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Deformability and internal ordering are key features related to cell function, particularly critical for cells that routinely undergo large deformations, like T cells during extravasation and migration. In the measurement of cell deformability, a considerable variability is typically obtained, masking the identification of possible interrelationships between deformability, internal ordering and cell function. We report the development of a single-cell methodology that combines measurements of living-cell deformability, using micropipette aspiration, and three-dimensional confocal analysis of the nucleus and cytoskeleton. We show that this single-cell approach can serve as a powerful tool to identify appropriate parameters that characterize deformability within a population of cells, not readably discernable in population-averaged data. By applying this single-cell methodology to mouse CD4+ T cells, our results demonstrate that the relative size of the nucleus, better than other geometrical or cytoskeletal features, effectively determines the overall deformability of the cells within the population.
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Linfocitos T CD4-Positivos/citología , Modelos Biológicos , Animales , Fenómenos Biofísicos , Núcleo Celular , Dimetilpolisiloxanos , Módulo de Elasticidad , Femenino , Fluorescencia , Ratones Endogámicos ICR , Microscopía Confocal , Análisis de la Célula Individual , ViscosidadRESUMEN
Introduction: Gestation under chronic hypoxia causes pulmonary hypertension, cardiovascular remodeling, and increased aortic stiffness in the offspring. To mitigate the neonatal cardiovascular risk, pharmacological treatments (such as hemin and sildenafil) have been proposed to improve pulmonary vasodilation. However, little is known about the effects of these treatments on the aorta. Therefore, we studied the effect of hemin and sildenafil treatments in the aorta of lambs gestated and raised at highlands, thereby subjected to chronic hypoxia. Methods: Several biomechanical tests were conducted in the descending thoracic aorta (DTA) and the distal abdominal aorta (DAA), assessing 3 groups of study of hypoxic animals: non-treated (Control) and treated either with hemin or sildenafil. Based on them, the stiffness level has been quantified in both zones, along with the physiological strain in the unloaded aortic duct. Furthermore, a morphological study by histology was conducted in the DTA. Results: Biomechanical results indicate that treatments trigger an increment of axial pre-stress and circumferential residual stress levels in DTA and DAA of lambs exposed to high-altitude chronic hypoxia, which reveals a vasodilatation improvement along with an anti-hypertensive response under this characteristic environmental condition. In addition, histological findings do not reveal significant differences in either structure or microstructural content. Discussion: The biomechanics approach emerges as a valuable study perspective, providing insights to explain the physiological mechanisms of vascular function. According to established results, alterations in the function of the aortic wall may not necessarily be explained by morphostructural changes, but rather by the characteristic mechanical state of the microstructural components that are part of the studied tissue. In this sense, the reported biomechanical changes are beneficial in mitigating the adverse effects of hypobaric hypoxia exposure during gestation and early postnatal life.
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The Constrained Mixture Model (CMM) is a novel approach to describe arterial wall mechanics, whose formulation is based on a referential physiological state. The CMM considers the arterial wall as a mixture of load-bearing constituents, each of them with characteristic mass fraction, material properties, and deposition stretch levels from its stress-free state to the in-vivo configuration. Although some reports of this model successfully assess its capabilities, they barely explore experimental approaches to model patient-specific scenarios. In this sense, we propose an iterative fitting procedure of numerical-experimental nature to determine material parameters and deposition stretch values. To this end, the model has been implemented in a finite element framework, and it is calibrated using reported experimental data of descending thoracic aorta. The main results obtained from the proposed procedure consist of a set of material parameters for each constituent. Moreover, a relationship between deposition stretches and residual strain measurements (opening angle and axial stretch) has been numerically proved, establishing a strong consistency between the model and experimental data.
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BACKGROUND: Biometrical and blood flow examinations are fundamental for assessing fetoplacental development during pregnancy. Guinea pigs have been proposed as a good model to study fetal development and related gestational complications; however, longitudinal growth and blood flow changes in utero have not been properly described. This study aimed to describe fetal and placental growth and blood flow of the main intrauterine vascular beds across normal guinea pig pregnancy and to discuss the relevance of this data for human pregnancy. METHODS: Pregnant guinea pigs were studied from day 25 of pregnancy until term (day ~70) by ultrasound and Doppler assessment. The results were compared to human data from the literature. RESULTS: Measurements of biparietal diameter (BPD), cranial circumference (CC), abdominal circumference, and placental biometry, as well as pulsatility index determination of umbilical artery, middle cerebral artery (MCA), and cerebroplacental ratio (CPR), were feasible to determine across pregnancy, and they could be adjusted to linear or nonlinear functions. In addition, several of these parameters showed a high correlation coefficient and could be used to assess gestational age in guinea pigs. We further compared these data to ultrasound variables from human pregnancy with high similarities. CONCLUSIONS: BPD and CC are the most reliable measurements to assess fetal growth in guinea pigs. Furthermore, this is the first report in which the MCA pulsatility index and CPR are described across guinea pig gestation. The guinea pig is a valuable model to assess fetal growth and blood flow distribution, variables that are comparable with human pregnancy.
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We present a rare radiographic abnormality found in a patient who consulted us for progressive left hearing loss.
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Hueso Petroso/anomalías , Variación Anatómica , Humanos , Imagen por Resonancia Magnética , Hueso Petroso/diagnóstico por imagen , Hueso Petroso/patología , Tomografía Computarizada por Rayos XRESUMEN
This work presents a characterization of the active response of the carotid artery of guinea pig fetuses through a methodology that encompasses experiments, modeling and numerical simulation. To this end, the isometric contraction test is carried out in ring samples subjected to different levels of KCl concentrations and pre-stretching. Then, a coupled mechanochemical model, aimed at describing the smooth cell behavior and its influence on the passive and active mechanical response of the vascular tissue, is calibrated from the experimental measurements. Due to the complex stress and strain fields developed in the artery, a finite element numerical simulation of the test is performed to fit the model parameters, where those related to the phosphorylation and dephosphorylation activity along with the load-bearing capacity of the myosin cross-bridges are found to be the most predominant when sensitizing the active response. The main strengths of the model are associated with the prediction of the stationary state of the active mechanical response of the tissue through a realistic description of the mechanochemical process carried out at its cellular level.
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High altitude hypoxia is a condition experienced by diverse populations worldwide. In addition, several jobs require working shifts where workers are exposed to repetitive cycles of hypobaric hypoxia and normobaric normoxia. Currently, few is known about the biomechanical cardiovascular responses of this condition. In the present study, we investigate the cycle-dependent biomechanical effects of intermittent hypobaric hypoxia (IHH) on the thoracic aorta artery, in terms of both structure and function. To determine the vascular effects of IHH, functional, mechanical and histological approaches were carried out in the thoracic aorta artery, using uniaxial, pre-stretch, ring opening, myography, and histological tests. Three groups of rats were established: control (normobaric normoxia, NN), 4-cycles of intermittent hypoxia (short-term intermittent hypobaric hypoxia, STH), and 10-cycles of intermittent hypoxia (long-term intermittent hypobaric hypoxia, LTH). The pre-stretch and ring opening tests, aimed at quantifying residual strains of the tissues in longitudinal and circumferential directions, showed that the hypoxia condition leads to an increase in the longitudinal stretch and a marked decrease of the circumferential residual strain. The uniaxial mechanical tests were used to determine the elastic properties of the tissues, showing that a general stiffening process occurs during the early stages of the IH (STH group), specially leading to a significative increase in the high strain elastic modulus ([Formula: see text]) and an increasing trend of low strain elastic modulus ([Formula: see text]). In contrast, the LTH group showed a more control-like mechanical behavior. Myography test, used to assess the vasoactive function, revealed that IH induces a high sensitivity to vasoconstrictor agents as a function of hypoxic cycles. In addition, the aorta showed an increased muscle-dependent vasorelaxation on the LTH group. Histological tests, used to quantify the elastic fiber, nuclei, and geometrical properties, showed that the STH group presents a state of vascular fibrosis, with a significant increase in elastin content, and a tendency towards an increase in collagen fibers. In addition, advanced stages of IH (LTH), showed a vascular remodeling effect with a significant increase of internal and external diameters. Considering all the multidimensional vascular effects, we propose the existence of a long-term passive adaptation mechanism and vascular dysfunction as cycle-dependent effects of intermittent exposures to hypobaric hypoxia.
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Mal de Altura , Hipoxia , Animales , Aorta/patología , Corazón/fisiología , Ratas , VasodilataciónRESUMEN
BACKGROUND: Fetal chronic hypoxia is associated with blood flow redistribution and oxidative damage in the brain, leading to increased perinatal morbimortality. Melatonin reduces oxidative stress, improves vascular function, and has neuroprotective effects. OBJECTIVES: This study aimed to determine the effects of an oral melatonin treatment to pregnant ewes at high-altitude, on the cerebrovascular function of their neonates. STUDY DESIGN: Ten high-altitude pregnant sheep received either vehicle or melatonin (10 mg/d) during the last third of gestation until delivery. Postnatal daily hemodynamic measurements were recorded from lambs until 12 days old. In addition, lambs were submitted to a graded oxygenation protocol to assess cerebrovascular responses. Subsequently, lambs were euthanized, and middle cerebral arteries (MCA) were collected for vascular function, protein levels, and morphostructural analyses. RESULTS: Antenatal treatment doubled plasma levels of melatonin in pregnant ewes. Melatonin increased carotid flow and decreased carotid vascular resistance in the lambs by the end of the first week. Furthermore, melatonin increased MCA's maximal vasoconstrictor and vasodilator responses, associated with nitric oxide-dependent and independent mechanisms. CONCLUSIONS: An oral treatment with melatonin during pregnancy promotes postnatal cerebral perfusion in chronically hypoxic neonates. Melatonin is a potential treatment for cerebrovascular dysfunction due to perinatal chronic hypoxia.
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Melatonina , Animales , Antioxidantes/farmacología , Femenino , Hipoxia/tratamiento farmacológico , Pulmón , Melatonina/farmacología , Estrés Oxidativo , Embarazo , OvinosRESUMEN
In this work, a novel numerical-experimental procedure is proposed, through the use of the Cardiac Simulation Test (CST), device that allows the exposure of the arterial tissue to in-vitro conditions, mimicking cardiac cycles generated by the heart. The main goal is to describe mechanical response of the arterial wall under physiological conditions, when it is subjected to a variable pressure wave over time, which causes a stress state affecting the biomechanical behavior of the artery wall. In order to get information related to stress and strain states, numerical simulation via finite element method, is performed under a condition of systolic and diastolic pressure. The description of this methodological procedure is performed with a sample corresponding to a sheep aorta without cardiovascular pathologies. There are two major findings: the evaluation of the mechanical properties of the sheep aorta through the above-mentioned tests and, the numerical simulation of the mechanical response under the conditions present in the CST. The results state that differences between numerical and experimental circumferential stretch in diastole and systole to distinct zones studied do not exceed 1%. However, greater discrepancies can be seen in the distensibility and incremental modulus, two main indicators, which are in the order of 30%. In addition, numerical results determine an increase of the principal maximum stress and strain between the case of systolic and diastolic pressure, corresponding to 31.1% and 14.9% for the stress and strain measurement respectively; where maximum values of these variables are located in the zone of the ascending aorta and the aortic arch.
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Aorta Torácica , Aorta , Animales , Presión Sanguínea , Flujo Pulsátil , Ovinos , Estrés MecánicoRESUMEN
In this study, we assessed the effects of Atrial Natriuretic Peptide (ANP) and Cinaciguat, as experimental medicines to treat neonatal lambs exposed to chronic hypoxic conditions. To compare the different treatments, the mechanical responses of aorta, carotid, and femoral arterial walls were analyzed by means of axial pre-stretch and ring-opening tests, through a study with n = 6 animals for each group analyzed. The axial pre-stretch test measures the level of shortening in different zones of the arteries when extracted from lambs, while the ring-opening test is used to quantify the degree of residual circumferential deformation in a given zone of an artery. In addition, histological studies were carried out to measure elastin, collagen, and smooth muscle cell (SMC) nuclei densities, both in control and treated groups. The results show that mechanical response is related with histological results, specifically in the proximal abdominal aorta (PAA) and distal carotid zones (DCA), where the cell nuclei content is related to a decrease of residual deformations. The opening angle and the elastic fibers of the aorta artery were statistically correlated (p < 0.05). Specifically, in PAA zone, there are significant differences of opening angle and cell nuclei density values between control and treated groups (p-values to opening angle: Control-ANP = 2 â 10-2, Control-Cinaciguat = 1 â 10-2; p-values to cell nuclei density: Control-ANP = 5 â 10-4, Control-Cinaciguat = 2 â 10-2). Respect to distal carotid zone (DCA), significant differences between Control and Cinaciguat groups were observed to opening angle (p-value = 4 â 10-2), and cell nuclei density (p-value = 1 â 10-2). Our findings add evidence that medical treatments may have effects on the mechanical responses of arterial walls and should be taken into account when evaluating the complete medical outcome.
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This work presents numerical simulations and an experimental validation of sheet laser forming processes using general scanning paths with different laser beam operating parameters (i.e., power, diameter, and scanning speed) in two specific graphite coated stainless steel blanks (i.e., with thicknesses of 0.3 mm and 0.6 mm for the AISI 302 and 304 alloys, respectively). To this end, three specific laser forming tests involving single S-shaped, multiple circular, and single piecewise linear scanning paths are carried out. On the other hand, the numerical simulation of these tests is performed via a coupled thermomechanical finite element formulation, accounting for large viscoplastic strains, temperature-dependent material properties, and convection-radiation phenomena. The final bending angles provided by this model are found to be in good agreement with the experimental measurements for all of the cases studied. Therefore, this modeling framework can be established as a reliable approach to predict the material thermomechanical response during sheet laser forming using general scanning paths.
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We present a pilot study to evaluate the benefit of static facial suspension with Silhouette sutures. We operated on a female patient with complete facial palsy secondary to otic tuberculosis. The patient has currently achieved satisfactory facial symmetry, mastication and speech production. As a result, self-esteem and social interaction have also been recovered. Static facial suspension with Silhouette sutures is an alternative to dynamic techniques in patients who do not wish to or cannot undergo those more complex surgeries.
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Músculos Faciales/cirugía , Parálisis Facial/cirugía , Procedimientos de Cirugía Plástica , Técnicas de Sutura , Anciano , Trastornos de la Articulación/etiología , Trastornos de la Articulación/psicología , Trastornos de la Articulación/cirugía , Estética , Asimetría Facial/etiología , Asimetría Facial/psicología , Asimetría Facial/cirugía , Parálisis Facial/etiología , Parálisis Facial/psicología , Femenino , Humanos , Relaciones Interpersonales , Masticación , Osteomielitis/complicaciones , Satisfacción del Paciente , Hueso Petroso , Proyectos Piloto , Autoimagen , Tuberculosis Osteoarticular/complicacionesRESUMEN
When otologic procedures that involve tympanic membrane repairs are performed, biomaterials or biological tissues as normal as grafts are used. At the moment, biological material from the own patient is used with varying success rates. The procedure used and the patient's tissue repair capabilities tend to determine the outcome. We present a preliminary study on tympanic membrane perforation repairs using an autograft obtained by manipulating platelet degranulation and the coagulation cascade and reinforced with a seal using platelet growth factors. We present three cases in which we used this procedure. The results will be valued based on the tympanic perforation closure index. With this study, we want to assess the effectiveness of tympanic perforation repairs with this technically simple method. If this method was objectively proved to be effective, it would lead to lower patient morbidity and sanitary costs.
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INTRODUCTION AND OBJECTIVES: Therapeutic indication of peripheral facial paralysis depends on the degree of nerve injury. Severe facial palsy (electroneuronographic study less than or equal to 10%) leads to healing with sequelae. The sequelae of facial paralysis are contractures, hemifacial spasm and synkinesis.Our purpose was to demonstrate that these patients could benefit from rehabilitation treatment. METHODS: We present a study of 48 patients with severe peripheral facial paralysis. They were treated from the beginning of reinnervation with botulinum toxin and facial exercises according to the Wisconsin School. RESULTS: The subjective efficacy of rehabilitation is high. CONCLUSIONS: Rehabilitation treatment can inform patients about their chances of recovery, give them control over and quality of facial expression and help to achieve greater facial symmetry. These factors provide better functionality and quality of life.