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Purpose.The goal of this work is present results of field output factors (OF) using an IBA CC003 (Razor NanoChamber) and compare these results with PTW 60019 (MicroDiamond) and IBA Razor Diode. The experimental results for IBA CC003 were also compared with Monte Carlo (MC) Simulation, using Penelope and Ulysses programs. In addition, field output correction factors (kQclin,Qmsrfclin,fmsr) for IBA CC003 were derived with three different methods: (1) using PTW 60019 and IBA Razor as reference detectors; (2) comparison between MC and experimental measurements; and (3) using only MC.Material and Methods. The beam collimation included in this study were (1) square field size between 10 × 10 and 0.5 × 0.5 cm2defined by the MLC and jaws and (2) cones of different diameters. For IBA CC003 it was determined the polarity and ion collection efficiency correction factors in parallel and perpendicular orientation.Results.The results indicate (1) the variation of polarity effect with the field size is relevant for the determination of OF using IBA CC003, especially for parallel orientation; (2) there is no significant variation of the ion collection efficiency with the field size using IBA CC003 in parallel orientation; (3) OF differences between IBA CC003 and PTW 60019/IBA Razor, and experimental and MC results, increase with decreasing field size;ThekQclin,Qmsrfclin,fmsrresults indicate (1) using the first and second method,kQclin,Qmsrfclin,fmsrincrease with decreasing field size, which can be related with the influence of the volume effect and (2) using the third method,kQclin,Qmsrfclin,fmsrdecrease with decreasing field size, which can be explained by the perturbation effect.Conclusions. Our results demonstrate the need of applyingkQclin,Qmsrfclin,fmsrfor IBA CC003 forSclin≤1 cm, to compensate for volume averaging and perturbations effects.
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Simulación por Computador , Método de MontecarloRESUMEN
The primary replication site of Inï¬uenza A virus (IAV) is type II alveolar epithelial cells (AECII), which are central to normal lung function and present important immune functions. Surfactant components are synthesized primarily by AECII, which play a crucial role in host defense against infection. The aim of this study was to analyze if the impact of influenza infection is differential between A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) on costimulatory molecules and ProSP-C expression in AECII from BALB/c mice infected and A549 cell line infected with both strains. Pandemic A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) were used to infect BALB/c mice and the A549 cell line. We evaluated the surface expression of co-stimulatory molecules (CD45/CD31/CD74/ProSP-C) in AECII and A549 cell lines. Our results showed a significant decrease in ProSP-C+ CD31- CD45- and CD74+ CD31- CD45- expression in AECII and A549 cell line with the virus strain A(H1N1)pdm09 versus A/Victoria/3/75 (H3N2) and controls (non-infection conditions). Our findings indicate that changes in the expression of ProSP-C in AECII and A549 cell lines in infection conditions could result in dysfunction leading to decreased lung compliance, increased work of breathing and increased susceptibility to injury.
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Alphainfluenzavirus , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Animales , Humanos , Ratones , Células Epiteliales Alveolares , Subtipo H3N2 del Virus de la Influenza A , TensoactivosRESUMEN
BACKGROUND: Whole-of-school programs have demonstrated success in improving student physical activity levels, but few have progressed beyond efficacy testing to implementation at-scale. The purpose of our study was to evaluate the scale-up of the 'Internet-based Professional Learning to help teachers promote Activity in Youth' (iPLAY) intervention in primary schools using the RE-AIM framework. METHODS: We conducted a type 3 hybrid implementation-effectiveness study and collected data between April 2016 and June 2021, in New South Wales (NSW), Australia. RE-AIM was operationalised as: (i) Reach: Number and representativeness of students exposed to iPLAY; (ii) Effectiveness: Impact of iPLAY in a sub-sample of students (n = 5,959); (iii) Adoption: Number and representativeness of schools that received iPLAY; (iv) Implementation: Extent to which the three curricular and three non-curricular components of iPLAY were delivered as intended; (v) Maintenance: Extent to which iPLAY was sustained in schools. We conducted 43 semi-structured interviews with teachers (n = 14), leaders (n = 19), and principals (n = 10) from 18 schools (11 from urban and 7 from rural locations) to determine program maintenance. RESULTS: Reach: iPLAY reached ~ 31,000 students from a variety of socio-economic strata (35% of students were in the bottom quartile, almost half in the middle two quartiles, and 20% in the top quartile). EFFECTIVENESS: We observed small positive intervention effects for enjoyment of PE/sport (0.12 units, 95% CI: 0.05 to 0.20, d = 0.17), perceptions of need support from teachers (0.26 units, 95% CI: 0.16 to 0.53, d = 0.40), physical activity participation (0.28 units, 95% CI: 0.10 to 0.47, d = 0.14), and subjective well-being (0.82 units, 95% CI: 0.32 to 1.32, d = 0.12) at 24-months. Adoption: 115 schools received iPLAY. IMPLEMENTATION: Most schools implemented the curricular (59%) and non-curricular (55%) strategies as intended. Maintenance: Based on our qualitative data, changes in teacher practices and school culture resulting from iPLAY were sustained. CONCLUSIONS: iPLAY had extensive reach and adoption in NSW primary schools. Most of the schools implemented iPLAY as intended and effectiveness data suggest the positive effects observed in our cluster RCT were sustained when the intervention was delivered at-scale. TRIAL REGISTRATION: ACTRN12621001132831.
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Internet , Instituciones Académicas , Humanos , Adolescente , Estudiantes , Recolección de Datos , PlacerRESUMEN
INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38+ in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.
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Enfermedad de Alzheimer , Enfermedad de Parkinson , Linfocitos T CD4-Positivos , Citometría de Flujo , Humanos , FenotipoAsunto(s)
Humanos , Femenino , Preescolar , Parálisis/etiología , Poliomielitis/etiología , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/tratamiento farmacológico , Hipotonía Muscular , Enfermedades Neuromusculares/diagnóstico , Enfermedades Neuromusculares/terapia , Infecciones del Sistema Respiratorio , Brotes de Enfermedades , MielitisRESUMEN
BACKGROUND: It is estimated that less than one third of women (28%) worldwide, are not sufficiently active, and there is evidence indicating physical activity (PA) participation is lower during pregnancy and the postpartum period. Despite the importance of educating and encouraging postpartum women to engage in PA, existing systematic reviews have only focused on examining the impact of individually tailored PA interventions and on specific postpartum populations such as women who are inactive (i.e., do not meet PA recommendations) or women at risk of gestational diabetes mellitus or postnatal depression. This review aims to fill this gap by examining the impact of group-based PA interventions on postpartum women's PA levels or other health behavior outcomes. METHODS: A systematic literature search was conducted using four electronic databases (MEDLINE, CINAHL, EMBASE and PsychInfo) of published studies between 1st January 2000 and 31st October 2020. Studies were included if they targeted postpartum women with no current health conditions, had children aged 0-5 years, and engaged postpartum women in a group-based PA program that reported PA or other health behavior outcomes. Out of a total of 1091 articles that were initially identified, six were included. RESULTS: Group-based PA interventions were moderately successful in changing or increasing postpartum women's self-reported PA levels and psychological wellbeing in the first 2 years of their offspring's life. Overall, group-based PA interventions were not successful in changing or increasing postpartum women's objectively measured PA levels, but only one study objectively measured postpartum women's PA levels. Narrative synthesis highlights the heterogeneity of the outcomes and methodologies used, and the low to medium risk of bias in the included studies. CONCLUSION: To strengthen the evidence-base for group-based PA programs with postpartum women there is an on-going need for more rigorous randomised controlled trials of appropriate length (at least 3 months in duration) with an adequate dose of group-based PA sessions per week (to meet PA guidelines), and that utilise objective measures of PA. In addition, future PA interventions for this population should include, at the very least, fidelity and process data to capture the characteristics or design features that appeal most to postpartum women.
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Depresión Posparto , Periodo Posparto , Niño , Preescolar , Depresión Posparto/prevención & control , Ejercicio Físico , Femenino , Humanos , Lactante , Recién Nacido , Embarazo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND AND OBJECTIVE: Total Variation (TV) minimization algorithms have achieved great attention due to the virtue of decreasing noise while preserving edges. The purpose of this work is to implement and evaluate two TV minimization methods in 3D. Their performance is analyzed through 3D visualization of digital breast tomosynthesis (DBT) data with volume rendering. METHODS: Both filters were studied with real phantom and one clinical DBT data. One algorithm was applied sequentially to all slices and the other was applied to the entire volume at once. The suitable Lagrange multiplier used in each filter equation was studied to reach the minimum 3D TV and the maximum contrast-to-noise ratio (CNR). Imaging blur was measured at 0° and 90° using two disks with different diameters (0.5 mm and 5.0 mm) and equal thickness. The quality of unfiltered and filtered data was analyzed with volume rendering at 0° and 90°. RESULTS: For phantom data, with the sequential filter, a decrease of 25% in 3D TV value and an increase of 19% and 30% in CNR at 0° and 90°, respectively, were observed. When the filter is applied directly in 3D, TV value was reduced by 35% and an increase of 36% was achieved both for CNR at 0° and 90°. For the smaller disk, variations of 0% in width at half maximum (FWHM) at 0° and a decrease of about 2.5% for FWHM at 90° were observed for both filters. For the larger disk, there was a 2.5% increase in FWHM at 0° for both filters and a decrease of 6.28% and 1.69% in FWHM at 90° with the sequential filter and the 3D filter, respectively. When applied to clinical data, the performance of each filter was consistent with that obtained with the phantom. CONCLUSIONS: Data analysis confirmed the relevance of these methods in improving quality of DBT images. Additionally, this type of 3D visualization showed that it may play an important complementary role in DBT imaging. It allows to visualize all DBT data at once and to analyze properly filters applied to all the three dimensions. Concise Abstract Total Variation (TV) minimization algorithms are one compressed sensing technique that has achieved great attention due to the virtue of decrease noise while preserve edges transitions. The purpose of this work is to solve the same TV minimization problem in DBT data, by studying two 3D filters. The obtained results were analyzed at 0° and 90° with a 3D visualization through volume rendering. The filters differ in their application. One considers a slice-by-slice optimization, sequentially traversing all slices of the data. The other considers the intensity values of adjacent slices to make this optimization on each voxel. The performance of each filter was also tested with a clinical case. The results obtained were very encouraging with a significantly increased contrast to noise ratio at 0° and 90° and a small reduction in blur at 90° (slight reduction of the out-of-plane artifact).
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Mama , Mamografía , Algoritmos , Artefactos , Mama/diagnóstico por imagen , Fantasmas de ImagenRESUMEN
OBJECTIVE: To explore whether the IFNL3/4 rs12979860 genotype may influence serum levels or production of interferon-inducible protein-10 (IP-10) by peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE). METHODS: Sixty-six patients with SLE and 22 healthy blood donors (controls) were included. The IFNL3/4 rs12979860 polymorphism was genotyped by real-time polymerase chain reaction. IP-10 levels in sera supernatants of IFNα stimulated peripheral blood mononuclear cells were measured by enzime-linked immunosorbent assay. RESULTS: Allelic frequencies were CC (29%), CT (52%) and TT (20%) in SLE, and CC (32%), CT (41%) and TT (27%) in healthy controls. Median serum IP-10 levels were higher in SLE patients than in controls (190.8 versus 118.1 pg/ml; p < 0.001), particularly in those with high disease activity (278.5 versus 177.2 pg/ml; p = 0.037). However, serum IP-10 levels were not influenced by IFNL3/4 genotypes. Higher IP-10 production by peripheral blood mononuclear cells was found in both SLE patients (median 519.3 versus 207.6 pg/ml; p = 0.012) and controls (median 454.0 versus 201.7 pg/ml; p = 0.034) carrying the IFNL3/4 C allele compared with carriers of the T allele. CONCLUSIONS: Although IFNL3/4 rs12979860 allele C does not appear to influence serum IP-10 levels in SLE, it plays an important role in the production of IP-10 by peripheral blood mononuclear cells after IFNα stimulation.
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Quimiocina CXCL10/sangre , Interferones/genética , Interleucinas/genética , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Sistémico/genética , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Lupus Eritematoso Sistémico/sangre , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
Neglected tropical diseases (NTDs) share certain traits: they are parasitic infections, prevailing in tropical environments and affecting marginalized sectors of the population. Six NTDs - ascariasis, cysticercosis, echinococcosis, hookworm infection, onchocerciasis and trichuriasis - all of them endemic in Latin America and the Caribbean (LAC), are analysed in this work. This review aims to discuss key information on the function of excretory/secretory (E/S) proteins from these parasites in their infectivity, pathogeny and diagnosis. The modulation of the host immune system to favour the permanence and survival of the parasite is also discussed. An updated knowledge on the function of E/S molecules in endemic parasitoses in LAC may lead to new approaches for the clinical management and diagnosis of these diseases. In turn, this could allow us to optimize their treatment and make it more affordable - a relevant goal given the economic constraints that the region is facing.
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Enfermedades Endémicas , Proteínas del Helminto/fisiología , Helmintiasis/epidemiología , Sistema Inmunológico/parasitología , Enfermedades Desatendidas/parasitología , Animales , Región del Caribe/epidemiología , Manejo de la Enfermedad , Helmintiasis/inmunología , Helmintiasis/parasitología , Interacciones Huésped-Parásitos , Humanos , América Latina/epidemiología , Enfermedades Desatendidas/epidemiología , Enfermedades Desatendidas/inmunología , Medicina TropicalRESUMEN
Notwithstanding evidence that tuberculosis (TB) is declining, one of the greatest concerns to public health is the emergence and spread of multi-drug resistant strains of Mycobacterium tuberculosis (MDR-TB). MDR-TB are defined as strains which are resistant to at least isoniazid (INH) and rifampicin, the two most potent TB drugs, and their increasing incidence is a serious concern. Recently, notable efforts have been spent on research to pursue novel treatments against MDR-TB, especially on synergistic drug combinations as they have the potential to improve TB treatment. Our research group has previously reported promising synergistic antimicrobial effects between transition-metal compounds and antibiotics in Gram-negative and Gram-positive bacteria. In this work, we evaluated antimycobacterial activity of transition-metals/antibiotics combinatorial treatments against first-line drug resistant strains of Mycobacterium tuberculosis. Our data showed that INH/AgNO3 combinatorial treatment had an additive effect (bactericidal activity) in an isoniazid-resistant clinical strain of Mycobacterium tuberculosis. Moreover, in vitro evaluation of cytotoxicity induced by both, the individual tratments of AgNO3 and INH and the combinatorial treatment of INH/AgNO3 in murine RAW 264.7 macrophages and human A549 lung cells; showed no toxic effects. Together, this data suggests that the INH/AgNO3 combinatorial treatment could be used in the development of new strategies to treat resistant strains of Mycobacterium tuberculosis.
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Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Isoniazida/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Nitrato de Plata/farmacología , Células A549 , Animales , Antituberculosos/toxicidad , Proliferación Celular , Supervivencia Celular , Sinergismo Farmacológico , Humanos , Isoniazida/toxicidad , Ratones , Pruebas de Sensibilidad Microbiana , Células RAW 264.7 , Nitrato de Plata/toxicidad , Pruebas de ToxicidadRESUMEN
INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38 + in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.
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Nonlinear constitutive mechanical parameters, predominantly governed by micro-damage, interact with ultrasound to generate harmonics that are not present in the excitation. In principle, this phenomenon therefore permits early stage damage identification if these higher harmonics can be measured. To understand the underlying mechanism of harmonic generation, a nonlinear micro-mechanical approach is proposed here, that relates a distribution of clapping micro-cracks to the measurable macroscopic acoustic nonlinearity by representing the crack as an effective inclusion with Landau type nonlinearity at small strain. The clapping mechanism inside each micro-crack is represented by a Taylor expansion of the stress-strain constitutive law, whereby nonlinear terms arise. The micro-cracks are considered distributed in a macroscopic medium and the effective nonlinearity parameter associated with compression is determined via a nonlinear Mori-Tanaka homogenization theory. Relationships are thus obtained between the measurable acoustic nonlinearity and the Landau-type nonlinearity. The framework developed therefore yields links with nonlinear ultrasound, where the dependency of measurable acoustic nonlinearity is, under certain hypotheses, formally related to the density of micro-cracks and the bulk material properties.
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In this work, we present and describe the program ALPHACAL, specifically developed for the calibration of alpha-particle sources. It is therefore more user-friendly and less time-consuming than multipurpose codes developed for a wide range of applications. The program is based on the recently developed code AlfaMC, which simulates specifically the transport of alpha particles. Both cylindrical and point sources mounted on the surface of polished backings can be simulated, as is the convention in experimental measurements of alpha-particle sources. In addition to the efficiency calculation and determination of the backscattering coefficient, some additional tools are available to the user, like the visualization of energy spectrum, use of energy cut-off or low-energy tail corrections. ALPHACAL has been implemented in C++ language using QT library, so it is available for Windows, MacOs and Linux platforms. It is free and can be provided under request to the authors.
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In the study of mechanical properties of human bone, specimens may be defatted before experiments to prevent contamination and the risk of infections. High energy synchrotron radiation micro-computed tomography (SR-µCT) is a popular technique to study bone microstructure. However, little is known about the effects of defatting or irradiation during SR-µCT imaging on different elastic coefficients including shear and longitudinal moduli in different anatomical directions. In this work, these effects are evaluated on a set of 24 samples using resonant ultrasound spectroscopy (RUS), which allows one to accurately measure the complete set of elastic coefficients of cortical bone non destructively. The results show that defatting with diethylether and methanol and irradiation up to 2.5kGy has no detectable effect on any of the elastic coefficients of human cortical bone.
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Hueso Cortical/fisiología , Elasticidad , Humanos , Análisis Espectral , Sincrotrones , Microtomografía por Rayos X , Rayos XRESUMEN
Elasticity assessment based on bulk wave velocity (BWV) measurements is the most popular technique to characterize the anisotropic stiffness tensor in cortical bone. Typically, a cuboid bone specimen is cut with its sides along the different anatomical directions. Then, the velocity of shear and longitudinal waves propagating along different directions are assessed, from which stiffness coefficients are calculated. Despite the importance of obtaining accurate elasticity values for bone research, there is no generally accepted protocol to measure BWV and the precision of the technique has been seldom investigated. The purpose of this work is to critically assess the method to measure BWV on cuboid specimens in terms of ultrasound frequency, specimen size and signal processing technique. In this study, we measured polycarbonate specimens of different dimensions and 55 human bone specimens with different transducers using frequencies ranging from 2.25 to 10MHz and 1-5MHz for longitudinal and shear waves, respectively. We compared four signal processing methods to detect the wave arrival time. The main results are that, (1) the measurement of shear waves is more complex than that of longitudinal wave, being less precise and more sensitive to sample size; (2) the estimated stiffness depends on the signal processing technique used (up to 10% variation for shear coefficients of bone); and (3) bone stiffness assessed from BWV using the first arrival of the signal to determine the time-of-flight is not different from stiffness assessed using resonant ultrasound spectroscopy (RUS). These results evidence that the measurement method can have an effect on the stiffness values estimates and hence, a well-defined protocol is needed to accurately measure bone stiffness coefficients based on BWV.
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Hueso Cortical/diagnóstico por imagen , Diagnóstico por Imagen de Elasticidad/métodos , Fémur/diagnóstico por imagen , Anciano , Femenino , Humanos , Técnicas In Vitro , Masculino , Fantasmas de Imagen , Procesamiento de Señales Asistido por Computador , TransductoresRESUMEN
Neurocysticercosis is a clinically and radiologically heterogeneous disease, ranging from asymptomatic infection to a severe, potentially fatal clinical picture. The intensity and extension of the parasite-elicited inflammatory reaction is a key factor for such variability. The main features of the inflammatory process found in the brain and in the peripheral blood of neurocysticercosis patients will be discussed in this review, and the factors involved in its modulation will be herein presented.
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Encéfalo/patología , Inflamación/patología , Neurocisticercosis/inmunología , Neurocisticercosis/patología , Taenia solium/patogenicidad , Animales , Infecciones Asintomáticas , Encéfalo/parasitología , Humanos , Inflamación/inmunología , Inflamación/parasitología , Masculino , Neurocisticercosis/parasitología , Taenia solium/inmunologíaRESUMEN
Neurocysticercosis is caused by the establishment of Taenia solium cysticerci in the central nervous system. It is considered that, during co-evolution, the parasite developed strategies to modulate the host's immune response. The action mechanisms of regulatory T cells in controlling the immune response in neurocysticercosis are studied in this work. Higher blood levels of regulatory T cells with CD4(+) CD45RO(+) forkhead box protein 3 (FoxP3)(high) and CD4(+) CD25(high) FoxP3(+) CD95(high) phenotype and of non-regulatory CD4(+) CD45RO(+) FoxP3(med) T cells were found in neurocysticercosis patients with respect to controls. Interestingly, regulatory T cells express higher levels of cytotoxic T lymphocyte antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor (GITR), suggesting a cell-to-cell contact mechanism with dendritic cells. Furthermore, higher IL-10 and regulatory T cell type 1 (Tr1) levels were found in neurocysticercosis patients' peripheral blood, suggesting that the action mechanism of regulatory T cells involves the release of immunomodulatory cytokines. No evidence was found of the regulatory T cell role in inhibiting the proliferative response. Suppressive regulatory T cells from neurocysticercosis patients correlated negatively with late activated lymphocytes (CD4(+) CD38(+) ). Our results suggest that, during neurocysticercosis, regulatory T cells could control the immune response, probably by a cell-to-cell contact with dendritic cells and interleukin (IL)-10 release by Tr1, to create an immunomodulatory environment that may favour the development of T. solium cysticerci and their permanence in the central nervous system.
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Comunicación Celular/inmunología , Células Dendríticas/inmunología , Interacciones Huésped-Parásitos/inmunología , Interleucina-10/inmunología , Neurocisticercosis/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Anciano , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Antígeno CTLA-4/genética , Antígeno CTLA-4/metabolismo , Proliferación Celular , Citocinas/sangre , Citocinas/líquido cefalorraquídeo , Femenino , Proteína Relacionada con TNFR Inducida por Glucocorticoide/genética , Proteína Relacionada con TNFR Inducida por Glucocorticoide/metabolismo , Humanos , Interleucina-10/sangre , Antígenos Comunes de Leucocito , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Fenotipo , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/metabolismo , Taenia solium/inmunología , Proteína del Gen 3 de Activación de LinfocitosRESUMEN
BACKGROUND: During pregnancy, immunological and hormonal alterations place women at increased risk for influenza-related severe illnesses including hospitalization and death. Although A(H1N1) pdm09 infection resulted in increased disease severity in pregnant women, the precise mechanisms responsible for this risk have yet to be established. OBJECTIVES: The present study was aimed to investigate the role of host chemokines and cytokine profiles in A(H1N1) pdm09 infection regarding disease severity in pregnant women. STUDY DESIGN: This retrospective survey examined 41 pregnant women with confirmed A(H1N1) pdm09 infection. Of them, 12 died (D), 29 survived (S), and 17 remained uninfected and served as controls (C). Antiviral response was evaluated for IFN-ß expression and gene expression profiles of cytokines (TNF-α, IL-6, IL-12, TGF-ß) and chemokines (IL-8, RANTES, MCP-1, IP-10), and the viral Matrix (M1) gene was quantified and normalized using the housekeeping gene product ß-actin mRNA. RESULTS: Higher IL-8 and TNF-α mRNA expression were found in D and S compared with C, while IL-6 showed higher expression in D. Interestingly, these results were associated with a decrease in the anti-inflammatory response of TGF-ß mRNA and IFN-ß. These alterations would lead to an imbalance in the immune response of those patients. CONCLUSIONS: Pregnancy-related reductions in IFN-ß and TGF-ß expression levels and elevated levels of pro-inflammatory cytokines could explain the increased severity of infection and death of pregnant women. These findings may help improve the understanding of the high susceptibility and disease severity to influenza virus infection during pregnancy.
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Quimiocinas/genética , Citocinas/genética , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , Adulto , Quimiocinas/inmunología , Quimiocinas/aislamiento & purificación , Citocinas/inmunología , Citocinas/aislamiento & purificación , Femenino , Perfilación de la Expresión Génica , Humanos , Gripe Humana/mortalidad , Gripe Humana/virología , Interferón beta/genética , Interferón beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Interleucina-8/genética , Interleucina-8/inmunología , Embarazo , Complicaciones Infecciosas del Embarazo/mortalidad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/inmunología , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
During the gestation and the cervical remodelling, several changes occur progressively in the structure of the tissue. An increase in the hydration, disorganisation of collagen network and decrease in elasticity can be observed. The collagen structure disorganisation is particularly complex: collagen fibres turn thicker and more wavy as the gestation progresses in a transition from relatively straight fibres to wavy fibres, while pores between collagen fibres become larger and separated. Shear wave elastography is a promising but not yet fully understood tool to assess these structural changes and the cervix׳s ability to dilate. To this end, a numerical histo-mechanical model is proposed in the present study, which aims at linking variations in the microscopic histo-biomechanical processes with shear wave propagation characteristics. Parametric simulations are carried out for a broad range of mechanical and geometrical parameters. Results show a direct relationship between the histological and morphological changes during pregnancy and the viscoelastic behaviour of the tissue.