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BACKGROUND: Over the past decades, thrombophilia testing in patients with venous thrombo-embolism has increased tremendously. However, the role of inherited thrombophilie in prediction the risk of recurrence remains controversial. Consequently, it is still unclear whether thrombophilia testing influences decisions regarding duration of anticoagulation in clinical practices. The aim of this study was to evaluate the impact if inherited thrombophilia on venous thrombosis treatment decisions and on predicting the risk of recurrence. METHODS: A retrospective longitudinal study (January 2011-Decembre 2016) including 131 patients with confirmed venous thrombo-embolism referred to the hematology laboratory from the internal medicine department for inherited thrombophilia screening was carried out. RESULTS: The mean age patients was 39.4 years and the sex ratio (M/F) was 0.61. Inherited thrombophilia was confirmed in 27.5% of patients. A long term anticoagulation was decided in 46.9% of patients with thrombophilia. There was no significant difference in the duration of anticoagulation between patients with or without thrombophilia. Thrombosis recurrence was recorded in 16 (17%) patients. The 24 years cumulative incidence of recurrence was 19% in patients with thrombophilia and 17% in those without (plog Rank= 0.6). Inherited thrombophilia was not associated with increased risk of recurrence after treatment withdrawal (Hazard ratio=1.31 IC (0.47-3.63); P=0.6). CONCLUSION: In clinical practice, inherited thrombophilia did not influence anticoagulation duration and was not associated with a higher venous thrombosis risk of recurrence. It seems to be less relevant for decision making than presumed.
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Tromboembolia Venosa , Trombosis de la Vena , Adulto , Anticoagulantes/uso terapéutico , Humanos , Estudios Longitudinales , Estudios Retrospectivos , Factores de Riesgo , Trombofilia , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/epidemiología , Trombosis de la Vena/etiologíaRESUMEN
Polymerase chain reaction (PCR) is the most widely used method for nucleic acids amplification. To date, a huge number of versatile PCR techniques have been developed. One of the relevant goals is to shorten PCR duration, which can be achieved in several ways. Here, we report on the results regarding nucleic acids amplification by convective PCR (cPCR) in standard 0.2 ml polypropylene microtubes. The following conditions were found to be optimal for such amplification: 1) 70 µl reaction volume, 2) the supply of external temperature 145°Ð¡ for the denaturation zone and 0°Ð¡ for the annealing zone, 3) â¼30° inclination of the microtube main axis, 4) the use of nearby primers, and 5) duration of the reaction 15-20 min. At these conditions, the amplification products are accumulated in an amount sufficient to be registered by gel electrophoresis, and high sensitivity of the reaction comparable to that of conventional PCR is achieved. cPCR provided the reliable detection of SARS-CoV-2 coronavirus RNA isolated from nasopharyngeal swabs of COVID-19 patients.
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Prueba de Ácido Nucleico para COVID-19/instrumentación , COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa/instrumentación , SARS-CoV-2/aislamiento & purificación , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19/economía , Prueba de Ácido Nucleico para COVID-19/métodos , Convección , Humanos , Reacción en Cadena de la Polimerasa/economía , Reacción en Cadena de la Polimerasa/métodos , ARN Viral/análisis , ARN Viral/genética , SARS-CoV-2/genética , Temperatura , Factores de TiempoRESUMEN
The main goals of the present investigation were to develop O/W nanoemulsion fungicides based on cold-pressed Nigella sativa (black seed) oil to prevent Penicillium verrucosum infection of maize seeds and to test their antifungal activity against this fungus. Additionally, the effect of these nanoemulsions on plant physiological parameters was also investigated. Two nonionic surfactants namely Tween 20 and Tween 80 were used as emulsifying agents in these formulations. The effect of sonication time and surfactant type on the mean droplet size, polydispersity index (PDI), and zeta potential of the nanoemulsions were determined by dynamic light scattering (DLS). Results indicated that both sonication time and emulsifier type had pronounced effects on the stability of O/W nanoemulsions with a small particle size range (168.6-345.3 nm), acceptable PDI (0.181-0.353), and high zeta potential (-27.24 to -48.82 mV). Tween 20 showed superior stability compared to Tween 80 nanoemulsions. The in vitro results showed that complete inhibition of P. verrucosum-growth was obtained by 10_T80 and 10_T20 nanoemulsions at 100% concentration. All nanoemulsions had increment effects on maize seed germination by 101% in the case of 10_T20 and 10_T80 compared to untreated seeds or the chemical fungicide treatment. Nanoemulsions (10_T20 and 10_T80) were able to stimulate root and shoot length as compared to the fungicide treatment. Seed treatment with 10_T80 nanoemulsion showed the highest AI and protease activity by 75 and 70%, respectively, as compared to the infected control. The produced nanoemulsions might provide an effective protectant coating layer for the stored maize seeds.
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Owing to the toxic effects of polycyclic aromatic hydrocarbons (PAHs) on humans and the environment, their sensitive biomonitoring is essential and significant. In this work, a sensitive, simple and rapid bioanalytical method was established for the simultaneous determination of 13 PAHs in rat plasma depending on QuEChERS (Quick, easy, cheap, effective and rugged method) as a preliminary step and gas chromatography-mass spectrometry (GC-MS) for identification. QuEChERS procedure was optimized where acetonitrile was employed for plasma samples extraction, which was further cleaned using primary secondary amine as the sorbent material. Optimization of GC-MS conditions was performed to produce optimum selectivity of the proposed method. The method was fully validated for rat plasma samples where recoveries, matrix effects, limit of quantitation (LOQ), linearity and precision were evaluated. Linearity range was 5-100 ng/mL for most of the 13 analytes. Average recoveries of the 13 PAHs ranged between 85.57% and 109.64% in fortified rat plasma with standard deviations <8.91 except for anthracene that showed 19.24. The limits of detection and LOQs for the 13 compounds ranged from 0.045 to 0.372 ppb and from 0.137 to 1.128 ppb, respectively. The established method was successfully implemented to perform a minor toxicokinetic study in intraperitoneally dosed rats (0.25 and 2 mg/kg in vegetable oil). The 13 PAHs were tracked in rat plasma samples for 6 h after administration, and most of the target compounds were recognized in plasma samples only at the higher dose.
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Hidrocarburos Policíclicos Aromáticos , Animales , Cromatografía de Gases y Espectrometría de Masas/métodos , Límite de Detección , Hidrocarburos Policíclicos Aromáticos/análisis , RatasRESUMEN
A new series of alginate/chitosan-based nanocomposite microspheres was developed to achieve the maximum health benefit and to minimize the oxidation of omega-3 rich oils (flaxseed or fish oils). The nanocomposite microspheres incorporate curcumin (Cur) as natural antioxidant, and have been prepared using a three-step procedure (oil-in-water (o/w) emulsification, gelation and microencapsulation). The average particle size of Cur-free and Cur-loaded nanocomposites ranged between 139 and 153â¯nm. The presence of omega-3 rich oils in core of the formulated microspheres was confirmed by XRD and FTIR. Optical microscopy, stereo microscopy, SEM and AFM showed a spherical shape of the microspheres. Microencapsulation efficiency, oxidative stability, release profile of oils as well as the antioxidant and antibacterial activities were investigated. The results suggested that the microspheres could be applied as effective and safe edible vehicles for hydrophobic nutraceuticals like omega-3 rich oils with broad spectrum antibacterial activity.
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Alginatos/química , Antibacterianos/farmacología , Antioxidantes/farmacología , Quitosano/química , Sistemas de Liberación de Medicamentos , Ácidos Grasos Omega-3/farmacología , Microesferas , Nanocompuestos/química , Antibacterianos/química , Antioxidantes/química , Compuestos de Bifenilo/antagonistas & inhibidores , Portadores de Fármacos/química , Grano Comestible/química , Ácidos Grasos Omega-3/química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Oxidación-Reducción , Tamaño de la Partícula , Picratos/antagonistas & inhibidores , Propiedades de SuperficieRESUMEN
Omega-3 fatty acids can be considered as potential alternative therapeutic agents because of their antimicrobial and antioxidant properties. Two investigated omega-3 rich oils (flaxseed or fish) have been nanoemulsified with and without the natural antioxidant (curcumin, Cur) followed by their incorporation into crosslinked polymeric microbeads. The microbeads were developed from chitosan (CS), alginate (AL) and their combination (CSAL). Results indicated that the mean droplet diameter of the plain and Cur-loaded nanoemulsions ranged from 62.3 to 111.29â¯nm. The microbeads produced from AL, CS and their combination without Cur had predominantly shriveled surfaces compared to Cur-loaded ones. Addition of Cur was found to enhance oxidative stability, encapsulation efficiency, loading capacity, and antioxidant activity of the formulated microbeads. Plain fish oil revealed more antibacterial activity than plain flaxseed oil. Fish oil nanoemulsion-in-AL microbeads had more antibacterial activity than nanoemulsions of flaxseed oil-in-AL, fish oil-in-CS and the combined (CSAL) microbeads. However, flaxseed oil nanoemulsion-in-CS microbeads showed higher antibacterial activity than nanoemulsions of fish oil-in-CS, flaxseed oil-in-AL and the combined microbeads. The obtained results suggested the suitability of the formulated nanoemulsions-loaded microbeads to be used in food and pharmaceuticals products.
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Alginatos/química , Antibacterianos/química , Antioxidantes/química , Quitosano/química , Curcumina/química , Emulsiones/química , Ácidos Grasos Omega-3/química , Nanoestructuras/química , Aceites de Pescado/química , Lino/química , Microesferas , Oxidación-Reducción , Tamaño de la Partícula , Aceites de Plantas/química , Tensoactivos/químicaRESUMEN
In this paper, we present a novel Pt/CuO/Pt metal-oxide-metal (MOM) glucose sensor. The devices are fabricated using a simple, low-cost standard photolithography process. The unique planar structure of the device provides a large electrochemically active surface area, which acts as a nonenzymatic reservoir for glucose oxidation. The sensor has a linear sensing range between 2.2 mM and 10 mM of glucose concentration, which covers the blood glucose levels for an adult human. The distinguishing property of this sensor is its ability to measure glucose at neutral pH conditions (i.e. pH = 7). Furthermore, the dilution step commonly needed for CuO-based nonenzymatic electrochemical sensors to achieve an alkaline medium, which is essential to perform redox reactions in the absence of glucose oxidase, is eliminated, resulting in a lower-cost and more compact device.
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BACKGROUND: Although cutaneous and mucosal involvement is a major manifestation in Behçet's disease, ulcerated lesions of the extremities are exceptional and poorly known. CASE REPORT: A 57-year-old male patient was diagnosed 7 years ago with Behçet's disease. This diagnosis was made in the presence of recurrent bipolar aphtous ulcers, pseudofolliculitis lesions and retinal vasculitis. After having been lost to follow up for two years, during which his treatment was discontinued, he presented centimetric necrotic ulcerations of the fingers of the hand and of the right big toe. The biopsy revealed leucocytoclastic and necrotizing vasculitis. The patient improved with antibiotic, oral corticosteroids, colchicine and local care. CONCLUSION: Linking extremity ulcers with Behçet's disease, though sometimes difficult, is essential for proper management.
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Síndrome de Behçet/diagnóstico , Enfermedades de la Piel/etiología , Úlcera/etiología , Corticoesteroides/administración & dosificación , Síndrome de Behçet/complicaciones , Síndrome de Behçet/tratamiento farmacológico , Colchicina/administración & dosificación , Extremidades/patología , Humanos , Masculino , Persona de Mediana Edad , Pristinamicina/administración & dosificación , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/tratamiento farmacológico , Úlcera/diagnóstico , Úlcera/tratamiento farmacológico , Úlcera/patología , Vasculitis/diagnóstico , Vasculitis/tratamiento farmacológico , Vasculitis/patologíaRESUMEN
Neural tissue engineering provides enormous potential for restoring and improving the function of diseased/damaged tissues and promising opportunities in regenerative medicine, stem cell technology, and drug discovery. The conventional 2D cell cultures have many limitations to provide informative and realistic neural interactions and network formation. Hence, there is a need to develop three-dimensional (3D) bioscaffolds to facilitate culturing cells with matched microenvironment for cell growth and interconnected pores for penetration and migration of cells. Herein, we report the synthesis and characterization of 3D composite bioscaffolds based on graphene-biopolymer with porous structure and improved performance for tissue engineering. A simple, eco-friendly synthetic method is introduced and optimized for synthesis of this hybrid fibrous scaffold by combining Graphene Oxide (GO) and Sodium Alginate (Na-ALG) which are specifically selected to match the mechanical strength of the central nervous system (CNS) tissue and provide porous structure for connective tissue engineering. Properties of the developed scaffold in terms of the structure, porosity, thermal stability, mechanical properties, and electrical conductivity are presented. These properties were optimised through key synthesis conditions including GO concentrations, reduction process and crosslinking time. In contrast to other studies, the presented structure maintains its stability in aqueous media and uses a bio-friendly reducing agent which enable the structure to enhance neuron cell interactions and act as nerve conduits for neurological diseases.
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INTRODUCTION: To investigate the thrombotic tendency in patients with systemic lupus erythematosus (SLE) by evaluating congenital and acquired abnormalities with an increased risk of thrombosis. PATIENTS AND METHODS: A total of 53 patients with SLE were included in the study. Fifty-three healthy controls paired by age and sex were assessed. Anticardiolipin antibodies (aCL), anti ß2 glycoprotein (aß2GP), lupus anticoagulant (LAC), protein C (PC), protein S (PS), antithrombin (AT), acquired activated protein C, and homocysteinemia were evaluated. Comparisons for categorical variables were analyzed by Chi2 and student tests. RESULTS: The patients were all female and had a mean age of 30.6 years (16/58). The healthy controls were all female and their mean age was 30.8 years (17/56). Five patients (9.4%) developed venous thrombosis during the 24 months of follow-up. The antiphospholipid antibodies were positive in 17 patients (32.1%) and negative in all healthy controls (P=0.01). PS deficiency was noted in 17 patients (32.1%) and in 5 controls (P=0.004). Hyperhomocysteinemia was noted in 16 patients (30.2%) versus 3 controls (5.6%) (P=0.002). Test for PC deficiency and acquired activated protein C showed no significant difference between the two groups. No AT deficiency was found in the patients. The study of clinical and biological correlations based on the presence and absence of thrombophilic parameters concluded to a significant association between Protein C deficit and thrombosis (P=0.02) and acquired activated protein C resistance and thrombosis (P=0.04). There was no significant association between the APL and thrombosis. CONCLUSION: Thrombophilic abnormalities were significantly more frequent in lupus patients than in healthy controls. Thrombotic events were significantly associated with PC deficit and acquired protein C resistance. There was no correlation between antiphospholipid antibodies and thrombosis.
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Resistencia a la Proteína C Activada/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Deficiencia de Proteína C/complicaciones , Trombosis/etiología , Resistencia a la Proteína C Activada/sangre , Resistencia a la Proteína C Activada/diagnóstico , Adulto , Anticuerpos Anticardiolipina/sangre , Biomarcadores/sangre , Factores de Coagulación Sanguínea/análisis , Estudios de Casos y Controles , Femenino , Homocisteína/sangre , Humanos , Inhibidor de Coagulación del Lupus/sangre , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Deficiencia de Proteína C/sangre , Deficiencia de Proteína C/diagnóstico , Trombosis/sangre , Trombosis/diagnóstico , Microglobulina beta-2/inmunologíaRESUMEN
Hypothyroidism is exceptionnally revealed by hypertrophic myopathy, known as Hoffmann syndrome. We report two new cases of severe hypothyroidism presenting as hypertrophic myopathy, occurring in two men of 49 and 57 years-old.
La myopathie hypertrophique associée à l'hypothyroïdie, connue sous le nom de syndrome de Hoffmann, est une manifestation rare de l'hypothyroïdie et peut à titre exceptionnel en constituer la manifestation initiale. Nous rapportons deux nouveaux cas de myopathie hypertrophique sévère révélant une hypothyroïdie profonde, chez deux adultes âgés respectivement de 49 et 57 ans.
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Hipotiroidismo/diagnóstico , Enfermedades Musculares/diagnóstico , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/patología , Masculino , Persona de Mediana Edad , Enfermedades Musculares/etiología , Enfermedades Musculares/patología , Índice de Severidad de la Enfermedad , SíndromeRESUMEN
Ectopic parathyroid glands can be located at any anatomical location from the base of the tongue to the mediastinum. One-third of these glands migrate deep into the mediastinum, which are not accessible with a low cervical incision. In this article, we described the robotic approach to an ectopic mediastinal parathyroid gland. This management method of mediastinal adenomas has significant advantages when compared to conventional surgery.
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OBJECTIVE: Against the background of well-described associations between oral and general health, the cooperation between general practitioners (GPs) and dentists is crucial. Besides treatment, this includes prevention. Administrative referral between these two professions is not provided by statute. Thus, the study addresses the question: How do dentists and GPs integrate the associations between oral and systemic health in daily routine? METHODS: A total of 28 semi-structured interviews were conducted with GPs and dentists from 3 structurally different regions in the Federal State of Baden-Wurttemberg. Participants were visited in their office. The interviews were recorded, transcribed and analysed by 2 dentists and sociologists using Mayrings' qualitative content analysis. RESULTS: Associations between general and oral health are partially known to both practitioners. However, contact between them is limited. GPs send patients directly to dentists, without contacting them - mainly due to a desolate dental status, rarely due to therapy-resistant headache or facial pain. Dentists contact GPs to clarify mainly medication or anticoagulation medications taken by patients prior to invasive procedures. Preventive aspects play a minor part. Consultation essentially depends on acquaintanceship. CONCLUSION: Separation by statute determines the cooperation. Oral cavity in daily care is demarcated. Holistic patient care is hindered by a lack of knowledge and daily routines.
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Odontólogos , Médicos Generales , Relaciones Interprofesionales , Actitud del Personal de Salud , Alemania , Humanos , Salud Bucal , Investigación Cualitativa , Derivación y ConsultaRESUMEN
Susac syndrome is a rare disease characterized by the clinical triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss. This underdiagnosed condition needs to be considered in the differential diagnosis of a broad variety of disorders. An early diagnosis is important as treatment can halt disease progression and prevent permanent disability. Herein, we report a case of Susac syndrome in a 31-year-old woman and we highlight how challenging an early diagnosis was and the importance of an aggressive therapeutic approach, including the combination of steroids and other cytotoxic drugs.
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Cefalea/etiología , Síndrome de Susac/diagnóstico , Adulto , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Diagnóstico Precoz , Femenino , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Unilateral/etiología , Humanos , Imagen por Resonancia Magnética , Metilprednisolona/uso terapéutico , Neuroimagen , Síndrome de Susac/diagnóstico por imagen , Síndrome de Susac/tratamiento farmacológico , Trastornos de la Visión/etiología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
OBJECTIVE: Comparability of topographical data of implant surfaces in literature is low and their clinical relevance often equivocal. The aim of this study was to investigate the ability of scanning electron microscopy and optical interferometry to assess statistically similar 3-dimensional roughness parameter results and to evaluate these data based on predefined criteria regarded relevant for a favorable biological response. METHODS: Four different commercial dental screw-type implants (NanoTite Certain Prevail, TiUnite Brånemark Mk III, XiVE S Plus and SLA Standard Plus) were analyzed by stereo scanning electron microscopy and white light interferometry. Surface height, spatial and hybrid roughness parameters (Sa, Sz, Ssk, Sku, Sal, Str, Sdr) were assessed from raw and filtered data (Gaussian 50µm and 5µm cut-off-filters), respectively. Data were statistically compared by one-way ANOVA and Tukey-Kramer post-hoc test. For a clinically relevant interpretation, a categorizing evaluation approach was used based on predefined threshold criteria for each roughness parameter. RESULTS: The two methods exhibited predominantly statistical differences. Dependent on roughness parameters and filter settings, both methods showed variations in rankings of the implant surfaces and differed in their ability to discriminate the different topographies. Overall, the analyses revealed scale-dependent roughness data. Compared to the pure statistical approach, the categorizing evaluation resulted in much more similarities between the two methods. SIGNIFICANCE: This study suggests to reconsider current approaches for the topographical evaluation of implant surfaces and to further seek after proper experimental settings. Furthermore, the specific role of different roughness parameters for the bioresponse has to be studied in detail in order to better define clinically relevant, scale-dependent and parameter-specific thresholds and ranges.
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Implantes Dentales , Microscopía Electrónica de Rastreo , Interferometría , Luz , Propiedades de Superficie , TitanioRESUMEN
Adult-onset Still's disease (AOSD) is an uncommon inflammatory condition of unknown origin. In chronic disease, joint involvement is often predominant and erosions are noted in one third of patients. Therapeutic strategies derive from observational data. Corticosteroids are usually the first-line treatment. With inadequate response to corticosteroids, methotrexate appears the best choice to control disease activity and allow for tapering of steroid use. For refractory disease, biological therapy seems the most promising. We report here the case of a 38-year-old female patient with AOSD refractory to cytotoxic agents, treated by rituximab infusion therapy with favorable outcome.
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Antirreumáticos/uso terapéutico , Rituximab/uso terapéutico , Enfermedad de Still del Adulto/tratamiento farmacológico , Adulto , Femenino , Humanos , Enfermedad de Still del Adulto/diagnóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Progressive activation delay after premature stimulation has been associated with ventricular fibrillation in nonischemic cardiomyopathy (NICM). OBJECTIVES: The objectives of this study were (1) to investigate prolongation of the paced QRS duration (QRSd) after premature stimulation as a marker of activation delay in NICM, (2) to assess its relation to induced ventricular arrhythmias, and (3) to analyze its underlying substrate by late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) and endomyocardial biopsy. METHODS: Patients with NICM were prospectively enrolled in the Leiden Nonischemic Cardiomyopathy Study and underwent a comprehensive evaluation including LGE-CMR, electrophysiology study, and endomyocardial biopsy. Patients without structural heart disease served as controls for electrophysiology study. RESULTS: Forty patients with NICM were included (mean age 57 ± 14 years; 33 men [83%]; left ventricular ejection fraction 30% ± 13%). After the 400-ms drive train and progressively premature stimulation, the maximum increase in QRSd was larger in patients with NICM than in controls (35 ± 18 ms vs. 23 ± 12 ms; P = .005) and the coupling interval window with QRSd prolongation was wider (47 ± 23 ms vs. 31 ± 14 ms; P = .005). The maximum paced QRSd exceeded the ventricular effective refractory period, allowing for pacing before the offset of the QRS complex in 20 of 39 patients with NICM vs. 1 of 20 controls (P < .001). In patients with NICM, QRSd prolongation was associated with the inducibility of polymorphic ventricular tachycardia (16 of 39 patients) and was related to long, thick strands of fibrosis in biopsies, but not to focal enhancement on LGE-CMR. CONCLUSION: QRSd is a simple parameter used to quantify activation delay after premature stimulation, and its prolongation is associated with the inducibility of polymorphic ventricular tachycardia and with the pattern of myocardial fibrosis in biopsies.
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Cardiomiopatías/fisiopatología , Estimulación Eléctrica/métodos , Electrocardiografía , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca/fisiología , Taquicardia Ventricular/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cardiomiopatías/complicaciones , Cardiomiopatías/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/terapia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Electrical cardioversion (ECV), a mainstay in atrial fibrillation (AF) treatment, is unsuccessful in up to 10-20% of patients. An important aspect of the remodeling process caused by AF is the constitutive activition of the atrium-specific acetylcholine-dependent potassium current (IK,ACh â IK,ACh-c), which is associated with ECV failure. This study investigated the role of IK,ACh-c in ECV failure and setting the atrial defibrillation threshold (aDFT) in optically mapped neonatal rat cardiomyocyte monolayers. AF was induced by burst pacing followed by application of biphasic shocks of 25-100 V to determine aDFT. Blocking IK,ACh-c by tertiapin significantly decreased DFT, which correlated with a significant increase in wavelength during reentry. Genetic knockdown experiments, using lentiviral vectors encoding a Kcnj5-specific shRNA to modulate IK,ACh-c, yielded similar results. Mechanistically, failed ECV was attributed to incomplete phase singularity (PS) removal or reemergence of PSs (i.e. re-initiation) through unidirectional propagation of shock-induced action potentials. Re-initiation occurred at significantly higher voltages than incomplete PS-removal and was inhibited by IK,ACh-c blockade. Whole-heart mapping confirmed our findings showing a 60% increase in ECV success rate after IK,ACh-c blockade. This study provides new mechanistic insight into failing ECV of AF and identifies IK,ACh-c as possible atrium-specific target to increase ECV effectiveness, while decreasing its harmfulness.
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Acetilcolina/metabolismo , Fibrilación Atrial/metabolismo , Cardioversión Eléctrica/efectos adversos , Canales de Potasio de Rectificación Interna/metabolismo , Canales de Potasio/metabolismo , Potenciales de Acción , Animales , Fibrilación Atrial/genética , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Técnicas de Silenciamiento del Gen , Atrios Cardíacos/metabolismo , Atrios Cardíacos/fisiopatología , Humanos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Técnicas de Placa-Clamp , Canales de Potasio/genética , Canales de Potasio de Rectificación Interna/genética , RatasRESUMEN
Physical unclonable functions (PUFs) exploit the intrinsic complexity and irreproducibility of physical systems to generate secret information. The advantage is that PUFs have the potential to provide fundamentally higher security than traditional cryptographic methods by preventing the cloning of devices and the extraction of secret keys. Most PUF designs focus on exploiting process variations in Complementary Metal Oxide Semiconductor (CMOS) technology. In recent years, progress in nanoelectronic devices such as memristors has demonstrated the prevalence of process variations in scaling electronics down to the nano region. In this paper, we exploit the extremely large information density available in nanocrossbar architectures and the significant resistance variations of memristors to develop an on-chip memristive device based strong PUF (mrSPUF). Our novel architecture demonstrates desirable characteristics of PUFs, including uniqueness, reliability, and large number of challenge-response pairs (CRPs) and desirable characteristics of strong PUFs. More significantly, in contrast to most existing PUFs, our PUF can act as a reconfigurable PUF (rPUF) without additional hardware and is of benefit to applications needing revocation or update of secure key information.
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AIMS: Fibrosis increases arrhythmogenicity in myocardial tissue by causing structural and functional disruptions in the cardiac syncytium. Forced fusion of fibroblastic cells with adjacent cardiomyocytes may theoretically resolve these disruptions. Therefore, the electrophysiological effects of such electrical and structural integration of fibroblastic cells into a cardiac syncytium were studied. METHODS AND RESULTS: Human ventricular scar cells (hVSCs) were transduced with lentiviral vectors encoding enhanced green fluorescent protein alone (eGFP↑-hVSCs) or together with the fusogenic vesicular stomatitis virus G protein (VSV-G/eGFP↑-hVSCs) and subsequently co-cultured (1:4 ratio) with neonatal rat ventricular cardiomyocytes (NRVMs) in confluent monolayers yielding eGFP↑- and VSV-G/eGFP↑-co-cultures, respectively. Cellular fusion was induced by brief exposure to pH = 6.0 medium. Optical mapping experiments showed eGFP↑-co-cultures to be highly arrhythmogenic [43.3% early afterdepolarization (EAD) incidence vs. 7.7% in control NRVM cultures, P < 0.0001], with heterogeneous prolongation of action potential (AP) duration (APD). Fused VSV-G/eGFP↑-co-cultures displayed markedly lower EAD incidence (4.6%, P < 0.001) than unfused co-cultures, associated with decreases in APD, APD dispersion, and decay time of cytosolic Ca(2+) waves. Heterokaryons strongly expressed connexin43 (Cx43). Also, maximum diastolic potential in co-cultures was more negative after fusion, while heterokaryons exhibited diverse mixed NRVM/hVSC whole-cell current profiles, but consistently showed increased outward Kv currents compared with NRVMs or hVSCs. Inhibition of Kv channels by tetraethylammonium chloride abrogated the anti-arrhythmic effects of fusion in VSV-G/eGFP↑-co-cultures raising EAD incidence from 7.9 to 34.2% (P < 0.001). CONCLUSION: Forced fusion of cultured hVSCs with NRVMs yields electrically functional heterokaryons and reduces arrhythmogenicity by preventing EADs, which is, at least partly, attributable to increased repolarization force.