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Acute pancreatic panniculitis in a domestic ferret (Mustela putorius furo): diagnostic insights and a potential drug-induced etiology
Get PDFPanniculitis is a rare condition in ferrets (Mustela putorius furo), previously linked to nutritional deficiencies, infections, trauma, and injections. Pancreatic panniculitis, caused by the systemic release of pancreatic enzymes during pancreatic injury, has been documented in humans and other animal species, but not in ferrets. This report describes the first known case in a domestic ferret. A 2-year-old male ferret presented with ulcerated cutaneous nodules predominantly affecting the hind limbs and inguinal abdominal region. The ferret had been treated with rifampicin and clarithromycin for suspected mycobacterial infection. Hyperglycemia, hyperglobulinemia, and elevated alkaline phosphatase were noted. Cytology and culture of the lesions revealed neutrophilic inflammation and Pseudomonas aeruginosa, respectively. The animal developed acute abdominal discomfort and died shortly after. Post-mortem examination revealed severe pancreatic necrosis and peripancreatic panniculitis, with splenic pyogranulomatous inflammation. Immunohistochemistry detected systemic coronavirus antigen (clone FCV3-70) only in the spleen. In this patient, prolonged use of rifampicin and clarithromycin is considered a potential contributing factor to the development of acute pancreatic necrosis. This case highlights the clinical relevance of pancreatic panniculitis in ferrets and suggests a possible association between extended rifampicin/clarithromycin therapy and pancreatic necrosis. Ultrasonography and serum glucose, lipase, and amylase measurements are recommended for early diagnosis. Histopathological evaluation remains essential for confirmation
Developing science-informed maps and climate service for extreme rainfall in Spain
Get PDFThis study introduces the first high-resolution hazard probability maps of extreme precipitation for Spain, marking a significant step toward a national climate service for hydrometeorological extremes. Using long-term daily precipitation records from a dense network of stations and incorporating topographic data, the methodology combines the Generalized Pareto distribution with universal kriging to spatially interpolate distribution parameters. These maps offer reliable estimates of extreme precipitation quantiles, validated against station-level observations, and are based on a stationary modelling framework—an approach supported by recent findings showing the temporal stability of such extremes in Spain and considered more robust than non-stationary alternatives. Distinct spatial patterns emerge, with intense daily precipitation distributed mainly along the Mediterranean coast and high total event precipitation in the northwest and southwest, reflecting the influence of varied weather systems. To support decision-making, the study aggregates these high-resolution data at the provincial level, aligning risk information with administrative boundaries, and enhancing its relevance for policy and planning. Furthermore, the maps are made accessible via an interactive online platform (https://retornolluvias.csic.es), enabling users to explore localized hazard probabilities, thereby supporting adaptation in water management and civil protection, among others
PINGing Sunshine: A Review of the Evidence for Adding Non-Filtering Photoprotective Ingredients to Sunscreens
Get PDFBackground: Photoprotective INGredients (PINGs) are non-filtering agents that enhance the skin's intrinsic defenses against solar radiation. Acting through antioxidant, DNA repair, immunomodulatory, anti-inflammatory, and pigmentation-regulating
mechanisms, PINGs may prevent or repair photodamage. When incorporated into sunscreens, they offer protection beyond ultraviolet (UV) filters. This strategy of biological photoprotection could address key limitations of traditional sunscreens and
reduce dependence on high UV filter concentrations.
Methods: We conducted a focused literature review based on our prior evidence-based classification of over 1700 topical PINGs. We selected ingredients with the strongest clinical and mechanistic support and assessed their biological activity, formulation compatibility, and relevance to key endpoints such as erythema, pigmentation, photoaging, and immunosuppression.
Results: Top-ranked PINGs, including L-ascorbic acid, tocopherol, photolyase, and nicotinamide, demonstrated efficacy across multiple photodamage endpoints. Antioxidants like L-ascorbic acid and tocopherol enhanced protection against UVR and IR-A-
induced oxidative stress. DNA repair enzymes, such as photolyase, reduced cyclobutane pyrimidine dimer formation and supported immune function. Nicotinamide improved DNA repair and prevented UV-induced immunosuppression. Pigmentation modulators such as p-coumaric acid and isobutylamido thiazolyl resorcinol showed benefits in darker phototypes.
Conclusions: Fewer than 2% of candidate PINGs are clinically validated, and only 18 are approved for use in sunscreens. Protection against visible and infrared radiation remains largely underexplored. Standardized testing and additional clinical
trials are needed to advance PINGs as effective components of next-generation sunscreens
Can five chemically different lamellar crystals self-assemble in a single spherulite?
Get PDFSemicrystalline polymers with multiple crystallizable blocks provide opportunities to develop materials with hierarchical structures and customized properties, but they also pose unique challenges for understanding their crystallization. In this work, we investigate the crystallization from a miscible melt of a pentablock quintopolymer composed of five potentially crystallizable and biocompatible blocks, composed of polyethylene (PE), poly(ethylene oxide) (PEO), poly(ε-caprolactone) (PCL), poly(L-lactide) (PLLA), and polyglycolide (PGA), with a composition optimized to allow the crystallization of all blocks. Using Differential Scanning Calorimetry, synchrotron Fourier Transform Infrared Spectroscopy, synchrotron in situ Wide-angle and Small-angle X-Ray Scattering, Transmission Electron Microscopy, and Polarized Light Optical Microscopy, we demonstrate that upon cooling from the melt, all covalently linked blocks crystallize in a well-defined sequence: PGA > PLLA > PE > PCL > PEO. During crystallization, well-developed pentacrystalline positive spherulites are produced. This unprecedented level of self-assembly reveals the potential of complex block polymers to design multifunctional crystalline materials
Learning to deal with hate speech: An online collective intelligence experiment on the Collective Learning platform
Get PDFOnline hate speech on social networks and the Internet is an increasingly pervasive phenomenon to which both children and adolescents are exposed. Objective: Our study’s main objective was to ascertain whether collective intelligence can improve their handling of hate speech. Methods: We conducted the study on the Collective Learning platform, comparing results between three groups of Spanish adolescents aged 15–16 years. The groups were of different sizes: one large group (G1, n = 123) and two smaller groups (G2, n = 18; G3, n = 23). Results: The experiment showed that the conditions for the emergence of collective intelligence were met within the large group (G1) but not in the two small groups (G2 and G3). The large group, as a collective, acquired capacities to deal with hate speech; however, this did not occur in the two smaller groups. Conclusions: Our study explains how the emergence of collective intelligence in online environments helps group members acquire a series of competencies. In particular, collective intelligence can help adolescents learn to deal with hate speech
Cardiovascular risk factors in immigrants: an intersectional real world data approach to understand health inequalities
Get PDFCardiovascular risk factors (CVRFs) are shaped by social determinants of health. Lower CVRFs frequency in immigrants, as reported in the literature, may oversimplify a group affected by multiple and intersecting social inequities. Using the framework of intersectionality, we aim to analyse the prevalence of CVRFs using Real-World Data (RWD), in immigrants to better understand how overlapping social identities shape health outcomes.
Methods. A cross-sectional observational study was conducted in the immigrant population of the CARhES cohort (45,861) a population cohort of RWD of CVRFs’ patients. In order to characterise the most privileged and oppressed immigrant groups, we considered the impact of country of origin, age group, gender, income level and place of residence on the prevalence of CVRFs. Logistic regression models were used to estimate the effect of socioeconomic characteristics on the presence of three CVRFs. To explore intersectionality, logistic regression models with interactions assessed how sociodemographic variables jointly influenced the presence of three CVRFs. Coefficients were tested for significance using the Wald test, and odds ratios (ORs) were calculated with their 95% confidence intervals (CI).
Results. The prevalence of CVRFs was higher in immigrant men, living in urban areas, and increased with aging and low income. The strongest association between socioeconomic variables and the presence of three CVRFs was found in people 65–79 years and among Europeans. This association was independent of their time in the country. Intersectional strata with more CVRFs included individuals aged 65–79 in urban areas, Latin American and Caribbean men and African women. Intersectional analyses showed that African immigrants from urban areas had a higher probability of having the three CVRFs (OR: 1.66, CI = 1.30–2.11), as did African women (OR: 1.40, CI = 1.15–1.69). Females in the most oppressed axes of inequality showed a higher frequency of CVRFs than males. Conclusions. Intersectional approach reveals that the most disadvantaged groups regarding CVRFs include older Latin American and Caribbean men and African women in urban areas. Women facing multiple layers of social oppression are particularly at risk. This RWD-based approach enables the identification of at-risk groups and supports the design of equitable, data-driven health interventions
Cortisol awakening response and autobiographical memory in healthy older adults: The moderating role of negative reminiscence
Get PDFThe Hypothalamic-Pituitary-Adrenal (HPA) axis’s response to stress, with cortisol as a key hormone, has an important impact on cognitive function. Specifically, the Cortisol Awakening Response (CAR), an index of HPA axis functioning, has been linked to declarative memory performance. Autobiographical Memory (AM), a specific form of declarative memory, becomes especially relevant in aging due to its relationship with identity, emotional regulation, and cognitive functioning. However, engaging with the autobiographical past can become maladaptive when it is dominated by negative, self-critical reflections, a pattern referred to as negative reminiscence. This study aimed to examine whether the CAR and negative reminiscence independently predict the specificity of personal memories in healthy older adults, and whether their interaction further explains variability in AM specificity. A sample of 150 healthy older adults (aged 56–81) provided eight saliva samples over two consecutive days to assess the CAR, and they completed standardized measures of AM and reminiscence. Our results showed no significant direct associations between the CAR or negative reminiscence and AM specificity. However, moderation analyses revealed that the CAR significantly predicted a greater tendency to retrieve overgeneral memories, that is, less specific autobiographical memories, but only among individuals with higher negative reminiscence. These results suggest that the way individuals relate to their past plays a key role in the impact of physiological stress on autobiographical recall. The findings underscore the importance of considering both biological and emotional factors to better understand AM in aging
Per- and polyfluoroalkyl substances exposure in hexavalent chromium exposed workers and the effects of exposure mixtures on oxidative stress and genomic instability
Get PDFHexavalent chromium (Cr(VI)) can induce oxidative stress, genomic instability, and epigenetic modifications. In occupational settings, Cr(VI)-exposed workers may also be exposed to other toxicants, such as elements besides Cr, and per- and polyfluoroalkyl substances (PFAS). However, research on the extent of these co-exposures and their combined effects remains limited. The objective of this study was to characterize the exposure levels of ten elements and eight PFAS in Cr(VI)-exposed workers and to assess the combined effects of these exposure mixtures on biomarkers of oxidative stress and genomic instability. This study included 138 Cr(VI)-exposed workers and 96 controls from Swedish SafeChrom and Danish SAM-Krom studies. Concentrations of elements were measured by inductively coupled plasma mass spectrometry (ICP-MS), and PFAS were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Effect biomarkers, including 8-hydroxy-2′-deoxyguanosine (8-OHdG), mitochondrial DNA copy number (mtDNA-cn), telomere length (TL) and O6-methylguanine-DNA methyltransferase promoter (MGMT) methylation, were analyzed in blood. Bayesian Kernel Machine Regression and quantile-based g-computation models were used to evaluate the mixture effects. Exposed workers had higher concentrations of Cr, manganese, copper, zinc, lead, and perfluoroheptanoic acid (PFHpA), lower mtDNA-cn and longer TL compared to controls. In the SAM-Krom study, perfluorooctane sulfonic acid (PFOS) levels were significantly elevated among exposed workers, with the P95 reaching 2044 ng/mL. The exposure mixtures were associated with increased 8-OHdG and MGMT hypermethylation. Together, these findings highlight the complexity of multiple occupational exposures in Cr(VI)-related work environments and suggest that combined exposure may contribute to early biological alterations related to oxidative stress and DNA methylation
Effectiveness of a guided mobile app intervention for depression and anxiety in university students (PROMES-U study): protocol of a multicenter randomized controlled trial
Get PDFSymptoms of depression and anxiety are common among Spanish university students. Minimally guided online interventions have shown promise in reducing symptomatology and preventing increased mental distress. Here we describe the protocol of a controlled study which aims to evaluate the effectiveness of a guided preventive mental health intervention for depression and anxiety in Spanish university students.
Methods. Ongoing two-arm multicenter randomized controlled trial (RCT) targeting undergraduate students from 6 public universities with symptoms of depression and/or anxiety. Students are evaluated (between February and November 2024) through a web-based survey assessing mental health problems, use of mental health services, self-perceived health, childhood and adolescent adversities, recent stressful events, social networks, university experiences, as well as sociodemographic variables. A total of 428 students, fulfilling the inclusion criteria, are randomly assigned to: intervention group (minimally guided mhealth prevention intervention) or control group (treatment as usual plus self-monitoring including periodic evaluations on mood and stress). The intervention is based on cognitive behavioral therapy principles, such as relaxation and cognitive restructuring, and includes weekly asynchronous feedback from a psychologist based on content and participation, along with self-monitoring. Participants are assessed at baseline, and 3, 6 and 12 months after randomization. The primary outcome consists of the reduction of depressive and/or anxiety symptoms post-intervention, assessed with the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Patient Health Questionnaire-Anxiety and Depression Scale. Secondary outcomes of the RCT will be symptoms of other mental health conditions, psychological wellbeing, academic stress, acceptability and adherence. Primary analyses will be conducted on an intention-to-treat basis.
Discussion. The results of the PROMES-U RCT will provide valuable information on the effectiveness of a minimally guided preventive mental health intervention to reduce symptoms of depression and anxiety among university students that could be delivered in the campus context. Results will also provide information on the potential impact of the intervention on other relevant factors involved in mental health among university students and on the acceptability and adherence of this intervention. Trial registration number: NCT0607800
Nuevos Complejos Organometálicos de Oro(I) y Plata(I): Desde la Síntesis Sostenible hasta las Aplicaciones Biomédicas y los Materiales Luminiscentes
No full textLa investigación desarrollada en esta tesis doctoral ha permitido avanzar significativamente en la química de coordinación de metales del grupo 11, centrando el estudio en la síntesis y caracterización de nuevos complejos de Au(I) y Ag(I) con una amplia variedad de ligandos, incluyendo carbenos N-heterocíclicos (NHC), fosfinas mono y bidentadas, alquinilos y bases conjugadas de distintos ácidos débiles. La mayoría de los complejos obtenidos no habían sido previamente descritos en la literatura, lo que resalta el carácter innovador del trabajo y la contribución original al campo de la química organometálica. Además de su interés desde el punto de vista estructural y sintético, los complejos desarrollados han sido evaluados en distintos contextos, incluyendo aplicaciones con potencial biológico, propiedades luminiscentes y como plataformas versátiles en síntesis organometálica. En conjunto, este trabajo sienta las bases para futuras investigaciones en el diseño racional de complejos de metales nobles con aplicaciones funcionales, y pone de manifiesto el papel clave de la innovación en los métodos de síntesis para el desarrollo de nuevas especies con propiedades emergentes.Una de las aportaciones más relevantes de esta tesis es el desarrollo de un método sintético eficiente y versátil para la obtención de complejos con fórmula general [M(acac)(L)n] (M = Au(I) o Ag(I); L = IPr, PPh3 o JohnPhos), basado en la sustitución del precursor Tl(acac) por Ag(acac), lo que representa una alternativa más segura, económica y sostenible. Este enfoque permitió acceder a una nueva familia de complejos que demostraron ser excelentes precursores sintéticos. La reactividad de estos complejos frente a diversos sustratos ácidos, como ácidos carboxílicos, alquinos, tioles y sales de imidazolio, ha sido evaluada de forma sistemática. En todos los casos se ha logrado la obtención de los productos deseados con altos rendimientos, tiempos de reacción cortos y condiciones suaves, evidenciando su potencial como herramientas sintéticas eficientes.En el capítulo tres, se ha explorado la síntesis de una nueva familia de complejos de oro(I) con ligandos alquinilo funcionalizados con unidades fenilcarbazol, que han mostrado propiedades luminiscentes notables. Dentro de esta serie, ha destacado la diversidad de ligandos auxiliares empleados -desde mono y difosfinas hasta isocianuros y azoles- así como la formación de distintas geometrías de coordinación en los complejos (lineal, trigonal plana y tetraédrica). Además, estos sistemas se han utilizado como plataformas para reacciones tipo iClick, que han permitido incorporar nuevas funcionalidades mediante la síntesis de complejos triazol-oro(I). Los estudios fotofísicos han revelado que estos compuestos son emisores fosforescentes en el rango del azul al amarillo, con una luminiscencia originada principalmente en transiciones intraligando e intramoleculares, potenciadas por la coordinación al metal, que también ha favorecido un desplazamiento de la emisión hacia menores energías. Especialmente relevante ha sido el complejo con 2-piridildifenilfosfina, que ha exhibido fluorescencia retardada inducida térmicamente (TADF), a pesar de un notable gap energético entre los estados singlete y triplete, lo que podría indicar la coexistencia de múltiples estados excitados triplete. Por otro lado, el complejo bimetálico 3.10 ha mostrado una emisión secundaria a 600 nm que se ha intensificado a bajas temperaturas y cuya luminiscencia es sensible a la presencia de metales de transición, lo que sugiere su potencial como sensor catiónico. Estos resultados han ampliado significativamente el conocimiento sobre sistemas luminiscentes de Au(I) y han abierto nuevas posibilidades para el diseño de materiales emisores inteligentes.En el capítulo cuatro, se han sintetizado cuatro nuevas sales de imidazolio funcionalizadas con cromóforos y 26 complejos de Au(I) y Ag(I), cuyas estructuras han sido confirmadas mediante espectroscopía y difracción de rayos X. Los estudios fotofísicos han indicado que la emisión en estos sistemas se origina principalmente en transiciones intraligando (IL), sin participación electrónica significativa del centro metálico, salvo en los biscarbenos con antraceno, donde se ha observado un desplazamiento de la emisión atribuible a fenómenos de agregación.Los estudios biológicos en células A549 han mostrado que los complejos cargados presentan mayor citotoxicidad (menor IC50) en comparación con los neutros, mostrando actividades excelentes en el rango de nanomolar. Se ha confirmado la inducción de apoptosis como mecanismo principal de muerte celular, junto con alteraciones del potencial mitocondrial y generación de especies reactivas de oxígeno (ROS). Algunos complejos con antraceno han provocado retención en fase G2/M, lo que sugiere daño al ADN. Además, los estudios de microscopía confocal han evidenciado colocalización mitocondrial en complejos con metilacridina, identificando a este orgánulo como una diana biológica relevante. Finalmente, varios de estos complejos han mostrado una inhibición significativa de la enzima tiorredoxina reductasa (TrxR), superando incluso al fármaco Auranofin en algunos casos, especialmente en los compuestos sin grupo metileno. Estos resultados han resaltado el potencial terapéutico y de diagnóstico de los complejos del grupo 11, subrayando su versatilidad estructural y funcional.En el capítulo cinco, se han desarrollado dos nuevas sales de imidazolio con carga localizada: una zwitteriónica (Im5.1) y otra catiónica (Im5.2). A partir de ellas, se han sintetizado complejos zwitteriónicos tanto de Ag(I) como de Au(I), estos últimos mediante transmetalación in situ. Los ensayos MTT en líneas celulares tumorales han revelado una destacada actividad antitumoral para los complejos de Au(I), especialmente aquellos con JohnPhos, que han mostrado buena selectividad frente a la línea A549. Los complejos de Ag(I) han resultado aún más activos, destacando nuevamente el derivado con JohnPhos por su bajo IC50. Los análisis por citometría de flujo han confirmado que todos los complejos poseen un perfil citostático, inducen apoptosis, generan ROS, y provocan alteraciones en el ciclo celular con retención en G2/M. Asimismo, tanto los complejos de oro como de plata han demostrado inhibir eficazmente la TrxR, alcanzando niveles comparables o superiores a los del Auranofin. Estos resultados han reforzado el interés en estas especies como candidatos prometedores en el desarrollo de agentes terapéuticos multifuncionales basados en metales nobles, combinando actividad biológica selectiva con mecanismos de acción complementarios.<br /