Nanoparticulated Bimodal Contrast Agent for Ultra-High-Field Magnetic Resonance Imaging and Spectral X-ray Computed Tomography.

Bimodal medical imaging based on magnetic resonance imaging (MRI) and computed tomography (CT) is a well-known strategy to increase the diagnostic accuracy. The most recent advances in MRI and CT instrumentation are related to the use of ultra-high magnetic fields (UHF-MRI) and different working voltages (spectral CT), respectively. Such advances require the parallel development of bimodal contrast agents (CAs) that are efficient under new instrumental conditions. In this work, we have synthesized, through a precipitation reaction from a glycerol solution of the precursors, uniform barium dysprosium fluoride nanospheres with a cubic fluorite structure, whose size was found to depend on the Ba/(Ba + Dy) ratio of the starting solution. Moreover, irrespective of the starting Ba/(Ba + Dy) ratio, the experimental Ba/(Ba + Dy) values were always lower than those used in the starting solutions. This result was assigned to lower precipitation kinetics of barium fluoride compared to dysprosium fluoride, as inferred from the detailed analysis of the effect of reaction time on the chemical composition of the precipitates. A sample composed of 34 nm nanospheres with a Ba0.51Dy0.49F2.49 stoichiometry showed a transversal relaxivity (r2) value of 147.11 mM-1·s-1 at 9.4 T and gave a high negative contrast in the phantom image. Likewise, it produced high X-ray attenuation in a large range of working voltages (from 80 to 140 kVp), which can be attributed to the presence of different K-edge values and high Z elements (Ba and Dy) in the nanospheres. Finally, these nanospheres showed negligible cytotoxicity for different biocompatibility tests. Taken together, these results show that the reported nanoparticles are excellent candidates for UHF-MRI/spectral CT bimodal imaging CAs.

Tumor versus Tumor Cell Targeting in Metal-Based Nanoparticles for Cancer Theranostics.

The application of metal-based nanoparticles (mNPs) in cancer therapy and diagnostics (theranostics) has been a hot research topic since the early days of nanotechnology, becoming even more relevant in recent years. However, the clinical translation of this technology has been notably poor, with one of the main reasons being a lack of understanding of the disease and conceptual errors in the design of mNPs. Strikingly, throughout the reported studies to date on in vivo experiments, the concepts of "tumor targeting" and "tumor cell targeting" are often intertwined, particularly in the context of active targeting. These misconceptions may lead to design flaws, resulting in failed theranostic strategies. In the context of mNPs, tumor targeting can be described as the process by which mNPs reach the tumor mass (as a tissue), while tumor cell targeting refers to the specific interaction of mNPs with tumor cells once they have reached the tumor tissue. In this review, we conduct a critical analysis of key challenges that must be addressed for the successful targeting of either tumor tissue or cancer cells within the tumor tissue. Additionally, we explore essential features necessary for the smart design of theranostic mNPs, where 'smart design' refers to the process involving advanced consideration of the physicochemical features of the mNPs, targeting motifs, and physiological barriers that must be overcome for successful tumor targeting and/or tumor cell targeting.

Design of a Stem Cell-Based Therapy for Ependymal Repair in Hydrocephalus Associated With Germinal Matrix Hemorrhages.

BACKGROUND: In preterm birth germinal matrix hemorrhages (GMHs) and the consequent posthemorrhagic hydrocephalus (PHH), the neuroepithelium/ependyma development is disrupted. This work is aimed to explore the possibilities of ependymal repair in GMH/PHH using a combination of neural stem cells, ependymal progenitors (EpPs), and mesenchymal stem cells. METHODS: GMH/PHH was induced in 4-day-old mice using collagenase, blood, or blood serum injections. PHH severity was characterized 2 weeks later using magnetic resonance, immunofluorescence, and protein expression quantification with mass spectrometry. Ependymal restoration and wall regeneration after stem cell treatments were tested in vivo and in an ex vivo experimental approach using ventricular walls from mice developing moderate and severe GMH/PHH. The effect of the GMH environment on EpP differentiation was tested in vitro. Two-tailed Student t or Wilcoxon-Mann-Whitney U test was used to find differences between the treated and nontreated groups. ANOVA and Kruskal-Wallis tests were used to compare >2 groups with post hoc Tukey and Dunn multiple comparison tests, respectively. RESULTS: PHH severity was correlated with the extension of GMH and ependymal disruption (means, 88.22% severe versus 19.4% moderate). GMH/PHH hindered the survival rates of the transplanted neural stem cells/EpPs. New multiciliated ependymal cells could be generated from transplanted neural stem cells and more efficiently from EpPs (15% mean increase). Blood and TNFα (tumor necrosis factor alpha) negatively affected ciliogenesis in cells committed to ependyma differentiation (expressing Foxj1 [forkhead box J1] transcription factor). Pretreatment with mesenchymal stem cells improved the survival rates of EpPs and ependymal differentiation while reducing the edematous (means, 18% to 0.5% decrease in severe edema) and inflammatory conditions in the explants. The effectiveness of this therapeutical strategy was corroborated in vivo (means, 29% to 0% in severe edema). CONCLUSIONS: In GMH/PHH, the ependyma can be restored and edema decreased from either neural stem cell or EpP transplantation in vitro and in vivo. Mesenchymal stem cell pretreatment improved the success of the ependymal restoration.

Smart Design of ZnFe and ZnFe@Fe Nanoparticles for MRI-Tracked Magnetic Hyperthermia Therapy: Challenging Classical Theories of Nanoparticles Growth and Nanomagnetism.

Iron Oxide Nanoparticles (IONPs) hold the potential to exert significant influence on fighting cancer through their theranostics capabilities as contrast agents (CAs) for magnetic resonance imaging (MRI) and as mediators for magnetic hyperthermia (MH). In addition, these capabilities can be improved by doping IONPs with other elements. In this work, the synthesis and characterization of single-core and alloy ZnFe novel magnetic nanoparticles (MNPs), with improved magnetic properties and more efficient magnetic-to-heat conversion, are reported. Remarkably, the results challenge classical nucleation and growth theories, which cannot fully predict the final size/shape of these nanoparticles and, consequently, their magnetic properties, implying the need for further studies to better understand the nanomagnetism phenomenon. On the other hand, leveraging the enhanced properties of these new NPs, successful tumor therapy by MH is achieved following their intravenous administration and tumor accumulation via the enhanced permeability and retention (EPR) effect. Notably, these results are obtained using a single low dose of MNPs and a single exposure to clinically suitable alternating magnetic fields (AMF). Therefore, as far as the authors are aware, for the first time, the successful application of intravenously administered MNPs for MRI-tracked MH tumor therapy in passively targeted tumor xenografts using clinically suitable conditions is demonstrated.

Ribonucleotide reductase inhibition improves the symptoms of a Caenorhabditis elegans model of Alzheimer's disease.

Alzheimer's disease is the main cause of aging-associated dementia, for which there is no effective treatment. In this work, we reanalyze the information of a previous genome wide association study, using a new pipeline design to identify novel potential drugs. With this approach, ribonucleoside-diphosphate reductase gene (RRM2B) emerged as a candidate target and its inhibitor, 2', 2'-difluoro 2'deoxycytidine (gemcitabine), as a potential pharmaceutical drug against Alzheimer's disease. We functionally verified the effect of inhibiting the RRM2B homolog, rnr-2, in an Alzheimer's model of Caenorhabditis elegans, which accumulates human Aß1-42 peptide to an irreversible paralysis. RNA interference against rnr-2 and also treatment with 200 ng/ml of gemcitabine, showed an improvement of the phenotype. Gemcitabine treatment increased the intracellular ATP level 3.03 times, which may point to its mechanism of action. Gemcitabine has been extensively used in humans for cancer treatment but at higher concentrations. The 200 ng/ml concentration did not exert a significant effect over cell cycle, or affected cell viability when assayed in the microglia N13 cell line. Thus, the inhibitory drug of the RRM2B activity could be of potential use to treat Alzheimer's disease and particularly gemcitabine might be considered as a promising candidate to be repurposed for its treatment.

Appraising biocultural approaches to sustainability in the scientific literature in Spanish.

Biocultural approaches that acknowledge the multiple and dynamic relationships between the diversity of cultures and nature are growing in popularity in sustainability research. Scientific contributions to biocultural approaches written in Spanish are numerous, including influential work on biocultural memory, biocultural heritage and biocultural ethics. However, despite linguistic diversity being considered essential in knowledge production for assuring broad and balanced evidence to successfully cope with sustainability challenges, non-English literature is rarely reviewed and taken into account in English-language scientific knowledge production and publications. This review assesses how the scientific literature in Spanish conceptualizes and applies biocultural approaches, showing their richness beyond the Anglophone predominance in academic knowledge production and communication. The results suggest that insights from Spanish-language scientific literature could contribute alternative methodological and theoretical pathways for biocultural approaches that might foster transformations for more sustainable human-nature relationships. We conclude by highlighting avenues that could bring more plural biocultural studies.

RESUMEN: Los enfoques bioculturales, que reconocen relaciones múltiples y dinámicas entre la diversidad de culturas y la naturaleza, son cada vez más populares en la investigación sobre la sostenibilidad. Las contribuciones científicas en español son numerosas, incluyendo trabajos sobre la memoria, la ética y el patrimonio biocultural. La diversidad lingüística se considera esencial en la producción de conocimientos para asegurar una base equilibrada de evidencias que permita afrontar los retos de la sostenibilidad. Sin embargo, rara vez se considera la literatura de habla no inglesa en la producción científica en inglés. Esta revisión evalúa cómo la literatura científica en español conceptualiza y aplica enfoques bioculturales, mostrando su riqueza más allá de la predominancia anglosajona en la producción de conocimiento académico. Los resultados sugieren que las perspectivas de la literatura en español podrían aportar propuestas teóricas y metodológicas alternativas. Concluimos destacando maneras que podrían contribuir a hacer más plurales las investigaciones bioculturales.

Light-to-Heat Conversion of Optically Trapped Hot Brownian Particles.

Anisotropic hybrid nanostructures stand out as promising therapeutic agents in photothermal conversion-based treatments. Accordingly, understanding local heat generation mediated by light-to-heat conversion of absorbing multicomponent nanoparticles at the single-particle level has forthwith become a subject of broad and current interest. Nonetheless, evaluating reliable temperature profiles around a single trapped nanoparticle is challenging from all of the experimental, computational, and fundamental viewpoints. Committed to filling this gap, the heat generation of an anisotropic hybrid nanostructure is explored by means of two different experimental approaches from which the local temperature is measured in a direct or indirect way, all in the context of hot Brownian motion theory. The results were compared with analytical results supported by the numerical computation of the wavelength-dependent absorption efficiencies in the discrete dipole approximation for scattering calculations, which has been extended to inhomogeneous nanostructures. Overall, we provide a consistent and comprehensive view of the heat generation in optical traps of highly absorbing particles from the viewpoint of the hot Brownian motion theory.

Why has farming in Europe changed? A farmers' perspective on the development since the 1960s.

Farming in Europe has been the scene of several important socio-economic and environmental developments and crises throughout the last century. Therefore, an understanding of the historical driving forces of farm change helps identifying potentials for navigating future pathways of agricultural development. However, long-term driving forces have so far been studied, e.g. in anecdotal local case studies or in systematic literature reviews, which often lack context dependency. In this study, we bridged local and continental scales by conducting 123 oral history interviews (OHIs) with elderly farmers across 13 study sites in 10 European countries. We applied a driving forces framework to systematically analyse the OHIs. We find that the most prevalent driving forces were the introduction of new technologies, developments in agricultural markets that pushed farmers for farm size enlargement and technological optimisation, agricultural policies, but also cultural aspects such as cooperation and intergenerational arrangements. However, we find considerable heterogeneity in the specific influence of individual driving forces across the study sites, implying that generic assumptions about the dynamics and impacts of European agricultural change drivers hold limited explanatory power on the local scale. Our results suggest that site-specific factors and their historical development will need to be considered when addressing the future of agriculture in Europe in a scientific or policy context. Supplementary Information: The online version contains supplementary material available at 10.1007/s10113-023-02150-y.

Optimization of iron oxide nanoparticles for MRI-guided magnetic hyperthermia tumor therapy: reassessing the role of shape in their magnetocaloric effect.

Superparamagnetic iron oxide nanoparticles have hogged the limelight in different fields of nanotechnology. Surprisingly, notwithstanding the prominent role played as agents in magnetic hyperthermia treatments, the effects of nanoparticle size and shape on the magnetic hyperthermia performance have not been entirely elucidated yet. Here, spherical or cubical magnetic nanoparticles synthesized by a thermal decomposition method with the same magnetic and hyperthermia properties are evaluated. Interestingly, spherical nanoparticles displayed significantly higher magnetic relaxivity than cubic nanoparticles; however, comparable differences were not observed in specific absorption rate (SAR), pointing out the need for additional research to better understand the connection between these two parameters. Additionally, the as-synthetized spherical nanoparticles showed negligible cytotoxicity and, therefore, were tested in vivo in tumor-bearing mice. Following intratumoral administration of these spherical nanoparticles and a single exposure to alternating magnetic fields (AMF) closely mimicking clinical conditions, a significant delay in tumor growth was observed. Although further in vivo experiments are warranted to optimize the magnetic hyperthermia conditions, our findings support the great potential of these nanoparticles as magnetic hyperthermia mediators for tumor therapy.

New insights in the targets of action of dimethyl fumarate in endothelial cells: effects on energetic metabolism and serine synthesis in vitro and in vivo.

Dimethyl fumarate is an ester from the Krebs cycle intermediate fumarate. This drug is approved and currently used for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity was reported some years ago. Due to the current clinical relevance of this compound and the recently manifested importance of endothelial cell metabolism on the angiogenic switch, we wanted to elucidate whether dimethyl fumarate has an effect on energetic metabolism of endothelial cells. Different experimental approximations were performed in endothelial cells, including proteomics, isotope tracing and metabolomics experimental approaches, in this work we studied the possible role of dimethyl fumarate in endothelial cell energetic metabolism. We demonstrate for the first time that dimethyl fumarate promotes glycolysis and diminishes cell respiration in endothelial cells, which could be a consequence of a down-regulation of serine and glycine synthesis through inhibition of PHGDH activity in these cells. Dimethyl fumarate alters the energetic metabolism of endothelial cells in vitro and in vivo through an unknown mechanism, which could be the cause or the consequence of its pharmacological activity. This new discovery on the targets of this compound could open a new field of study regarding the mechanism of action of dimethyl fumarate.

Similarity network fusion to identify phenotypes of small-for-gestational-age fetuses.

Fetal growth restriction (FGR) affects 5-10% of pregnancies, is the largest contributor to fetal death, and can have long-term consequences for the child. Implementation of a standard clinical classification system is hampered by the multiphenotypic spectrum of small fetuses with substantial differences in perinatal risks. Machine learning and multiomics data can potentially revolutionize clinical decision-making in FGR by identifying new phenotypes. Herein, we describe a cluster analysis of FGR based on an unbiased machine-learning method. Our results confirm the existence of two subtypes of human FGR with distinct molecular and clinical features based on multiomic analysis. In addition, we demonstrated that clusters generated by machine learning significantly outperform single data subtype analysis and biologically support the current clinical classification in predicting adverse maternal and neonatal outcomes. Our approach can aid in the refinement of clinical classification systems for FGR supported by molecular and clinical signatures.

Intervención psicoeducativa para potenciar la rehabilitación cardiovascular integral en pacientes convalecientes de infarto agudo de miocardio / A psychoeducational intervention to enhance comprehensive cardiovascular rehabilitation in patients convalescent from acute myocardial infarction

Introducción: La rehabilitación cardiovascular integral del paciente con infarto agudo de miocardio resulta fundamental para el logro de su bienestar físico y psicológico, y su reinserción a la vida social. Objetivo: Elaborar una estrategia de intervención psicoeducativa para potenciar la rehabilitación cardiovascular integral en pacientes convalecientes de infarto agudo de miocardio, con la visión de especialistas consultados. Métodos: Se realizó un estudio observacional, descriptivo y de corte transversal en el Hospital Universitario «Dr. Celestino Hernández Robau», de Santa Clara, entre octubre de 2019 y enero de 2021. La muestra estuvo conformada por 27 pacientes que asistieron a la consulta de Cardiología, y 7 especialistas según criterios de inclusión. Las técnicas aplicadas fueron: la revisión de historia clínica, entrevistas semiestructuradas a pacientes y especialistas, la encuesta sobre el conocimiento de la enfermedad, un autorreporte vivencial y la evaluación del estilo vida. Se utilizaron estadísticos descriptivos acorde a la medición de las variables, análisis de contenido y triangulación de la información. Resultados: En los pacientes diagnosticados con estilo de vida poco saludable, predominó un conocimiento medianamente suficiente de la enfermedad; la hipertensión arterial fue el principal factor de riesgo asociado. Se elaboró la estrategia de intervención según las necesidades psicoeducativas identificadas por los pacientes con la visión de especialistas consultados. Se constató que presentan carencia de habilidades para autocontrolar las reacciones emocionales posteriores al suceso cardiovascular. Conclusiones: La estrategia elaborada fue valorada satisfactoriamente por juicio de profesionales, indicándose la posibilidad de ser aplicada en los usuarios a los que está dirigida.

Introduction: comprehensive cardiovascular rehabilitation of patients with acute myocardial infarction is essential to achieve their physical and psychological well-being, and their reintegration into social life. Objective: to develop a psychoeducational intervention strategy to enhance comprehensive cardiovascular rehabilitation in patients convalescent from acute myocardial infarction, with the vision of consulted specialists. Methods: an observational, descriptive and cross-sectional study was carried out at "Dr. Celestino Hernández Robau" University Hospital, in Santa Clara, between October 2019 and January 2021. The sample consisted of 27 patients who come to the Cardiology consultation, and 7 specialists according to inclusion criteria. Medical history review, semi-structured interviews with patients and specialists, a survey on knowledge of the disease, an experiential self-report, and a lifestyle evaluation were the techniques applied. Descriptive statistics were used according to the measurement of the variables as well as content analysis and triangulation of the information. Results: a moderately sufficient knowledge of the disease prevailed in patients diagnosed with an unhealthy lifestyle; arterial hypertension was the main associated risk factor. The intervention strategy was developed according to the psychoeducational needs identified by the patients with the vision of the consulted specialists. We verified that they have a lack of abilities to self-control their emotional reactions after the cardiovascular event. Conclusions: the elaborated strategy was satisfactorily valued by professional judgment, which indicates the possibility of being applied to the users to whom it is directed.

Multi-stimuli-responsive chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles as theranostic platforms for combined tumor magnetic resonance imaging and chemotherapy.

Chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles were formulated by interfacial polymer disposition plus coacervation, and loaded with gemcitabine. That (core/shell)/shell nanostructure was confirmed by electron microscopy, elemental analysis, electrophoretic, and Fourier transform infrared characterizations. A short-term stability study proved the protection against particle aggregation provided by the chitosan shell. Superparamagnetic properties of the nanoparticles were characterized in vitro, while the definition of the longitudinal and transverse relaxivities was an initial indication of their capacity as T2 contrast agents. Safety of the particles was demonstrated in vitro on HFF-1 human fibroblasts, and ex vivo on SCID mice. The nanoparticles demonstrated in vitro pH- and heat-responsive gemcitabine release capabilities. In vivo magnetic resonance imaging studies and Prussian blue visualization of iron deposits in tissue samples defined the improvement in nanoparticle targeting into the tumor when using a magnetic field. This tri-stimuli (magnetite/poly(ε-caprolactone))/chitosan nanostructure could find theranostic applications (biomedical imaging & chemotherapy) against tumors.

Hot Brownian Motion of Thermoresponsive Microgels in Optical Tweezers Shows Discontinuous Volume Phase Transition and Bistability.

Microgels are soft microparticles that often exhibit thermoresponsiveness and feature a transformation at a critical temperature, referred to as the volume phase transition temperature. Whether this transformation occurs as a smooth or as a discontinuous one is still a matter of debate. This question can be addressed by studying individual microgels trapped in optical tweezers. For this aim, composite particles are obtained by decorating  Poly-N-isopropylacrylamide (pNIPAM) microgels with iron oxide nanocubes. These composites become self-heating when illuminated by the infrared trapping laser, performing hot Brownian motion within the trap. Above a certain laser power, a single decorated microgel features a volume phase transition that is discontinuous, while the usual continuous sigmoidal-like dependence is recovered after averaging over different microgels. The collective sigmoidal behavior enables the application of a power-to-temperature calibration and provides the effective drag coefficient of the self-heating microgels, thus establishing these composite particles as potential micro-thermometers and micro-heaters. Moreover, the self-heating microgels also exhibit an unexpected and intriguing bistability behavior above the critical temperature, probably due to partial collapses of the microgel. These results set the stage for further studies and the development of applications based on the hot Brownian motion of soft particles.

Lanthanide vanadate-based trimodal probes for near-infrared luminescent bioimaging, high-field magnetic resonance imaging, and X-ray computed tomography.

We have developed a trimodal bioimaging probe for near-infrared luminescent imaging, high-field magnetic resonance imaging, and X-ray computed tomography using Dy3+ as the paramagnetic component and Nd3+ as the luminescent cation, both of them incorporated in a vanadate matrix. Among different essayed architectures (single phase and core-shell nanoparticles) the one showing the best luminescent properties is that consisting of uniform DyVO4 nanoparticles coated with a first uniform layer of LaVO4 and a second layer of Nd3+-doped LaVO4. The magnetic relaxivity (r2) at high field (9.4 T) of these nanoparticles was among the highest values ever reported for this kind of probes and their X-ray attenuation properties, due to the presence of lanthanide cations, were also better than those of a commercial contrast agent (iohexol) commonly used for X-ray computed tomography. In addition, they were chemically stable in a physiological medium in which they could be easily dispersed owing to their one-pot functionalization with polyacrylic acid, and, finally, they were non-toxic for human fibroblast cells. Such a probe is, therefore, an excellent multimodal contrast agent for near-infrared luminescent imaging, high-field magnetic resonance imaging, and X-ray computed tomography.

Predictors of changing patterns of adherence to containment measures during the early stage of COVID-19 pandemic: an international longitudinal study.

BACKGROUND: Identifying common factors that affect public adherence to COVID-19 containment measures can directly inform the development of official public health communication strategies. The present international longitudinal study aimed to examine whether prosociality, together with other theoretically derived motivating factors (self-efficacy, perceived susceptibility and severity of COVID-19, perceived social support) predict the change in adherence to COVID-19 containment strategies. METHOD: In wave 1 of data collection, adults from eight geographical regions completed online surveys beginning in April 2020, and wave 2 began in June and ended in September 2020. Hypothesized predictors included prosociality, self-efficacy in following COVID-19 containment measures, perceived susceptibility to COVID-19, perceived severity of COVID-19 and perceived social support. Baseline covariates included age, sex, history of COVID-19 infection and geographical regions. Participants who reported adhering to specific containment measures, including physical distancing, avoidance of non-essential travel and hand hygiene, were classified as adherence. The dependent variable was the category of adherence, which was constructed based on changes in adherence across the survey period and included four categories: non-adherence, less adherence, greater adherence and sustained adherence (which was designated as the reference category). RESULTS: In total, 2189 adult participants (82% female, 57.2% aged 31-59 years) from East Asia (217 [9.7%]), West Asia (246 [11.2%]), North and South America (131 [6.0%]), Northern Europe (600 [27.4%]), Western Europe (322 [14.7%]), Southern Europe (433 [19.8%]), Eastern Europe (148 [6.8%]) and other regions (96 [4.4%]) were analyzed. Adjusted multinomial logistic regression analyses showed that prosociality, self-efficacy, perceived susceptibility and severity of COVID-19 were significant factors affecting adherence. Participants with greater self-efficacy at wave 1 were less likely to become non-adherence at wave 2 by 26% (adjusted odds ratio [aOR], 0.74; 95% CI, 0.71 to 0.77; P < .001), while those with greater prosociality at wave 1 were less likely to become less adherence at wave 2 by 23% (aOR, 0.77; 95% CI, 0.75 to 0.79; P = .04). CONCLUSIONS: This study provides evidence that in addition to emphasizing the potential severity of COVID-19 and the potential susceptibility to contact with the virus, fostering self-efficacy in following containment strategies and prosociality appears to be a viable public health education or communication strategy to combat COVID-19.

A novel biocompatible polymer derived from D-mannitol used as a vector in the field of genetic engineering of eukaryotic cells.

The design and preparation of new vectors to transport genetic material and increase the transfection efficiency continue being an important research line. Here, a novel biocompatible sugar-based polymer derived from D-mannitol has been synthesized to be used as a gene material nanocarrier in human (gene transfection) and microalga cells (transformation process). Its low toxicity allows its use in processes with both medical and industrial applications. A multidisciplinary study about the formation of polymer/p-DNA polyplexes has been carried out using techniques such as gel electrophoresis, zeta potential, dynamic light scattering, atomic force microscopy, and circular dichroism spectroscopy. The nucleic acids used were the eukaryotic expression plasmid pEGFP-C1 and the microalgal expression plasmid Phyco69, which showed different behaviors. The importance of DNA supercoiling in both transfection and transformation processes was demonstrated. Better results were obtained in microalga cells nuclear transformation than in human cells gene transfection. This was related to the plasmid's conformational changes, in particular to their superhelical structure. It is noteworthy that the same nanocarrier has been used with eukaryotic cells from both human and microalga.

[Studying loneliness and social support networks among older people: a systematic review in Europe.] / La investigación sobre soledad y redes de apoyo social en las personas mayores: una revisión sistemática en Europa.

OBJECTIVE: During the ageing process the loss of family and social relationships is frequent which conditions loneliness, similarly the current COVID-19 pandemic has generated more social limitations in this age group and has increased the risk factors to trigger feelings of loneliness. This paper aimed to examine how loneliness among older people had been studied in Europe over the last ten years. Specific objectives were: i) to describe the methodological aspects; ii) to identify the scales or questions for the assessment of loneliness; iii) what were the main variables or dimensions that were related to loneliness in old age. METHODS: A total of 1,591 articles were found in WoS and Scopus digital platforms. After initial assessment of titles and abstracts, full text reading and review of the established criteria, 42 scientific articles were finally included in the systematic review. RESULTS: The countries that had carried out the most studies were the Netherlands and Spain. Most of the research was quantitative and uses the De Jong Gierveld Loneliness Scale (DJGLS) and the University of California at Los Angeles (UCLA) Loneliness Scale. The most analysed variables were: marital status, household structure, social support networks, social participation, depression, health problems, co-morbidity and physical functioning. CONCLUSIONS: The scientific interest in studying loneliness, with a focus on social support networks, in older people in Europe and strategically addressing loneliness as a public health problem is confirmed.

OBJETIVO: Durante el proceso de envejecimiento es frecuente la pérdida de relaciones familiares y sociales, lo cual condiciona la soledad. Además, la actual pandemia de la COVID-19 ha generado más limitaciones en las relaciones sociales de este grupo de edad y ha aumentado los factores de riesgo para desencadenar sentimientos de soledad. Este trabajo tuvo el objetivo de examinar cómo se había estudiado la soledad en las personas mayores en Europa en los últimos diez años. Se propusieron como objetivos específicos: i) describir los aspectos metodológicos; ii) identificar las escalas o preguntas para la valoración de la soledad; iii) cuáles eran las principales variables o dimensiones que se relacionaban con la soledad en la vejez, priorizando el rol de las redes de apoyo social. METODOS: Se encontraron 1.591 artículos en total en las plataformas digitales WoS y Scopus. Tras la valoración inicial de los títulos y resúmenes, lectura de texto completo y revisión de los criterios establecidos, al final se incluyeron en la revisión sistemática 42 artículos científicos. RESULTADOS: Los países que más estudios habían realizado eran Países Bajos y España, en su mayoría las investigaciones eran cuantitativas y utilizaban las escalas De Jong Gierveld Loneliness Scale (DJGLS) y University of California at Los Angeles (UCLA) Loneliness Scale. Las variables más analizadas fueron: estado civil, estructura del hogar, redes de apoyo social, participación social, depresión, problemas de salud, comorbilidad y funcionalidad física. CONCLUSIONES: Se confirma el interés científico por estudiar la soledad, con un énfasis central en las redes de apoyo social, en las personas mayores en Europa y abordar estratégicamente la soledad como un problema de Salud Pública.

Multifaceted Analysis of Cerebrospinal Fluid and Serum from Progressive Multiple Sclerosis Patients: Potential Role of Vitamin C and Metal Ion Imbalance in the Divergence of Primary Progressive Multiple Sclerosis and Secondary Progressive Multiple Sclerosis.

The progressive forms of multiple sclerosis (MS) primary progressive MS (PPMS) and secondary progressive MS (SPMS) are clinically distinguished by the rate at which symptoms worsen. Little is however known about the pathological mechanisms underlying the differential rate of accumulation of pathological changes. In this study, 1H NMR spectroscopy was used to measure low-molecular-weight metabolites in paired cerebrospinal fluid (CSF) and serum of PPMS, SPMS, and control patients, as well as to determine lipoproteins and glycoproteins in serum samples. Additionally, neurodegenerative and inflammatory markers, neurofilament light (NFL) and chitinase-3-like protein 1 (CHI3L1), and the concentration of seven metal elements, Mg, Mn, Cu, Fe, Pb, Zn, and Ca, were also determined in both CSF and serum. The results indicate that the pathological changes associated with progressive MS are mainly localized in the central nervous system (CNS). More so, PPMS and SPMS patients with comparable disability status are pathologically similar in relation to neurodegeneration, neuroinflammation, and some metabolites that distinguish them from controls. However, the rapid progression of PPMS from the onset may be driven by a combination of neurotoxicity induced by heavy metals coupled with diminished CNS antioxidative capacity associated with differential intrathecal ascorbate retention and imbalance of Mg and Cu.

La investigación sobre soledad y redes de apoyo social en las personas mayores: una revisión sistemática en Europa / Studying loneliness and social support networks among older people: a systematic review in Europe

FUNDAMENTOS: Durante el proceso de envejecimiento es frecuente la pérdida de relaciones familiares y sociales, lo cual condiciona la soledad. Además, la actual pandemia de la COVID-19 ha generado más limitaciones en las relaciones sociales de este grupo de edad y ha aumentado los factores de riesgo para desencadenar sentimientos de soledad. Este trabajo tuvo el objetivo de examinar cómo se había estudiado la soledad en las personas mayores en Europa en los últimos diez años. Se propusieron como objetivos específicos: i) describir los aspectos metodológicos; ii) identificar las escalas o preguntas para la valoración de la soledad; iii) cuáles eran las principales variables o dimensiones que se relacionaban con la soledad en la vejez, priorizando el rol de las redes de apoyo social. MÉTODOS: Se encontraron 1.591 artículos en total en las plataformas digitales WoS y Scopus. Tras la valoración inicial de los títulos y resúmenes, lectura de texto completo y revisión de los criterios establecidos, al final se incluyeron en la revisión sistemática 42 artículos científicos. RESULTADOS: Los países que más estudios habían realizado eran Países Bajos y España, en su mayoría las investigaciones eran cuantitativas y utilizaban las escalas De Jong Gierveld Loneliness Scale (DJGLS) y University of California at Los Angeles (UCLA) Loneliness Scale. Las variables más analizadas fueron: estado civil, estructura del hogar, redes de apoyo social, participación social, depresión, problemas de salud, comorbilidad y funcionalidad física. CONCLUSIONES: Se confirma el interés científico por estudiar la soledad, con un énfasis central en las redes de apoyo social, en las personas mayores en Europa y abordar estratégicamente la soledad como un problema de Salud Pública.(AU)

BACKGROUND: During the ageing process the loss of family and social relationships is frequent which conditions loneliness, similarly the current COVID-19 pandemic has generated more social limitations in this age group and has increased the risk factors to trigger feelings of loneliness. This paper aimed to examine how loneliness among older people had been studied in Europe over the last ten years. Specific objectives were: i) to describe the methodological aspects; ii) to identify the scales or questions for the assessment of loneliness; iii) what were the main variables or dimensions that were related to loneliness in old age. METHODS: A total of 1,591 articles were found in WoS and Scopus digital platforms. After initial assessment of titles and abstracts, full text reading and review of the established criteria, 42 scientific articles were finally included in the systematic review. RESULTS: The countries that had carried out the most studies were the Netherlands and Spain. Most of the research was quantitative and uses the De Jong Gierveld Loneliness Scale (DJGLS) and the University of California at Los Angeles (UCLA) Loneliness Scale. The most analysed variables were: marital status, household structure, social support networks, social participation, depression, health problems, co-morbidity and physical functioning. CONCLUSIONS: The scientific interest in studying loneliness, with a focus on social support networks, in older people in Europe and strategically addressing loneliness as a public health problem is confirmed.(AU)