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Navigating the landscape of RNA delivery systems in cardiovascular disease therapeutics
No full textCardiovascular diseases (CVDs) stand as the leading cause of death worldwide, posing a significant global health challenge. Consequently, the development of innovative therapeutic strategies to enhance CVDs treatment is imperative. RNA-based therapies, encompassing non-coding RNAs, mRNA, aptamers, and CRISPR/Cas9 technology, have emerged as promising tools for addressing CVDs. However, inherent challenges associated with RNA, such as poor cellular uptake, susceptibility to RNase degradation, and capture by the reticuloendothelial system, underscore the necessity of combining these therapies with effective drug delivery systems. Various non-viral delivery systems, including extracellular vesicles, lipid-based carriers, polymeric and inorganic nanoparticles, as well as hydrogels, have shown promise in enhancing the efficacy of RNA therapeutics. In this review, we offer an overview of the most relevant RNA-based therapeutic strategies explored for addressing CVDs and emphasize the pivotal role of delivery systems in augmenting their effectiveness. Additionally, we discuss the current status of these therapies and the challenges that hinder their clinical translation
Fichas de buenas prácticas para la atención a problemas de salud mental en Educación Secundaria. Una herramienta de ayuda para los centros educativos
No full textMaterial elaborado en el marco del proyecto de investigación orientado a la transferencia del conocimiento,
"Revisión y valoración de políticas de prevención e intervención en salud mental infanto-juvenil
en centros educativos” (IP, Martiño Rodríguez-González, ICS-UNAV) desarrollado por la Universidad
de Navarra en colaboración con la Universidad Internacional de La Rioja UNIR- ITEI. Esta guía pretende proporcionar al profesorado un marco de comprensión sencillo acerca de los problemas de salud mental en la etapa de secundaria, así como identificar señales de alarma y ofrecer pautas para un primer abordaje con los estudiantes que puedan estar experimentando tales problemas. La guía busca promover y prevenir la salud mental, pero en ningún diagnosticar u orientar sobre la forma de intervenir. El objetivo de este documento es prevenir y detectar los problemas de salud mental, además de planificar el acompañamiento, cuidado y, en caso necesario, derivación a los servicios especializados de salud mental. Ayudar al alumno es, en gran medida, conseguir coordinarse y colaborar con las familias y otros profesionales externos al centro educativo. Para cada una de las fichas incluidas en este documento, se sigue la misma estructura: primero, una introducción sobre el problema de salud mental o el trastorno en cuestión; segundo, se detallan las principales señales de alarma que pueden ser observadas por el docente en diferentes espacios y situaciones escolares; finalmente, se proporcionan sugerencias sobre su abordaje, ¿qué puede hacer el maestro o profesor ante esto
FNDC4 reduces hepatocyte inflammatory cell death via AMPKa in metabolic dysfunction-associated steatotic liver disease
No full textBackground: The molecular mediators responsible for the progression of metabolic dysfunction-
associated steatotic liver disease (MASLD) to steatohepatitis (MASH) have not yet been completely disentangled. We sought to analyze whether FNDC4, an hepatokine and adipokine with anti-inflammatory
properties, is involved in TNF-a-induced inflammatory cell death in patients with MASLD.
Methods: Plasma FNDC4 (n 1⁄4 168) and hepatic FNDC4 and inflammatory cell death (n 1⁄4 65) were
measured in samples from patients with severe obesity with available liver biopsy-proven MASLD
diagnosis. The effect of FNDC4 on TNF-a-induced pyroptosis, apoptosis and necroptosis (PANoptosis) and
mitochondrial dysfunction was studied in vitro using human HepG2 hepatocytes.
Results: Compared with individuals with normal liver, patients with type 2 diabetes and MASLD
exhibited decreased hepatic FNDC4 mRNA and protein levels, which were related to liver inflammation.
An overexpression of TNF-a, its receptor TNF-R1 and factors involved in inflammatory cell death was also
found in the liver of these patients. FNDC4-knockdown in HepG2 hepatocytes increased apoptotic cell
death, while FNDC4 treatment blunted NLRP3 inflammasome-induced pyroptosis, apoptosis and necroptosis in TNF-a-stimulated hepatocytes. Moreover, FNDC4 improved TNF-a-induced hepatocyte
mitochondrial dysfunction by enhancing mitochondrial DNA (mtDNA) copy number and OXPHOS
complex subunits I, II, III and V protein expression. Mechanistically, AMP-activated protein kinase a
(AMPKa) was required for the FNDC4-mediated inhibition of cell death and increase in mtDNA content.
Conclusions: FNDC4 acts as a hepatocyte survival factor favouring mitochondrial homeostasis and
decreasing inflammatory cell death via AMPKa. Collectively, our study identifies FNDC4 as an attractive
target to prevent hepatocellular damage in patients with MASLD
Single-step fabrication of highly tunable blazed gratings using triangular-shaped femtosecond laser pulses
No full textBlazed gratings are periodic surface structures of great interest for applications such as friction control, light trapping, and spectrometry. While different laser processing methods have been explored to produce these elements, they have not yet surpassed conventional surface manufacturing techniques, often based on lithography processes or mechanical ruling. This work introduces a new approach based on the combination of ultrashort pulses and triangular beam shaping, which enables the generation of asymmetrical grooves in a single step. The main advantage of this strategy is that by simply changing the laser processing direction we can induce a significant modification in the ratio of asymmetry between the sidewall angles of the machined channels. The paper includes a comprehensive study, which has been supported by statistical tools, of the effect of this and other experimental parameters on the morphology of grooves machined on stainless steel. As a result, we achieved a wide range of geometries, with asymmetry ratios spanning from 1 to 5 and channel depths between 3 and 15 mu m. Furthermore, we demonstrate the validity of the approach through the successful manufacture of blazed gratings of various slopes. The results reflect the versatility and cost-efficiency of the proposed fabrication strategy, and thus its potential to streamline the production of sawtooth gratings and other devices that are based on asymmetrical features
Personal Experience of Suffering: Reflections Inspired by Elements of Karol Wojtyła’s Philosophical Anthropology
No full textUsing elements of K. Wojtyła’s philosophical anthropology, I make an attempt to look at the phenomenon of suffering through the experience of the suffering subject, through the uniquely personal experience of ‘I am suffering.’ The personal experience of suffering involves the inclusion of the phenomena of pain and suffering within the domain of self-consciousness, i.e. within the field of experiencing oneself, the sense of one's own identity, including the striving for fulfilment. In this perspective, the experience of suffering has to do with the person-specific openness to transcendence, which makes it possible to show the positive side to the experience of suffering. Both in the field of self-consciousness and in the personal experience of self-determination, the experience of ‘I am suffering’ can serve the person in the realisation of personal truth (about the good), involving and stimulating actions towards fulfilment
Serum Amyloid A as a potential biomarker for disease activity in chronic spontaneous urticaria
Get PDFBackground: Chronic spontaneous urticaria (CSU) is an inflammatory skin disease with a complex physiopathology. Serum amyloid A (SAA), an acute-phase reactant, has been proposed as a potential biomarker in urticaria but has yet to be studied in a population with CSU or correlated with disease activity as indicated by the Urticaria Activity Score summed over 7 days (UAS7).
Objective: We sought to determine SAA-1 levels in patients with CSU and correlate them with its activity and control, as well as with clinical features of CSU and other potential blood biomarkers.
Methods: We conducted a retrospective multicenter study of 67 patients with CSU, from whom we obtained demographic and clinical data, UAS7 as an indicator of CSU activity, and blood and serum markers.
Results: SAA-1 levels positively correlated with UAS7 (rs = 0.47, P 6) CSU than in those with controlled (UAS ≤ 6) CSU (P < .001) and were also higher in patients with concomitant angioedema (P = .003) or delayed pressure urticaria (P = .003).
Conclusion: We propose SAA-1 as a potential biomarker for activity in CSU. Further studies are required to evaluate its potential role as a biomarker for other CSU outcomes, such as response to treatment
Percepción económica y polarización política en tiempos de crisis
No full textLa polarización se ha convertido en uno de los fenómenos políticos protagonistas de la actualidad. Diversos estudios empíricos demuestran que el aumento de la polarización es un fenómeno habitual tras una crisis de carácter financiera. En este artículo, se ahondará en la relación entre la polarización política y la percepción de la situación económica familiar y general en España. Los resultados muestran que, al evaluar cuestiones cercanas, como la percepción de la situación económica familiar, los ciudadanos emiten opiniones vinculadas a su nivel de ingresos ¿una variable económica. Sin embargo, en cuestiones abstractas como la evaluación de la situación económica general de España, la orientación ideológica de los ciudadanos es la variable más influyente. Este alineamiento indica que los españoles asumen un enfoque ideológico en lugar de uno puramente económico y, por lo tanto, más susceptible de influencia polarizadora del discurso de las élites y la cobertura periodística
Revised European Association for Palliative Care (EAPC) recommended framework on palliative sedation: An international Delphi study
No full textBackground: The European Association for Palliative Care (EAPC) acknowledges palliative sedation as an important, broadly accepted intervention for patients with life-limiting disease experiencing refractory symptoms. The EAPC therefore developed 2009 a framework on palliative sedation. A revision was needed due to new evidence from literature, ongoing debate and criticism of methodology, terminology and applicability.Aim: To provide evidence- and consensus-based guidance on palliative sedation for healthcare professionals involved in end-of-life care, for medical associations and health policy decision-makers.Design: Revision between June 2020 and September 2022 of the 2009 framework using a literature update and a Delphi procedure.Setting: European.Participants: International experts on palliative sedation (identified through literature search and nomination by national palliative care associations) and a European patient organisation.Results: A framework with 42 statements for which high or very high level of consensus was reached. Terminology is defined more precisely with the terms suffering used to encompass distressing physical and psychological symptoms as well as existential suffering and refractory to describe the untreatable (healthcare professionals) and intolerable (patient) nature of the suffering. The principle of proportionality is introduced in the definition of palliative sedation. No specific period of remaining life expectancy is defined, based on the principles of refractoriness of suffering, proportionality and independent decision-making for hydration. Patient autonomy is emphasised. A stepwise pharmacological approach and a guidance on hydration decision-making are provided.Conclusions: This is the first framework on palliative sedation using a strict consensus methodology. It should serve as comprehensive and soundly developed information for healthcare professionals
Unlocking the potential of 1,4-naphthoquinones: A comprehensive review of their anticancer properties
No full textCancer encompasses a group of pathologies with common characteristics, high incidence, and prevalence in all countries. Although there are treatments available for this disease, they are not always effective or safe, often failing to achieve the desired results. This is why it is necessary to continue the search for new therapies. One of the strategies for obtaining new antitumor drugs is the use of 1,4-naphthoquinone as a scaffold in synthetic or natural products with antitumor activity. This review focuses on compiling studies related to the antitumor activity of 1,4-naphthoquinone and its natural and synthetic derivatives over the last 10 years. The work describes the main natural naphthoquinones with antitumor activity and classifies the synthetic naphthoquinones based on the structural modifications made to the scaffold. Additionally, the formation of metal complexes using naphthoquinones as a ligand is considered. After a thorough review, 197 synthetic compounds with potent biological activity against cancer have been classified according to their chemical structures and their mechanisms of action have been described
A multicentre evaluation of the NG-test DetecTool OXA-23 for the rapid detection of OXA-23 carbapenemase directly from blood cultures
No full textObjectives
A multicentre study evaluating NG-Test DetecTool OXA-23 for the detection of OXA-23 carbapenemase directly from positive blood cultures (PBCs).
Methods
The NG-Test DetecTool OXA-23 is an immunoassay that integrates a sample preparation device. We evaluated NG-Test DetecTool OXA-23 on 189 spiked and 126 clinical PBCs. The clinical samples’ standard-of-care procedure consisted of bacterial identification from the first day of positivity by MALDI-TOF MS, conventional culture and antimicrobial susceptibility testing. The immunoassay results were verified molecularly. The strains used for the spiked samples consisted of well-characterized Acinetobacter baumannii and Proteus mirabilis strains.
Results
The NG-Test DetecTool OXA-23 was evaluated on 315 PBCs and revealed sensitivity of 100% (95% CI: 98.21%–100.00%) and specificity of 100% (95% CI: 96.73%–100.00%). It provided 204 true-positive results for OXA-23 in 196 bottles with carbapenem-resistant A. baumannii (CRAB) and 8 bottles with carbapenem-resistant P. mirabilis and also provided 111 true-negative results. There were no false-positive and no false-negative results. Among the 315 PBCs studied, 83 clinical blood cultures collected in the ICU of a Greek university hospital, which were tested prospectively, all yielded CRAB, and OXA-23 was correctly detected in all samples from the first day of positivity using the NG-Test DetecTool OXA-23.
Conclusions
The NG-Test DetecTool OXA-23 has exhibited excellent sensitivity and specificity for OXA-23 detection in PBCs and can provide valuable information for appropriate selection of antibiotic therapy and early implementation of infection control measures