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Abstract Background Element-equivalent matched theranostic pairs facilitate quantitative in vivo imaging to establish pharmacokinetics and dosimetry estimates in the development of preclinical radiopharmaceuticals. Terbium radionuclides have significant potential as matched theranostic pairs for multipurpose applications in nuclear medicine. In particular, 155Tb (t1/2 = 5.32 d) and 161Tb (t1/2 = 6.89 d) have been proposed as a theranostic pair for their respective applications in single photon emission computed tomography (SPECT) imaging and targeted beta therapy. Our study assessed the performance of preclinical quantitative SPECT imaging with 155Tb and 161Tb. A hot rod resolution phantom with rod diameters ranging between 0.85 and 1.70 mm was filled with either 155Tb (21.8 ± 1.7 MBq/mL) or 161Tb (23.6 ± 1.9 MBq/mL) and scanned with the VECTor preclinical SPECT/CT scanner. Image performance was evaluated with two collimators: a high energy ultra high resolution (HEUHR) collimator and an extra ultra high sensitivity (UHS) collimator. SPECT images were reconstructed from photopeaks at 43.0 keV, 86.6 keV, and 105.3 keV for 155Tb and 48.9 keV and 74.6 keV for 161Tb. Quantitative SPECT images of the resolution phantoms were analyzed to report inter-rod contrast, recovery coefficients, and contrast-to-noise metrics. Results Quantitative SPECT images of the resolution phantom established that the HEUHR collimator resolved all rods for 155Tb and 161Tb, and the UHS collimator resolved rods ≥ 1.10 mm for 161Tb and ≥ 1.30 mm for 155Tb. The HEUHR collimator maintained better quantitative accuracy than the UHS collimator with recovery coefficients up to 92%. Contrast-to-noise metrics were also superior with the HEUHR collimator. Conclusions Both 155Tb and 161Tb demonstrated potential for applications in preclinical quantitative SPECT imaging. The high-resolution collimator achieves

Abstract Background Adipose and muscle tissue wasting outlines the cachectic process during tumor progression. The sympathetic nervous system (SNS) is known to promote tumor progression and research suggests that it might also contribute to cancer-associated cachexia (CAC) energetic expenditure through fat wasting. Methods We sympathectomized L5178Y-R tumor-bearing male BALB/c mice by intraperitoneally administering 6-hydroxydopamine to evaluate morphometric, inflammatory, and molecular indicators of CAC and tumor progression. Results Tumor burden was associated with cachexia indicators, including a 10.5% body mass index (BMI) decrease, 40.19% interscapular, 54% inguinal, and 37.17% visceral adipose tissue loss, a 12% food intake decrease, and significant (p = 0.038 and p = 0.0037) increases in the plasmatic inflammatory cytokines IL-6 and IFN-γ respectively. Sympathectomy of tumor-bearing mice was associated with attenuated BMI and visceral adipose tissue loss, decreased interscapular Ucp-1 gene expression to basal levels, and 2.6-fold reduction in Mmp-9 relative gene expression, as compared with the unsympathectomized mice control group. Conclusion The SNS contributes to CAC-associated morphometric and adipose tissue alterations and promotes tumor progression in a murine model.

En un contexto de globalización internacional, en el cual gran parte de las empresas llevan a cabo actividades comerciales más allá de las fronteras nacionales, resulta esencial la mediación de un especialista que establezca puentes entre países y, por ende, entre culturas. Por las características de su formación y sus conocimientos en materia de interculturalidad y de traducción especializada, tanto traductores como intérpretes se erigen, potencialmente, como una figura clave en el marco de la negociación internacional. Sin embargo, la mayoría de los planes de estudio del Grado en Traducción e Interpretación no contemplan asignaturas destinadas a la formación específica de estos profesionales, por lo que esta especialización posee una tendencia natural a plantearse una vez el discente ha culminado dichos estudios. Por otro lado, las instituciones especializadas en formación en comercio exterior únicamente abordan aspectos puramente económicos y de marketing, y toman en consideración la formación en mediación intercultural. A partir de un análisis de las necesidades formativas para este perfil profesional y de la oferta existente al respecto en los distintos grados en Traducción e Interpretación de las universidades españolas, en el presente trabajo presentamos una propuesta formativa para traductores e intérpretes dentro del ámbito del comercio exterior y la mediación lingüística. Nuestra propuesta consiste en un módulo de aprendizaje compuesto por seis bloques temáticos que tratan aspectos relativos a la internacionalización, el marketing o el derecho y se plantea, de manera abstracta, como asignatura o como módulo de contenido que podría insertarse en otra asignatura o, incluso, en un curso de posgrado. De este modo, se podrían eliminar bloques de contenido o reducir algunas de las actividades planteadas.

Early detection and intervention play a crucial role in the prognosis of children with specific learning disabilities. Due to the complexity of the writing process and its persistence into adulthood, tools for early detection are essential. Curriculum-based measures (CBMs) are quick, reliable, and evidence-based tools used for early assessments. This systematic review aims to summarize the technical features of CBM in writing for kindergarten students following the PRISMA guidelines. A total of 311 articles from PsycINFO, SCOPUS, ERIC, and WOS were examined, and five studies met the inclusion criteria. Production measures and transcription skills were the most studied. The reviewed tasks demonstrated criterion validity, reliability, sensitivity to the timing of assessment, or diagnostic accuracy in at least one of their measures, with a greater presence of the dependent production measures. The findings emphasize the scarcity of evidence-based tools for identifying early writing difficulty, underscoring the need for rigorous research in early childhood education.

Summary: The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use.We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions.We found that continuous intravenous administration of rGOT within the first 8 h after ischemic onset significantly reduced the infarct size in both severe (30%) and mild lesions (48%). Cerebrospinal fluid and proteomics analysis, in combination with positron emission tomography imaging, indicated that rGOT can reach the brain and induce cytoprotective autophagy and induce local protection by alleviating neuronal apoptosis.Our results suggest that rGOT can be safely used immediately in patients suspected of having a stroke. This study requires further validation in clinical stroke populations.

La presente investigación tiene como objetivo profundizar en el estudio del comportamiento de los usuarios frente a las noticias falsas. Se ha realizado una encuesta (n=1350) a población de entre 18 y 80 años sobre las actitudes, los sentimientos y los sesgos cognitivos que operan en procesos de desinformación. Entre las conclusiones cabe destacar que el 89,2 % dice recibir noticias falsas. De ellos, el 25,9 % semanalmente y el 54 % declara recibirlas a través de las redes sociales, principalmente Facebook. El 41,4 % de los que alguna vez han compartido una noticia falsa confiesa haberlo hecho porque pensaba que era verdadera; el 23 %, porque estaba de acuerdo con el contenido, y un 10,1 % lo hizo porque hablaba mal de un partido político contrario al suyo. La preocupación es el sentimiento que aflora en un 66,8 % de los encuestados, seguido del 61 % que siente enfado. Sin embargo, un 38,1 % de los encuestados confiesa que las noticias falsas refuerzan lo que piensan. La investigación demuestra la prevalencia de sesgos cognitivos como el de confirmación y el de conformidad, así como la teoría de flujo en dos pasos en el proceso por el que el usuario da credibilidad a los contenidos que recibe y procede a distribuirlos.

Abstract Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, independent of its protein-coding function, confers mesenchymal properties to the cell, promoting migration, invasiveness, and resistance to anoikis and increasing glycolytic activity by sequestering miRNAs. Expression of Serpine1 mRNA upregulates the expression of the TRA2B splicing factor without affecting its mRNA levels. Through transcriptional profiling, we found that Serpine1 mRNA expression downregulates through TRA2B the expression of genes involved in the immune response. Analysis of human colon tumor samples showed an inverse correlation between SERPINE1 mRNA expression and CD8+ T cell infiltration, unveiling the potential value of SERPINE1 mRNA as a promising therapeutic target for colon tumors.

Abstract Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10−8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

Background: Despite the availability of effective antidepressant strategies, numerous people with depressive disorders remain untreated. The Covid-19 pandemic has affected healthcare services, especially the mental health sector. This study aims to explore the coverage of depression treatments in the general Spanish population and the impact of the Covid-19 pandemic. Methods: We used longitudinal data (2018 and 2022) from the general Spanish population: pre-pandemic n = 1512; mean age = 65.43 years ± 14.90; 56 % females; post-pandemic n = 909; mean age = 68.00 years ± 14.24; 54 % women. The International Classification of Disease 10th edition was used to diagnose lifetime depressive episodes and severity. We explored psychological and pharmacological treatment coverage via multiple logistic regressions adjusted for 4 covariates (sex assigned at birth, education level, age, Covid-19 pandemic) for participants with a diagnosis of depression. Results: Treatment coverage for depression in the pre-pandemic and post-pandemic samples was, respectively, 53.3 % and 51.9 %. We observed an association between severe depression and treatment coverage (OR = 2.77, 95%CI 1.05 to 7.75). We found no association between the COVID-19 pandemic and treatment coverage. Conclusions: The pharmacological treatment coverage was associated with severe types of depression. The prevalence rates of treatment coverage were similar in the pre- and post-COVID-19 pandemic attesting to the resilience of the mental health system in Spain.

The purpose of this article is to find a relationship between the organizational architecture and technological architecture for Small and Medium Enterprises (SMES) in Tehuacán city, which is a medium size town at southeast of México city, according to two aspects, the first is to know how much the businessmen are educated to apply tactics for industry 4.0 on order to gain competitiveness, based in their perceptions; and the second is, what have they done to make some implementation in their facilities to reach better productivity. The methodology used in this work is a survey for 574 business, through a questionnaire with answer options in Likert scale. The results exhibit that there is high knowledge about the industry 4.0, and the most of the firms which are made implementations are related to Trade, Manufacturing, Construction and Restaurants. This works a good view on the practices for make modern business in a medium size town.

Chlorella species are fast-growing microalgae with significant industrial applications. The aim of the present study was to investigate the antitumor, antioxidant, and hemolytic activities of Chlorella sorokiniana UTEX 1230 crude methanol extracts and fractions. Ch. sorokiniana crude methanol extracts and collective fractions (CFs) were obtained from lyophilized biomass by maceration and column chromatography. Antitumor assays against murine lymphoma L5178Y-R and human breast cancer MCF-7 cells were performed by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction technique, using human peripheral blood mononuclear cells (PBMC) as the control group. Antioxidant and hemolytic activities were evaluated using the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (DPPH) and erythrocyte hemolysis, respectively. We showed that crude methanol extracts (IC50) increased L5178Y-R and MCF-7 cell growth inhibition, without affecting PBMC. In addition, all evaluated CFs showed significantly higher antioxidant activity than the positive control (ascorbic acid). CF3 and CF4 showed the highest cytotoxicity against L5178Y-R, whereas CF3, CF4, and CF5 caused the highest antitumor activity against MCF-7 cells. CF3, CF4, and CF5 induced significantly higher hemolytic activity compared with all other fractions. CF characterization revealed loliolide, cinnamic acid, methyl dihydrojasmonate, salsalvamide A, 1-monolinolenin, cryptophycin 29, costunolide, riboflavin lumicrome, and germicidin B, which have been related to antitumor and antioxidant activities. In conclusion, we demonstrated that Ch. sorokiniana extracts and fractions possess antitumor and antioxidant potential, without affecting human erythrocytes and PBMC.

Background. Mansoa alliacea is a native plant renowned for its medicinal properties in traditional healing in the Amazon Region. This plant is rich in polyphenols, flavonoids, anthocyanins, phenolic acids, tannins, ketones, triterpenes, as well as other bioactive compounds. Objectives. This study aims to develop an innovative, eco-friendly method for synthesizing silver nanoparticles using an aqueous extract of M. alliacea (Ma-AgNPs), enhancing the biological activities of AgNPs by leveraging the therapeutic potential of the plant’s bioactive compounds. Methods. Silver nanoparticles were synthesized using the aqueous extract of M. alliacea. The biological activities of Ma-AgNPs were assessed, including antibacterial, anti-inflammatory, antioxidant, antitumor, and anti-biofilm effects, along with evaluating their hemolytic activity. Results. Quantitative analysis revealed that Ma-AgNPs exhibit potent antibacterial activity against multidrug and non-multidrug-resistant bacteria, with MIC values ranging from 1.3 to 10.0 µg/mL. The Ma-AgNPs significantly reduced NO production by 86.9% at 4 µg/mL, indicating strong anti-inflammatory effects. They demonstrated robust antioxidant activity with an IC50 of 5.54 ± 1.48 µg/mL and minimal hemolytic activity, with no hemolysis observed up to 20 µg/mL and only 4.5% at 40 µg/mL. Their antitumor properties were notable, with IC50 values between 2.9 and 5.4 µg/mL across various cell lines, and they achieved over 50% biofilm inhibition at concentrations of 30–40 µg/mL. Conclusions. These findings underscore the potential of Ma-AgNPs for biomedical applications, particularly in developing new antimicrobial agents and bioactive coatings with reduced toxicity. This research highlights a sustainable approach that not only preserves but also amplifies the inherent biological activities of plant extracts, paving the way for innovative therapeutic solutions.

Cancer therapy is constantly evolving, with a growing emphasis on targeted and efficient treatment options. In this context, graphene quantum dots (GQDs) have emerged as promising agents for precise drug and gene delivery due to their unique attributes, such as high surface area, photoluminescence, up-conversion photoluminescence, and biocompatibility. GQDs can damage cancer cells and exhibit intrinsic photothermal conversion and singlet oxygen generation efficiency under specific light irradiation, enhancing their effectiveness. They serve as direct therapeutic agents and versatile drug delivery platforms capable of being easily functionalized with various targeting molecules and therapeutic agents. However, challenges such as achieving uniform size and morphology, precise bandgap engineering, and scalability, along with minimizing cytotoxicity and the environmental impact of their production, must be addressed. Additionally, there is a need for a more comprehensive understanding of cellular mechanisms and drug release processes, as well as improved purification methods. Integrating GQDs into existing drug delivery systems enhances the efficacy of traditional treatments, offering more efficient and less invasive options for cancer patients. This review highlights the transformative potential of GQDs in cancer therapy while acknowledging the challenges that researchers must overcome for broader application.

Skeletal muscle regeneration relies on the intricate interplay of various cell populations within the muscle niche—an environment crucial for regulating the behavior of muscle stem cells (MuSCs) and ensuring postnatal tissue maintenance and regeneration. This review delves into the dynamic interactions among key players of this process, including MuSCs, macrophages (MPs), fibro-adipogenic progenitors (FAPs), endothelial cells (ECs), and pericytes (PCs), each assuming pivotal roles in orchestrating homeostasis and regeneration. Dysfunctions in these interactions can lead not only to pathological conditions but also exacerbate muscular dystrophies. The exploration of cellular and molecular crosstalk among these populations in both physiological and dystrophic conditions provides insights into the multifaceted communication networks governing muscle regeneration. Furthermore, this review discusses emerging strategies to modulate the muscle-regenerating niche, presenting a comprehensive overview of current understanding and innovative approaches.

The increasing risk of amputation due to diabetic foot ulcer calls for new therapeutic options; for that, we determined the role of IMMUNEPOTENT CRP (ICRP) and its parts in the wound healing process of superficial wounds in diabetic BALB/c mice. A potency test was performed to confirm the batch of ICRP, and then its parts were separated into pellets, supernatants, and exosomes, and another group of exosomes loaded with insulin was added. Viability and scratch healing were assessed in NIH-3T3, HUVEC, and HACAT cell lines. Diabetes was induced with streptozotocin, and wounds were made by dissecting the back skin. Treatments were topically applied, and closure was monitored; inflammatory cytokines in sera were also evaluated by flow cytometry, and histological analysis was performed by Masson’s staining and immunohistochemistry for p-AKT, p-FOXO, p-P21, and p-TSC2. ICRP pellets and exosomes increased cellular viability, and exosomes and exosome–insulin accelerated scratch healing in vitro. Exosome–insulin releases insulin constantly over time in vitro. In vivo, treatments accelerated wound closure, and better performance was observed in pellet, exosome, and exosome–insulin treatments. Best collagen expression was induced by ICRP. P-AKT and p-FOXO were overexpressed in healing tissues. Inflammatory cytokines were downregulated by all treatments. In conclusion, IMMUNEPOTENT CRP components, especially exosomes, and the process of encapsulation of exosome–insulin accelerate diabetic wound healing and enhance cellular proliferation, collagen production, and inflammation modulation through the phosphorylation of components of the AKT pathway.

GoalTo describe the experience of a dispensing model of outpatient hospital medicines (OHM) via collaboration of hospital and community pharmacies, and to explore patient satisfaction with the strategy as compared with the hospital pharmacy only service.BackgroundPatient satisfaction is an important component of the quality of health care.StudyA new model of dispensing OHM was conducted in the Outpatients Unit of the Service of Hospital Pharmacy of Hospital del Mar, in Barcelona, Spain. Participants were patients on stable chronic treatment with clinical or social fragility, immunocompromised patients, and those whose residence was located at a distance from the hospital that justified drug delivery through the community pharmacy. A cross sectional study was done using an ad hoc 14-item questionnaire collecting demographic data, duration of treatment, usual mode of collecting medication, and the degree of satisfaction regarding waiting time for the collection of medication, attention received by professionals, information received on treatment, and confidentiality.ResultsThe study population included a total of 4,057 patients (66.8% men) with a mean age of 53 (15.5) years, of whom 1,286 responded, with a response rate of 31.7%. Variables significantly associated with response to the survey were age over 44 years, particularly the age segment of 55–64 years (odds ratio [OR] 2.51) and receiving OHM via the community pharmacy (OR 12.76). Patients in the community pharmacy group (n = 927) as compared with those in the hospital pharmacy group (n = 359) showed significantly higher percentages of ‘satisfied’ and ‘very satisfied’ (p

IntroductionThe emergence of multi-drug-resistant bacteria is one of the main concerns in the health sector worldwide. The conventional strategies for treatment and prophylaxis against microbial infections include the use of antibiotics. However, these drugs are failing due to the increasing antimicrobial resistance. The unavailability of effective antibiotics highlights the need to discover effective alternatives to combat bacterial infections. One option is the use of metallic nanoparticles, which are toxic to some microorganisms due to their nanometric size.MethodsIn this study we (1) synthesize and characterize bismuth and silver nanoparticles, (2) evaluate the antibacterial activity of NPs against Staphylococcus aureus and Escherichia coli in several infection models (in vivo models: infected wound and sepsis and in vitro model: mastitis), and we (3) determine the cytotoxic effect on several cell lines representative of the skin tissue.Results and discussionWe obtained bimetallic nanoparticles of bismuth and silver in a stable aqueous solution from a single reaction by chemical synthesis. These nanoparticles show antibacterial activity on S. aureus and E. coli in vitro without cytotoxic effects on fibroblast, endothelial vascular, and mammary epithelium cell lines. In an infected-wound mice model, antibacterial effect was observed, without effect on in vitro mastitis and sepsis models.

Background: SARS-CoV-2 genomic analysis has been key to the provision of valuable data to meet both epidemiological and clinical demands. High-throughput sequencing, generally Illumina-based, has been necessary to ensure the widest coverage in global variant tracking. However, a speedier response is needed for nosocomial outbreak analyses and rapid identification of patients infected by emerging VOCs. An alternative based on nanopore sequencing may be better suited to delivering a faster response when required; however, although there are several studies offering side-by-side comparisons of Illumina and nanopore sequencing, evaluations of the usefulness in the hospital routine of the faster availability of data provided by nanopore are still lacking. Results: We performed a prospective 10-week nanopore-based sequencing in MinION in a routine laboratory setting, including 83 specimens where a faster response time was necessary. The specimens analyzed corresponded to i) international travellers in which lineages were assigned to determine the proper management/special isolation of the patients; ii) nosocomial infections and health-care-worker infections, where SNP-based comparisons were required to rule in/out epidemiological relationships and tailor specific interventions iii) sentinel cases and breakthrough infections to timely report to the Public Health authorities. MinION-based sequencing was compared with the standard procedures, supported on Illumina sequencing; MinION accelerated the delivery of results (anticipating results 1-12 days) and reduced costs per sample by 28€ compared to Illumina, without reducing accuracy in SNP calling. Conclusions: Parallel integration of Illumina and nanopore sequencing strategies is a suitable solution to ensure both high-throughput and rapid response to cope with accelerating the surveillance demands of SARS-CoV-2 while also maintaining accuracy.

Abstract Background There are a lot of tools to use for fall assessment, but there is not yet one that predicts the risk of falls in the elderly. This study aims to evaluate the use of the G-STRIDE prototype in the analysis of fall risk, defining the cut-off points to predict the risk of falling and developing a predictive model that allows discriminating between subjects with and without fall risks and those at risk of future falls. Methods An observational, multicenter case–control study was conducted with older people coming from two different public hospitals and three different nursing homes. We gathered clinical variables ( Short Physical Performance Battery (SPPB), Standardized Frailty Criteria, Speed 4 m walk, Falls Efficacy Scale-International (FES-I), Time-Up Go Test, and Global Deterioration Scale (GDS)) and measured gait kinematics using an inertial measure unit (IMU). We performed a logistic regression model using a training set of observations (70% of the participants) to predict the probability of falls. Results A total of 163 participants were included, 86 people with gait and balance disorders or falls and 77 without falls; 67,8% were females, with a mean age of 82,63 ± 6,01 years. G-STRIDE made it possible to measure gait parameters under normal living conditions. There are 46 cut-off values of conventional clinical parameters and those estimated with the G-STRIDE solution. A logistic regression mixed model, with four conventional and 2 kinematic variables allows us to identify people at risk of falls showing good predictive value with AUC of 77,6% (sensitivity 0,773 y specificity 0,780). In addition, we could predict the fallers in the test group (30% observations not in the model) with similar performance to conventional methods. Conclusions The G-STRIDE IMU device allows to predict the risk of falls using a mixed model with an accuracy of 0,776 with similar performance to conventional model. This approach allows better precision, low cost and less infrastructures for an early intervention and prevention of future falls.

This study explores the valorization of tea leaf waste by extracting polyphenols through reflux extraction, subsequently using them to synthesize zero-valent iron nanoparticles (nZVI). The in situ generated nanoparticles, when combined with fixed amounts of hydrogen peroxide, facilitated the removal of various dyes (methylene blue, methyl orange, and orange G) via a hetero-catalytic Fenton process. The iron nanoparticles were thoroughly characterized by gas adsorption of N2 at 77 K, scanning electron microscopy (SEM), Transmission Electron Microscopy (TEM), FT-IR spectroscopy, X-ray diffraction (XRD), and thermal analysis, including thermogravimetric analysis (TG) and temperature-programmed reduction (TPR). A statistical design of experiments and response surface methodology were employed to analyze the influence of polyphenol, Fe(III), and H2O2 concentrations on dye removal efficiency. The results demonstrated that optimizing the operational conditions could achieve 100% dye removal efficiency. This study highlights the potential of nZVI synthesized through eco-friendly methods as a promising solution for water decontamination involving diverse model dyes, thus contributing to sustainable waste management and environmental protection.

Despite the high diversity of elasmobranch fishes in the Balearic Islands, knowledge of their biology and population dynamics is still scarce. A recent mark-and-recapture experiment off the Balearic Islands tagged 3738 individuals of 23 shark and batoid species during MEDITS and CANAL bottom trawl scientific surveys from June 2021 to August 2023. Retrieval was reported for the sharks Scyliorhinus canicula and Mustelus mustelus, revealing relatively small home ranges for these species (0.2–38.5 km and 7.8–15.3 km for S. canicula and M. mustelus, respectively). Recapture efficiency was higher from scientific surveys than from commercial catches, highlighting potential challenges in collaboration with fishermen and recapture reports. Density estimates obtained from the MEDITS bottom trawl survey suggest a much larger population for S. canicula than estimates from the mark–recapture data, indicating MEDITS density estimates for this species may be overestimated due to its scavenger behavior perhaps favoring individuals searching for discards aggregated in the fishing grounds. This study emphasizes the importance of monitoring, collaborative efforts, and improved reporting mechanisms to enhance our understanding of elasmobranch populations and provide support for sustainable management of these vulnerable marine species.

Pemphigus is an autoimmune disease that affects the skin and mucous membranes, induced by the deposition of pemphigus IgG, which mainly targets desmogleins 1 and 3 (Dsg1 and 3). This autoantibody causes steric interference between Dsg1 and 3 and the loss of cell adhesion, producing acantholysis. This molecule and its cellular effects are clinically reflected as intraepidermal blistering. Pemphigus vulgaris-IgG (PV-IgG) binding involves p38MAPK-signaling-dependent caspase-3 activation. The present work assessed the in vitro effect of PV-IgG on the adherence of HaCaT cells dependent on caspase-3. PV-IgG induced cell detachment and apoptotic changes, as demonstrated by annexin fluorescent assays. The effect of caspase-3 induced by PV-IgG was suppressed in cells pre-treated with caspase-3-shRNA, and normal IgG (N-IgG) as a control had no relevant effects on the aforementioned parameters. The results demonstrated that shRNA reduces caspase-3 expression, as measured via qRT-PCR and via Western blot and immunofluorescence, and increases cell adhesion. In conclusion, shRNA prevented in vitro cell detachment and the late effects of apoptosis induced by PV-IgG on HaCaT cells, furthering our understanding of the molecular role of caspase-3 cell adhesion dependence in pemphigus disease.

Breast cancer is the most diagnosed type of cancer worldwide and the second cause of death in women. Triple-negative breast cancer (TNBC) is the most aggressive, and due to the lack of specific targets, it is considered the most challenging subtype to treat and the subtype with the worst prognosis. The present study aims to determine the antitumor effect of beta-D-glucose-reduced silver nanoparticles (AgNPs-G) in a murine model of TNBC, as well as to study its effect on the tumor microenvironment. In an airbag model with 4T1 tumor cell implantation, the administration of AgNPs-G or doxorubicin showed antitumoral activity. Using immunohistochemistry it was demonstrated that treatment with AgNPs-G decreased the expression of PCNA, IDO, and GAL-3 and increased the expression of Caspase-3. In the tumor microenvironment, the treatment increased the percentage of memory T cells and innate effector cells and decreased CD4+ cells and regulatory T cells. There was also an increase in the levels of TNF-α, IFN-γ, and IL-6, while TNF-α was increased in serum. In conclusion, we suggest that AgNPs-G treatment has an antitumor effect that is demonstrated by its ability to remodel the tumor microenvironment in mice with TNBC.

Nanotechnology, a rapidly growing field, holds tremendous promise as it harnesses the unique properties and applications of nanoparticulate materials on a nanoscale. In parallel, the pressing global environmental concerns call for the development of sustainable chemical processes and the creation of new materials through eco-friendly synthesis methods. In this work, zero-valent iron nanoparticles (nZVI) were synthesized using an innovative and environmentally friendly approach as an alternative to conventional methods. This method leverages the antioxidant capacity of natural plant extracts to effectively reduce dissolved metals and produce nZVI. The chosen extract of green tea plays a pivotal role in this process. With the extract in focus, this study delves into the remarkable capability of nZVI in degrading two dyes commonly used in medicine, chrysoidine G and methylene blue, in aqueous solutions. Additionally, Fenton-type oxidation processes are explored by incorporating hydrogen peroxide into the nanoparticle mixture. By applying the statistical design of experiments and Response Surface Methodology, the influence of four key parameters—initial concentrations of Fe2+, Fe3+, H2O2, and polyphenols—on dye elimination efficiency in aqueous solutions is thoroughly analyzed. The obtained results demonstrate that advanced oxidation technologies, such as Fenton-type reactions in conjunction with nanoparticles, achieve an excellent efficiency of nearly 100% in eliminating the dyes. Moreover, this study reveals the synergistic effect achieved by simultaneously employing nZVI and the Fenton process, showcasing the potential for further advancements in the field.

Obesity is frequently accompanied by non-alcoholic fatty liver disease (NAFLD). These two diseases are associated with altered lipid metabolism, in which reverse cholesterol transport (LXRα/ABCA1/ABCG1) and leptin response (leptin receptor (Ob-Rb)/Sam68) are involved. The two pathways were evaluated in peripheral blood mononuclear cells (PBMCs) from 86 patients with morbid obesity (MO) before and six months after Roux-en-Y gastric bypass (RYGB) and 38 non-obese subjects. In the LXRα pathway, LXRα, ABCA1, and ABCG1 mRNA expressions were decreased in MO compared to non-obese subjects (p < 0.001, respectively). Ob-Rb was decreased (p < 0.001), whereas Sam68 was increased (p < 0.001) in MO. RYGB did not change mRNA gene expressions. In the MO group, the LXRα pathway (LXRα/ABCA1/ABCG1) negatively correlated with obesity-related variables (weight, body mass index, and hip), inflammation (C-reactive protein), and liver function (alanine-aminotransferase, alkaline phosphatase, and fatty liver index), and positively with serum albumin. In the Ob-R pathway, Ob-Rb and Sam68 negatively correlated with alanine-aminotransferase and positively with albumin. The alteration of LXRα and Ob-R pathways may play an important role in NAFLD development in MO. It is possible that MO patients may require more than 6 months following RYBGB to normalize gene expression related to reverse cholesterol transport or leptin responsiveness.

T-cell malignancies, including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), present significant challenges to treatment due to their aggressive nature and chemoresistance. Chemotherapies remain a mainstay for their management, but the aggressiveness of these cancers and their associated toxicities pose limitations. Immunepotent CRP (ICRP), a bovine dialyzable leukocyte extract, has shown promise in inducing cytotoxicity against various cancer types, including hematological cancers. In this study, we investigated the combined effect of ICRP with a panel of chemotherapies on cell line models of T-ALL and T-LBL (CEM and L5178Y-R cells, respectively) and its impact on immune system cells (peripheral blood mononuclear cells, splenic and bone marrow cells). Our findings demonstrate that combining ICRP with chemotherapies enhances cytotoxicity against tumoral T-cell lymphoblasts. ICRP + Cyclophosphamide (CTX) cytotoxicity is induced through a caspase-, reactive oxygen species (ROS)-, and calcium-dependent mechanism involving the loss of mitochondrial membrane potential, an increase in ROS production, and caspase activation. Low doses of ICRP in combination with CTX spare non-tumoral immune cells, overcome the bone marrow-induced resistance to CTX cell death, and improves the CTX antitumor effect in vivo in syngeneic Balb/c mice challenged with L5178Y-R. This led to a reduction in tumor volume and a decrease in Ki-67 proliferation marker expression and the granulocyte/lymphocyte ratio. These results set the basis for further research into the clinical application of ICRP in combination with chemotherapeutic regimens for improving outcomes in T-cell malignancies.

Knowledge of the microbiota present in food processing environments is a significant advance that will allow for better evaluation of the risk of food contamination and a better design of the procedures for sanitization. The levels of microbial group indicators of hygienic quality were determined in different areas of the slaughter lines of two poultry slaughterhouses in the northwest of Spain (22 surfaces in each slaughterhouse were studied). The average microbial levels (cfu/cm2) were 2.15 × 102 ± 4.26 × 102 (total aerobic counts, TAC), 1.99 × 102 ± 5.00 × 102 (psychrotrophic microorganisms), 3.10 × 100 ± 1.37 × 101 (enterobacteria), 3.96 × 100 ± 2.55 × 101 (coliforms), 1.80 × 10−1 ± 7.79 × 10−1 (enterococci), and 1.12 × 10−1 ± 3.35 × 10−1 (vancomycin-resistant enterococci, VRE). TAC and psychrotrophic microorganisms were the most abundant groups in all samples (p < 0.05). The counts of both microbial groups were higher (p < 0.05) in samples of Slaughterhouse A than in those of Slaughterhouse B. Microbial loads for the rest of the bacteria were not influenced by the slaughterhouse sampled (p > 0.05). All 44 samples showed TAC and psychrotrophic microorganisms. Colonies of the rest of the microbial groups were only found in 26 samples (59.1% of the total). The isolates (one from each sample) were identified with MALDI-TOF and PCR. Gram-negative bacteria (all Enterobacteriaceae) were isolated in 23 samples, and Gram-positive bacteria were isolated in 16 (9 Enterococcus spp., 2 Enterococcus spp. and VRE, 3 VRE, 1 Enterococcus spp. and Listeria spp., and 1 Listeria spp.). The resistance of the strains to 11 (Enterococcus spp.) or 17 (Enterobacteriaceae) antibiotics was determined (disk diffusion, CLSI), finding an average of 2.05 ± 2.06 resistances per strain (3.46 ± 2.27 if reduced susceptibility reactions are included). A total of 37.3% of the Enterobacteriaceae isolates had a gene for resistance to beta-lactam antibiotics (blaTEM, blaCTX-M-15, blaKPC, blaCMY-2 or blaNDM). The high prevalence of resistant bacteria and resistance genes highlights the need to establish measures to control the spread of antibiotic resistance in poultry slaughterhouses. The findings of this work could contribute to the design of more effective sanitation procedures.

This review article addresses the increasing environmental concerns posed by synthetic dyes in water, exploring innovative approaches for their removal with a focus on zero-valent iron nanoparticles (nZVIs) synthesized through environmentally friendly methods. The article begins by highlighting the persistent nature of synthetic dyes and the limitations of conventional degradation processes. The role of nanoparticles in environmental applications is then discussed, covering diverse methods for metallic nanoparticle production aligned with green chemistry principles. Various methods, including the incorporation of secondary metals, surface coating, emulsification, fixed support, encapsulation, and electrostatic stabilization, are detailed in relation to the stabilization of nZVIs. A novel aspect is introduced in the use of plant extract or biomimetic approaches for chemical reduction during nZVI synthesis. The review investigates the specific challenges posed by dye pollution in wastewater from industrial sources, particularly in the context of garment coloring. Current approaches for dye removal in aqueous environments are discussed, with an emphasis on the effectiveness of green-synthesized nZVIs. The article concludes by offering insights into future perspectives and challenges in the field. The intricate landscape of environmentally friendly nZVI synthesis has been presented, showcasing its potential as a sustainable solution for addressing dye pollution in water.

Centers for Disease Control and Prevention guidelines consider SARS-CoV-2 reinfection when sequential COVID-19 episodes occur >90 days apart. However, genomic diversity acquired over recent COVID-19 waves could mean previous infection provides insufficient cross-protection. We used genomic analysis to assess the percentage of early reinfections in a sample of 26 patients with 2 COVID-19 episodes separated by 20–45 days. Among sampled patients, 11 (42%) had reinfections involving different SARS-CoV-2 variants or subvariants. Another 4 cases were probable reinfections; 3 involved different strains from the same lineage or sublineage. Host genomic analysis confirmed the 2 sequential specimens belonged to the same patient. Among all reinfections, 36.4% involved non-Omicron, then Omicron lineages. Early reinfections showed no specific clinical patterns; 45% were among unvaccinated or incompletely vaccinated persons, 27% were among persons

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF. Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. Design: Retrospective observational study. Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

Pretargeting, which is the separation of target accumulation and the administration of a secondary imaging agent into two sequential steps, offers the potential to improve image contrast and reduce radiation burden for nuclear imaging. In recent years, the tetrazine ligation has emerged as a promising approach to facilitate covalent pretargeted imaging due to its unprecedented kinetics and bioorthogonality. Pretargeted bone imaging with TCO-modified alendronic acid (Aln-TCO) is an attractive model that allows the evaluation of tetrazines in healthy animals without the need for complex disease models or targeting regimens. Recent structure-activity relationship studies of tetrazines evaluated important parameters for the design of potent tetrazine-radiotracers for pretargeted imaging. However, limited information is available for 99mTc-labeled tetrazines. In this study, four tetrazines intended for labeling with fac-[99mTc(OH2)3 (CO)3]+ were synthesized and evaluated using an Aln-TCO mouse model. 3,6-bis(2-pyridyl)-1,2,4,5-Tz without additional linker showed higher pretargeted bone uptake and less background activity compared to the same scaffold with a PEG8 linker or 3-phenyl-1,2,4,5-Tz-based compounds. Additionally, improved bone/blood ratios were observed in pretargeted animals compared to animals receiving directly labeled Aln-TCO. The results of this study implicate 3,6-bis(2-pyridyl)-1,2,4,5-Tz as a promising scaffold for potential 99mTc-labeled tetrazines.

Introduction: Neoadjuvant therapy constitutes a valuable modality for diminishing tumor volume prior to surgical resection. Nonetheless, its application encounters limitations in the context of recurrent tumors, which manifest resistance to conventional treatments. Silver nanoparticles (AgNPs) have emerged as a promising alternative for cancer treatment owing to their cytotoxic effects.Methods: Cellular viability was assessed by Alamar blue assay in 4T1 breast cancer cell line. Silver biodistribution was detected by an inductively coupled plasma optical emission spectrometer in an in vivo mice model. For neoadjuvant evaluation, mice were randomized and treated intratumoral with AgNPs-G or intraperitoneally with doxorubicin (DOX) as a control. Recurrence was determined after 170 days by counting lung metastatic nodules (dyed with Bouin solution) with histological confirmation by H&E. Masson’s stain, Ki67 immunohistochemistry, and a TUNEL assay were performed in lungs from treated mice.Results: AgNPs-G reduced 4T1 cell viability and in an ex vivo assay the AgNPs-G decreased the tumor cell viability. After intravenous administration of AgNPs-G were detected in different organs. After intratumor administration, AgNPs-G are retained. The AgNPs-G treatment significantly reduced tumor volume before its surgical resection. AgNPs-G reduced the development of lung metastatic nodules and the expression of Ki67. TUNEL assay indicated that AgNPs-G didn’t induce apoptosis.Conclusions: We concluded that intratumor administration of AgNPs-G reduced tumor volume before surgical resection, alongside a reduction in lung metastatic nodules, and Ki67 expression. These findings provide valuable insights into the AgNPs-G potential for intratumor and neoadjuvant cancer therapies. However, further research is needed to explore their full potential and optimize their use in clinical settings.

El presente artículo aborda el acceso de la mujer a la formación artística de carácter público en la Barcelona de finales del siglo XIX, tomando como hilo conductor la figura, inédita todavía, de Francisca García Ortiz (1853-1923). Como primera profesora de la Escuela de Dibujo para Niñas y Adultas de la ciudad, puesta en funcionamiento en 1883, García es una pionera de la didáctica del arte de nuestra historia reciente. En este artículo analizamos su trayectoria profesional y su aportación como docente de dibujo y pintura en clases dirigidas exclusivamente al alumnado femenino. El artículo ofrece datos de interés en torno a las etapas de la carrera académica hacia 1900 y las limitaciones experimentadas por las mujeres en este contexto. Se mencionan y sitúan, asimismo, otras artistas y profesoras que protagonizaron las primeras décadas de presencia femenina en la enseñanza de las artes en la ciudad. En última instancia, su ejemplo nos sirve para proponer una reflexión más amplia en torno a la trayectoria de las mujeres en las instituciones educativas públicas del momento y las vías que tenían a su alcance para profesionalizarse, en la España del cambio de siglo.

Abstract Succinate is enhanced during initial reperfusion in blood from the coronary sinus in ST-segment elevation myocardial infarction (STEMI) patients and in pigs submitted to transient coronary occlusion. Succinate levels might have a prognostic value, as they may correlate with edema volume or myocardial infarct size. However, blood from the coronary sinus is not routinely obtained in the CathLab. As succinate might be also increased in peripheral blood, we aimed to investigate whether peripheral plasma concentrations of succinate and other metabolites obtained during coronary revascularization correlate with edema volume or infarct size in STEMI patients. Plasma samples were obtained from peripheral blood within the first 10 min of revascularization in 102 STEMI patients included in the COMBAT-MI trial (initial TIMI 1) and from 9 additional patients with restituted coronary blood flow (TIMI 2). Metabolite concentrations were analyzed by 1H-NMR. Succinate concentration averaged 0.069 ± 0.0073 mmol/L in patients with TIMI flow ≤ 1 and was significantly increased in those with TIMI 2 at admission (0.141 ± 0.058 mmol/L, p

Infertility affects 15% of the population in developed countries, and its prevalence is increasing. Fertility can be influenced by different factors. Although key factors like maternal age cannot be changed, there is growing evidence that other modifiable factors, such as diet, can have an impact on fertility. Diet has become increasingly important in recent years for a number of reasons: the new trend toward a healthy lifestyle, the higher prevalence of certain digestive disorders, a lack of time that leads people to consume more prepared and processed food, and personal choice to not eat meat, among others. To meet these needs, several diets have recently become popular, such as the Mediterranean diet, known as the gold standard of health; the DASH diet, known for preventing hypertension; the Western diet, characterized by processed food; the ketogenic diet, characterized by low carbohydrate intake; and the vegetarian diet, which is the choice for people who do not eat meat or animal by-products. Diets present a unique composition characterized by the presence or absence of specific nutrients, which have also been associated with male and female fertility individually. This review assesses the impact of these diets and of macro- and micronutrients on both female and male fertility.

Lysyl oxidase (LOX)-mediated extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease; however, this enzyme also induces oxidative stress. We addressed the contribution of LOX-dependent oxidative stress to cardiovascular calcification. LOX is upregulated in human-calcified atherosclerotic lesions and atheromas from atherosclerosis-challenged LOX transgenic mice (TgLOXVSMC) and colocalized with a marker of oxidative stress (8-oxo-deoxyguanosine) in vascular smooth muscle cells (VSMCs). Similarly, in calcific aortic valves, high LOX expression was detected in valvular interstitial cells (VICs) positive for 8-oxo-deoxyguanosine, while LOX and LOXL2 expression correlated with osteogenic markers (SPP1 and RUNX2) and NOX2. In human VICs, mito-TEMPO and TEMPOL attenuated the increase in superoxide anion levels and the mineralization induced by osteogenic media (OM). Likewise, in OM-exposed VICs, β-aminopropionitrile (a LOX inhibitor) ameliorated both oxidative stress and calcification. Gain- and loss-of-function approaches in VICs demonstrated that while LOX silencing negatively modulates oxidative stress and calcification induced by OM, lentiviral LOX overexpression exacerbated oxidative stress and VIC calcification, effects that were prevented by mito-TEMPO, TEMPOL, and β-aminopropionitrile. Our data indicate that LOX-induced oxidative stress participates in the procalcifying effects of LOX activity in ectopic cardiovascular calcification, and highlight the multifaceted role played by LOX isoenzymes in cardiovascular diseases.

Cancer immunotherapies include monoclonal antibodies, cytokines, oncolytic viruses, cellular therapies, and other biological and synthetic immunomodulators. These are traditionally studied for their effect on the immune system’s role in eliminating cancer cells. However, some of these therapies have the unique ability to directly induce cytotoxicity in cancer cells by inducing immunogenic cell death (ICD). Unlike general immune stimulation, ICD triggers specific therapy-induced cell death pathways, based on the release of damage-associated molecular patterns (DAMPs) from dying tumour cells. These activate innate pattern recognition receptors (PRRs) and subsequent adaptive immune responses, offering the promise of sustained anticancer drug efficacy and durable antitumour immune memory. Exploring how onco-immunotherapies can trigger ICD, enhances our understanding of their mechanisms and potential for combination strategies. This review explores the complexities of these immunotherapeutic approaches that induce ICD, highlighting their implications for the innate immune system, addressing challenges in cancer treatment, and emphasising the pivotal role of ICD in contemporary cancer research.

Extracellular matrix (ECM) is an active player in cardiovascular calcification (CVC), a major public health issue with an unmet need for effective therapies. Lysyl oxidase (LOX) conditions ECM biomechanical properties; thus, we hypothesized that LOX might impact on mineral deposition in calcific aortic valve disease (CAVD) and atherosclerosis. LOX was upregulated in calcified valves from two cohorts of CAVD patients. Strong LOX immunostaining was detected surrounding calcified foci in calcified human valves and atherosclerotic lesions colocalizing with RUNX2 on valvular interstitial cells (VICs) or vascular smooth muscle cells (VSMCs). Both LOX secretion and organized collagen deposition were enhanced in calcifying VICs exposed to osteogenic media. β-aminopropionitrile (BAPN), an inhibitor of LOX, attenuated collagen deposition and calcification. VICs seeded onto decellularized matrices from BAPN-treated VICs calcified less than cells cultured onto control scaffolds; instead, VICs exposed to conditioned media from cells over-expressing LOX or cultured onto LOX-crosslinked matrices calcified more. Atherosclerosis was induced in WT and transgenic mice that overexpress LOX in VSMC (TgLOXVSMC) by AAV-PCSK9D374Y injection and high-fat feeding. In atherosclerosis-challenged TgLOXVSMC mice both atherosclerosis burden and calcification assessed by near-infrared fluorescence (NIRF) imaging were higher than in WT mice. These animals also exhibited larger calcified areas in atherosclerotic lesions from aortic arches and brachiocephalic arteries. Moreover, LOX transgenesis exacerbated plaque inflammation, and increased VSMC cellularity, the rate of RUNX2-positive cells and both connective tissue content and collagen cross-linking. Our findings highlight the relevance of LOX in CVC and postulate this enzyme as a potential therapeutic target for CVC.

The molecular mechanisms underlying metastasis in pheochromocytoma/paraganglioma (mPPGL) remain to be explored. Here, the authors perform genomic and immunogenomic profiling of mPPGL tumors and suggest potential biomarkers for risk of metastasis and immunotherapy response.

La anemia es el resultado de una baja en las cifras del total de eritrocitos y/o en la concentración de hemoglobina en una persona y es un problema que afecta el desarrollo físico y mental además se vincula en la mayoría de los casos a sensaciones de fatiga y debilidad, lo que puede llegar a dificultar el buen desempeño en otras actividades incluso como las escolares, por consiguiente el objetivo del presente estudio fue estimar la prevalencia de anemia en el grupo de estudiantes de nuevo ingreso del área de la salud en una institución de educación superior (IES) en el sureste de México, con un enfoque de tipo cuantitativo, descriptivo y transversal. Se incluyen en el estudio 66 sujetos (68% son mujeres y 32 %son hombres). Se determinó que el 19.69 % presentan anemia normocítica, normocrómica, siendo el género femenino el más afectado. Dichos resultados indican que la presencia de anemia existe en los jóvenes universitarios, a pesar de ser un porcentaje bajo, cabe considerar el tamaño de la muestra. Aunque los resultados no demuestren que es un problema grave que deba ser atendido; se considera importante generar estrategia de intervención para mejorar el estado de salud, así como aumentar el número de participantes y una posible relación con el rendimiento escolar. Palabras clave: Anemia, rendimiento académico, universitarios. ABSTRACT It is considered as a didactic guide the digital or printed instrument that constitutes a resource for learning through which the action of the teacher and the students within the teaching process is specified, in a planned and organized way, it provides technical information to the student and has as a premise education as conduction and active process. It is based on didactics as a science to generate cognitive development and learning styles from itself. It constitutes a transcendental resource because it perfects the teacher's work in the preparation and orientation of teaching tasks as a basic cell of the teaching-learning process, whose realization is subsequently controlled in the curricular activities themselves. This didactic guide contemplates seven fundamental steps, 1) Title, 2) Abstract, 3) Keywords, 4) Introduction, 5) Presentation, 6) Discussion, 7) Conclusions, 8) References and 9) Others. This sequence of steps allows the systematic review of a clinical case with a nutritional perspective in the undergraduate, with the aim of facilitating the transformation of learning, which contributes to the change that education requires so that future professionals graduate capable of corresponding to today's society. Keywords: Didactic guide, nutritional assessment, food plan.

Breast cancer (BC) is one of the leading causes of cancer death worldwide. Cyclophosphamide (CTX) remains a mainstay in cancer therapy despite harmful adverse effects and cell death-resistances. To face this, combinational therapy of chemotherapies and immunotherapies has been proposed. IMMUNEPOTENT CRP (ICRP) is an immunotherapy that has cytotoxic effects in several cancer cells without affecting peripheral blood mononuclear cells (PBMC) and CD3+ cells. The aim of this study was to evaluate cytotoxicity, the type of cytotoxic effect, and several features involved in cell death induced by the combination of CTX with ICRP (ICRP+CTX) in breast cancer cells as well as their effect on healthy cells. For this purpose, human and murine breast cancer cells, MCF-7, MDA-MB-231 and 4T1, or PBMC were treated for 24 hours with ICRP, CTX or ICRP+CTX in different combination ratios for the assessment of cell death. Flow cytometry and microscopy were used to determine biochemical and morphological characteristics of cell death. Assays showed that ICRP in combination with CTX induce potentiated cell death manifested with morphological changes, loss of mitochondrial membrane potential, reactive oxygen species (ROS) production, and caspase activation. In addition, it was determined that ICRP+CTX-cell death is caspase-independent in all the breast cancer cells assessed. On the other hand, ICRP did not affect CTX-cytotoxicity in PBMC. For all the above, we can propose that the combination of ICRP with CTX an effective combination therapy, promoting their use even in tumoral cells with defects on proteins implicated in the apoptotic pathway.

This paper arises from the subject Errors in Spanish as a Foreign Language, taught in the Master of Teaching Spanish at Masaryk University of Brno, Czech Republic. Its main objective is to show how the analysis of lexical errors can be used as a tool in the training of non‑native teachers of Spanish, in this case, Czech and Slovak. To achieve this goal, firstly, the paper presents a brief review of the trends that have investigated errors in foreign language learning, such as contrastive analysis, error analysis and interlanguage studies. Secondly, it analyzes a corpus of texts written by learners of Spanish according to the error analysis methodology (Corder, 1967), as an activity for the Master students. Thirdly, it shows a typological classification of different lexical errors found in the texts and it reflects on the possible connection between mistakes and teaching methodology. Based on the results of the analysis, the paper discusses the usefulness of the analysis of these errors not only for the training of non‑native teachers of Spanish as a foreign language, but also for a better understanding of vocabulary teaching.

Introduction: Pertussis is a respiratory infection caused by bacteria of the genus Bordetella, mainly pertussis and parapertussis species. Despite the high vaccination coverage in developed countries, it is considered a re-emerging disease that is also underreported and underdiagnosed, especially in patients who do not require hospital referral. Material and methods: Descriptive, prospective and multicentre study of pertussis diagnosis and contact investigation in 17 primary care paediatric clinics through collection of samples for polymerase chain reaction (PCR) testing over a period of 4 years and after the implementation of routine vaccination against pertussis during pregnancy. Results: Pertussis was diagnosed in a total of 50 patients; the estimated incidence in these years was higher compared to previous rates in the paediatric age group. Fourteen percent of the cases occurred in children aged less than 1 year. The mean age was 6.7 years. Cough was present in 100% of cases, followed in frequency by vomiting and rhinorrhoea. Only 1 patient required hospital admission, and none died or developed complications. B. pertussis was the predominant causative agent. Only 40% knew the source of infection. In 26% of the cases, pertussis was confirmed in contacts of the patient by PCR, and in 46% it was suspected based on the clinical presentation but without microbiological confirmation. Conclusions: Access to diagnostic tests (PCR) for pertussis in primary care allows us to optimise its diagnosis and treatment, to break the chain of transmission, to know the real incidence rates and to assess the impact of routine vaccination of pregnant women on this disease. Resumen: Introducción: La tos ferina es una infección respiratoria causada por bacterias del género Bordetella, principalmente por las especies pertussis y parapertussis. A pesar de las altas coberturas vacunales en países desarrollados, está considerada como una enfermedad reemergente existiendo, además, una infranotificación y un infradiagnóstico especialmente en los pacientes que no precisan derivación hospitalaria. Material y métodos: Estudio descriptivo, prospectivo y multicéntrico de diagnóstico de casos de tos ferina, así como el estudio de sus contactos en 17 consultas de pediatría de atención primaria mediante la toma de muestras para realización de técnicas de PCR (reacción en cadena de la polimerasa) a lo largo de cuatro años y tras la implantación de la vacunación sistemática de la tos ferina en el embarazo. Resultados: Se diagnostican un total de 50 pacientes; la tasa de incidencia estimada en estos años fue superior a las publicadas en edad pediátrica. Un 14% de los casos sucedieron en menores de 1 año. La media de edad fue de 6,7 años. La tos estuvo presente en el 100% de los casos, seguida de los vómitos y rinorrea como síntomas más frecuentes. Sólo 1 paciente precisó ingreso y ninguno falleció ni presentó complicaciones. B. pertussis fue el agente causal predominante. Sólo un 40% conocía la fuente de contagio. En un 26% de los casos se comprobó mediante PCR tos ferina en sus contactos y en un 46% se sospechó clínicamente, aunque sin confirmación microbiológica. Conclusiones: El acceso a pruebas diagnósticas (PCR) para tos ferina en Atención Primaria permite optimizar su diagnóstico y tratamiento, cortar la cadena de transmisión, conocer las tasas de incidencia reales y valorar el impacto de la vacunación sistemática de las embarazadas en esta enfermedad.