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1.
Cancer Epidemiol ; 91: 102608, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38970918

RESUMEN

BACKGROUND: Predictive modelling using pre-epidemic data have long been used to guide public health responses to communicable disease outbreaks and other health disruptions. In this study, cancer registry and related health data available 2-3 months from diagnosis were used to predict changes in cancer detection that otherwise would not have been identified until full registry processing was completed about 18-24 months later. A key question was whether these earlier data could be used to predict cancer incidence ahead of full processing by the cancer registry as a guide to more timely health responses. The setting was the Australian State of New South Wales, covering 31 % of the Australian population. The study year was 2020, the year of emergence of the COVID-19 pandemic. METHODS: Cancer detection in 2020 was modelled using data available 2-3 months after diagnosis. This was compared with data from full registry processing available from 2022. Data from pre-pandemic 2018 were used for exploratory model building. Models were tested using pre-pandemic 2019 data. Candidate predictor variables included pathology, surgery and radiation therapy reports, numbers of breast screens, colonoscopies, PSA tests, and melanoma excisions recorded by the universal Medical Benefits Schedule (MBS). Data were analysed for all cancers collectively and 5 leading types. RESULTS: Compared with full registry processing, modelled data for 2020 had a >95 % accuracy overall, indicating key points of inflexion of cancer detection over the COVID-disrupted 2020 period. These findings highlight the potential of predictive modelling of cancer-related data soon after diagnosis to reveal changes in cancer detection during epidemics and other health disruptions. CONCLUSIONS: Data available 2-3 months from diagnosis in the pandemic year indicated changes in cancer detection that were ultimately confirmed by fully-processed cancer registry data about 24 months later. This indicates the potential utility of using these early data in an early-warning system.


Asunto(s)
COVID-19 , Detección Precoz del Cáncer , Neoplasias , Pandemias , Sistema de Registros , Humanos , COVID-19/epidemiología , COVID-19/diagnóstico , Neoplasias/epidemiología , Neoplasias/diagnóstico , Incidencia , Detección Precoz del Cáncer/estadística & datos numéricos , Detección Precoz del Cáncer/métodos , Femenino , Masculino , SARS-CoV-2/aislamiento & purificación , Australia/epidemiología , Nueva Gales del Sur/epidemiología , Epidemias , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/diagnóstico
2.
RSC Adv ; 14(25): 17507-17518, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38818361

RESUMEN

Water pollution is a global environmental issue, and the presence of pharmaceutical compounds, such as tetracyclines (TCs), in aquatic ecosystems has raised growing concerns due to the potential risks to both the environment and human health. A high surface area CeO2 was prepared via atmospheric thermal treatment of a metal-organic framework of cerium and benzene-1,3,5-tricarboxylate. The effects of calcination temperature on the morphology, structure, light absorption properties and tetracycline removal efficiency were studied. The best activity of the photocatalysts could be achieved when the heat treatment temperature is 300 °C, which enhances the photocatalytic degradation performance towards tetracycline under visible light. The resulting CeO2 particles have high capacity for adsorbing TCs from aqueous solution: 90 mg g-1 for 60 mg L-1 TCs. As a result, 98% of the initial TC can be removed under simulated sunlight irradiation. The cooperation of moderate defect concentration and disordered structure showed tetracycline removal activity about 10 times higher than the initial Ce-MOF. An embryotoxicity assessment on zebrafish revealed that treatment with CeO2 particles significantly decreased the toxicity of TC solutions.

3.
BMJ Open ; 14(5): e082350, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806433

RESUMEN

INTRODUCTION: Radiologist shortages threaten the sustainability of breast cancer screening programmes. Artificial intelligence (AI) products that can interpret mammograms could mitigate this risk. While previous studies have suggested this technology has accuracy comparable to radiologists most have been limited by using 'enriched' datasets and/or not considering the interaction between the algorithm and human readers. This study will address these limitations by comparing the accuracy of a workflow using AI alongside radiologists on a large consecutive cohort of examinations from a breast cancer screening programme. The study will combine the strengths of a large retrospective design with the benefit of prospective data collection. It will test this technology without risk to screening programme participants nor the need to wait for follow-up data. With a sample of 2 years of consecutive screening examinations, it is likely the largest test of this technology to date. The study will help determine whether this technology can safely be introduced into the BreastScreen New South Wales (NSW) population-based screening programme to address radiology workforce risks without compromising cancer detection rates or increasing false-positive recalls. METHODS AND ANALYSIS: A retrospective, consecutive cohort of digital mammography screens from 658 207 examinations from BreastScreen NSW will be reinterpreted by the Lunit Insight MMG AI product. The cohort includes 4383 screen-detected and 1171 interval cancers. The results will be compared with radiologist single reading and the AI results will also be used to replace the second reader in a double-reading model. New adjudication reading will be performed where the AI disagrees with the first reader. Recall rates and cancer detection rates of combined AI-radiologist reading will be compared with the rates obtained at the time of screening. ETHICS AND DISSEMINATION: This study has ethical approval from the NSW Health Population Health Services Research Ethics Committee (2022/ETH02397). Findings will be published in peer-reviewed journals and presented at conferences. The findings of this evaluation will be provided to programme managers, governance bodies and other stakeholders in Australian breast cancer screening programmes.


Asunto(s)
Inteligencia Artificial , Neoplasias de la Mama , Detección Precoz del Cáncer , Mamografía , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico , Femenino , Mamografía/métodos , Nueva Gales del Sur , Detección Precoz del Cáncer/métodos , Estudios Retrospectivos , Tamizaje Masivo/métodos , Persona de Mediana Edad , Proyectos de Investigación
4.
Inorg Chem ; 63(20): 9184-9194, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38722234

RESUMEN

We report a new nickel hydroxyfluoride diaspore Ni(OH)F prepared using hydrothermal synthesis from NiCl2·6H2O and NaF. Magnetic characterization reveals that, contrary to other reported transition-metal hydroxyfluoride diaspores, Ni(OH)F displays weak ferromagnetism below the magnetic ordering temperature. To understand this difference, neutron diffraction is used to determine the long-range magnetic structure. The magnetic structure is found to be distinct from those reported for other hydroxyfluoride diaspores and shows an antiferromagnetic spin ordering in which ferromagnetic canting is allowed by symmetry. Furthermore, neutron powder diffraction on a deuterated sample, Ni(OD)F, reveals partial anion ordering that is distinctive to what has previously been reported for Co(OH)F and Fe(OH)F. Density functional theory calculations show that OH/F ordering can have a directing influence on the lowest energy magnetic ground state. Our results point toward a subtle interplay between the sign of magnetic exchange interactions, the electronic configuration, and anion disordering.

5.
ACS Appl Nano Mater ; 7(9): 10120-10129, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38752019

RESUMEN

Nanostructured niobium-titanium carbonitrides, (Nb,Ti)C1-xNx, with the cubic-rock salt structure are prepared without the use of reactive gases via thermal treatment (700-1200 °C) under nitrogen of mixtures of guanidine carbonate and ammonium niobate (V) oxalate hydrate, with addition of ammonium titanyl oxalate monohydrate as a titanium source. The bulk structure and chemical composition of the materials are characterized using powder X-ray diffraction (XRD) and powder neutron diffraction, elemental homogeneity is studied using energy dispersive spectroscopy (EDS) mapping using transmission electron microscopy (TEM), and surface chemical analysis is examined using X-ray photoelectron spectroscopy (XPS). Nanoscale crystallites of between 10 and 50 nm are observed by TEM, where EDS reveals the homogeneity of metal distribution for the mixed-metal materials. Titanium carbonitrides are found to be air sensitive, reacting with air under ambient conditions, while titanium-niobium carbonitrides are found to degrade in aqueous sulfuric acid. The niobium carbonitrides, however, show some stability toward acidic solutions. Materials are produced with composition NbC1-xNx with x between 0.35 and 0.45, and more carbon-rich materials (x ≈ 0.35) are found as the synthesis temperature is increased, as proven by Rietveld refinement of crystal structure against powder neutron diffraction data. Despite phase purity seen by diffraction and negligible bulk carbon content, XPS shows a complex surface chemistry for the NbC1-xNx materials, with evidence for Nb2O5-like oxide species in a carbon-rich environment. The NbC1-xNx prepared at 900 °C has a surface area around 50 m2 g-1, making it suitable as a catalyst support. Loading with iridium provides a material active for the oxygen evolution reaction in 0.1 M sulfuric acid, with minimal leaching of either Nb or Ir after 1000 cycles.

6.
Artículo en Inglés | MEDLINE | ID: mdl-38661605

RESUMEN

BACKGROUND: Recent clinical studies have indicated the presence of localized electrical abnormalities in idiopathic ventricular fibrillation and J-wave syndrome patients. OBJECTIVES: This study aims to characterize the specific electrical signatures of localized repolarization and conduction heterogeneities and their respective role in vulnerability to arrhythmias. METHODS: Optical mapping was performed in porcine right ventricles with local: 1) repolarization shortening; 2) conduction slowing; or 3) structural heterogeneity induced by locally perfusing: 1) pinacidil (20 µmol/L, n = 13); or 2) flecainide (2 µmol/L, n = 13) via an epicardial catheter; or 3) by local epicardial tissue destruction (9 radiofrequency lesions n = 12). Electrograms were recorded (n = 5 in each group) and spontaneous and induced arrhythmias were quantified and optically mapped. RESULTS: Electrograms were normal in (1) but showed local fragmentation in 40% of preparations in (2) with greater effects observed at high pacing frequencies dependent on the wavefront direction. In (3), the structural substrate alone increased the width and number of peaks in the electrograms, and addition of flecainide induced pronounced fragmentation (≥3 peaks and ≥70 ms) in all cases. Occurrence of spontaneous arrhythmias was significantly increased in (1) and (2) (P < 0.0001 and 0.05, respectively, vs baseline) and were triggered by ectopies. Vulnerability to arrhythmias at high pacing frequencies (≥2 Hz) was the lowest in (1) and greatest in (2). CONCLUSIONS: Microstructural substrates have the most pronounced impact on electrograms, especially when combined with sodium channel blockers, whereas local action potential duration shortening does not lead to electrogram fragmentation even though it is associated with the highest prevalence of spontaneous arrhythmias.

7.
Chem Sci ; 15(12): 4374-4385, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38516069

RESUMEN

We report the first synthesis of the mixed-metal chabazite-type AlxGa1-xPO4-34(mim) solid solution, containing 1-methylimidazolium, mim, as structure directing agent (SDA), from the parent mixed-metal oxide solid solution, γ-(AlxGa1-x)2O3. This hitherto unreported family of materials exhibits complex disorder, arising from the possible distributions of cations over available sites, the orientation of the SDA and the presence of variable amounts of water, which provides a prototype for understanding structural subtleties in nanoporous materials. In the as-made forms of the phosphate frameworks, there are three crystallographically distinct metal sites: two tetrahedral MO4 and one octahedral MO4F2 (M = Al, Ga). A combination of solid-state NMR spectroscopy and periodic DFT calculations reveals that the octahedral site is preferentially occupied by Al and the tetrahedral sites by Ga, leading to a non-random distribution of cations within the framework. Upon calcination to the AlxGa1-xPO4-34 framework, all metal sites are tetrahedral and crystallographically equivalent in the average R3̄ symmetry. The cation distribution was explored by 31P solid-state NMR spectroscopy, and it is shown that the non-random distribution demonstrated to exist in the as-made materials would be expected to give remarkably similar patterns of peak intensities to a random distribution owing to the change in average symmetry in the calcined materials.

8.
Small Methods ; : e2301703, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38461543

RESUMEN

The crystal structures of four coordination polymers constructed from Sn(II) and polydentate carboxylate ligands are reported. All are prepared under hydrothermal conditions in KOH or LiOH solutions (either water or methanol-water) at 130-180 °C and crystallize as small crystals, microns or less in size. Single-crystal structure solution and refinement are performed using synchrotron X-ray diffraction for two materials and using 3D electron diffraction (3DED) for the others. Sn2 (1,3,5-BTC)(OH), where 1,3,5-BTC is benzene-1,3,5-tricarboxylate, is a new polymorph of this composition and has a three-dimensionally connected structure with potential for porosity. Sn(H-1,3,5-BTC) retains a partially protonated ligand and has a 1D chain structure bound by hydrogen bonding via ─COOH groups. Sn(H-1,2,4-BTC) contains an isomeric ligand, benzene-1,2,4-tricarboxylate, and contains inorganic chains in a layered structure held by hydrogen bonding. Sn2 (DOBDC), where DOBDC is 2,5-dioxido-benzene-1,4-dicarboxylate, is a new polymorph for this composition and has a three-dimensionally connected structure where both carboxylate and oxido groups bind to the tin centers to create a dense network with dimers of tin. In all materials, the Sn centers are found in highly asymmetric coordination, as expected for Sn(II). For all materials phase purity of the bulk is confirmed using powder X-ray diffraction, thermogravimetric analysis, and infrared spectroscopy.

9.
Sci Rep ; 14(1): 167, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168512

RESUMEN

Respiratory rate (RR) is a critical vital sign used to assess pulmonary function. Currently, RR estimating instrumentation is specialized and bulky, therefore unsuitable for remote health monitoring. Previously, RR was estimated using proprietary software that extract surface electrocardiogram (ECG) waveform features obtained at several thoracic locations. However, developing a non-proprietary method that uses minimal ECG leads, generally available from mobile cardiac monitors is highly desirable. Here, we introduce an open-source and well-documented Python-based algorithm that estimates RR requiring only single-stream ECG signals. The algorithm was first developed using ECGs from awake, spontaneously breathing adult human subjects. The algorithm-estimated RRs exhibited close linear correlation to the subjects' true RR values demonstrating an R2 of 0.9092 and root mean square error of 2.2 bpm. The algorithm robustness was then tested using ECGs generated by the ischemic hearts of anesthetized, mechanically ventilated sheep. Although the ECG waveforms during ischemia exhibited severe morphologic changes, the algorithm-determined RRs exhibited high fidelity with a resolution of 1 bpm, an absolute error of 0.07 ± 0.07 bpm, and a relative error of 0.67 ± 0.64%. This optimized Python-based RR estimation technique will likely be widely adapted for remote lung function assessment in patients with cardiopulmonary disease.


Asunto(s)
Respiración , Frecuencia Respiratoria , Adulto , Humanos , Animales , Ovinos , Programas Informáticos , Algoritmos , Electrocardiografía , Procesamiento de Señales Asistido por Computador
10.
Cancer ; 130(1): 77-85, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37632356

RESUMEN

BACKGROUND: Women living with mental health conditions may not have shared in improvements in breast cancer screening and care. No studies have directly examined the link between reduced screening participation and breast cancer spread in women using mental health (MH) services. METHODS: Population-wide linkage of a population cancer register, BreastScreen register, and mental health service data set in women aged 50 to 74 years in New South Wales, Australia, from 2008 to 2017. Incident invasive breast cancers were identified. Predictors of degree of spread (local, regional, metastatic) at diagnosis were examined using partial proportional odds regression, adjusting for age, socioeconomic status, rurality, and patterns of screening participation. RESULTS: A total of 29 966 incident cancers were identified and included 686 (2.4%) in women with MH service before cancer diagnoses. More than half of MH service users had regional or metastatic spread at diagnosis (adjusted odds ratio, 1.63; 95% CI, 1.41-1.89). MH service users had lower screening participation; however, advanced cancer was more common even when adjusting for screening status (adjusted odds ratio, 1.53; 95% CI, 1.32-1.77). Advanced cancer was more common in women with severe or persistent MH conditions. CONCLUSIONS: Low screening participation rates explain only small part of the risk of more advanced breast cancer in women who use MH services. More study is needed to understand possible mechanisms contributing to more advanced breast cancer in women living with MH conditions. Health systems need strategies to ensure that women living with MH conditions enjoy population gains in breast cancer outcomes.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Mamografía , Detección Precoz del Cáncer , Australia/epidemiología , Clase Social , Tamizaje Masivo
11.
J Cardiovasc Magn Reson ; 25(1): 78, 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38093273

RESUMEN

BACKGROUND: While the microstructure of the left ventricle (LV) has been largely described, only a few studies investigated the right ventricular insertion point (RVIP). It was accepted that the aggregate cardiomyocytes organization was much more complex due to the intersection of the ventricular cavities but a precise structural characterization in the human heart was lacking even if clinical phenotypes related to right ventricular wall stress or arrhythmia were observed in this region. METHODS: MRI-derived anatomical imaging (150 µm3) and diffusion tensor imaging (600 µm3) were performed in large mammalian whole hearts (human: N = 5, sheep: N = 5). Fractional anisotropy, aggregate cardiomyocytes orientations and tractography were compared within both species. Aggregate cardiomyocytes orientation on one ex-vivo sheep whole heart was then computed using structure tensor imaging (STI) from 21 µm isotropic acquisition acquired with micro computed tomography (MicroCT) imaging. Macroscopic and histological examination were performed. Lastly, experimental cardiomyocytes orientation distribution was then compared to the usual rule-based model using electrophysiological (EP) modeling. Electrical activity was modeled with the monodomain formulation. RESULTS: The RVIP at the level of the inferior ventricular septum presented a unique arrangement of aggregate cardiomyocytes. An abrupt, mid-myocardial change in cardiomyocytes orientation was observed, delimiting a triangle-shaped region, present in both sheep and human hearts. FA's histogram distribution (mean ± std: 0.29 ± 0.06) of the identified region as well as the main dimension (22.2 mm ± 5.6 mm) was found homogeneous across samples and species. Averaged volume is 0.34 cm3 ± 0.15 cm3. Both local activation time (LAT) and morphology of pseudo-ECGs were strongly impacted with delayed LAT and change in peak-to-peak amplitude in the simulated wedge model. CONCLUSION: The study was the first to describe the 3D cardiomyocytes architecture of the basal inferoseptal left ventricle region in human hearts and identify the presence of a well-organized aggregate cardiomyocytes arrangement and cardiac structural discontinuities. The results might offer a better appreciation of clinical phenotypes like RVIP-late gadolinium enhancement or uncommon idiopathic ventricular arrhythmias (VA) originating from this region.


Asunto(s)
Imagen de Difusión Tensora , Ventrículos Cardíacos , Humanos , Animales , Ovinos , Ventrículos Cardíacos/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Medios de Contraste , Microtomografía por Rayos X , Valor Predictivo de las Pruebas , Gadolinio , Miocitos Cardíacos/fisiología , Arritmias Cardíacas , Mamíferos
12.
Artículo en Inglés | MEDLINE | ID: mdl-38083585

RESUMEN

Heart rate variability (HRV) is an important clinical parameter that depicts the autonomic balance. Diminished HRV has been associated with diseased hearts and incorporating stochasticity in pacing has been investigated as a potential mechanism for restoring the altered autonomic balance and preventing cardiac arrhythmias. We studied the change in HRV with the development of chronic myocardial infarction (MI) in adult sheep (n=16). Next, we investigated the utility of stochastic pacing in modulating HRV in-vivo in both sham and MI hearts. The propensity of the heart to the development of cardiac alternans, a known precursor to tachyarrhythmias, was studied under three different pacing techniques, namely periodic pacing, stochastic pacing and constant diastolic interval (DI) pacing in one sham and one MI sheep. Autonomic balance was observed to be altered after 6 weeks of chronic MI. Increased heart rate, QTc interval, standard deviation of the R-R intervals and LF/HF ratio was observed in MI hearts. Stochastic pacing was found to be proarrhythmic and increased T-wave alternans burden was observed with increase in stochasticity. Maintaining a constant DI on every beat demonstrated reduced alternans levels compared to both periodic and stochastic pacing.Clinical Relevance-Our results demonstrate that precise control of the diastolic interval may be more beneficial in inhibiting arrhythmias than stochastic pacing.


Asunto(s)
Corazón , Infarto del Miocardio , Animales , Ovinos , Frecuencia Cardíaca/fisiología , Potenciales de Acción/fisiología , Corazón/fisiología , Arritmias Cardíacas
13.
Artículo en Inglés | MEDLINE | ID: mdl-38083720

RESUMEN

The right-ventricular (RV) outflow tract (RVOT) and the transition to the RV free wall are recognized sources of arrhythmia in human hearts. However, we do not fully understand myocardial tissue structures in this region. Human heart tissue was processed for optical clarity, labelled with wheat-germ agglutin (WGA) and anti-Cx43, and imaged on a custom-built line scanning confocal microscope. The 3D images were analyzed for myocyte gross structures and cell morphology. There were regions of high organization as well as rapid changes to more heterogeneous regions. Preliminary cell segmentations were used to estimate cell morphology. Observed RVOT/RV structure is consistent with known arrhythmic substrates.Clinical Relevance- New views of human tissue structure enable clearer clinical understanding of arrhythmogenic activation pathways and targets for invasive treatment such as RF ablation.


Asunto(s)
Ventrículos Cardíacos , Corazón , Humanos , Miocardio , Arritmias Cardíacas , Imagenología Tridimensional
14.
Chem Commun (Camb) ; 59(90): 13502-13505, 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37882454

RESUMEN

A Mn2+-Li-Nb disordered rock-salt oxide cathode is prepared by a solid-state reaction under 5% H2/N2, and its electrochemical property shows a high voltage plateau at 4.8 V, with irreversible structural changes in the 1st cycle due to O redox processes; this is supported by powder X-ray diffraction and ex situ laboratory Mn K-edge XANES data.

15.
Chem Commun (Camb) ; 59(76): 11393-11396, 2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37668052

RESUMEN

Control of phase separation of VO43- and rare earth precursors in reverse microemulsions afforded ∼35 nm YVO4 nanoparticles with functionalisable ∼7 ± 3 nm nanopores. Doping by Eu3+ allowed luminescent probing of interfacial crystallisation while xylenol orange absorption showed molecular encapsulation in particle cavities. This provides potential multifunctional systems combining UV-Vis-NIR luminescence and (photo)active molecules for optical sensing.

17.
Dalton Trans ; 52(32): 11143-11157, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37496421

RESUMEN

An unprecedented synthesis method is used to form a series of Ce-UiO-66-X (X = NH2, OH, H, NO2, COOH) metal-organic frameworks by precipitation from mixed solvents, with instantaneous crystallisation on combining separate solutions of ligands and metal precursors. This allows the first direct synthesis of Ce-UiO-66-OH. Powder X-ray diffraction (PXRD) shows that all materials are pure phase with a broadened profile that indicates nano-scale crystallite domain size. The effect of different functional groups on the benzene-1,4-dicarboxylate linker within the UiO-66 structure has been investigated on degradation of two cationic (methylene blue and rhodamine B) and two anionic (Congo red, and Alizarin red S) dyes under UV and visible light irradiation at room temperature. Analysis of the dye adsorption in the absence of light is accounted for using pseudo-first order kinetics, and the Ce-UiO-66-NH2, Ce-UiO-66-OH, and Ce-UiO-66-H materials display a considerable photocatalytic activity to degrade Alizarin red S and Congo red rapidly between 1 and 3 minutes. The materials show excellent photostability and recyclability under UV and visible light, with no loss of crystallinity seen by PXRD and activity maintained over 5 cycles, with 16 hours photostability for Ce-UiO-66-NH2.

18.
JACC Clin Electrophysiol ; 9(8 Pt 1): 1248-1261, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37227351

RESUMEN

BACKGROUND: Brugada syndrome is a significant cause of sudden cardiac death (SCD), but the underlying mechanisms remain hypothetical. OBJECTIVES: This study aimed to elucidate this knowledge gap through detailed ex vivo human heart studies. METHODS: A heart was obtained from a 15-year-old adolescent boy with normal electrocardiogram who experienced SCD. Postmortem genotyping was performed, and clinical examinations were done on first-degree relatives. The right ventricle was optically mapped, followed by high-field magnetic resonance imaging and histology. Connexin-43 and NaV1.5 were localized by immunofluorescence, and RNA and protein expression levels were studied. HEK-293 cell surface biotinylation assays were performed to examine NaV1.5 trafficking. RESULTS: A Brugada-related SCD diagnosis was established for the donor because of a SCN5A Brugada-related variant (p.D356N) inherited from his mother, together with a concomitant NKX2.5 variant of unknown significance. Optical mapping demonstrated a localized epicardial region of impaired conduction near the outflow tract, in the absence of repolarization alterations and microstructural defects, leading to conduction blocks and figure-of-8 patterns. NaV1.5 and connexin-43 localizations were normal in this region, consistent with the finding that the p.D356N variant does not affect the trafficking, nor the expression of NaV1.5. Trends of decreased NaV1.5, connexin-43, and desmoglein-2 protein levels were noted; however, the RT-qPCR results suggested that the NKX2-5 variant was unlikely to be involved. CONCLUSIONS: This study demonstrates for the first time that SCD associated with a Brugada-SCN5A variant can be caused by localized functionally, not structurally, impaired conduction.


Asunto(s)
Síndrome de Brugada , Masculino , Adolescente , Humanos , Células HEK293 , Electrocardiografía , Trastorno del Sistema de Conducción Cardíaco , Muerte Súbita Cardíaca , Conexinas
19.
PLoS One ; 18(4): e0284471, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37093832

RESUMEN

After percutaneous implantation of a cardiac occluder, a complex healing process leads to the device coverage within several months. An incomplete device coverage increases the risk of device related complications such as thrombosis or endocarditis. We aimed to assess the device coverage process of atrial septal defect (ASD) occluders in a chronic sheep model using micro-computed tomography (micro-CT). After percutaneous creation of an ASD, 8 ewes were implanted with a 16-mm Nit-Occlud ASD-R occluder (PFM medical, Cologne, Germany) and were followed for 1 month (N = 3) and 3 months (N = 5). After heart explant, the device coverage was assessed using micro-CT (resolution of 41.7 µm) and was compared to histological analysis. The micro-CT image reconstruction was performed in 2D and 3D allowing measurement of the coverage thickness and surface for each device. Macroscopic assessment of devices showed that the coverage was complete for the left-side disk in all cases. Yet incomplete coverage of the right-side disk was observed in 5 of the 8 cases. 2D and 3D micro-CT analysis allowed an accurate evaluation of device coverage of each disk and was overall well correlated to histology sections. Surface calculation from micro-CT images of the 8 cases showed that the median surface of coverage was 93±8% for the left-side disk and 55±31% for the right-side disk. The assessment of tissue reactions, including endothelialisation, after implantation of an ASD occluder can rely on in vitro micro-CT analysis. The translation to clinical practice is challenging but the potential for individual follow-up is shown, to avoid thrombotic or infective complications.


Asunto(s)
Defectos del Tabique Interatrial , Dispositivo Oclusor Septal , Femenino , Animales , Ovinos , Microtomografía por Rayos X , Diseño de Prótesis , Resultado del Tratamiento , Cateterismo Cardíaco/métodos , Atrios Cardíacos
20.
Front Physiol ; 14: 1154157, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37089427

RESUMEN

Purkinje fibres (PFs) play an important role in some ventricular arrhythmias and acute ventricular stretch can evoke mechanically-induced arrhythmias. We tested whether Purkinje fibres, play a role in these arrhythmias. Pseudo-ECGs were recorded in isolated, Langendorff-perfused, rabbit hearts in which the left ventricular endocardial surface was also irrigated with Tyrode, via an indwelling catheter placed in the left ventricular lumen. The number and period of ectopic activations was measured during left ventricular lumen inflation via an indwelling fluid-filled balloon (500 µL added over 2 s and maintained for 15 s in total). Mechanically-induced arrhythmias occurred in 70% of balloon inflations: they were maximal in the first 5 s and ceased within 15 s. Brief, (10 s) irrigation of the left ventricular lumen with Lugol solution (IK/I2), via the indwelling catheter, reduced inflation-induced ectopics by 98% (p < 0.05). Ablation of endocardial PFs by Lugol was confirmed by Triphenyltetrazolium Chloride staining. Optical mapping revealed the left ventricular epicardial activation patterns of ectopics could have PF-mediated and focal sources. In silico modelling predicted ectopic sources originating in the endocardial region propagate to and through the Purkinje fibres network. Acute distention-induced ectopics are multi-focal, their attenuation by Lugol, their activation patterns and in silico modelling indicate a participation of Purkinje fibres in these arrhythmias.

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