit fees may be reduced. UEFA should monitor audit fees as well as the quality of the audit reports, which have become crucial to obtaining the license to participate in UEFA competitions.

The objective of this work is to present the results of an investigation on the technological, pedagogical and content knowledge evidenced by mathematics teachers in the second-level of initial training (preservice) at the Universidad Nacional, from the TPACK model perspective, on the subject of functions. The research has a qualitative approach with an interpretive hermeneutical stance. A sample of 27 teachers in training who were enrolled in courses related to the three base domains of the TPACK model (pedagogical, technological and content of quadratic function) during the first semester (I cycle) of 2020 was used. A theoretical inquiry was carried out that allowed the creation of an instrument that made possible the description of the participants’ knowledge based on this model focused on the topic of quadratic function. The results show that participants possess instrumental dominance over the basic forms of knowledge underlying the model. It is concluded that, although participants have already experimented in courses related to these forms of knowledge, there is insufficient evidence to ascertain that their current knowledge would allow them to integrate technologies as a didactic resource within the teaching of the subject of quadratic function.

The use of flexible sensors has tripled over the last decade due to the increased demand in various fields including health monitoring, food packaging, electronic skins and soft robotics. Flexible sensors have the ability to be bent and stretched during use and can still maintain their electrical and mechanical properties. This gives them an advantage over rigid sensors that lose their sensitivity when subject to bending. Advancements in 3D printing have enabled the development of tailored flexible sensors. Various additive manufacturing methods are being used to develop these sensors including inkjet printing, aerosol jet printing, fused deposition modelling, direct ink writing, selective laser melting and others. Hydrogels have gained much attention in the literature due to their self-healing and shape transforming. Self-healing enables the sensor to recover from damages such as cracks and cuts incurred during use and this enables the sensor to have a longer operating life and stability. Various polymers are used as substrates on which the sensing conductive material is placed. Polymers including polydimethylsiloxane (PDMS), polyvinyl acetate (PVA), and Kapton are extensively used in flexible sensors. The most widely used nanomaterials in flexible sensors are carbon and silver, however, other nanomaterials such as iron, copper, manganese dioxide and gold are also used to provide controlled levels of conductivity or other functional properties.

This paper introduces the implementation of a genetic programming (GP)-based procedure to the automatic design and tuning of process controllers. The proposed approach makes a significant contribution to the field of artificial intelligence (AI) in control engineering. Unlike other controller design methods, the GP-based program handles the entire design in the time domain, including differential operations like derivatives and integrals, without the need for intermediate inverse Laplace transformation. This approach not only simplifies the design process but also ensures that all generated controllers are implementable in physical systems. Furthermore, GP’s functions set includes various mathematical operations beyond basic arithmetic operators, such as trigonometric, exponential, and logarithmic operators. The performance and validity of the resulting controllers generated by the proposed GP-based approach are evaluated by verifying whether the generator can replicate the structure and performance of those produced by traditional controller design methods and, in some cases, achieve even better results. As a result, the GP-based approach presents a promising solution for automating the controller design process and addressing control problems in various engineering applications.

The development of a remote sensing system is proposed in the present study for monitoring of the electrical resistance of concrete in real time. The sensor is embedded in the concrete bulk, and the data are sent via a gateway to a computer for the data analysis. The sensibility of the sensors to the effect of the presence of a crystalline admixture has been also assessed in the study. Different cycles of drying and water penetration have been considered to assess the sensor performance in different water content conditions. Sensors have shown to capable of detecting changes in electrical resistance when humidity changes. The sensitive of the sensors to the action of waterproofing admixtures in the mortar has been also confirmed. The contribution of the temperature plays a critical role on the sensor response, and its simultaneous monitoring is recommended.

Women's empowerment represents a process in which they are recognized as subjects of rights. Despite advances in women's rights, inequalities persist in various areas. This study aims to validate a psychometric scale of 31 items in seven factors: Participatory Empowerment, Temerity, External Influences, Independence, Social Satisfaction and Equality. The objective is to measure the empowerment of women in the university context. The research was carried out in a transversal and non-experimental manner, with the participants' voluntary collaboration, including the participation of 1,478 university students from four Higher Education Institutions in Zone 4 of Ecuador. The data was analyzed through inferential statistics, including exploratory and confirmatory factor analysis. The results indicated that the instrument for measuring empowerment can be made up of 24 items grouped into six factors, and this model showed a good fit.

In the provinces of the region, empirical constructions reached maximum points with these practices. The effects and pathologies appear as physical, chemical and mechanical failures in pillars, walls and roofs, generating uncertainty for the user. The current powerful design can detect the interior deterioration of coatings in adobe, brick and concrete constructions, and prevent collapses, material and economic losses. Experimental methods performed affirm the serious validity. The accuracy of the simulation and design provide a pre-test reliability of 95%. Five piles constructed of various materials participate in the prototype performance test, there is a correlation (R=0.9997) between the magnetic field range "B" (cm) and density "ρ" (g/cm³), also by increasing the current (i) in transit Q1 and coil L1, the induction of the "B" increases proportionally until penetrating the density of the wall of the building, having 5% reading error.

Corneal ulcer (CU) is an ophthalmopathy characterized by depression of the corneal surface with at least one stromal loss. CU is common in canine and feline species and is usually caused, among others, by trauma, infections, toxic contamination and endocrine disorders. They usually result from an increased inflammatory response and are associated with some clinical signs such as blepharospasm, photophobia, epiphora, pain and loss of corneal transparency. Despite advances in conventional and pharmacological therapy, in many cases indolent and recurrent ulcer treatments still lead to loss of visual acuity of the animal. This paper aims to report the effect of topical application of canine adipose tissue-derived mesenchymal stem cell (cATMSCs) as treatment of recurrent CU in a Poodle dog breed that showed clear difficulty in the healing process associated with diabetes. The animal was submitted to two applications of cATMSCs and showed improvement in the blepharospasm, conjunctival hyperemia, mucopurulent ocular secretion, photophobia, corneal opacity, chemosis, pigmentation, neovascularization, and pain parameters. Besides, Fluorescein test, Schirmer test and ocular fundus exam also showed improvement in their values concomitantly with lesion resolution. Due this, we showed that cATMSC therapy contribute to the regeneration of corneal tissue in CU and may contribute to the treatment to others ophthalmopathies.

Human societies demand sustainable alternatives for goods and services. Plants are sustainable sources of important metabolites with beneficial impacts on human health. There are many reported methodologies and commercial suppliers for extract preparations from the plant Mucuna sp. They usually claim to be enriched in L-dopa, their distinctive metabolite. However, there are poor characterizations of the metabolite's components in that extracts. Here, we present the metabolite characterization of a Mucuna seed extract, emphasizing the L-dopa identification and quantification. To obtain the extracts, we follow a green and sustainable extraction protocol. The lyophilized extract was subject to liquid chromatography and mass spectrometry to identify its primary metabolites. Additionally, we follow thin-layer chromatography to identify some carbohydrates in the sample. The resultant extract has a 56% L-dopa. Other main components in the extract were arginine, stizolamine, and the fructooligosaccharides sucrose and nystose. The characterized Mucuna extract can be easily standardized as powder presentation and used in several biomedical applications.

Magnesium nanoparticles of various mean diameters (53 – 239 nm) were synthesized herein via Pulsed Laser Ablation in Liquid (PLAL) from millimeter sized magnesium powders within iso-propyl alcohol. It was observed via a 3x3 full factorial DOE that the processing parameters can control the nanoparticle distribution to produce three size-distribution types (bimodal, skewed and normal). Ablation times of 2, 5, and 25 minutes where investigated. An ablation time of 2 minutes produced a bimodal distribution with the other types seen at higher periods of processing. Mg nanoparticle UV-Vis absorbance at 204 nm increased linearly with increasing ablation time, indicating an increase in nanoparticle count. The colloidal density (mg/ml) generally increased with increasing nanoparticle mean diameter as noted via increasing UV-vis absorbance. High la-ser scan speeds (within the studied range of 3000 - 3500 mm/s) tend to increase the nanoparticle count/yield. For the first time, the effect of scan speed on colloidal density, UV-vis absorbance and nanoparticle diameter from metallic powder ablation was investigated and is reported herein. The nanoparticles formed dendritic structures after being drop cast on aluminum foil as observed via FESEM analysis. Dynamic light scattering was used to measure the size of the nanoparticles. Magnesium nanoparticles have promising use in the fabrication of wearables, such as in conductive tracks or battery electrodes, owing to their low heat capacity, high melting point and bio-compatibility.

Cardiovascular disease (CVD), a group of disorders affecting the heart or blood vessels, are the primary cause of death worldwide, with an immense impact on patient quality of life and disa-bility. According to the World Health Organization, CVD takes an estimated 17.9 million lives each year, where more than four out of five CVD deaths are due to heart attacks and strokes. In the decades to come, increased prevalence of age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular heart disease, and heart failure (HF) will contribute to even greater health and economic burden as the global average life expectancy increases and consequently the world’s population continues to age. Considering this, it is important to focus our research efforts on understanding the fundamental mechanisms underlying CVD. In this review, we focus on cellular senescence and mitochondrial dysfunction, which have long been established to contribute to CVD. We also assess the recent advances in targeting mitochondrial dysfunction and senescence with a focus on therapies that influence both and therefore perhaps represent strategies with the most clinical potential, range, and utility.

Identifying groups that share common features among datasets through clustering analysis is a typical problem in many fields of science, particularly in post-omics and systems biology research. In respect of this, quantifying how a measure can cluster or organize intrinsic groups is important since currently there is no statistical evaluation of how ordered is, or how much noise is embedded in the resulting clustered vector. Many of the literature focuses on how well the clustering algorithm orders the data, with several measures regarding external and internal statistical measures; but none measure has been developed to statistically quantify the noise in an arranged vector posterior a clustering algorithm, i.e., how much of the clustering is due to randomness. Here, we present a quantitative methodology, based on autocorrelation, to assess this problem.

Since its adoption in September 2015, the 2030 Agenda has laid the foundations for a model of shared prosperity for a sustainable world. We are going through a complicated pandemic that shows profound inequalities affecting our economies, health, and quality of life. For this reason, our aim in this work is to make known the state of the art of scientific research related to inequality, poverty, and climate change and to propose lines of improvement that can contribute to achieving 3 of the 17 SDGs (End poverty-SDG 1-, Reduce inequality-SDG 10-, and Climate action -SDG 13-), proposed in the 2030 Agenda. To do so, we have used a systematic literature review methodology. The results show that poverty, inequality and climate change is a subject that has been little studied and articulated by researchers, with significant differences between the different areas studied. Topics related to sustainability and economics are those with the highest number of publications (51.7%). The rest are distributed among the 12 existing departments. Another relevant finding is that the effects of climate change are more pressing for more vulnerable populations, including impoverished women from rural areas and children from underdeveloped countries. This is a gender and social inequality that has been little addressed in climate change studies. Food security and energy poverty is another under-exploited aspect in this area. According to the results obtained in this work, we consider that the circular economy could improve these indicators, constituting a line of future research. Thus, one of its main objectives is to eliminate negative externalities, specifically existing social inequalities within the current linear economy model.

The aim of this study was to determine the relationship between levels of leisure-time sports and physical activity and the stages of change in high school students with goal orientations. Methods: The sample consisted of 2168 students randomly selected to participate in a longitudinal study in Costa Rica (423), Mexico (408) and Spain (1337), with 1052 being boys, 1037 girls and 79 who did not specify sex, aged between 11 and 16 years old (M = 12.49, SD = .81). We used a questionnaire to ask students about their leisure-time sports and physical activity, about stages of change and to measure achievement goals. Results: The results show that students are more active in Costa Rica, most of them being in the stage of active change. Conclusions: We found significant differences in achievement goals in all three countries, which shows that students in active stages have higher values than those in the inactive stage.

Mexico´s inhabitants have approximately 7 million dogs and cats as pets, of which there is no accurate information about their environmental impacts as a result of their feeding and comfort requirements. The objective of this study is to compare the environmental footprint between a dog and a cat in a family environment. For this purpose, a life cycle analysis was performed including, among other factors, its feeding and waste management in one year of life. Different environmental indicators including the carbon footprint were considered. It was found that the equivalent CO2 emission of a dog is twice that estimated for a domestic cat and that the main contribution is due to the food production. The ecological footprint that is generated when satisfying the requirements for pet´s well-being impacts in the environment contributes primarily to the carbon footprint.

The sugar company Valdez S.A. Entity located within the geographical limits of the city of Milagro, needs to reduce its emissions to the environment and does not always comply with the air emissions standards for stationary combustion sources, which indicates that for equipment installed before 2003 they have a maximum limit of 300 mg / m³. A mist eliminator was designed to work inside the original wet gas scrubber of the water-tube cauldron #10, which uses Bagasse as fuel, for the generation of steam for industrial use. The research is documentary and field. The methodology used was mixed. focusing on the comparison of three types of technologies to meet the objectives, the fog eliminators types: Demister, Cyclone and Chevron. To find the appropriate complement, a comparison sheet was made, which is a table of contents evaluated quantitatively, analyzing indicators formulated in each of the contents. The results, supported by the Multiple Criteria Decision Analysis methodology, select the Chevron type fog eliminator, with the best efficiency for capture. Using AutoCAD, allows to visualize in 3D, the structural design in the gas scrubber.

The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer´s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related de-mentias, little is known about the impact of this sensorial impairment in MixD at molecular level. To address this gap in knowledge, we have assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n=6) respect to neurologically intact controls (n=7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolisms and neuron projection regeneration. In addition, net-work-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT and PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, being also deregulated across different tauopathies, synucleinopathies and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phe-notypes.

A comparative study of organic and conventional farming systems was conducted in almond orchards to determine the effect of management practices on their fungal and bacterial communities. Soils from two orchards under organic (OM) and conventional (CM), and nearby nonmanaged soil (NM) were analyzed and compared. Several biochemical and biological parameters were measured (soil pH, electrical conductivity, total nitrogen, organic material, total phosphorous, total DNA, and fungal and bacterial DNA copies). Massive parallel sequencing of regions from fungal ITS rRNA and bacterial 16S genes was done to characterize their diversity in the soil. We report a larger abundance of bacteria and fungi in soils under OM, with a more balanced fungi:bacteria ratio, compared to bacteria-skewed proportions under CM and NM. The fungal phylum Ascomycota corresponded to around the 75% relative abundance in the soil, whereas for bacteria, the phyla Proteobacteria, Acidobacteriota and Bacteroidota integrated around 50% of their diversity. Alpha diversity was similar across practices, but beta diversity was highly clustered by soil management. Linear discriminant analysis effect size (LEfSE) identified bacterial and fungal taxa associated to each type of soil management. Analyses of fungal functional guilds revealed 3-4 times larger abundance of pathogenic fungi under CM compared to OM and NM treatments. Among them, the genus Cylindrocarpon was more abundant under CM and Fusarium under OM.

The utilization of vegetal fabric reinforced cementitious matrix (FRCM) represents an innovative approach to composite materials, offering distinct sustainable advantages when compared to traditional steel-reinforced concrete and conventional FRCM composites employing synthetic fibers. This article introduces a design for sandwich solutions based on a core of extruded polystyrene and composite skins combining mortar as a matrix and diverse vegetal fabrics as fabrics such as hemp and sisal. The structural behavior of the resulting sandwich panel is predominantly driven by the interaction between materials (mortar and polyurethane) and the influence of shear connectors penetrating the insulation layer. This study encompasses an experimental campaign involving double-shear tests, accompanied by heuristic bond-slip models for potential design of sandwich solutions. The analysis extends to the examination of various connector types, including hemp, sisal, and steel, and their impact on the shear performance of the sandwich specimens. The results obtained emphasize the competitiveness of vegetal fabrics in achieving effective composite strength comparable to other synthetic fabrics like glass fiber. Nevertheless, the study reveals that the stiffness of steel connectors outperforms vegetal connectors, contributing to an enhanced improvement in both stiffness and shear strength of the sandwich solutions

Nanotechnology has enabled the development of novel therapeutic strategies such as targeted nanodrug delivery systems, control and stimulus-responsive release mechanisms, and the production of theranostic agents. As a prerequisite for the use of nanoparticles as drug delivery systems, the amount of loaded drug must be precisely quantified, a task for which two approaches are currently used. However, both approaches suffer from the inefficiencies of drug extraction and of the solid-liquid separation process, as well as from dilution errors. This work describes a new, reliable, and simple method for direct drug quantification in polymeric nanoparticles using attenuated total reflection Fourier transform infrared spectroscopy, which can be adapted for a wide variety of drug delivery systems. Silk fibroin nanoparticles and naringenin were used as model polymeric nanoparticle carrier and drug, respectively. The specificity, linearity, detection limit, precision and accuracy of the spectroscopic approach were determined in order to validate the method. A good linear relation was observed within 0.00 to 7.89 % of naringenin relative mass with an R2 of 0.973. The accuracy was determined by the spike and recovery method. Results showed an average 104% recovery. The limit of detection and limit of quantification of the drug loading content were determined to be 0.3 and 1.0 %, respectively. The method's robustness is demonstrated by the notable similarities between the calibrations carried out in two different equipment and institutions.

Prostanoids modulate the pathogenesis of vascular diseases such as atherosclerosis, in which inflammation has an important role. It is well known that inducible Ciclooxygenase-2 (COX-2) is responsible for prostanoid production associated with inflammation. Angiotensin II may be implicated through the expression of COX-2 in the vascular wall. The purpose of this study was to examine in angiotensin II-stimulated adventitial fibroblasts the anti-inflammatory activity of different food peptides by inhibiting COX-2 expression, and the production of pro-inflammatory prostanoids. Fibroblasts from aorta of Sprague-Dawley rats were incubated with different food derived peptides followed by incubation with Angiotensin II. COX-2 expression was determined by western blot, transcriptional activity by luciferase assays and prostaglandin E2 by enzyme immunoassay. COX-2 expression was inhibited in the presence of Val-Pro-Pro (bovine β-casein 84–86), Arg-Asp-Ile-Leu-Asn-Gln (ovalbumin 84–89) and Tyr-Arg-Gly-Gly-Leu-Glu-Pro-Ile-Asn-Phe (ovalbumin 125–134). Angiotensin II-induced prostaglandin E2 production was also reduced by all the above-mentioned sequences. The incubation with ovalbumin-derived peptides displayed a significant reduction of COX-2 promoter activity compared to the stimuli with Angiotensin II in transiently transfected cells. These three sequences could potentially be used as functional food ingredients to reduce inflammation related to cardiovascular diseases.

Twenty-four extensively-reared Iberian pigs were used to study the influence of fattening period length (30, 60 or 90 days) on the fatty acid profiles of intramuscular and subcutaneous fat and the relationships between both profiles. Regarding fatty acid (FA) percentage, PUFA was greater in backfat and MUFA was greater in intramuscular fat (IMF), regardless fattening period length. The longer fattening period increased MUFA content in backfat (which had a more marked change in oleic acid) and decreased PUFA content in backfat and IMF, but it did not affect SFA content. Within the 3-layers subcutaneous backfat, SFA content was greater in the inner layer, MUFA was greater in the outer layer and PUFA was greater in both of these layers. The few differences in FA composition between both adipose tissues suggest that the changes due to the feeding regime are slow and, therefore, although the length of the fattening phase was increased, the fatty acid profile did not change substantially. The strong relationship between the FA profiles of IMF and backfat might be used to predict one profile from the other one when this latter was more readily available for sampling or analytical reasons.

Abstract: Chemical burns are one of the most dangerous and aggressive types of burns as they can cause significant tissue damage, leading to pain, inflammation, necrosis, and scarring. We present a burn case report associated with the use of Acellular Dermal Matrix (MatriDerm® MedSkin Solution Dr. Suwelack AG, Billerbeck, Germany) for the reconstruction of a Hallux after the patient was mistakenly administered intramuscular Nitric Acid at another institution. The patient presented with a third degree burn that compromised the medial aspect of the hallux’s skin, the distal phalanx and nail bed. Early debridement was performed, and Negative Pressure Wound Therapy (NPWT VAC, 3M, US) was used to preserve and promote tissue viability. Eight days later, the patient was taken to the OR, and Acellular Dermal Matrix and split-thickness skin graft were used to reconstruct her right hallux’s defect. The patient achieved adequate clinical evolution and was discharged with complete reconstruction of the burned area. Acellular Dermal Matrix proved to be an important and viable option for reconstructive surgery after a chemical burn, and further studies are warranted to ensure its routine usage in this kind of lesions. Keywords: chemical burn, acellular matrix, hallux reconstruction, NPWT

A reliability-based criterion to estimate strength amplification factors for buildings with asymmetric yielding located within a seismic region presenting different soil conditions is proposed and applied. The approach involves the calculation of the mean annual rate of exceedance of structural demands of systems with different levels of asymmetric yielding. Two simplified mathematical expressions are developed considering different soil conditions of the valley of Mexico. The mathematical expressions depend on the ductility of the structural systems, their level of asymmetric yielding, their fundamental vibration period and the dominant period of the soil. In addition, the proposed expressions are compared with that recommended by the current Mexico City Building Code (MCBC). Since the expressions are developed with the help of simplified structural systems, the validity of such expressions is corroborated by comparing the expected ductility demand of multi-degree of freedom (MDOF) structural systems with respect to that of their equivalent simplified systems. Both structural representations are associated with a given annual rate of exceedance value of an engineering demand parameter. The expressions proposed in this study will be incorporated in the new version of the MCBC.

Histoplasmosis is a systemic mycosis of universal distribution, highly endemic in the Americas. It is caused by a dimorphic fungus Histoplasma capsulatum var. capsulatum. It affects both immunocompetent and immunocompromised individuals where progressive and disseminated forms are observed. A very important risk factor is HIV infection/AIDS, with a mortality rate of 20-40% in Latin America. The diagnosis of this mycosis is made by conventional and molecular methods or by antigen and antibody detection. This study evaluated the sensitivity and specificity of a commercial kit for the detection of Histoplasma antigen by an EIA (HC-Ag) technique in 50 patients with histoplasmosis associated with AIDS. In addition, its performance was compared with that of other diagnostic techniques routinely used in our laboratory. HC-Ag had a sensitivity (S) of 94%, specificity (E) 95.5%, positive predictive value (PPV) 94% and negative predictive value (NPV) 95.5%. The delay time of the results was 4 days, similar to that of antibody detection and n-PCR and much less than that of blood cultures. The combination of methods improved S and NPV: 100%; with similar values in E and PPV. The HC-Ag method demonstrated its usefulness in the diagnosis of progressive disseminated histoplasmosis and the combination of methods is a good option to increase sensitivity and decrease the time to reach the diagnosis of certainty. This allows improving the strategy in the management of the disease and decreasing its case-fatality rate.

Graphene-based nanomaterials have emerged as promising materials for a wide range of applications.. Therefore, in the last years carbon nanoparticles have attracted great attention due to their low toxicity, high biocompatibility and easy preparation. Recently, N-doped carbon nanoparticles have been shown to have improved antibacterial activity over the undoped nanomaterial, but it is difficult to find correlations between the structure of the nanoparticle and its antibacterial activity. With this purpose, here, we analyze the effect of both, the nanoparticle size and the surface chemical composition of four N-doped carbon nanoparticles on the growth of Escherichia coli bacteria. Our results were analyzed using a Ligand-Substrate model based on the Monod´s equation, which allows us to interpret the dependence of the nanoparticle-bacteria affinity with the nanomaterial structure.

Lentil (Lens culinaris Medik) is an annual herb that belongs to family Fabaceae, it is one of the most ancient food crops that has been grown in the world, and originated from southwestern Asia as early as 7000 BC. In Spain lentil acreage raised 42,200 ha in 2022, two authonomous regions Castilla-León and Castilla-La Mancha are traditionally the large producers. Lentils have the capacity to fix atmospheric N2 in symbiosis with rhizobia and, additionally it is considered moderately tolerant to drought which in turn makes this pulse a low water and carbon fingerprint crop. The aim of this study was to assess the symbiotic responsiveness to rhizobia strains of several lentil accessions from the Spanish germplasm bank, to determine the nutritional value and mineral seed composition and, to evaluate the agronomic performance of six selected accessions in two regions under rainfed conditions and different management systems. The protein content of all genotypes was higher than 25%, with two outstanding seeds from accessions: BGE025596 and BGE026702 which account for >30% of protein and <2% of fat. Accessions BGE016362 and, BGE026702 had an exceptional Fe content, > 1 g/100 g of seed flour. The agronomic performance varied depending upon the cropping región.

Tomato brown rugose fruit virus (ToBRFV) is a causal agent of severe emergent diseases in Solanaceae hosts with agronomic relevance, such as tomato and pepper. Herein, we analyzed the seed transmission rate and efficacy of different seed disinfection treatments and performed a comparison of molecular biology techniques seeking rapid and sensitive detection in seed lots. We evaluated several total RNA extraction and RT-PCR protocols using a distinct combination of PCR primers to test for the presence of the ToBRFV Mexican strain in tobacco host. Our results showed that the percentage of seed and seedlings transmission was less than 1% and that a 3% sodium hypochlorite solution was effective as a seed disinfection treatment. Finally, the most sensitive molecular method identified for virus detection consisted of a CTAB-Trizol RNA extraction followed by nested PCR using primers reported by Dovas et al. (2004). Additionally, we tested potential natural hosts in selected Cucurbitaceae and Solanaceae species. Our results showed that the ToBRFV Mexican strain is capable of experimentally infecting eggplant (Solanum melongena), tomatillo (Physalis ixocarpa), and tobacco (Nicotiana rustica).

The consumption of sweet beverages, including sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB) and fruit juices (FJ) is associated with the risk of different cardiometabolic diseases and probably with some tumors as well. We carried out a systematic review and meta-analysis of observational studies aimed at evaluating the association between sweet beverage intake and different types of cancer risk. Suitable papers published up to June 2020 were searched through PubMed, Web of Science and SCOPUS databases, using relevant keywords. Overall, 64 studies were identified for the systematic review, of which 27 were selected for the meta-analysis. This was performed by analyzing the multivariable-adjusted OR, RR or HR of the highest compared with the lowest sweet beverage intake categories. Random effects showed significant positive association between SSBs intake and breast (RR: 1.14, 95% CI: 1.01 – 1.30) and prostate cancer risk (RR: 1.18, 95% CI: 1.10 – 1.27), also between FJs and prostate cancer risk (RR: 1.03, 95% CI: 1.01 – 1.05). Associations between SSBs and colorectal and pancreatic cancer risk, FJs and breast, colorectal and pancreatic cancer risk, ASBs and pancreatic cancer risk tended to be positive but did not reach the statistically significant threshold. This study supports the recommendation to limit the consumption of SSBs and FJs for cancer prevention and proposes to further investigate the potential harmful role of ASBs intake in cancer risk.

Nowadays the preservation and restoration of historical building needs to be faced in accordance with a novel sensibility regarding environment to preserve the future generations. In this context, the scientific community is focusing on novel and sustainable materials and techniques allowing durability and mechanical performances and at the same time compatibility with the existing heritage. Alkali activated materials represent a great challenge to produce new materials starting from the existing ones with reducing consumption, emission of greenhouse gases and environmental impact. This study deals with the valorization of waste materials coming from demolition and construction activities in the manufacture of geocomposites suitable for restoration and conservation of historical heritage. In particular, waste from tuff sawing and brick grinding were used as raw materials, then the geopolymeric samples produced were characterized from physical-chemical and mechanical point of view in order to investigate their performance and evaluate their suitability as materials for historical buildings recovery. Brick waste based geocomposites resulted to be more compact than the tuff-based ones as showed by the higher density values and the lower values of open porosity and water absorption and as further confirmed by the trend of the mechanical performance. Moreover, experimental data showed that physical and mechanical properties of both bricks and tuff waste-based geocomposites, even with different waste content, are compatible with existing building materials and to all the traditional repairing products.

We present a numerical calculation of the heat transport in a Bragg mirror configuration made of materials that do not obey Fourier's law of heat conduction. The Bragg mirror is made of materials that are described by the Cattaneo-Vernotte equation. By analyzing the Cattaneo-Vernotte equation's solutions, we define the thermal wave surface impedance to design highly reflective thermal Bragg mirrors. Even for mirrors with a few layers, very high reflectance is achieved ($>90\%$). The Bragg mirror configuration is also a system that makes evident the wave-like nature of the solution of the Cattaneo-Vernotte equation by showing frequency pass-bands that are absent if the materials obey the usual Fourier's law.

Despite the number of studies on bankruptcy prediction using financial ratios, very little is known about how external audit information can contribute to anticipating financial distress. A handful of papers show that a combination of ratios and audit data can provide significant predictive purposes, but a recent paper by Muñoz-Izquierdo et al. (2018) provided an 80% predictive accuracy solely by using the disclosures of audit reports. We complement this study. Applying an artificial intelligence method (the PART algorithm), we examine the predictive ability of more easily extracted information from the report and suggest a practical implication for each user. Simply by (1) finding the audit opinion, (2) identifying if a matter section exist, (3) and the number of comments disclosed, then any user may predict a bankruptcy situation with the same accuracy as if they had scrutinised the whole report. In addition, we also provide an extended literature review about previous studies on the interaction between bankruptcy prediction and the external audit information.

Iberian holm oak meadows are savannah-like ecosystems that result from traditional silvo pastoral practices. However, such traditional uses are declining, driving changes in the typical tree – open grassland structure of these systems. Yet, there are no studies integrating the whole ecosystem — including the arboreal and the herbaceous layer — as drivers of greenhouse gas (GHG: CO2, CH4 and N2O) dynamics. Here we aim at integrating the influence of tree canopies and interactions among plant functional types (PFT: grasses, forbs, and legumes) of the herbaceous layer as GHG exchange drivers. For that purpose, we performed chamber based GHG surveys in plots dominated by representative canopy types of Iberian holm oak meadows, including Quercus species and Pinus pinea stands, the last a common tree plantation replacing traditional stands; and unravelled GHG drivers through a diversity interaction model approach. Our results show that the tree – open grassland structure especially drove CO2 and N2O fluxes, with higher emissions under the canopy than in the open grassland. Emissions under P. pinea canopies being higher than those under Quercus species. In addition, the inclusion of diversity and compositional terms of the herbaceous layer improve the explained variability, legumes enhancing CO2 uptake and N2O emissions. Changes in the tree cover and tree species composition, in combination with changes in the structure and composition of the herbaceous layer, will imply deep changes in the GHG exchange of Iberian holm oak meadows. These results may provide some guidelines to perform better management strategies of this vast but vulnerable ecosystem.

Background Aspergillus spp. is a widely distributed filamentous fungus in the environment due to its high sporulation capacity. Currently, invasive aspergillosis (IA) is the most common invasive fungal infection in patients with hematologic malignancies with high rates of mortality and morbidity. The multifactorial nature of the disease requires appropriate risk stratification to allow the most appropriate preventive measures to be adapted and implemented according to the characteristics of the patient. In this sense, the present research aims to identify recent risk factors and environmental control measures against invasive aspergillosis to establish preventive actions to reduce the incidence of invasive aspergillosis in hospitals; (2) Methods: We conducted a qualitative systematic review of the scientific literature on environmental risk factors and preventive measures for invasive aspergillosis in patients with hematological malignancies. The Medline, Cochrane and Scopus databases were consulted, following the PRISMA and STROBE guidelines; (3) Results Adequate implementation of environmental control measures is presented as the most efficient intervention in terms of prevention to decrease the incidence of invasive aspergillosis in hospitals. We identify neutropenia, fungal contamination, lack of adequate environmental control measures in hospitals and patients´ homes, duration of hospitalization, and anemia as independent risk factors. We show that HEPA, LAF and Plasmair® systems are suitable methods to reduce the concentration of airborne fungal spores. Antifungal prophylaxis did not influence the reduction of IA significantly in our study; (4) Conclusions: Proper professional training and environmental control measures in hospitals are essential for the prevention of invasive aspergillosis. We should optimize risk stratification for patients with hematologic malignancies. Antifungal prophylaxis should be complementary to environmental control measures and should never be substituted for these last ones. Studies should also be done to evaluate the efficiency of environmental control measures against IA at patients' homes.

The use of medicinal plants for the therapy of diseases of the digestive system; where the Andean peoples developed various forms of administration. The objective being the identification of medicinal plants used in the therapy of ailments of the digestive system by the Andean inhabitants of Pampas, Tayacaja, Huancavelica, Peru. Methods, non-probabilistic sampling, using the “snowball” technique, carrying out semi-structured surveys, allowing information to be collected on the prevalence of ailments or diseases of the digestive system treated with medicinal plants, with inhabitants over 20 years of age participating and using the medicinal plants in the therapy of your digestive system ailments; and, exclude those inhabitants who do not comply with it. Results, 16 families, 33 genera and 34 species are reported; where the families that present the greatest abundance of species are Asteraceae, Lamiaceae; Likewise, the widely used species are Minthostachys mollis (11.9%), Aloe vera (10.4%), Clinopodium bolivianum (9%), Artemisia absinthium (9%) and Matricaria chamomilla (8.2%). Concluding with the identification of a diversity of medicinal flora, used in the therapy of diseases of the digestive system, such as stomach pain, constipation, gallbladder ailments, gastritis, gastrointestinal and liver diseases.

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated, among them, four icetexanes, and one abietane (1–5), which are first reported. Their structures were established by spectroscopic means, mainly ¹H and ¹³C NMR, including 1D and 2D homo- and hetero-nuclear experiments. Most of the isolated diterpenoids were tested for their antiproliferative, anti-inflammatory, and radical scavenging activities using the sulforhodamine B assay on six cancer cell lines, the TPA induced ear edema test in mice, and the reduction of the DPPH assay, respectively. Some diterpenoids showed anti-proliferative activity, these being icetexanes 6 and 3, which were the most active with IC₅₀ (µM) = 0.27 ± 0.08 and 1.40 ± 0.03, respectively, for U251 (human glioblastoma) and IC₅₀ (µM) = 0.0.46 ± 0.05, and 0.82 ± 0.06 for SKLU-1 (human lung adenocarcinoma), when compared with adriamycin (IC₅₀ (µM) = 0.08 ± 0.003, and 0.05 ± 0.003, as the positive control, respectively. Compounds 3 and 10 showed significant reduction of the induced ear edema of 37.4 ± 2.8 and 25.4 ± 3.0% (at 1.0 µmol/ear), respectively. Compound 4 was the sole active diterpenoid in the antioxidant assay (IC₅₀ = 98. 4 ± 3.3), using α-tocopherol as positive control, IC₅₀ (µM) = 31.7 ± 1.04. The diterpenoid profile found is of chemotaxonomic relevance and reinforces the evolutionary link of S. ballotiflora with other members of the section Tomentellae.

The aim of this paper is to contribute to the body of knowledge about Project-Based Learning (PBL) methodology in higher education by describing and analysing interrelations between competencies, and their contribution to knowledge transfer (KT) and students’ rating of the project. The sample consisted of 464 students from the Universities of Huelva (N=347; 74.8%) and Murcia (N= 117; 25.2%), enrolled in the second year of a degree in either Infant or Primary Education. Data was collected through a self-administered questionnaire comprising a total of 53 items measuring General, Specific and Transversal competencies, as well as students’ rating of the project. Competencies were selected from the course programmes for the degrees in Infant and Primary Education. Preliminary results showed that competencies were moderately to highly acquired after PBL, and that students reported notable KT as well as a positive assessment of the project. KT showed a high degree of association with students’ ratings and was established as a key factor in learning and learner satisfaction in higher education.

The presence of escaped fish in aquaculture facilities as a result of harsh meteorological conditions (more pressing in a face of climate change) requires a better understanding of these dynamical behaviour through vigilant monitoring and validated numerical models. In this context, data from strain, stress sensors as well as meteorological and current sensors installed at an aquaculture farm in the Region of Murcia (Spain) were collected, processed and analysed. Among them, first results about the relationship between load and currents sensors are presented. Due to the complexity of the time series, various analyses were conducted to examine their interrelation, encompassing regression analysis of raw data and data segmented into different time intervals. Through this analysis, it was observed that employing distinct time windows better elucidated the data variability. Furthermore, an optimal data window of 240 data was identified, demonstrating significantly improved explanatory power, with the coefficient of determination (R2) increasing by approximately 0.8 depending on the section. This pave the way for optimizing the monitoring features that must be carried out to relate cause-and-effect variables in the behaviour of these off-shore infrastructures.

Vaccination has been one of the most successful and the most significant scientific advances in human health and life expectancy all around the globe. The World Health Organization considers that immunization should be recognized as the main component of human health right, due to the fact that vaccination prevents 2.5 million deaths annually (World Health Organization, 2011). The most successful vaccines have been developed using conventional methods that follow the paradigm established by Pasteur: "to isolate, inactivate and inject" the pathogen microorganism and mimic a natural infection. Recently, metagenomics have played an important role in the discovery of new immunogens for vaccine design and the selection of antigens based on genomic information. The main approach that has used this strategy has been called "reverse vaccinology". This promising and arising field allows the screening of the entire potential antigenic repertoire of an organism using predictive bioinformatic tools. Once the antigenic protein or proteins have been selected, they are expressed and purified using molecular cloning and in vitro expression techniques. Following the in vitro production step, they are probed in animal models to evaluate the in vivo protective strength of the immune response. The main aim of this in vivo approach is to evaluate the ability of the immune response to eliminate or neutralize the pathogen at the time of infection. Those antigens capable of generate a specific immune response with neutralizing activity for natural infections are the best candidate vaccines. In this review we summarize the evolution of vaccinology since its inception, with special emphasis on the development of VLPs as vaccine platforms and their future in preventive medicine and we introduce a new recombinant platform for antigen presentation based on Junin virus VLPs (JUNV-VLPs).

Abstract We aim to describe the diagnosis and surgical management of urinary tract endometriosis (UTE). We detail current diagnostic tools including advanced transvaginal ultrasound, magnetic resonance imaging, and surgical diagnostic tools such as cystourethroscopy. While discussing surgical treatment options, we emphasize the importance of an interdisciplinary team, for complex cases that involve the urinary tract. While bladder DE is more straightforward in its surgical treatment, ureteral DE requires a high level of surgical skill. Specialists should be aware of the important entity of UTE due to the serious health implications for women. When UTE exists, it is important to work within a interdisciplinary radiological and surgical team.

We are currently facing a potential ‘polycrisis’, a critical inflection point that requires a whole-of-society response aimed at building collective foresight and preparedness for short-, medium-, and long-term risks. The role of higher education institutions and social stakeholders is decisive to make an impact. This paper depicts the alignment of academia, governance, and industry with the aim to challenge, inspire, and encourage universities to go beyond commodified courses and mere employability, enhance student growth and bind macro-scale measures that lead to a sustainable future. A modest teaching innovation project has served as a transforming lever, with the private sector joining in, to create a platform that reaches more than 50 000 undergraduate students and teaching staff. The resulting structure, rooted in the University’s strategic plan, has served to channel local and regional initiatives, establish effective partnerships with broad social members, raise awareness and promote actions to advance in the pursuit of Sustainable Development Goals. Chronology, materials and methodology, together with a description of the different courses, programmes and actions are provided. The paper concludes with some recommendations for future research, policy and cooperation among stakeholders. Research methodology posted on clinicaltrials.gov under ID NCT04392869, NCT05598944, and NCT05775978.

We are currently facing a potential ‘polycrisis’, a critical inflection point that requires a whole-of-society response aimed at building collective foresight and preparedness for short-, medium-, and long-term risks. The role of higher education institutions and social stakeholders is decisive to make an impact. This paper depicts the alignment of academia, governance, and industry with the aim to challenge, inspire, and encourage universities to go beyond commodified courses and mere employability, enhance student growth and bind macro-scale measures that lead to a sustainable future. A modest teaching innovation project has served as a transforming lever, with the private sector joining in, to create a platform that reaches more than 50 000 undergraduate students and teaching staff. The resulting structure, rooted in the University’s strategic plan, has served to channel local and regional initiatives, establish effective partnerships with broad social members, raise awareness and promote actions to advance in the pursuit of Sustainable Development Goals. Chronology, materials and methodology, together with a description of the different courses, programmes and actions are provided. The paper concludes with some recommendations for future research, policy and cooperation among stakeholders. Research methodology posted on clinicaltrials.gov under ID NCT04392869, NCT05598944, and NCT05775978.

Nowadays, the transparency of governments with respect to the sustainability of public services is a very interesting issue for stakeholders and academics. It has led to previous research and international organisations (EU, IMF, OECD, United Nations, IFAC, G-20, World Bank) to recommend promotion of the online dissemination of economic, social and environmental information. Based on previous studies about e-government and the influence of administrative cultures on governmental accountability, this paper seeks to identify political actions useful to improve the practices of transparency on economic, social and environmental sustainability in European local governments. We perform a comparative analysis of sustainability information published on the websites of 72 local governments in 10 European countries grouped into main three cultural contexts (Anglo-Saxon, Southern European and Nordic). Using international sustainability reporting guidelines, our results reveal significant differences in local government transparency in each context. The most transparent local governments are the Anglo-Saxon ones, followed by Southern European and Nordic governments. Based on individualized empirical results for each administrative style, our conclusions propose useful policy interventions to enhance sustainability transparency within each cultural tradition, such as development of legal rules on transparency and sustainability, tools to motivate local managers for online diffusion of sustainability information and analysis of information needs of stakeholders.

Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 x 109/l. A count equal or above 0.5 x 109/l is considered eosinophilia, while a count equal or above 1.5 x 109/l is defined as hypereosinophilia. In bone marrow, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non- hematologic, whether non-neoplastic (allergic diseases, drugs, infections or immunological diseases) or neoplastic (solid tumors). Eosinophilia associated with a haematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphoid variant of hypereosinophilic syndrome and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia associated with a haematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with origin in stem cell (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with Core Binding Factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive o clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of haematological malignancies with eosinophilia.

Zucchini (Cucurbita pepo subsp. pepo) is a seasonal vegetable with high nutritional and medical value. Many useful properties of this fruit are attributed to its bioactive compounds. Zucchini fruits (“Yellow” and “Light Green” varieties) and four distinctive components (lutein, β-carotene, zeaxanthin and dehydroascorbic acid)were selected. Firstly it was determinated the lutein, β-carotene, zeaxanthin and dehydroascorbic acid content in these fruits and then, in order to measure the safety and suitability of their use different assays were carried out: (i) Genotoxicity and antigenotoxicity tests to determine the safety and DNA-protection against hydrogen peroxide; (ii) cytotoxicity and (iii) DNA fragmentation assay to evaluate the proapoptotic effect. Results showed that: (i) all the substances were non-genotoxic, (ii) all the substances were antigenotoxic except the highest concentration of lutein, (iii) “Yellow” Zucchini epicarp and mesocarp exhibited the highest cytotoxic activity (IC₅₀ > 0.1 mg/mL and 0.2 mg/mL, respectively) and iv) “Light Green” Zucchini skin and pulp induced internucleosomal DNA fragmentation . To sump up, Zucchini fruit could play a positive role in human health and nutrition due to this fruit and its components were safe, able to inhibit significantly the H₂O₂-induced damage and exhibit antiproliferative and pro-apoptotic properties toward HL60 tumour cells. The information generated from this research should take into account to select potential accessions for breeding programs purposes.

Leishmania major is the main causative agent of cutaneous leishmaniasis in humans. The Friedlin strain of this species (LmjF) was chosen when a multi-laboratory consortium undertook the objective of deciphering the first genome sequence for a parasite of the genus Leishmania. The objective was successfully attained in 2005, and this represented a milestone for Leishmania molecular biology studies around the world. Although the LmjF genome sequence was done following a shotgun strategy and using classical Sanger sequencing, the results were excellent and this genome assembly served as the reference for subsequent genome assemblies in other Leishmania species. Here, we present a new assembly for the genome of this strain (named LMJFC for clarity), generated by the combination of two high throughput sequencing platforms, Illumina short-read sequencing and PacBio Single Molecular Real-Time (SMRT) sequencing, which provides long-read sequences. Apart from resolving uncertain nucleotide positions, several genomic regions have been reorganized and a more precise composition of tandemly repeated gene loci was attained. Additionally, the genome annotation has been improved by adding 542 genes and more accurate coding-sequences defined for around two hundred genes, based on the transcriptome delimitation also carried out in this work. As a result, we are providing gene models (including untranslated regions and introns) for 11,238 genes. Genomic information ultimately determines the biology of every organism; therefore, our understanding of molecular mechanisms will depend on the availability of precise genome sequences and accurate gene annotations. In this regards, this work is providing an improved genome sequence and updated transcriptome annotations for the reference L. major Friedlin strain.

Cryptococcosis is one of the most serious opportunistic diseases in patients living with HIV. For this reason, it is important to have early diagnosis and appropriate treatment. Objectives. The aim of the study was to know the evolution of patients diagnosed with cryptococcosis by detection of Cryptococcus antigen in serum by lateral flow (CrAg LFA) without nervous system involvement and with treatment in accordance with the results. Materials and Methods. A retrospective, longitudinal, analytical study was performed. Seventy patients with cryptococcosis initially diagnosed by serum CrAg LFA without meningeal involvement between January 2019 and April 2022 were analyzed for medical records. The treatment regimen was adapted to the results of blood culture, respiratory material or pulmonary tomography imaging. Results. Seventy patients were included, 13 had probable pulmonary cryptococcosis, 4 had proven pulmonary cryptococcosis, 3 had fungemia and 50 had pre-emptive therapy without microbiological or imaging findings compatible with cryptococcosis. Among the 50 patients with pre-emptive therapy, none had meningeal involvement or cryptococcosis recurrences to date. Conclusion. Pre-emptive therapy avoided progression to meningitis in patients with CrAg LFA-positive patients. Pre-emptive therapy with dose adjustment of fluconazole in patients with the mentioned characteristics was useful despite the use of lower doses than recommended.

Leishmania infantum is causative of visceral leishmaniasis (kala-azar), the most severe form of leishmaniasis, lethal if untreated. Few years ago, re-sequencing and de novo assembling of the L. infantum (strain JPCM5) genome was accomplished, and now we aimed to describe and characterize the experimental proteome of this species. In this work, we have performed a proteomic analysis from axenic cultured promastigotes and carried out a detailed comparison with other Leishmania experimental proteomes published to date. We identified 2,352 proteins based on the search of mass spectrometry data against a database built from the six-frame translated genome sequence of L. infantum. We have detected many proteins belonging to organelles such as glycosomes, mitochondria or flagellum, as well as many metabolic enzymes, and a large number of putative RNA binding proteins and molecular chaperones. Moreover, we listed the proteins presenting post-translational modifications, such as phosphorylations, acetylations and methylations, among others. On the other hand, the identification of peptides mapping to genomic regions previously annotated as non-coding has allowed to correct annotations, leading to N-terminal extension of protein sequences, and the uncovering of eight novel protein-coding genes. The alliance of proteomics, genomics and transcriptomics has resulted in a powerful combination for improving the L. infantum reference genome annotation.

Immunohistochemistry is a powerful technique, widely used in biomedical research and clinics, that allows to determine the expression levels of some proteins of interest in tissue samples by means of the intensity of color due to the expression of biomarkers using specific antibodies. As such, immunohistochemical images are complex and problematic to be quantified. Recently we proposed a novel method including a first separation stage based on nonnegative matrix factorization (NMF) that achieved good results. However, that method was highly dependent on sparseness and non-negativity parameter choice and on algorithm initialization. Furthermore, the previously proposed method needed a reference image as starting point for the NMF algorithm. In the present work, we propose a new, simpler and robust method for the automated unsupervised scoring of immunohistochemical images based on bright field. Our work is focused on images from tumor tissues marked with blue (nuclei) and brown (protein of interest). The new proposed method represents a simpler approach that, in one side, avoids the use of NMF for the separation stage, and in the other side, circumvents the need for a control image. This new approach determines the subspace spanned by the two colors of interest by means of principal component analysis (PCA) with dimension reduction. This subspace is a two-dimensional space, allowing the finding of color vectors by considering the peaks of density of points. The method also develops a new scoring stage by avoiding, again, reference images, making the procedure more robust and less dependent on the parameters. Experiments for the semi-quantitative scoring of images in five categories exhibit promising and consistent results when compared to manual scoring carried out by experts.

Providing data on usage patterns is key to assessing the reduced-risk potential of novel tobacco and nicotine products at a population level. We performed a nationwide cross-sectional survey of the general population in Japan to assess usage patterns after the introduction of tobacco heating products (THPs). Eligible participants were Japanese residents, aged 20 years or older who consented to complete the survey. Individuals living in institutions were excluded. A three-stage probability sampling method was applied that was geographically stratified by street blocks proportionate to population density. Respondents self-reported patterns of product use and reasons for THP use. Complete responses were available from 5,306 individuals, of whom 933.5 (17.6%) were current users, 984.2 (18.5%) were former users and 3388.4 (63.9%) were never users of tobacco products. Cigarettes were used by 14.6% of current tobacco product users and THPs by 5.3%. Cigarettes and THPs were used exclusively by 64.5% and 12.2%, respectively, and both were used by 12.7%. The most common reasons reported for THP use were perceived reduction in harm to self and others compared to cigarettes. While the prevalence of cigarette use in Japan is decreasing, THPs seem to be increasingly used as long-term alternatives to cigarette smoking.

Acerola (Malpighia spp.) is a tropical plant genus of shrubs and trees whose fruit is rich in nutrients and bioactive compounds. However, its production generates significant waste that could pose an environmental issue. This review aims to summarize recent research on the potential uses of acerola wastes, including the extraction of bioactive compounds such as polyphenols, carotenoids, and pectins, as well as the development of materials such as nanomaterials, chitosan, and biofuels. Additionally, the paper discusses the potential medical applications of acerola wastes, such as wound healing, antioxidant, and anticancer effects. Finally, the paper explores the challenges and opportunities of using acerola waste as a sustainable source of raw materials and energy. The findings suggest that acerola waste could be a valuable resource for developing high-value products and promoting sustainable production practices in the fruit industry.

Pineapple is a highly demanded fruit in international markets, thanks to its unique appearance and flavor, high fiber content, vitamins, folic acid, and minerals. It makes the pineapple production and processing market a significant source of income for producing countries, such as Costa Rica. Nowadays, its processing produces a large amount of waste with negative consequences for the environment. However, pineapple waste is an essential source of cellulose, hemicellulose, lignin, and other high-value products like enzymes (bromelain). These by-products can be obtained by pineapple waste biorefinery, generating an additional source of export goods and foreign currency, framing pineapple processing in the concept of the circular economy. This review discusses how incorporating biorefinery in the pineapple production processes can contribute to the post-COVID 19 economy in Costa Rica. Pineapple production in Costa Rica is explored, and the contamination of generated residues is delineated. Furthermore, the primary processes for by-product extraction via biorefinery, their general characteristics and applications in the medical field, and their contribution to the circular economy are presented.

We aimed to provide a comprehensive assessment of exercise physiology of adult Fontan patients (FP) and factors limiting functional capacity (FC). A prospective single-centre study of 37 FP aged ≥16years and 19 healthy-controls (HC), who underwent CPET on cycle-ergometer in February-March 2022. Lung function was impaired in FP, mostly mild restrictive pattern (56.8%). Mean peakVO2 was 21±5.4ml/kg/min, 55% predicted. Morphologically left-single ventricle showed higher peakVO2%predicted (57.4±14.4% vs 43.4±8.1%, p=0.045). A lower peakVO2%predicted was observed in patients with an early flattened and/or descending O2 pulse at maximal exertion (52±14% vs 62±12.5, p=0.04 and 47.6±9% vs 60±14 respectively, p=0.018) and chronotropic insufficiency (53±12% vs 69.8±20%, p=0.008). Strong positive correlation was observed between %OUES and peakVO2%predicted (r=0.726, p>0.001). PeakVO2%predicted was progressively higher as the level of physical activity increased (low-level 49.5±14%, moderate-level 55±12%, intense-level 69±20%). FP showed lower inspiratory muscle strength compared to HC but it was no statistically associated with either peakVO2 or VE/VCO2 slope. In FP OUES is a useful submaximal parameter in those who fail to reach maximal exertion. Chronotropic insufficiency and early flattened or descending oxygen pulse slope were factors associated with low peakVO2. Regular intense physical activity improves FC. Although FP have inspiratory muscle weakness, its impact on FC is unclear.

The current work shows the optimization in the preparation of nanosized titanium carbide (TiC) in-situ through mechanical alloying (MA). Metallic titanium (Ti) powders, along with two carbon sources, carbon nanotubes (CNTs), and stearic acid (SA), were used to reduce the particle size using a high-energy Spex800 mill. The combined use of 2 wt % of these carbon sources and n-heptane as a liquid process control agent (PCA) proved crucial in generating nanoscale powder composites through a simple and scalable synthesis process within a 4-hour timeframe. The use of 20 wt % of both carbon sources was compared to determine the ability of CNTs to form carbides and the decomposition of PCAs during mechanical milling. The result reveals structures like nanoblocks and nanolumps with and important size reduction. The structure and morphology of the composites and starting materials were evaluated through x-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).

Objective: To investigate the use of blood levels of N-(2 cyanoethyl)valine (CEVal), a haemoglobin adduct of acrylonitrile, to assess lack of compliance with smoking cessation. Methods: We report CEVal concentrations and percentiles over time for 2 cessation groups, compliance was established using NNAL concentrations. CEVal half-life was estimated. Optimal thresholds were calculated based on receiver operating characteristics analysis. Results: At 180 days, among 67 participants in the continued smoking group and 159 assigned to smoking cessation or sole THP use. CEVal half-life was estimated to be approximately 30 days and the optimal thresholds were for NNAL at 40 pg/mL and CEVal at 35 pmol/g globin (81% sensitivity and specificity). Conclusions: A new generation of biomarkers of compliance is required, specific to the new generation of nicotine products. Methodological validation and standardisation could allow robust assessment of effects across clinical and observational studies while promoting comparability between studies. CEVal could play an important role as biomarker of compliance for smoking cessation and switching studies.

Few data are available on the health impact of tobacco heating products (THPs) at the population level. We used systems dynamics modelling to estimate effects in the established THP market in Japan. We projected effects of THP use in overall mortality up to 2100 and compare those projections against a baseline scenario based on smoking rates pre-THP launch, i.e., smoking only. The model was informed using data from publicly available sources and the literature, including population size, yearly deaths and smoking prevalence with initialisation year (2004) and, births and migration from 2004 to 2065. Transitions between products were estimated from cross-sectional population surveys in Japan. Potential life-years saved with the introduction of THPs was 13 million by 2100 compared with smoking only. In worst-case scenario, population health gains would be seen with THPs risk 10–50% lower risk than smoking. Assuming equal risk for dual use and smoking, THP risk would need to be at least 10% lower than smoking to achieve a population health benefit by 2100. In credible scenarios, substantial population health gains will follow the introduction of THPs in Japan in a relatively short time frame.

In recent years, numerous research studies have shown the excellent characteristics of silk fibroin nanoparticles as a vehicle for drugs delivery and it is foreseeable that their production could reach industrial scale in the coming years. For this reason, it is essential to know all the parameters that affect the formation of nanoparticles in order to standardize the process. Several studies have stated that the process used for sericin removal (degumming) from silk cocoons has a strong impact in the silk fibroin integrity and their mechanical properties after processing it into biomaterials. In this work, silk cocoons were degummed following four standard methods: autoclaving, short alkaline (Na2CO3) boiling, long alkaline (Na2CO3) boiling and ultrasounds. The resultant silk fibroin fibers were dissolved in the ionic liquid 1-ethyl-3-methylimidazolium acetate and used for nanoparticle synthesis by rapid desolvation in polar organic solvents. The relative efficiencies of the degumming processes and the integrity of the resulting fibroin fibers obtained were analyzed by weight loss, optical microscopy, thermogravimetric analysis, infrared spectroscopy and SDS-PAGE. Particle sizes and morphology were analyzed by Dynamic Light Scattering and Field Emission Scanning Electronic Microscopy. The results showed that the different treatments had a remarkable impact on the integrity of the silk fibroin chains, as confirmed by gel electrophoresis which can be correlated with particle mean size and size distribution changes. The study confirm that all the parameters of the process must be controlled in order to reach an optimum reproducibility of the nanoparticle production.

New resources of food, pharmaceuticals or biotechnological products are needed. The huge biodiversity of aero-terrestrial lichen-symbiont microalgae remains unexplored. Viability of these for human consumption demands the demonstration of the absence of toxic effects. In vitro biocompatibility of crude homogenates of axenic microalga Asterochloris erici, symbiotic in the lichen Cladonia cristatella, was analyzed after treatment of cultured L929 fibroblasts with different doses of microalgal homogenates. The results show that crude homogenates of A. erici do not induce fibroblast cytotoxicity but seem to have some cytostatic effect inducing slight cell cycle alterations and intracellular reactive oxygen species (ROS) increase at the highest dose. Carotenoid analysis demonstrates high content of lutein, a xanthophyll with antioxidant and cytostatic properties in vivo. These findings confirm that Asterochloris erici can be considered suitable for the development of alimentary or pharmaceutical applications. The cytostatic effects should be further investigated for antitumor agents.

The consumption of foods with fiber and phenolic compounds can be part of treating obesity through interaction with the gastrointestinal tract. Treatment with common bean leaves (BL) for obesity was evaluated in mice on a high-fat, high-fructose diet (HFFD). The proximal and phytochemical characterization of BL was determined. Obesity was induced with a HFFD for 14 weeks. Immediately after, the animals were supplemented with BL (10%) or standard diet (SD) as a strategy to seem a healthy diet (12 additional weeks). Changes in body composi-tion, lipid profile, and intestinal integrity were analyzed. BL contained 27.2% dietary fiber, total phenolics (475.04 mg/100 g), and saponins (2.2 mg/100 g). The VAT consumption of the BL group decreased by 52% compared to the HFFD group. Additionally, triglyceride concentrations were 23% lower in the BL consumption group compared to the HFFD group. The improvement in lipid profile was attributed to the (1.77-fold) higher fecal lipid excretion in the BL consumption group compared to the HFFD group. Likewise, pancreatic lipase decreased by 29%. Furthermore, BL supplementation reduced the level of IL-6 (4.4-fold) and FITC-dextran in serum by 50% compared with that in the HFFD group. Metabolic endotoxemia was inhibited after BL supplementation (-33%) compared to the HFFD group. BL consumption as a treatment in obese mice reduces adipose tissue accumulation and improves the lipid profile. Furthermore, we report for the first time that BL consumption improves intestinal integrity.

Wildfire is the main disturbance in forested ecosystems of southern Europe and is due to complex interactions between climate-weather, fuels and people. Warmer and drier conditions projected in this region are expected to profoundly affect wildfires, which will impact ecosystems and humans. We review the scientific literature addressing the assessment of climate change impacts on wildfires in southern Europe, with a twofold objective: (i) report the trends in wildfire danger and activity projected under warming climate in southern Europe and (ii) discuss the limitations of wildfire projections under the specific biogeographical context of southern Europe.We identified 22 projection studies that examined future wildfire danger or wildfire activity at local, regional or continental scale. Under the scenario with the highest greenhouse gas emissions, we found that projections studies estimate an increase in future fire danger and burnt areas varying, on average, from 2 to 4 % and from 15 to 25 % per decade, respectively. Fire-prone area expansion to the north and to Mediterranean mountains is a concern, while climate-induced burnt area increase might be limited by fuel availability in the most arid areas. While all studies agreed on the direction of changes, further comparisons on the magnitude of increase remained challenging because of heterogeneous methodological choices between projections studies (climate models, projection period, spatial scale and fire metrics). We then described three main sources of uncertainty that may affect the reliability of wildfire projections: climate projections, climate-fire models, and the influences of fuel load/structure and human related factors on the climate-fire relationships. We finally suggest research directions to address some of these issues for the purpose of refining fire danger and fire activity projections in southern Europe.

White and three types of black garlic (13, 32 and 45 days of fermentation, named 0C1, 1C2 and 2C1 respectively) were selected in order to check possible differences in their nutraceutic potential. For this purpose, garlic were physico-chemically characterised, and both in vivo and in vitro assays were carried out. Black garlic showed higher polyphenol content and antioxidant capacity than white garlic. The biological studies have shown that only white garlic was not safe showing toxicity effect. Furthermore, none garlic exert protective effects against H₂O₂, except the 0C1 black garlic. Moreover, garlic was non-genotoxic with the exception of the highest concentration of white garlic. On the other hand, 0C1 was the most antigenotoxic substance. The in vivo longevity assays yielded significant extension of lifespan results in some concentrations of white and 0C1and 1C2 black garlic. The in vitro experiments showed that all studied garlic induced a decrease in leukaemia cells growth. However, none type of garlic was able to induce proapoptotic internucleosomal DNA fragmentation. Taking into account the physicochemical and biological data, black garlic could be considered as a potential functional food and used in preventive treatment of age-related diseases. In addition, our findings could be relevant for the black garlic processing agrifood companies as the economical and timing costs are significantly reduced to 13 days aging.

Objective. To describe patient satisfaction with pre-hospital emergency knowledge and determine if patients and professionals share a common vision on the satisfaction predictors. Methods. A qualitative study conducted in two phases. First, a systematic review following the PRISMA protocol was carried out searching publications between January 2000 and July 2016 in Medline, Scopus, and Cochrane. Second, three focus groups involving professionals (advisers and healthcare providers) and a total of 79 semi-structured interviews involving patients were conducted to obtain information about what dimensions of care were a priority for patients. Results. Thirty-three relevant studies were identified. A majority conducted in Europe using questionnaires. They pointed out a very high level of satisfaction of callers and patients. Delay with the assistance and the ability for resolution of the case are the elements that overlap in fostering satisfaction. The published studies neither reviewed the overall care process nor related the measurement of the real time in responding to an emergency with the satisfaction. The patients and professionals concurred in their assessments about the most relevant elements for patient satisfaction, although safety was not a predictive factor for patients. Response capacity and perceived capacity for resolving the situation were crucial factors for satisfaction. This qualitative approach yielded assistance targets to be improved. Conclusions. Published studies have assessed similar dimensions of satisfaction. Furthermore, despite the fact that few explanations may be given due to the no face to face attention, taking into account the patient’s emotional needs or maintaining contact with the patient until the emergency services arrive are high predictors of the satisfaction.

Escape room’s games are educational gamification technologies that consist of introducing a team of players into a physical or digital space to solve a mystery or a problem in search of clues to solve puzzles, riddles, or enigmas. This study aims to determine the effectiveness of escape room’s games on the training of nurses and nursing students. A systematic review was carried out in MEDLINE, WOS, SCOPUS, CINAHL and LILACS databases using the MeSH terms: "Education, Nursing" and "Educational Technology", and the free term "Escape room", combining with Boolean operators AND/OR. Intervention studies in Spanish, English and Portuguese were included, without limitation for the year of publication. Selection and critical appraisal were conducted by two independent reviewers. A total of n=15 interventional studies were included (n=2 Randomized Clinical Trials and n=12 quasi-experimental). Escape rooms are a recent and booming educational methodology, which is increasingly used in academia and training of nurses and nursing students; however, it is necessary to expand their use to more countries, as well as the number and quality of interventional studies, being necessary to homogenize and standardize criteria and to use validated instruments to evaluate the effectiveness of escape rooms in the field of nursing.

BACKGROUND: It has been known for decades that breastfeeding leads to a lower risk of asthma, respiratory infections, or metabolic syndrome at school age. In addition, evidence is now accumulating on the influence of breast milk on the shape, volume, or function of the heart and lungs. Within this field of research into the effects of breast milk on the structure of the heart and lungs, we have set out to analyze the differential electrocardiographic characteristics of schoolchildren who were once breastfed. METHOD: Observational cross-sectional study including 138 children aged 6 or 12 consecutively presenting to a well-child clinic between May and December 2022. Inclusion criteria: the ability to perform reproducible ECG records, the feasibility of weighing and measuring patient, and breastfeeding data collected from birth. RESULTS: Using the 40º cut-off value for the mean P-wave axis among schoolchildren, 76% of never breastfed children in our sample have a P-wave axis in a more vertical position than the mean as compared to 58% of ever-breastfed children (OR:2.25;95%CI:3.13-1.36); there was no other significant difference between infant feeding groups in somatometric characteristics or ECG parameters, CONCLUSION: We found a significant difference of the mean values of the P-wave axis between never and ever breastfed children. Although this report should be approached cautiously, these findings add to the renewed interest in discerning developmental interventions to improve cardiovascular health.

Clinical and analytical differences between adult patients monoinfected with Borrelia burgdorferi sensu lato (s.l.) and patients infected with B. burgdorferi s.l. who also had IgG antibodies against Babesia divergens have not been reported so far. Both Lyme disease caused by B. burgdorferi and babesiosis caused by B. divergens, endemic in Asturias, Northwestern Spain, are transmitted by Ixodes tick bites. Clinical, laboratory and other diagnostic tests characteristics (imaging, electro-cardiographic-ECG) of 120 residents of Asturias with confirmed B. burgdorferi s.l. infection, di-agnosed during 2015-2017, of whom 47 (39.2%) had B. divergens IgG antibodies, were retrospec-tively compared. Cardiorespiratory symptoms were reported in 9/47 (19.2%) patients with Lyme disease and B. divergens IgG antibodies compared to 4/73 (5.5%) patients with B. burgdorferi s.l. monoinfection (P=0.02). Dyspnea was recorded in 4/47 (8.5%) patients with Lyme disease and B. divergens IgG antibodies compared to 1/73 (1.4%) monoinfected (P=0.07). In addition ECG atri-oventricular (AV) block, mostly 1st degree, was detected in 5/47 (15.6%) patients with Lyme dis-ease and B. divergens IgG antibodies compared to 1/73 (2.6%) B. burgdorferi s.l. monoinfected (P=0.09). No other clinical, laboratory or other tests differences were observed between B. burgdorferi and B. divergens IgG antibodies carriers and B. burgdorferi monoinfected. We con-cluded that patients with Lyme disease and B. divergens IgG antibodies had more frequent car-diorespiratory symptoms, mainly dyspnea, compared to B. burgdorferi monoinfected patients. These symptoms were unrelated to anemia. ECG AV block, perhaps induced by summative myo-cardial damage due to either infections or B. divergens induced lung microcirculation slow-ing-down, might play a role in the cardiorespiratory dysfunction.

Background: Since March 2020, Spain is severely hit by the ongoing pandemic of coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding and disrupting the early transmission dynamics of the infection is crucial for impeding sustained transmission. Methods: We recorded all COVID-19 cases and traced their contacts in an isolated rural community. We also sampled 10 households, 6 public service sites and the wastewater from the village sewage for environmental SARS-CoV-2 RNA. Results: The first village patient diagnosed with COVID-19-compatible symptoms occurred on March 3, 2020, twelve days before lockdown. A peak of 39 cases occurred on March 30. By May 15, the accumulated number of symptomatic cases was 53 (6% of the population), of which only 22 (41%) had been tested and confirmed by RT-PCR as SARS-CoV-2 infected, including 16 hospitalized patients. Contacts (n=144) were six times more likely to develop symptoms. Environmental sampling detected SARS-CoV-2 RNA in two households with known active cases and in two public service sites: the petrol station and the pharmacy. Samples from other sites and the wastewater tested negative. Conclusions: The low proportion of patients tested by RT-PCR calls for urgent changes in disease management. We propose that early testing of all cases and their close contacts would reduce infection spread, reducing the disease burden and fatalities. In a context of restricted testing, environmental RNA surveillance might prove useful for early warning and to identify high-risk settings enabling a targeted resource deployment.

When the zoonotic parasite of rodents that can cause human neuroangiostrongyliasis, i.e., Angiostrongylus cantonensis, is found in its natural definitive hosts, it is usually reported in isolation, as if the rat lungworm were the only component of the within-rat parasite community. In this study we report the coinfections found in rats naturally infected by A. cantonensis in urban populations of Rattus norvegicus and Rattus rattus in Valencia, Spain. In addition to the rat lungworms, which were found in 14 of the 125 rats studied (a prevalence of 11.20%), 18 other parasite infrapopulations (intestinal and tissular protists, microsporidia, and helminths) were found; some of them with high burdens. Fourteen of these 19 species found are potential zoonotic parasites, namely Blastocystis, Giardia duodenalis, Cryptosporidium spp., Enterocytozoon bieneusi, Encephalitozoon hellem, Toxoplasma gondii, Brachylaima spp., Hydatigera taeniaeformis larvae, Hymenolepis nana, Hymenolepis diminuta, Angiostrongylus cantonensis, Calodium hepaticum, Gongylonema neoplasticum and Moniliformis moniliformis. Despite the limited number of rats studied, the total predominance of coinfected rats as well as their high parasite loads seem to indicate a clear trend towards parasite tolerance.

Manual material handling tasks in industry cause work-related musculoskeletal disorders. Exoskeletons are being introduced to reduce the risk of musculoskeletal injuries. This study investigated the effect of using a passive lumbar exoskeleton in terms of moderate ergonomic risk. Eight participants were monitored by electromyogram (EMG) and motion capture (MoCap) while performing tasks with and without the lumbar exoskeleton. The results showed a significant reduction in the root mean square (VRMS) for all muscles tracked: erector spinae (8%), semitendinosus (14%), gluteus (5%), and quadriceps (10.2%). The classic fatigue parameters showed a significant reduction in the case of the semitendinosus: 1.7% zero-crossing rate, 0.9% mean frequency, and 1.12% median frequency. In addition, the logarithm of the normalized Dimitrov’s index showed reductions of 11.5, 8, and 14% in erector spinae, semitendinosus, and gluteus, respectively. The calculation of range of motion in the relevant joints demonstrated significant differences, but in almost all cases, the differences were smaller than 10. The findings of the study indicate that the passive exoskeleton reduces muscle activity and introduces a minor change of strategies for motion. Thus, EMG and MoCap appear to be appropriate measurements for designing an exoskeleton assessment procedure.

Pineapple is a highly demanded fruit in international markets, thanks to its unique appearance and flavor, high fiber content, vitamins, folic acid, and minerals. It makes the pineapple production and processing market a significant source of income for producing countries, such as Costa Rica. Nowadays, its processing produces a large amount of waste with negative consequences for the environment. However, pineapple waste is an essential source of cellulose, hemicellulose, lignin, and other high-value products like enzymes (bromelain). These by-products can be obtained by pineapple waste biorefinery, generating an additional source of export goods and foreign currency, framing pineapple processing in the concept of the circular economy. This review discusses how incorporating biorefinery in the pineapple production processes can contribute to the post-COVID 19 economy in Costa Rica. Pineapple production in Costa Rica is explored, and the contamination of generated residues is delineated. Furthermore, the primary processes for by-product extraction via biorefinery, their general characteristics and applications in the medical field, and their contribution to the circular economy are presented.

MT4-MMP (or MMP-17) belongs to the Membrane-Type Matrix Metalloproteinases (MT-MMPs), a distinct subset of the MMP family that is anchored to the cell surface by a glycosylphosphatidylinositol (GPI) motif. Its expression in a variety of cancers is well documented. However, the molecular mechanisms by which MT4-MMP contributes to tumor development need further investigation. In this review, we aim to summarize the contribution of MT4-MMP in tumorigenesis, focusing on the molecular mechanisms triggered by the enzyme in tumor cell migration, invasiveness, and proliferation, in the tumor vasculature and microenvironment, as well as during metastasis. In particular, we highlight the putative substrates processed and signaling cascades activated by MT4-MMP that may underlie these malignancy processes and compare this with what is known about its role during embryonic development. Finally, MT4-MMP is a relevant biomarker of malignancy that can be used for monitoring cancer diseases progression in patients as well as a potential target for future therapeutic drug development.

Mesenchymal stem cells (MSCs) have emerged as a promising treatment for inflammatory diseases. It is described that the immunomodulatory effect of MSCs takes place both by direct cell-to-cell contact and by means of soluble factors that leads to an increased accumulation of regulatory immune cells at the sites of inflammation. Similar efficacy of MSCs has been described regardless the route of administration used, the inflammation conditions and the MHC context. These observations arise the question as to whether the migration of the MSCs to the inflamed tissues is a pre-requisite to achieve their beneficial effect. To address this, we examined the biodistribution and the efficacy of intraperitoneal luciferase-expressing human expanded adipose derived stem cells (Luci-eASCs) in a mouse model of colitis. Luci-eASC-infused mice were stratified according to their response to the Luci-eASC treatment. According to the stratification criteria, there was a tendency to increase the bioluminescence signal in the intestine at the expense of a decrease in the bioluminescence signal in the liver in the `responder´ mice. These data thus suggest that the accumulation of the eASCs to the inflamed tissues is beneficial to achieve an optimal modulation of inflammation.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

The use of botanical extracts of the plant Jatropha curcas (Euphorbiaceae) represents a valuable alternative to control insect pests and avoid the detrimental effects on the environment and health that arise due to synthetic chemical insecticides. Thus, we conducted a systematic review to summarize the published evidence on the bioactivity of J. curcas against insect pests. Electronic databases were searched to identify studies that assessed J. curcas extracts against insect pests in various types of crops. We included 39 articles that reported the insecticidal and insectistatic activity of several botanical extracts from J. curcas against insects of eight different taxonomic orders. The evidence demonstrates that aqueous and methanolic extracts from seeds and leaves, seed oil, and petroleum ether seed extracts were effective against insect pests of stored grains, aphids of cabbage, sorghum, fruit flies, and desert locusts. The extracts caused high mortality, controlled the populations, reduced oviposition, diminished hatchability, and increased the antifeedant effect. However, the type of solvent used to obtain the botanical extract and the method of application (contact or food) are fundamental to increase its bioactivity. Therefore, botanical extracts from seeds and leaves of J. curcas should be considered as an alternative against insect pests and may be incorporated into integrative and sustainable management for insect control.

Boron (B) toxicity is an important stress that negatively affects maize yield and quality production. The excessive B content in agricultural lands is a growing problem due to the increase in arid and semi-arid areas because of climate change. Recently, two Peruvian maize landraces, Sama and Pachía, were physiologically characterized based on their tolerance to B toxicity, the former being more tolerant to B excess than Pachía. However, many aspects regarding the molecular mechanisms of these two maize landraces against B toxicity are still unknown. In this study, a leaf proteomic analysis of Sama and Pachía was performed. Out of a total of 2793 proteins identified only 303 proteins were differentially accumulated. Functional analysis indicated that many of these proteins are involved in transcription and translation processes, amino acids metabolism, photosynthesis, carbohydrate metabolism, protein degradation, and protein stabilization and folding. Compared to Sama, Pachía had a higher number of differentially expressed proteins related to protein degradation, and transcription and translation processes under B toxicity conditions, which might reflect the greater protein damage caused by B toxicity in Pachía. Our results suggest that higher tolerance to B toxicity of Sama can be attributed to more stable photosynthesis that would avoid damage caused by stromal over-reduction under this stress condition.

Background: The course of obesity and type 2 diabetes (T2D) development is highly dependent on adipose tissue (AT) angiogenesis. Moreover, angiogenic microRNAs (miRNAs) play pivotal role in AT functionality. The aim of this study was to analyze the relationship of the human AT miR-221-3p/222-3p cluster and their regulatory network with obesity and T2D. Methods: miR-221-3p/222-3p and their target genes (TG) expression levels were measured in visceral and subcutaneous ATs from patients classified according to their BMI and to their glycemic status with a high degree of insulin resistance (IR) and T2D. In silico analyses of miR-221-3p/222-3p and their TGs were performed to identify relevant signaling pathways. Results: A multivariate analysis, including the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, showed significant differences considering the variables; tissue depot, obesity, IR and T2D altogether as independent variables. In addition, miRNAs and their TGs were differentially expressed according to obesity degree, glycemic status, and AT depot type. Our in silico analysis showed that miR-221-3p/222-3p cluster TGs are mostly involved in angiogenesis, WNT signaling pathway and apoptosis. Conclusion: These findings suggest that the miR-221-3p/222-3p cluster and their related regulatory networks could represent tangible targets for the management of obesity and associated metabolic disorders

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Adult human thymus degenerates into adipose tissue (TAT). In contrast to subcutaneous adipose tissue (SAT), TAT has been reported to exhibit enhanced angiogenic properties in elderly people. We have previously shown that vascular endothelial growth factor A (VEGFA) is the most abundant angiogenic growth factor in TAT of patients with ischemic cardiomyopathy (IC), and that VEGFA levels are increased in elderly (&gt;70 years) compared with middle-aged patients. This makes TAT a promising candidate for angiogenic therapies and the regeneration of ischemic tissues following coronary surgery. MicroRNAs (miRNAs) have emerged as attractive therapeutic targets, especially those that regulate angiogenic processes. The study's purpose is to determine the miRNA network associated with both VEGFA pathway regulation and enrichment of age-linked angiogenesis in the TAT.

Fatty acids and glucose are the main bioenergetic substrates in mammals that are alternatively used during the transition between fasting and feeding. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data show that Aldh2+/- mice exhibits impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in CoQ biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.

The Folla Redonda grape is indigenous to the region of Rias Bajas in Galicia, Spain. This grape is distinguished by its characteristic acid flavor and pulp of remarkable coloration. Despite the wine obtained from this grape is highly valued by consumers of this region for its surprising acidic notes and thickness, it is important to note that it is not a variety of Vitis vinifera and its production is not legally regulated. In the present study, an evaluation of the physicochemical properties of the Folla Redonda grape (pH, °Brix, °Bé, density, acidity, sugar content, etc.) as well as its content in bioactive compounds (total polyphenols and anthocyanins) was carried out. Additionally, the antioxidant potential of the extracts obtained from this grape was demonstrated. This study proved the interesting organoleptic characteristics of the grape, along with a high content of compounds of interest and an important antioxidant activity comparable to that of Vitis vinifera grapes. Therefore, the grape's natural consumption and its application in different industries such as nutraceutical or pharmacological would result in an important revaluation of the grape and significant health benefits. In case that the production of wine from this variety is legalized, consumers will not only be able to enjoy a wine with a characteristic dense reddish color and important acid tones, but also with interesting concentrations of bioactive compounds.

Hazelnut, pistachio and cashew are tree nuts with health benefits but also with allergenic properties being prevalent food allergens in Europe. The allergic characteristics of these tree nuts after processing combining heat, pressure and enzymatic digestion were analyzed through in vitro (Western blot and ELISA) and in vivo test (Prick-Prick). In the analyzed population, the patients sensitized to Cor a 8 (nsLTP) were predominant over those sensitized against hazelnut seed storage proteins (Sprot, Cor a 9 and 14), which displayed higher IgE reactivity. The protease E5 effectively hydrolyzed proteins from hazelnut and pistachio, while E7 was efficient for cashew protein hydrolysis. When combined with pressured heating (autoclave and Controlled Instantaneous Depressurization (DIC)), these proteases notably reduced the allergenic reactivity. The combination of DIC treatment before enzymatic digestion resulted in the most effective methodology to drastically reduce or indeed eliminate the allergenic capacity of tree nuts.

The RNA-binding protein Human antigen R (HuR) regulates stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. The protein has been progressively recognized as a relevant therapeutic target for several pathologies like cancer, neurodegeneration, as well as inflammation. Inhibitors of mRNA binding to HuR might thus be beneficial against a variety of diseases. Here we present the rational identification of structurally novel HuR inhibitors. In particular, by combining chemoinformatics approaches, high throughput virtual screening and RNA–protein pull-down assays, we show that the 4-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)benzoate ligand exhibits dose-dependent HuR inhibition in binding experiments. Importantly, the chemical scaffold is new with respect to the so-far known HuR inhibitors, opening up a new avenue for the design of pharmaceutical agents targeting this important protein.

Background: Deficiency of alpha-1 antitrypsin (AAT1) is a rare disorder that represents a significant health threat and early diagnostic a priority issue. We investigate the usefulness of the serum protein electrophoresis (SPE) as an opportunistic screening tool for AAT1 deficiency. Methods: For 6 months, all SPE carried out for any reasons were evaluated in our center. In those with less than 3% of Alpha-1 globulins, AAT1 concentrations were studied. The SERPINA1 gene was subsequently sequenced in those subjects displaying concentrations below 100 mg/dL. Results: Out of the total, 14 patients (0.3%) were identified with low AAT1 concentrations, 11 of them agreeing to enter the study. Of those, mutations in the SERPINA1 gene were discovered in 10 subjects (91%). Heterozygous mutations were detected in 7 patients; 3 had the c.1096G>A mutation (p.Glu366Lys; Pi*Z), 2 the c.863A>T mutation (p.Glu288Val; Pi*S), one the c.221_223delTCT mutation (p.Phe76del; Pi*Malton) having the last one the c.1066G>A (p.Ala356Thr) mutation not previously described. Finally one patient had the c.863A>T mutation in homozygosis whereas two double heterozygous patients c.863A> T/ c.1096G>A were detected. Conclusions: an altered result in the concentration of AAT1 anticipates a mutation in the SERPINA1 gene in a manner close to 91%. The relationship between a decrease in the Alpha-1 globulin band of the SPE and an alteration in the AAT1 concentration is direct in basal states of health. The SPE is presented as a highly sensitive test for opportunistic screening of AAT1 deficiency.

Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A correlation was found between IL-10 and IL-6 concentrations and age group; lymphocyte subpopulations and nutritional status and steroid use; IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.