Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 332
Filtrar
1.
Spectrochim Acta A Mol Biomol Spectrosc ; 323: 124926, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39116593

RESUMEN

Lanthanide photoluminescence (PL) emission has attracted much attention for technological and bioimaging applications because of its particularly interesting features, such as narrow emission bands and very long PL lifetimes. However, this emission process necessitates a preceding step of energy transfer from suitable antennas. While biocompatible applications require luminophores that are stable in aqueous media, most lanthanide-based emitters are quenched by water molecules. Previously, we described a small luminophore, 8-methoxy-2-oxo-1,2,4,5-tetrahydrocyclopenta[de]quinoline-3-phosphonic acid (PAnt), which is capable of dynamically coordinating with Tb(III) and Eu(III), and its exchangeable behavior improved their performance in PL lifetime imaging microscopy (PLIM) compared with conventional lanthanide cryptate imaging agents. Herein, we report an in-depth photophysical and time-dependent density functional theory (TD-DFT) computational study that reveals different sensitization mechanisms for Eu(III) and Tb(III) in stable complexes formed in water. Understanding this unique behavior in aqueous media enables the exploration of different applications in bioimaging or novel emitting materials.

2.
bioRxiv ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39091814

RESUMEN

Biallelic pathogenic variants in the essential DNA repair gene BRCA2 causes Fanconi anemia, complementation group FA-D1. Patients in this group are highly prone to develop embryonal tumors, most commonly medulloblastoma arising from the cerebellar granule cell progenitors (GCPs). GCPs undergo high proliferation in the postnatal cerebellum under SHH activation, but the type of DNA lesions that require the function of the BRCA2 to prevent tumorigenesis remains unknown. To identify such lesions, we assessed both GCP neurodevelopment and tumor formation using a mouse model with deletion of exons three and four of Brca2 in the central nervous system, coupled with global Trp53 loss. Brca2 Δex3-4 ;Trp53 -/- animals developed SHH subgroup medulloblastomas with complete penetrance. Whole-genome sequencing of the tumors identified structural variants with breakpoints enriched in areas overlapping G-quadruplexes (G4s). Brca2-deficient GCPs exhibited decreased replication speed in the presence of the G4-stabilizer pyridostatin. Pif1 helicase, which resolves G4s during replication, was highly upregulated in tumors, and Pif1 knockout in primary MB tumor cells resulted in increased genome instability upon pyridostatin treatment. These data suggest that G4s may represent sites prone to replication stalling in highly proliferative GCPs and without BRCA2, G4s become a source of genome instability. Tumor cells upregulate G4-resolving helicases to facilitate rapid proliferation through G4s highlighting PIF1 helicase as a potential therapeutic target for treatment of BRCA2-deficient medulloblastomas.

3.
Trials ; 25(1): 481, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014430

RESUMEN

BACKGROUND: In standard weaning from mechanical ventilation, a successful spontaneous breathing test (SBT) consisting of 30 min 8 cmH2O pressure-support ventilation (PSV8) without positive end-expiratory pressure (PEEP) is followed by extubation with continuous suctioning; however, these practices might promote derecruitment. Evidence supports the feasibility and safety of extubation without suctioning. Ultrasound can assess lung aeration and respiratory muscles. We hypothesize that weaning aiming to preserve lung volume can yield higher rates of successful extubation. METHODS: This multicenter superiority trial will randomly assign eligible patients to receive either standard weaning [SBT: 30-min PSV8 without PEEP followed by extubation with continuous suctioning] or lung-volume-preservation weaning [SBT: 30-min PSV8 + 5 cmH2O PEEP followed by extubation with positive pressure without suctioning]. We will compare the rates of successful extubation and reintubation, ICU and hospital stays, and ultrasound measurements of the volume of aerated lung (modified lung ultrasound score), diaphragm and intercostal muscle thickness, and thickening fraction before and after successful or failed SBT. Patients will be followed for 90 days after randomization. DISCUSSION: We aim to recruit a large sample of representative patients (N = 1600). Our study cannot elucidate the specific effects of PEEP during SBT and of positive pressure during extubation; the results will show the joint effects derived from the synergy of these two factors. Although universal ultrasound monitoring of lungs, diaphragm, and intercostal muscles throughout weaning is unfeasible, if derecruitment is a major cause of weaning failure, ultrasound may help clinicians decide about extubation in high-risk and borderline patients. TRIAL REGISTRATION: The Research Ethics Committee (CEIm) of the Fundació Unió Catalana d'Hospitals approved the study (CEI 22/67 and 23/26). Registered at ClinicalTrials.gov in August 2023. Identifier: NCT05526053.


Asunto(s)
Extubación Traqueal , Pulmón , Estudios Multicéntricos como Asunto , Respiración con Presión Positiva , Desconexión del Ventilador , Humanos , Desconexión del Ventilador/métodos , Respiración con Presión Positiva/métodos , Respiración con Presión Positiva/efectos adversos , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Mediciones del Volumen Pulmonar , Ultrasonografía , Resultado del Tratamiento , Masculino , Factores de Tiempo , Femenino , Adulto , Persona de Mediana Edad , Respiración Artificial/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Anciano , Succión/métodos , Estudios de Equivalencia como Asunto
4.
Sports (Basel) ; 12(7)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39058082

RESUMEN

In the school context, the teacher-student interaction style plays a pivotal role in ensuring optimal adolescent functioning. Over recent years, the significance of transformational teacher leadership in fostering student engagement and positive development has been underscored. This study aimed to examine the correlations between transformational leadership and adolescent self-esteem, motor self-efficacy, enjoyment in physical education classes, and intention for future physical activity. This research used an associative and predictive strategy. A total of 429 adolescents from Málaga, aged between 14 and 16 years (M = 14.97; SD = 0.85), participated in this research, which employed an associative, comparative, and predictive approach. The Transformational Teaching Questionnaire (TTQ), Motor Self-Efficacy Scale (MSES), Intrinsic Satisfaction in Sport Instrument (SSI-EF), and Intention of Being Physically Active Scale (MIFA) were utilized for variable assessment. Correlation, Multiple Regression, and cluster analyses revealed statistically significant correlations between transformational leadership and self-esteem, motor self-efficacy, enjoyment, and future activity intention. Specifically, it was revealed that motivational inspiration predicts self-esteem, motor self-efficacy, enjoyment, and intention for physical activity, whereas intellectual stimulation predicts motor self-efficacy, enjoyment, and intention for physical activity. Notably, the transformational leadership factors of intellectual stimulation and motivational inspiration were observed to predict scores across other variables, particularly enjoyment in physical education classes, both overall and by gender. These findings suggest that transformational leadership in physical education classes can significantly enhance student experiences, thereby promoting adherence to physical activity and healthy lifestyles among adolescents.

5.
Reprod Sci ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862859

RESUMEN

To compare effectiveness and safety of the Cook's balloon with vaginal dinoprostone to induce labor in patients with previous cesarean section. Observational, and retrospective study that included pregnant women at ≥ 37 weeks' gestation, with unfavorable cervix, singleton pregnancy, intact membranes, and a previous cesarean section, who had undergone labor induction in the period 2014-2019. 170 patients (86 balloon-84 dinoprostone) were analyzed. The proportion of women achieving vaginal delivery within 24 h was higher in the dinoprostone than in double-balloon group (RR, 3.24; 95% CI, 1.36-7.72). No significant differences were detected in the first 48 h in vaginal deliveries (P = .749) or in cesarean section rates (P = .634). Nor were there differences in maternal or fetal safety profiles. A body mass index > 35 increased the risk of cesarean section by 1.53 times (P = .017) and a Bishop's test score < 3 by 1.91 times (P = .009). A vaginal delivery following a cesarean section decreased the probability of another cesarean section by 0.46 times (P = .039). Labor induction with vaginal dinoprostone achieves better vaginal delivery rates in the first 24 h vs Cook's balloon. While the difference in uterine rupture rate did not reach significance, this was higher in women receiving prostaglandin.

6.
Semin Arthritis Rheum ; 68: 152470, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38924926

RESUMEN

BACKGROUND/AIM: The appropriate sonographic protocol for assessing urate crystal deposits in asymptomatic hyperuricemia (AH) is undefined, as well as how the choice would impact on deposit rates and accompanying sonographic, clinical and laboratory features. METHODS: Patients with AH (serum urate ≥7 mg/dL) underwent musculoskeletal ultrasound of 10 locations for OMERACT elementary gout lesions (double contour [DC] signs, tophi, aggregates). Different definitions for AH with deposits were applied, varying according to deposits (any deposits; only DC and/or tophi); gradation (any grade; only grade 2-3 deposits), location (10 locations; 4-joint scheme including knees and 1MTPs; >1 location with deposits), or pre-defined definitions (DC sign in femoral condyles/1MTP and/or tophi in 1MTP). We evaluated crystal deposits rates and compared between other sonographic features, clinical and laboratory variables. RESULTS: Seventy-seven participants with AH showed a median 1 location (IQR 0-2) with tophi, 1 (IQR 1-2) with aggregates, and 0 locations (IQR 0-1) with DC sign. The deposition rate ranged from 23.4% (in >1 location with grade 2-3 DC or tophi) to 87.0% (in any deposit in all 10 locations). Accompanying inflammation - assessed by a positive power-Doppler (PD) signal - and erosions were found in 19.5% and 28.4% of participants, respectively. Positive PD signal was better discriminated by criteria requiring grade 2-3 or >1 location with lesions. Erosions and the different clinical and laboratory variables were similar among protocols. CONCLUSION: Rates of sonographic deposition in AH varied dramatically among studied protocols, while some could discriminate accompanying inflammation, all highlighting the need for a validated, consensus-based definition.

7.
Neurosurg Rev ; 47(1): 201, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695962

RESUMEN

Optimizing the treatment of hydrocephalus remains a major challenge in adult and pediatric neurosurgery. Currently, clinical treatment relies heavily on anatomic imaging of ventricular size and clinical presentation. The emergence of functional and structural brain connectivity imaging has provided the basis for a new paradigm in the management of hydrocephalus. Here we review the pertinent advances in this field. Following PRISMA-ScR guidelines for scoping reviews, we searched PubMed for relevant literature from 1994 to April 2023 using hydrocephalus and MRI-related terms. Included articles reported original MRI data on human subjects with hydrocephalus, while excluding non-English or pre-1994 publications that didn't match the study framework. The review identified 44 studies that investigated functional and/or structural connectivity using various MRI techniques across different hydrocephalus populations. While there is significant heterogeneity in imaging technology and connectivity analysis, there is broad consensus in the literature that 1) hydrocephalus is associated with disruption of functional and structural connectivity, 2) this disruption in cerebral connectivity can be further associated with neurologic compromise 3) timely treatment of hydrocephalus restores both cerebral connectivity and neurologic compromise. The robustness and consistency of these findings vary as a function of patient age, hydrocephalus etiology, and the connectivity region of interest studied. Functional and structural brain connectivity imaging shows potential as an imaging biomarker that may facilitate optimization of hydrocephalus treatment. Future research should focus on standardizing regions of interest as well as identifying connectivity analysis most pertinent to clinical outcome.


Asunto(s)
Hidrocefalia , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patología
8.
Physiol Rep ; 12(10): e16056, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38777811

RESUMEN

Permeability transition pore (PTP) opening dissipates ion and electron gradients across the internal mitochondrial membrane (IMM), including excess Ca2+ in the mitochondrial matrix. After opening, immediate PTP closure must follow to prevent outer membrane disruption, loss of cytochrome c, and eventual apoptosis. Flickering, defined as the rapid alternative opening/closing of PTP, has been reported in heart, which undergoes frequent, large variations in Ca2+. In contrast, in tissues that undergo depolarization events less often, such as the liver, PTP would not need to be as dynamic and thus these tissues would not be as resistant to stress. To evaluate this idea, it was decided to follow the reversibility of the permeability transition (PT) in isolated murine mitochondria from two different tissues: the very dynamic heart, and the liver, which suffers depolarizations less frequently. It was observed that in heart mitochondria PT remained reversible for longer periods and at higher Ca2+ loads than in liver mitochondria. In all cases, Ca2+ uptake was inhibited by ruthenium red and PT was delayed by Cyclosporine A. Characterization of this phenomenon included measuring the rate of oxygen consumption, organelle swelling and Ca2+ uptake and retention. Results strongly suggest that there are tissue-specific differences in PTP physiology, as it resists many more Ca2+ additions before opening in a highly active organ such as the heart than in an organ that seldom suffers Ca2+ loading, such as the liver.


Asunto(s)
Calcio , Mitocondrias Cardíacas , Mitocondrias Hepáticas , Proteínas de Transporte de Membrana Mitocondrial , Poro de Transición de la Permeabilidad Mitocondrial , Ratas Wistar , Animales , Poro de Transición de la Permeabilidad Mitocondrial/metabolismo , Masculino , Calcio/metabolismo , Mitocondrias Cardíacas/metabolismo , Mitocondrias Hepáticas/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Ratas , Consumo de Oxígeno , Hígado/metabolismo , Dilatación Mitocondrial/efectos de los fármacos , Ciclosporina/farmacología
9.
RMD Open ; 10(2)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38631846

RESUMEN

OBJECTIVE: To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients. METHODS: Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3). RESULTS: Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p<0.001). SCORE, mSCORE EULAR 2015/2016 and QRISK3 effectively differentiated between low and high CV risk patients, although the cumulative rate of CV events observed over 7.5 years was lower than expected based on the frequency predicted by these risk scales. Additionally, model improvement was observed when combining QRISK3 with any other scale, particularly the combination of QRISK3 and SCORE2, which yielded the lowest Akaike information criterion (411.15) and Bayesian information criterion (420.10), making it the best predictive model. CONCLUSIONS: Risk chart algorithms are very useful for discriminating PsA at low and high CV risk. An integrated model featuring QRISK3 and SCORE2 yielded the optimal synergy of QRISK3's discrimination ability and SCORE2's calibration accuracy.


Asunto(s)
Artritis Psoriásica , Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/complicaciones , Estudios Prospectivos , Estudios Retrospectivos , Artritis Psoriásica/complicaciones , Teorema de Bayes , Estudios de Seguimiento , Algoritmos
10.
Environ Sci Pollut Res Int ; 31(21): 31213-31223, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38625470

RESUMEN

The establishment of sulfate (SO42-) reduction during methanogenesis may considerably hinder the efficient energetic exploitation of methane, once removing sulfide from biogas is obligate and can be costly. In addition, sulfide generation can negatively impact the performance of methanogens by triggering substrate competition and sulfide inhibition. This study investigated the impacts of removing SO42- during fermentation on the performance of a second-stage methanogenic continuous reactor (R2), comparing the results with those obtained in a single-stage system (R1) fed with SO42--rich wastewater (SO42- of up to 400 mg L-1, COD/SO42- of 3.12-12.50). The organic load (OL) was progressively increased to 5.0 g COD d-1 in both reactors, showing completely discrepant performances. Sulfate-reducing bacteria outperformed methanogens in the consumption for organic matter during the start-up phase (OL = 2.5 g COD d-1) in R1, directing up to 73% of the electron flow to SO42- reduction. An efficient methanogenic activity was established in R1 only after decreasing the OL to 0.625 g COD d-1, after which methanogenesis prevailed by consuming ca. 90% of the removed COD. Nevertheless, high sulfide proportions (up to 3.1%) were measured in biogas. Conversely, methanogenesis was promptly established in R2, resulting in a methane-rich (> 80%) and sulfide-free biogas regardless of the operating condition. From an economic perspective, processing the biogas evolved from R2 would be cheaper, although the techno-economic impacts of managing the sulfur pollution in the fermentative reactor still need to be understood.


Asunto(s)
Reactores Biológicos , Metano , Sulfuros , Metano/metabolismo , Aguas Residuales/química , Sulfatos/metabolismo , Separación de Fases
11.
Front Plant Sci ; 15: 1353991, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38463568

RESUMEN

Patterns of genetic variation in crops are the result of multiple processes that have occurred during their domestication and improvement, and are influenced by their wild progenitors that often remain understudied. The locoto chile, Capsicum pubescens, is a crop grown mainly in mid-highlands of South-Central America. This species is not known from the wild and exists only as a cultigen. The evolutionary affinities and exact origin of C. pubescens have still not been elucidated, with hypotheses suggesting its genetic relatedness and origin to two wild putative ancestral Capsicum species from the Central Andes, C. eximium and C. cardenasii. In the current study, RAD-sequencing was applied to obtain genome-wide data for 48 individuals of C. pubescens and its wild allies representing different geographical areas. Bayesian, Maximum Likelihood and coalescent-based analytical approaches were used to reconstruct population genetic patterns and phylogenetic relationships of the studied species. The results revealed that C. pubescens forms a well-defined monotypic lineage closely related to wild C. cardenasii and C. eximium, and also to C. eshbaughii. The primary lineages associated with the diversification under domestication of C. pubescens were also identified. Although direct ancestor-descendant relationship could not be inferred within this group of taxa, hybridization events were detected between C. pubescens and both C. cardenasii and C. eximium. Therefore, although hybrid origin of C. pubescens could not be inferred, gene flow involving its wild siblings was shown to be an important factor contributing to its contemporary genetic diversity. The data allowed for the inference of the center of origin of C. pubescens in central-western Bolivia highlands and for better understanding of the dynamics of its gene pool. The results of this study are essential for germplasm conservation and breeding purposes, and provide excellent basis for further research of the locoto chile and its wild relatives.

12.
Waste Manag ; 179: 192-204, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38484540

RESUMEN

Research to prevent releases of brominated flame retardants listed as persistent organic pollutants by the Stockholm Convention (POP-BFRs) was conducted through an international cooperation project in Colombia. Six waste electrical and electronic equipment (WEEE) management facilities implemented: 1) sorting e-waste by product type and color (black, white, and other; henceforth called chromoproducts), 2) sampling test products and their plastic fraction (called sets, separated by polymer type), 3) monitoring mass, bromine and antimony contents by hand-held X-ray fluorescence (XRF) and POP-BFRs such as polybrominated diphenyl ethers (PBDEs) by gas chromatography and mass spectrometry (GC-MS), and 4) differentiated treatment according to categories that used the Restriction of Hazardous Substances in Electrical and Electronic Equipment Directive (RoHS) hazardousness threshold of 1000 mg ∑PBDEs/kg. This scheme led to the proposal of a methodology for WEEE management called the "chromoproduct approach". 994,230 products were managed and grouped into 222 chromoproducts, from which 77 were analyzed: 50 below RoHS hazardousness (BRH), 16 above RoHS hazardousness (ARH), and 11 unknown RoHS hazardousness (URH). XRF indicators using bromine and antimony contents could rule out pollution in BRH chromoproducts; however, categorization still required GC-MS. One ARH plastics sample had 3620 mg ∑PBDEs/kg, while no POP-BFRs were found in the BRH plastics sample. The implementation of the chromoproduct approach traced 153.6 tonnes of ARH plastics. BRH plastics composition was estimated and used in a pilot-scale closed-loop economic activity. The chromoproduct approach seems promising for avoiding POP-BFR releases and promoting the upcycling of recyclable e-waste plastics.


Asunto(s)
Residuos Electrónicos , Retardadores de Llama , Plásticos/análisis , Residuos Electrónicos/análisis , Colombia , Antimonio/análisis , Bromo/análisis , Residuos/análisis , Retardadores de Llama/análisis , Éteres Difenilos Halogenados/análisis
13.
Int J Mol Sci ; 25(5)2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38474267

RESUMEN

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.


Asunto(s)
Lupus Eritematoso Sistémico , Humanos , Estudios Transversales , Biomarcadores , Complemento C4 , Índice de Severidad de la Enfermedad , Productos Finales de Glicación Avanzada
14.
Genome Biol ; 25(1): 68, 2024 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-38468286

RESUMEN

BACKGROUND: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. RESULTS: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.


Asunto(s)
Artritis Reumatoide , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Membrana Sinovial , Linfocitos B , Factor de Necrosis Tumoral alfa , Fenotipo
15.
Biomedicines ; 12(3)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38540223

RESUMEN

It has been postulated that advanced glycation end products (AGEs) and their soluble receptor (sRAGE) may play a relevant role as inducers in the chronic inflammatory pathway in various conditions, among them, in immune-mediated diseases such as systemic lupus erythematosus (SLE). However, previous studies show conflicting results about their association with SLE characteristics and their usefulness as disease biomarkers. We aimed to study the association of specific serum AGEs (pentosidine, Nξ-(carboxymethyl)lysine (CML), Nξ-(carboxyethyl)lysine (CEL)), sRAGE levels and AGEs (specific serum AGEs and skin AGEs) to sRAGE ratios with various disease parameters, in order to clarify their potential as new biomarkers in SLE and to study their relationship with cardiovascular disease (CVD). To this aim, serum pentosidine, CML, CEL and sRAGE were measured via ELISA, and skin AGEs levels were measured by skin autofluorescence. Correlations of pentosidine levels with demographic and clinical data, indexes of activity, accrual damage and patient-reported outcomes were analyzed through multiple linear regression models, while correlations of the rest of the AGEs, sRAGE and AGE to sRAGE ratios (non-normal) were analyzed using both an OLS regression model and a GML. All of the analyses were adjusted for confounders. A total of 119 SLE patients were recruited. Serum AGEs and sRAGEs were significantly associated with SLE activity indexes and/or demographic or disease characteristics: pentosidine with pulmonary manifestations; CML with anti-dsDNA antibodies, IL-6, disease duration and non-Caucasian ethnicities; CEL with anti-dsDNA antibodies, IL-6 and accumulated number of manifestations; and sRAGE with male gender, photosensitivity and being on specific immunosuppressants. These results suggest that the AGE-sRAGE axis may serve as a novel biomarker for managing and prognosticating this disease. Its correlation with certain antibodies, demographics and disease presentations may indicate a distinct clinical phenotype associated with varying levels of AGEs and/or sRAGE. The significance of specific AGE/sRAGE ratios, introduced in this study for the first time, warrants additional investigation in forthcoming research. Our study did not confirm the link between serum AGEs and CVD, which merits further exploration through studies designed for this specific purpose.

16.
J Neurosurg Pediatr ; 33(6): 574-582, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38489810

RESUMEN

OBJECTIVE: Craniovertebral junction (CVJ) abnormalities are common and well documented in mucopolysaccharidosis type I-Hurler syndrome (MPS IH), often causing severe spinal canal narrowing. However, the requirement for surgical decompression and/or fusion is uncommon. Although hematopoietic cell transplant (HCT) has been shown to prolong the lives of patients with MPS IH, its effect in halting or reversing musculoskeletal abnormalities is less clear. Unfortunately, there are currently no universal guidelines for imaging or indication for surgical interventions in these patients. The goal of this study was to track the progression of the CVJ anatomy in patients with MPS IH following HCT, and to examine radiographic features in patients who needed surgical intervention. METHODS: Patients with MPS IH treated at the University of Minnesota with allogeneic HCT between 2008 and 2020 were retrospectively reviewed. Patients who underwent CVJ surgery were identified with chart review. All MPS IH cervical scans were examined, and the odontoid retroflexion angle, clivoaxial angle (CXA), canal width, and Grabb-Oakes distance (pB-C2) were measured yearly for up to 7 years after HCT. Longitudinal models based on the measurements were made. An intraclass correlation coefficient was used to measure interrater reliability. Nine children without MPS IH were examined for control CVJ measurements. RESULTS: A total of 253 cervical spine MRI scans were reviewed in 54 patients with MPS IH. Only 4 (7.4%) patients in the study cohort required surgery. Three of them had posterior fossa and C1 decompression, and 1 had a C1-2 fusion. There was no statistically significant difference in the spinal parameters that were examined between surgery and nonsurgery groups. Among the measurements, canal width and CXA varied drastically in patients with different neck positions. Odontoid retroflexion angle and CXA tended to decrease with age. Canal width and pB-C2 tended to increase with age. CONCLUSIONS: Based on the data, the authors observed an increase in canal width and pB-C2, whereas the CXA and odontoid retroflexion angle became more acute as the patients aged after HCT. The longitudinal models derived from these data mirrored the development in children without MPS IH. Spinal measurements obtained on MR images alone are not sufficient in identifying patients who require surgical intervention. Symptom monitoring and clinical examination, as well as pathological spinal cord changes on MRI, are more crucial in assessing the need for surgery than is obtaining serial imaging.


Asunto(s)
Mucopolisacaridosis I , Humanos , Masculino , Femenino , Mucopolisacaridosis I/complicaciones , Mucopolisacaridosis I/cirugía , Mucopolisacaridosis I/diagnóstico por imagen , Mucopolisacaridosis I/patología , Preescolar , Niño , Estudios Retrospectivos , Adolescente , Lactante , Trasplante de Células Madre Hematopoyéticas , Descompresión Quirúrgica/métodos , Progresión de la Enfermedad , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Adulto Joven
17.
Biomater Adv ; 159: 213826, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38479241

RESUMEN

Thermosensitive hydrogels based on the N-vinyl caprolactam (VCL), capable of allowing for cell adhesion and proliferation, as well as non-aggressive detachment by controlled temperature drop, were functionalized with 23 % or lower molar percentages of the cationizable hydrophobic unit 2-(diisopropylamino) ethyl methacrylate (DPAEMA), to obtain networks with dual sensitivity to temperature and pH. The swelling analysis of the systems has shown a transition pK (pKb) close to physiological values, dependent on the temperature of the medium (pKb of 6.6 and 6.9 when the temperature of the medium is above and below the transition temperature VPTT, respectively) and little dependence on the degree of functionalization of DPAEMA. In addition, at temperatures below the transition temperature (VPTT), the systems have shown large swelling variations as a function of the pH (i.e. below and above the pKb), exhibiting greater absorption capacity at pHs below pKb, where the DPAEMA units are cationized. Cytocompatibility and transplant capacity have been evaluated using the C166-GFP endothelial cell line. None of the thermosensitive hydrogels with variable DPAEMA content showed a delay with respect to the control without DPAEMA neither in terms of adhesion nor in proliferation. However, by increasing the percentage of DPAEMA functionalization -and decreasing thermosensitivity-, a correlative decrease in mitochondrial activity was obtained in the transplant, with significant differences for the hydrogels with DPAEMA molar percentage of 3 % or higher. Taking advantage of the proximity of the pKb to the physiological value, we have evaluated the cellular response and the capacity for transplantation after lowering the pH to 6.5, below pKb. A direct relationship of the DPAEMA functionalization degree on the detachment efficiency was observed, since the hydrogels with the highest molar load of DPAEMA showed higher mitochondrial metabolic activity after cell detachment.


Asunto(s)
Hidrogeles , Metacrilatos , Temperatura , Línea Celular , Metacrilatos/farmacología , Metacrilatos/química , Interacciones Hidrofóbicas e Hidrofílicas
19.
Angew Chem Int Ed Engl ; 63(6): e202314595, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-37991081

RESUMEN

Lanthanides have unique photoluminescence (PL) emission properties, including very long PL lifetimes. This makes them ideal for biological imaging applications, especially using PL lifetime imaging microscopy (PLIM). PLIM is an inherently multidimensional technique with exceptional advantages for quantitative biological imaging. Unfortunately, due to the required prolonged acquisitions times, photobleaching of lanthanide PL emission currently constitutes one of the main drawbacks of PLIM. In this study, we report a small aqueous-soluble, lanthanide antenna, 8-methoxy-2-oxo-1,2,4,5-tetrahydrocyclopenta[de]quinoline-3-phosphonic acid, PAnt, specifically designed to dynamically interact with lanthanide ions, serving as exchangeable dye aimed at mitigating photobleaching in PLIM microscopy in cellulo. Thus, self-assembled lanthanide complexes that may be photobleached during image acquisition are continuously replenished by intact lanthanide antennas from a large reservoir. Remarkably, our self-assembled lanthanide complex clearly demonstrated a significant reduction of PL photobleaching when compared to well-established lanthanide cryptates, used for bioimaging. This concept of exchangeable lanthanide antennas opens new possibilities for quantitative PLIM bioimaging.


Asunto(s)
Elementos de la Serie de los Lantanoides , Microscopía , Luminiscencia , Fotoblanqueo
20.
J Hand Ther ; 37(1): 101-109, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37580200

RESUMEN

BACKGROUND: Handgrip strength is a common, simple, and inexpensive method to measure muscle strength. On the other hand, the functional performance measurement involves a usual task which implies repeating elements between the individuals' interaction and the environment. This is fundamental for projecting their results to daily life situation. PURPOSE: To explore the relationship between grip strength and measures of functional performance of the upper limbs (ULs) in people over 18 years of age, and to determine the influence of sociodemographic and anthropometric variables on the relationship. STUDY DESIGN: A cross-sectional study was conducted under the analytical empirical approach, using linear associations between handgrip strength and functional performance measurement tests (correspondence analysis). METHODS: Three hundred sixty-two male and female individuals between 18 and 91 years of age from 4 Colombian cities participated. The grip strength of both ULs measured with a digital dynamometry was associated with the Box and Block Test (BBT, manual dexterity), Nine-Hole Peg Test (NHPT, daily living tasks), and Jebsen-Taylor Hand Function Test (JJT, ability to grasp, pick up, and place). Multiple linear regression analyzes were performed to assess possible explanatory factors of a sociodemographic and anthropometric order. RESULTS: A significant association was found between the grip strength of dominant and non-dominant ULs with all functional performance tests (ρ > 0.27 and p < .001), except for the writing and simulated feeding subtests of the JJT (ρ ≤ 0.16). An interactive effect of age was found in the relationship between grip strength and the 3 functional performance tests. CONCLUSIONS: These results support the association between grip strength with the NHPT, JJT, and BBT measures and the interactive effect of age on the performance of all tests.


Asunto(s)
Fuerza de la Mano , Extremidad Superior , Humanos , Masculino , Femenino , Adolescente , Adulto , Fuerza de la Mano/fisiología , Estudios Transversales , Fuerza Muscular/fisiología , Rendimiento Físico Funcional
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA