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BACKGROUND AND OBJECTIVE: Papanicolaou staining has been successfully used to assist early detection of cervix cancer for several decades. We postulate that this staining technique can also be used for assisting early detection of oral cancer, which is responsible for about 300,000 deaths every year. The rational for such claim includes two key observations: (i) nuclear atypia, i.e., changes in volume, shape, and staining properties of the cell nuclei can be linked to rapid cell proliferation and genetic instability; and (ii) Papanicolaou staining allows one to reliably segment cells' nuclei and cytoplasms. While Papanicolaou staining is an attractive tool due to its low cost, its interpretation requires a trained pathologist. Our goal is to automate the segmentation and classification of morphological features needed to evaluate the use of Papanicolaou staining for early detection of mouth cancer. METHODS: We built a convolutional neural network (CNN) for automatic segmentation and classification of cells in Papanicolaou-stained images. Our CNN was trained and evaluated on a new image dataset of cells from oral mucosa consisting of 1,563 Full HD images from 52 patients, annotated by specialists. The effectiveness of our model was evaluated against a group of experts. Its robustness was also demonstrated on five public datasets of cervical images captured with different microscopes and cameras, and having different resolutions, colors, background intensities, and noise levels. RESULTS: Our CNN model achieved expert-level performance in a comparison with a group of three human experts on a set of 400 Papanicolaou-stained images of the oral mucosa from 20 patients. The results of this experiment exhibited high Interclass Correlation Coefficient (ICC) values. Despite being trained on images from the oral mucosa, it produced high-quality segmentation and plausible classification for five public datasets of cervical cells. Our Papanicolaou-stained image dataset is the most diverse publicly available image dataset for the oral mucosa in terms of number of patients. CONCLUSION: Our solution provides the means for exploring the potential of Papanicolaou-staining as a powerful and inexpensive tool for early detection of oral cancer. We are currently using our system to detect suspicious cells and cell clusters in oral mucosa slide images. Our trained model, code, and dataset are available and can help practitioners and stimulate research in early oral cancer detection.
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Risk of depression increased in the general population after the COVID-19 pandemic outbreak. By examining the interplay between genetics and individual environmental exposures during the COVID-19 lockdown, we have been able to gain an insight as to why some individuals are more vulnerable to depression, while others are more resilient. This study, conducted on a Spanish cohort of 9218 individuals (COVICAT), includes a comprehensive non-genetic risk analysis, the exposome, complemented by a genomics analysis in a subset of 2442 participants. Depression levels were evaluated using the Hospital Anxiety and Depression Scale. Together with Polygenic Risk Scores (PRS), we introduced a novel score; Poly-Environmental Risk Scores (PERS) for non-genetic risks to estimate the effect of each cumulative score and gene-environment interaction. We found significant positive associations for PERSSoc (Social and Household), PERSLife (Lifestyle and Behaviour), and PERSEnv (Wider Environment and Health) scores across all levels of depression severity, and for PRSB (Broad depression) only for moderate depression (OR 1.2, 95% CI 1.03-1.40). On average OR increased 1.2-fold for PERSEnv and 1.6-fold for PERLife and PERSoc from mild to severe depression level. The complete adjusted model explained 16.9% of the variance. We further observed an interaction between PERSEnv and PRSB showing a potential mitigating effect. In summary, stressors within the social and behavioral domains emerged as the primary drivers of depression risk in this population, unveiling a mitigating interaction effect that should be interpreted with caution.
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COVID-19 , Depresión , Exposoma , Interacción Gen-Ambiente , Humanos , COVID-19/epidemiología , COVID-19/psicología , COVID-19/virología , Depresión/epidemiología , Depresión/etiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , España/epidemiología , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/genética , Anciano , Factores de Riesgo , Pandemias , Cuarentena/psicología , Estudios de CohortesRESUMEN
This research proposes designing and implementing a system to produce hydrogen, utilizing the thermal energy from the exhaust gases in a natural gas engine. For the construction of the system, a thermoelectric generator was used to convert the thermal energy from the exhaust gases into electrical power and an electrolyzer bank to produce hydrogen. The system was evaluated using a natural gas engine, which operated at a constant speed (2400 rpm) and six load conditions (20 %, 40 %, 60 %, 80 %, and 100 %). The effect of hydrogen on the engine was evaluated with fuel mixtures (NG + 10 % HEF and NG + 15 % HEF). The results demonstrate that the NG + 10 % HEF and NG + 15 % HEF mixtures allow for a decrease of 1.84 % and 2.33 % in BSFC and an increase of 1.88 % and 2.38 % in BTE. Through the NG + 15 % HEF mixture, the engine achieved an energy efficiency of 34.15 % and an exergetic efficiency of 32.84 %. Additionally, the NG + 15 % HEF mixture reduces annual CO, CO2, and HC emissions by 9.52 %, 15.48 %, and 13.39 %, respectively. The addition of hydrogen positively impacts the engine's economic cost, allowing for a decrease of 1.56 % in the cost of useful work and a reduction of 3.32 % in the cost of exergy loss. In general, the proposed system for hydrogen production represents an alternative for utilizing the residual energy from exhaust gases, resulting in better performance parameters, reduced annual pollutant emissions, and lower economic costs.
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BACKGROUND: Prenatal ethylene oxide exposure may have adverse effects on fetal development. We examined the relationships between ethylene oxide hemoglobin (Hb) adduct levels and offspring's size at birth in a prospective European mother-child study. METHODS: This study included 1106 singletons from the NewGeneris project (2006-2010) with ethylene oxide Hb adducts measured in cord blood. We examined the relationships between adduct levels and offspring's size at birth among all infants and separately among infants of nonsmokers, using linear regression models for birth weight and birth head circumference and logarithmic binomial regression models for small for gestational age. We examined potential interactions between CYP2E1 single nucleotide polymorphisms in cord blood and the effects of ethylene oxide Hb adduct levels on offspring birth size. RESULTS: Higher quartiles of adduct levels as a measure of exposure were associated with decreasing birth weight and head circumference in the overall population. Compared to infants in the lowest quartile, those in the highest quartile exhibited lower birth weight (-70.73 g, 95% confidence interval = -141.16, -0.30) and reduced head circumference (-0.30 cm, 95% confidence interval = -0.58, -0.02). We observed similar, albeit less pronounced, patterns among infants of nonsmokers. There was no evidence of an association between ethylene oxide Hb adducts and risk of small for gestational age, nor consistent evidence of an interaction with CYP2E1 polymorphisms on the association between EO Hb adduct levels and offspring's size at birth. CONCLUSION: Results suggest that higher ethylene oxide Hb adduct levels in cord blood are associated with a reduction in offspring birth size.
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Peso al Nacer , Citocromo P-450 CYP2E1 , Óxido de Etileno , Sangre Fetal , Hemoglobinas , Humanos , Sangre Fetal/química , Femenino , Recién Nacido , Embarazo , Peso al Nacer/efectos de los fármacos , Citocromo P-450 CYP2E1/genética , Estudios Prospectivos , Masculino , Europa (Continente) , Hemoglobinas/análisis , Adulto , Polimorfismo de Nucleótido Simple , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Modelos Lineales , Recién Nacido Pequeño para la Edad Gestacional , Estudios de CohortesRESUMEN
BACKGROUND: Prostate cancer (PC) is the second most frequent tumor in men worldwide; however, its etiology remains largely unknown, with the exception of age and family history. The wide variability in incidence/mortality across countries suggests a certain role for environmental exposures that has not yet been clarified. OBJECTIVE: To evaluate the association between risk of PC (by clinical profile) and residential proximity to pollutant industrial installations (by industrial groups, groups of carcinogens, and specific pollutants released), within the context of a Spanish population-based multicase-control study of incident cancer (MCC-Spain). METHODS: This study included 1186 controls and 234 PC cases, frequency matched by age and province of residence. Distances from participants' residences to the 58 industries located in the study area were calculated and categorized into "near" (considering different limits between ≤1 km and ≤ 3 km) or "far" (>3 km). Odds ratios (ORs) and 95 % confidence intervals (95%CIs) were estimated using mixed and multinomial logistic regression models, adjusted for potential confounders and matching variables. RESULTS: No excess risk was detected near the overall industries, with ORs ranging from 0.66 (≤2 km) to 1.11 (≤1 km). However, positive associations (OR; 95%CI) were found, by industrial group, near (≤3 km) industries of ceramic (2.54; 1.28-5.07), food/beverage (2.18; 1.32-3.62), and disposal/recycling of animal waste (2.67; 1.12-6.37); and, by specific pollutant, near plants releasing fluorine (4.65; 1.45-14.91 at ≤1.5 km) and chlorine (5.21; 1.56-17.35 at ≤1 km). In contrast, inverse associations were detected near industries releasing ammonia, methane, dioxins+furans, polycyclic aromatic hydrocarbons, trichloroethylene, and vanadium to air. CONCLUSIONS: The results suggest no association between risk of PC and proximity to the overall industrial installations. However, some both positive and inverse associations were detected near certain industrial groups and industries emitting specific pollutants.
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Exposición a Riesgos Ambientales , Neoplasias de la Próstata , España/epidemiología , Masculino , Humanos , Neoplasias de la Próstata/epidemiología , Exposición a Riesgos Ambientales/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Industrias , Estudios de Casos y Controles , Factores de Riesgo , Contaminantes Ambientales/análisisRESUMEN
Introduction: Data on medulloblastoma outcomes and experiences in low- and middle-income countries, especially in Latin America, is limited. This study examines challenges in Mexico's healthcare system, focusing on assessing outcomes for children with medulloblastoma in a tertiary care setting. Methods: A retrospective analysis was conducted, involving 284 patients treated at 21 pediatric oncology centers in Mexico. Results: High-risk patients exhibited markedly lower event-free survival than standard-risk patients (43.5% vs. 78.3%, p<0.001). Influential factors on survival included anaplastic subtype (HR 2.4, p=0.003), metastatic disease (HR 1.9, p=0.001); residual tumor >1.5cm², and lower radiotherapy doses significantly impacted event-free survival (EFS) and overall survival (OS). Platinum-based chemotherapy showed better results compared to the ICE protocol in terms of OS and EFS, which was associated with higher toxicity. Patients under 3 years old displayed notably lower OS and EFS compared to older children (36.1% vs. 55.9%, p=0.01).
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Children with autism spectrum disorder (ASD) have deficits that affect their social relationships, communication, and flexibility in reasoning. There are different types of treatment (pharmacological, educational, psychological, and rehabilitative). Currently, one way to address this problem is by using robotic systems to address the abilities that are altered in these children. The aim of this review will be to analyse the effectiveness of the incorporation of the different robotic systems currently existing in the treatment of children up to 10 years of age diagnosed with autism. A systematic review has been carried out in the PubMed, Scopus, Web of Science, and Dialnet databases, with the following descriptors: child, autism, and robot. The search yielded 578 papers, and nine were selected after the application of the PRISMA guideline. The quality of the studies was analysed with the PEDRo scale, and only those with a score between four and six were selected. From this study, the conclusion is that the use of robots, in general, improves children's behaviour in the short term, but longer-term experiences are necessary to achieve more conclusive results.
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Trastorno del Espectro Autista , Robótica , Humanos , Robótica/métodos , Niño , Trastorno del Espectro Autista/terapia , Trastorno del Espectro Autista/psicología , Preescolar , Trastorno Autístico/terapia , Trastorno Autístico/psicologíaRESUMEN
BACKGROUND: Several studies have reported a relationship between retinal thickness and dementia. Therefore, optical coherence tomography (OCT) has been proposed as an early diagnosis method for Alzheimer's disease (AD). In this study, we performed a genome-wide association study (GWAS) aimed at identifying genes associated with retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness assessed by OCT and exploring the relationships between the spectrum of cognitive decline (including AD and non-AD cases) and retinal thickness. METHODS: RNFL and GCIPL thickness at the macula were determined using two different OCT devices (Triton and Maestro). These determinations were tested for association with common single nucleotide polymorphism (SNPs) using adjusted linear regression models and combined using meta-analysis methods. Polygenic risk scores (PRSs) for retinal thickness and AD were generated. RESULTS: Several genetic loci affecting retinal thickness were identified across the genome in accordance with previous reports. The genetic overlap between retinal thickness and dementia, however, was weak and limited to the GCIPL layer; only those observable with all-type dementia cases were considered. CONCLUSIONS: Our study does not support the existence of a genetic link between dementia and retinal thickness.
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Enfermedad de Alzheimer , Estudio de Asociación del Genoma Completo , Humanos , Puntuación de Riesgo Genético , Fibras Nerviosas , Tomografía de Coherencia Óptica/métodos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/complicaciones , CogniciónRESUMEN
BACKGROUND: The FACEmemory® online platform comprises a complex memory test and sociodemographic, medical, and family questions. This is the first study of a completely self-administered memory test with voice recognition, pre-tested in a memory clinic, sensitive to Alzheimer's disease, using information and communication technologies, and offered freely worldwide. OBJECTIVE: To investigate the demographic and clinical variables associated with the total FACEmemory score, and to identify distinct patterns of memory performance on FACEmemory. METHODS: Data from the first 3,000 subjects who completed the FACEmemory test were analyzed. Descriptive analyses were applied to demographic, FACEmemory, and medical and family variables; t-test and chi-square analyses were used to compare participants with preserved versus impaired performance on FACEmemory (cut-offâ=â32); multiple linear regression was used to identify variables that modulate FACEmemory performance; and machine learning techniques were applied to identify different memory patterns. RESULTS: Participants had a mean age of 50.57 years and 13.65 years of schooling; 64.07% were women, and 82.10% reported memory complaints with worries. The group with impaired FACEmemory performance (20.40%) was older, had less schooling, and had a higher prevalence of hypertension, diabetes, dyslipidemia, and family history of neurodegenerative disease than the group with preserved performance. Age, schooling, sex, country, and completion of the medical and family history questionnaire were associated with the FACEmemory score. Finally, machine learning techniques identified four patterns of FACEmemory performance: normal, dysexecutive, storage, and completely impaired. CONCLUSIONS: FACEmemory is a promising tool for assessing memory in people with subjective memory complaints and for raising awareness about cognitive decline in the community.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Memoria Episódica , Enfermedades Neurodegenerativas , Humanos , Femenino , Masculino , Cognición , Disfunción Cognitiva/psicología , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/psicología , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.
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COVID-19 , Humanos , SARS-CoV-2 , ARN Viral , Tratamiento Farmacológico de COVID-19 , Dexametasona/uso terapéuticoRESUMEN
BACKGROUND: Some researchers have suggested that zinc (Zn) could reduce the risk of prostate cancer (PC). However, research from observational studies on the relationship between PC risk and biomarkers of Zn exposure shows conflicting results. OBJECTIVES: To evaluate the association between toenail Zn and PC, considering tumour extension and aggressiveness, along with a gene-environment approach, exploring the interaction of individual genetic susceptibility to PC in the relationship between toenail Zn and PC. METHODS: In MCC-Spain study we invited all incident PC cases diagnosed in the study period (2008-2013) and recruited randomly selected general population controls. In this report we included 913 cases and 1198 controls with toenail Zn determined by inductively coupled plasma mass spectrometry. To measure individual genetic susceptibility, we constructed a polygenic risk score based on known PC-related single nucleotide polymorphisms. The association between toenail Zn and PC was explored with mixed logistic and multinomial regression models. RESULTS: Men with higher toenail Zn had higher risk of PC (OR quartile 4 vs.1: 1.41; 95% CI: 1.07-1.85). This association was slightly higher in high-grade PC [(ISUP≤2 Relative risk ratio (RRR) quartile 4 vs.1: 1.36; 1.01-1.83) vs. (ISUP3-5 RRR quartile 4 vs.1: 1.64; 1.06-2.54)] and in advanced tumours [(cT1-cT2a RRR quartile 4 vs.1: 1.40; 95% CI: 1.05-1.89) vs. (cT2b-cT4 RRR quartile 4 vs.1: 1.59; 1.00-2.53)]. Men with lower genetic susceptibility to PC were those at higher risk of PC associated with high toenail Zn (OR quartile 4 vs.1: 2.18; 95% CI: 1.08-4.40). DISCUSSION: High toenail Zn levels were related to a higher risk for PC, especially for more aggressive or advanced tumours. This effect was stronger among men with a lower genetic susceptibility to PC.
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Neoplasias de la Próstata , Zinc , Masculino , Humanos , Zinc/análisis , Estudios de Casos y Controles , España/epidemiología , Uñas/química , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/genética , Predisposición Genética a la Enfermedad , Compuestos Orgánicos , Factores de RiesgoRESUMEN
Metal nanocrystals (NCs) display unique physicochemical features that are highly dependent on nanoparticle dimensions, anisotropy, structure, and composition. The development of synthesis methodologies that allow us to tune such parameters finely emerges as crucial for the application of metal NCs in catalysis, optical materials, or biomedicine. Here, we describe a synthetic methodology to fabricate hollow multimetallic heterostructures using a combination of seed-mediated growth routes and femtosecond-pulsed laser irradiation. The envisaged methodology relies on the coreduction of Ag and Pd ions on gold nanorods (Au NRs) to form Au@PdAg core-shell nanostructures containing small cavities at the Au-PdAg interface. The excitation of Au@PdAg NRs with low fluence femtosecond pulses was employed to induce the coalescence and growth of large cavities, forming multihollow anisotropic Au@PdAg nanostructures. Moreover, single-hollow alloy AuPdAg could be achieved in high yield by increasing the irradiation energy. Advanced electron microscopy techniques, energy-dispersive X-ray spectroscopy (EDX) tomography, X-ray absorption near-edge structure (XANES) spectroscopy, and finite differences in the time domain (FDTD) simulations allowed us to characterize the morphology, structure, and elemental distribution of the irradiated NCs in detail. The ability of the reported synthesis route to fabricate multimetallic NCs with unprecedented hollow nanostructures offers attractive prospects for the fabrication of tailored high-entropy alloy nanoparticles.
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Luminescence nanothermometry allows measuring temperature remotely and in a minimally invasive way by using the luminescence signal provided by nanosized materials. This technology has allowed, for example, the determination of intracellular temperature and in vivo monitoring of thermal processes in animal models. However, in the biomedical context, this sensing technology is crippled by the presence of bias (cross-sensitivity) that reduces the reliability of the thermal readout. Bias occurs when the impact of environmental conditions different from temperature also modifies the luminescence of the nanothermometers. Several sources that cause loss of reliability have been identified, mostly related to spectral distortions due to interaction between photons and biological tissues. In this work, we unveil an unexpected source of bias induced by metal ions. Specifically, we demonstrate that the reliability of Ag2S nanothermometers is compromised during the monitoring of photothermal processes produced by iron oxide nanoparticles. The observed bias occurs due to the heat-induced release of iron ions, which interact with the surface of the Ag2S nanothermometers, enhancing their emission. The results herein reported raise a warning to the community working on luminescence nanothermometry, since they reveal that the possible sources of bias in complex biological environments, rich in molecules and ions, are more numerous than previously expected.
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Temperatura Corporal , Luminiscencia , Animales , Reproducibilidad de los Resultados , Temperatura , IonesRESUMEN
BACKGROUND AND AIMS: A gonadotropin-releasing hormone (GnRH)-based therapeutic vaccine candidate against hormone-sensitive prostate cancer has demonstrated its safety and signs of efficacy in phase I/II trials. In this study, we characterized the isotype/subclass profiles of the anti-GnRH humoral response generated by the vaccination and analyzed its association with patients' clinical outcomes. METHODS: The immunoglobulin isotypes and IgG subclasses of the antibody responses of 34 patients included in a randomized, open, prospective phase I/II clinical trial were characterized. Every patient included in the study had a diagnosis of locally advanced prostate adenocarcinoma at stages 3 and 4 and received immunization with the vaccine candidate. Additionally, serum testosterone and prostate specific antigen (PSA) concentrations, serving as indicators of tumor response, were determined. The type of anti-GnRH antibody response was correlated to the time elapsed until the first biochemical recurrence in patients and the outcome of the disease. RESULTS: All patients developed strong and prolonged anti-GnRH antibody responses, resulting in a short- to mid-term decrease in serum testosterone and PSA levels. Following immunizations, anti-GnRH antibodies of the IgM/IgG and IgG1/IgG3 subclasses were observed. Following radiotherapy, the humoral response switched to IgG (IgG1/IgG4). Patients who experienced a short-term biochemical relapse were characterized by significantly higher levels of anti-GnRH IgG titers, particularly IgG1 and IgG4 subclasses. These characteristics, along with a high response of specific IgM antibodies at the end of immunizations and the development of anti-GnRH IgA antibody responses following radiotherapy, were observed in patients whose disease progressed, compared to those with controlled disease. CONCLUSION: The nature of the humoral response against anti-GnRH, induced by vaccination may play a key role in activating additional immunological mechanisms. Collectively, these mechanisms could contribute significantly to the regulation of tumor growth.
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Adenocarcinoma , Neoplasias de la Próstata , Vacunas , Masculino , Humanos , Hormona Liberadora de Gonadotropina , Antígeno Prostático Específico , Estudios Prospectivos , Próstata , Recurrencia Local de Neoplasia , Inmunización , Neoplasias de la Próstata/terapia , Vacunación , Inmunoglobulina G , Testosterona , Castración , Adenocarcinoma/terapia , Inmunoglobulina MRESUMEN
With their distinctive physicochemical features, nanoparticles have gained recognition as effective multifunctional tools for biomedical applications, with designs and compositions tailored for specific uses. Notably, magnetic nanoparticles stand out as first-in-class examples of multiple modalities provided by the iron-based composition. They have long been exploited as contrast agents for magnetic resonance imaging (MRI) or as anti-cancer agents generating therapeutic hyperthermia through high-frequency magnetic field application, known as magnetic hyperthermia (MHT). This review focuses on two more recent applications in oncology using iron-based nanomaterials: photothermal therapy (PTT) and ferroptosis. In PTT, the iron oxide core responds to a near-infrared (NIR) excitation and generates heat in its surrounding area, rivaling the efficiency of plasmonic gold-standard nanoparticles. This opens up the possibility of a dual MHT + PTT approach using a single nanomaterial. Moreover, the iron composition of magnetic nanoparticles can be harnessed as a chemotherapeutic asset. Degradation in the intracellular environment triggers the release of iron ions, which can stimulate the production of reactive oxygen species (ROS) and induce cancer cell death through ferroptosis. Consequently, this review emphasizes these emerging physical and chemical approaches for anti-cancer therapy facilitated by magnetic nanoparticles, combining all-in-one functionalities.
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Hipertermia Inducida , Nanopartículas de Magnetita , Fotoquimioterapia , Fototerapia/métodos , Hipertermia Inducida/métodos , Nanopartículas de Magnetita/uso terapéutico , Nanopartículas de Magnetita/química , Fotoquimioterapia/métodos , HierroRESUMEN
Benzydamine is an active pharmaceutical compound used in the oral care pharmaceutical preparation as NSAID. Beside from its anti-inflammatory action, benzydamine local application effectively reliefs pain showing analgesic and anaesthetic properties. Benzydamine mechanism of action has been characterized on inflammatory cell types and mediators highlighting its capacity to inhibit pro-inflammatory mediators' synthesis and release. On the other hand, the role of benzydamine as neuronal excitability modulator has not yet fully explored. Thus, we studied benzydamine's effect over primary cultured DRG nociceptors excitability and after acute and chronic inflammatory sensitization, as a model to evaluate relative nociceptive response. Benzydamine demonstrated to effectively inhibit neuronal basal excitability reducing its firing frequency and increasing rheobase and afterhyperpolarization amplitude. Its effect was time and dose-dependent. At higher doses, benzydamine induced changes in action potential wavelength, decreasing its height and slightly increasing its duration. Moreover, the compound reduced neuronal acute and chronic inflammatory sensitization. It inhibited neuronal excitability mediated either by an inflammatory cocktail, acidic pH or high external KCl. Notably, higher potency was evidenced under inflammatory sensitized conditions. This effect could be explained either by modulation of inflammatory and/or neuronal sensitizing signalling cascades or by direct modulation of proalgesic and action potential firing initiating ion channels. Apparently, the compound inhibited Nav1.8 channel but had no effect over Kv7.2, Kv7.3, TRPV1 and TRPA1. In conclusion, the obtained results strengthen the analgesic and anti-inflammatory effect of benzydamine, highlighting its mode of action on local pain and inflammatory signalling.
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Bencidamina , Humanos , Bencidamina/metabolismo , Bencidamina/farmacología , Bencidamina/uso terapéutico , Dolor/tratamiento farmacológico , Dolor/metabolismo , Nociceptores/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Antiinflamatorios/uso terapéutico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Analgésicos/metabolismoRESUMEN
The new and unique possibilities that nanomaterials offer have greatly impacted biomedicine, from the treatment and diagnosis of diseases, to the specific and optimized delivery of therapeutic agents. Technological advances in the synthesis, characterization, standardization, and therapeutic performance of nanoparticles have enabled the approval of several nanomedicines and novel applications. Discoveries continue to rise exponentially in all disease areas, from cancer to neurodegenerative diseases. In Spain, there is a substantial net of researchers involved in the development of nanodiagnostics and nanomedicines. In this review, we summarize the state of the art of nanotechnology, focusing on nanoparticles, for the treatment of diseases in Spain (2017-2022), and give a perspective on the future trends and direction that nanomedicine research is taking.
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Ag2 S nanoparticles (NPs) emerge as a unique system that simultaneously features in vivo near-infrared (NIR) imaging, remote heating, and low toxicity thermal sensing. In this work, their capabilities are extended into the fields of optical coherence tomography (OCT), as contrast agents, and NIR probes in both ex vivo and in vivo experiments in eyeballs. The new dual property for ocular imaging is obtained by the preparation of Ag2 S NPs ensembles with a biocompatible amphiphilic block copolymer. Rather than a classical ligand exchange, where surface traps may arise due to incomplete replacement of surface sites, the use of this polymer provides a protective extra layer that preserves the photoluminescence properties of the NPs, and the procedure allows for the controlled preparation of submicrometric scattering centers. The resulting NPs ensembles show extraordinary colloidal stability with time and biocompatibility, enhancing the contrast in OCT with simultaneous NIR imaging in the second biological window.
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Nanopartículas , Tomografía de Coherencia Óptica , Medios de Contraste , Polímeros , Imagen ÓpticaRESUMEN
In this paper, the performance of ladle furnace slag (LFS), a by-product of secondary steel refining, is evaluated as a binder to stabilize clayey soils of low bearing capacity. The aim is to define whether additions of this by-product to clayey soil can stabilize the soil in accordance with the technical specifications of Spanish standards. To do so, three different soils stabilized with 5% LFS were compared with the same soils stabilized with 2% lime and with no stabilization, in order to investigate their different behaviors. The chemical and mineralogical characterizations of all the soil mixes were conducted using X-ray fluorescence, X-ray diffraction, and scanning electron microscopy. The Atterberg limit test was used to study the plastic behavior of the soils, and the results of compaction, bearing capacity, unconfined compressive strength, and direct shear strength (cohesion and friction angle) tests defined their strength characteristics. The analysis was completed with the pH monitoring of the mixes along the curing time in order to relate the pH changes with the strength evolution. The addition of LFS to the soils has resulted in an increase in the liquid limit and plastic limit, causing therefore a slight decrease in the plasticity index. All the soils showed increases between 30% and 70% in their California Bearing Ratios immediately after mixing with 5% LFS, and after 90 days of curing, improvements of 30-188% in their unconfined compressive strength were noted in comparison with untreated soil, which were higher than the lime-stabilized soils. The cohesion of soils stabilized with LFS at 28 days of curing obtained improvements ranging from 40 to 300% depending on the type of soil. However, the friction angle showed a slight increase of 10% in two of the soils and zero in another. The high initial pH in LFS-stabilized soils was maintained during the curing time, which favored the development of pozzolanic reactions that improve the soil strength. These results confirmed that the substitution of lime with LFS is a feasible option for soil stabilization.