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Since 2014, the Agricultural Operator Exposure Model (AOEM) has been the harmonised European model used for estimating non-dietary operator exposure to pesticide. It is based on studies conducted by the pesticide companies and it features 13 different crops including non-agricultural areas such as amenity grasslands. The objective of this study was to compare the dermal exposure measured during a field study conducted in a non-agricultural area with the corresponding values estimated by the model AOEM. The non-controlled field study was conducted in France in 2011 and included 24 private and public gardeners who apply glyphosate with knapsack sprayers. Dermal exposure was measured using the whole-body method and cotton gloves. Each measured value had an estimated value given by AOEM and we tested their correlation using linear regression. The model overestimated body exposure for all observations and there was no correlation between values. However, it underestimated hand exposure by 42 times and it systematically underestimated the exposure when the operators were wearing gloves, especially during the application. The model failed at being conservative regarding hand exposure and highly overestimated the protection afforded by the gloves. At a time of glyphosate renewed approval in Europe, non-controlled field studies conducted by academics are needed to improve AOEM model, especially in the non-agricultural sector. Indeed, among the 34 studies included in the model, none were conducted on a non-agricultural area and only four assessed the exposure when using a knapsack sprayer. Moreover, knapsack sprayers being the main equipment used worldwide in both agricultural and non-agricultural settings, it is also crucial to integrate new data specific to this equipment in the model. Operator exposure should be estimated with accuracy in the registration process of pesticides to ensure proper safety as well as in epidemiological studies to improve exposure assessment.
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Exposición Profesional , Plaguicidas , Plaguicidas/análisis , Parques Recreativos , Exposición Profesional/análisis , Agricultura , GlifosatoRESUMEN
BACKGROUND: Patients with glioblastomas have a dismal prognosis, and there is no circulating predictive or prognostic biomarker. Circulating progastrin, hPG80, is a tumor-promoting peptide present in the blood of patients with various cancers that has been shown to have prognostic value. We evaluated the prognostic value of plasma hPG80 in patients with isocitrate dehydrogenase-wild type glioblastoma after surgery. PATIENTS AND METHODS: A multicentric retrospective study in glioblastoma patients treated with standard radio-chemotherapy was conducted. The hPG80 levels were measured in plasma EDTA samples collected after surgery with an ELISA DxPG80.lab kit (Biodena Care, Montpellier, France), which has a detection threshold of 1.2 pM. The relationship between post-operative hPG80 plasma levels, in combination with other known prognostic factors, and patients' progression-free survival (PFS) and overall survival (OS) was evaluated. RESULTS: Sixty-nine patients were assessable. Plasma samples were collected after tumor biopsy (B), partial resection (PR), and complete resection (CR) for 22, 25, and 22 patients, respectively. At a median concentration of 5.37 pM (interquartile range 0.00-13.90 pM), hPG80 was detected in 48 (70%) patients (hPG80+). CR was associated with significant lower values of hPG80 levels: the median value was 0.7 versus 9.1 pM for PR (P = 0.02) and 8.3 pM for B (P = 0.004). The hPG80 detection rate was also significantly lower: 50% (CR) versus 72% (PR) versus 86% (B) (P = 0.005). The median follow-up was 39 months [22.4 months-not reached]. hPG80 post-operative detection was associated with numerically shorter PFS (6.4 versus 9.4 months, P = 0.13) and OS (14.5 versus 20.9 months, P = 0.11). In multivariate analysis, hPG80 was a prognostic factor for OS (P = 0.034). CONCLUSIONS: Circulating hPG80 could serve as a new prognostic biomarker after surgery in patients with glioblastoma treated with radio-chemotherapy.
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Glioblastoma , Humanos , Glioblastoma/cirugía , Glioblastoma/tratamiento farmacológico , Estudios Retrospectivos , Pronóstico , BiomarcadoresRESUMEN
OBJECTIVES: Among patients over 75 years, little is known about functional decline due to COVID-19. The aim of this study was to explore this functional decline, compare to other infectious pneumonia. DESIGN AND SETTING: This case-control study included all COVID-19 patients hospitalized from March to December 2020 in Acute Geriatric Ward in Nantes University Hospital matched 1/1 with patients with pneumonia hospitalized in geriatric department between March 2017 and March 2019 (controls) on sex, age. Functional decline was assessed at 3 month follow up as it is routinely done after hospitalization in geriatric ward. We performed multivariable analyses to compare clinical outcomes between patients with COVID-19 vs controls. RESULTS: 132 pairs were matched on age (mean: 87 y-o), and sex (61% of women). In multivariable logistic regression analysis, there were no statistical significant association between COVID-19 infection and functional decline (OR=0.89 p=0.72). A statistical significant association was found between functional decline and Charlson comorbidity index (OR=1.17, p=0.039); prior fall (OR=2.08, p=0.012); malnutrition (OR=1.97, p=0.018); length of hospital stay (OR=1.05, p=0.002) and preadmission ADL(OR=1.25, p=0.049). CONCLUSION: COVID-19 does not seem to be responsible for a more frequent or severe functional decline than other infectious pneumonia in older and comorbid population after 3 month follow up. In this population, pneumonia is associated with functional decline in almost 1 in 2 cases. The individual preadmission frailty seems to be a more important predictor of functional decline, encouraging multidimensional care management for this population.
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COVID-19 , Neumonía , Anciano , COVID-19/epidemiología , Estudios de Casos y Controles , Femenino , Evaluación Geriátrica/métodos , Hospitalización , Humanos , Neumonía/complicaciones , Neumonía/epidemiología , SobrevivientesRESUMEN
INTRODUCTION: Knowledge on the health of greenspace workers is scarce, even though they are exposed to many occupational hazards. The aim of this study was to analyze mortality by cause, prevalence of some non-cancer diseases, and incidence of the main cancers among greenspace workers. METHODS: A sub-cohort of greenspace workers was formed within the AGRICAN cohort. Demographic information, health characteristics and self-reported diseases at enrollment were described separately in terms of frequencies (%), median and Interquartile Range (IQR) for greenspace workers, farmers, and other non-agricultural workers. Causes of death and cancer incidence were identified through linkage with cancer registries from enrollment (2005-2007) to 2015. Hazard ratio (HR) and 95% Confidence Intervals [95% CI] were estimated using Cox proportional hazard regression with age as the underlying timescale. RESULTS: The sub-cohort included 6247 greenspace workers who were higher proportion men, younger and more frequently smokers than farmers and non-agricultural workers. Male and female greenspace workers reported more history of allergic diseases; and males, more history of depression. Compared to other workers male greenspace workers showed a non-significant higher mortality from ischemic cardiological diseases (HR = 1.14 [0.81-1.60]). Incidence was higher in male greenspace workers than farmers for overall cancer (HR = 1.15 [1.04-1.27]), cancer of the prostate (HR = 1.21 [1.02-1.44]), thyroid (HR = 2.84 [1.26-6.41]), testis (HR = 3.98 [1.50-10.58]) and skin melanoma (HR = 2.15 [1.33-3.47]). Non-significant increased risks were also found for sarcomas, larynx and breast. In women, risk of breast cancer was higher in greenspace workers than in farmers (HR = 1.71 [1.17-2.50]). CONCLUSIONS: Whereas greenspace workers have often been included with other pesticide applicators in epidemiological studies, our analyses highlighted the differences between these two populations. They demonstrate the need to study them separately and to investigate more thoroughly the role of specific occupational exposures such as pesticides as well as the effect on women.
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Neoplasias de la Mama , Exposición Profesional , Plaguicidas , Agricultores , Femenino , Humanos , Incidencia , Masculino , Parques RecreativosRESUMEN
CONTEXT: The greenspace sector includes a broad range of occupations: gardeners, landscapers, municipal workers, maintenance operators of public facilities, golf-course employees and other sports facilities, horticulturists, plant and tree nursery workers etc. The health impact of occupational pesticide exposure has mainly been studied among farmers. Other professionals such as greenspace workers are also extremely exposed, presenting specific exposure features (practices, types of pesticide used). The aim of this review was to summarize epidemiological literature that examine the relationship between pesticide exposure and the risk of cancer and long-term health effects in greenspace workers. METHOD: Six main groups of greenspace workers were identified and examined through a systematic literature review based on PubMed and Scopus. The studies were then grouped according to their design, health outcomes and the type of population studied. RESULTS: Forty-four articles were selected among the 1679 identified. Fifteen studies were conducted exclusively among greenspace workers, while ten also studied these workers with other pesticide applicators. Six were cohorts from the general population in which greenspace workers were identified. Elevated risks were found in several studies for leukaemia, soft-tissue sarcoma, multiple myeloma, non-Hodgkin lymphoma and Parkinson's disease. DISCUSSION: The majority of studies used rough parameters for defining exposure such as job titles which could lead to the misclassification of exposure, with the risk of false or positive negative conclusions. Health outcomes were mainly collected through registries or death certificates, and information regarding potential confounders was often missing. CONCLUSION: The review identified only 15 studies conducted exclusively among greenspace workers. Elevated risk was found for several sites of cancer and Parkinson's diseases. Further epidemiological research is needed, conducted specifically on these workers, to better characterize this population, its exposure to pesticides and the related health effects.
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Enfermedades de los Trabajadores Agrícolas , Neoplasias , Enfermedades del Sistema Nervioso , Exposición Profesional , Plaguicidas , Estudios Epidemiológicos , Humanos , Neoplasias/inducido químicamente , Neoplasias/epidemiología , Exposición Profesional/análisis , Parques Recreativos , Plaguicidas/análisis , Plaguicidas/toxicidadRESUMEN
OBJECTIVE: To estimate the impact of adding low-molecular-weight heparin (LMWH) or unfractionated heparin to low-dose aspirin started ≤ 16 weeks' gestation on the prevalence of pre-eclampsia (PE) and the delivery of a small-for-gestational-age (SGA) neonate. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed by searching the medical databases PubMed, EMBASE, Web of Science and Cochrane Central. Pregnant women randomized to receive LMWH or unfractionated heparin in addition to low-dose aspirin were compared with those who received low-dose aspirin alone. Outcome measures were PE, severe PE, early-onset PE and SGA. Pooled relative risks (RRs) with 95% CI were calculated using a random-effects model. RESULTS: Eight RCTs met the inclusion criteria; the indication for recruitment was previous recurrent miscarriage in five studies (three included women with thrombophilia) and a history of severe or early-onset PE in three studies (including women with thrombophilia in one). LMWH was administered in seven studies and unfractionated heparin in one. In women with a history of PE, treatment with LMWH and aspirin, compared with aspirin alone, was associated with a significant reduction in development of PE (three trials (n = 379); RR, 0.54 (95% CI, 0.31-0.92); P = 0.03) and in delivery of SGA neonates (two trials (n = 363); RR, 0.54 (95% CI, 0.32-0.91); P = 0.02). These outcomes were not significantly reduced in women with recurrent miscarriage who received LMWH and aspirin, compared with aspirin alone. The small number of studies precluded sensitivity analyses and the evaluation of publication biases. Blinding to the allocation treatment was absent in all RCTs. CONCLUSIONS: Based on limited evidence, the addition of LMWH to low-dose aspirin could reduce the prevalence of PE and SGA in women with a history of PE. This observation should be the basis of a well-conducted future trial rather than a recommendation for immediate clinical application. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
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Aspirina/administración & dosificación , Heparina de Bajo-Peso-Molecular/administración & dosificación , Preeclampsia/prevención & control , Aspirina/uso terapéutico , Quimioterapia Combinada/métodos , Femenino , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Embarazo , Primer Trimestre del Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Finite element (FE) analysis is a widely used tool for extensive preclinical testing of orthopaedic implants such as hip resurfacing femoral components, including evaluation of different stem fixation scenarios (cementation vs osseointegration, etc.). Most FE models use surface-to-surface contact elements to model the load-bearing interfaces that connect bone, cement and implant and neglect the mechanical effects of phenomena such as residual stresses from bone cement curing. The objective of the current study is to evaluate and quantify the effect of different stem fixation scenarios and related phenomena such as residual stresses from bone cement curing. Four models of a previously clinically available implant (Durom) were used to model different stem fixation scenarios of a new biomimetic stem: a cemented stem, a frictional stem, a partially and completely bonded stem, with and without residual stresses from bone cement curing. For the frictional stem, stem-bone micromotions were increased from 0% to 61% of the available surface subjected to micromotions between 10 and 40µm with the inclusion of residual stresses from bone cement curing. Bonding the stem, even partially, increased stress in the implant at the stem-head junction. Complete bonding of the stem decreased bone strain at step tip, at the cost of increased strain shielding when compared with the frictional stem and partially bonded stem. The increase of micromotions and changes in bone strain highlighted the influence of interfacial conditions on load transfer, and the need for a better modeling method, one capable of assessing the effect of phenomena such as interdigitation and residual stresses from bone cement curing.
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Artroplastia de Reemplazo de Cadera , Biomimética/instrumentación , Retención de la Prótesis/métodos , Cementos para Huesos , Densidad Ósea , Remodelación Ósea , Fémur/fisiología , Fémur/cirugía , Análisis de Elementos Finitos , Prótesis de Cadera , Humanos , Estrés Mecánico , Soporte de PesoRESUMEN
BACKGROUND: When activated, NF-κB can promote the nuclear import and transcription of DNA possessing NF-κB consensus sequences. Here, we investigated whether NF-κB is involved in the plasmid electrotransfer process. METHODS: Mouse tibial cranial muscles were transfected with plasmids encoding luciferase bearing or not NF-κB consensus sequences. Luciferase transgene expression was evaluated noninvasively by luminescence imaging and the number of pDNA copies in the same muscles by qPCR. RT-PCR of heat shock protein HsP70 mRNA evidenced cell stress. Western blots of phosphorylated IkBα were studied as a marker of NF-κB activation. RESULTS: Intra-muscular injection of a plasmid bearing a weak TATA-like promoter results in a very low muscle transfection level. Electrotransfer significantly increased both the number of pDNA copy and the transgene expression of this plasmid per DNA copy. Insertion of NF-κB consensus sequences into pDNA significantly increased the level of gene expression both with and without electrotransfer. Electrotransfer-induced cellular stress was evidenced by increased HsP70 mRNA. Phosphorylated IκBα was slightly increased by simple pDNA injection and a little more by electrotransfer. We also observed a basal level of phosphorylated IκBα and thus of free NF-κB in the absence of any stimulation. GENERAL SIGNIFICANCE: pDNA electrotransfer can increase transgene expression independently of NF-κB. The insertion of NF-κB consensus sequences into pDNA bearing a weak TATA-like promoter leads to enhanced transgene expression in muscle with or without gene electrotransfer. Finally, our results suggest that the basal amount of free NF-κB in muscle might be sufficient to enhance the activity of pDNA bearing NF-κB consensus sequences.
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Much of our knowledge of galaxies comes from analysing the radiation emitted by their stars, which depends on the present number of each type of star in the galaxy. The present number depends on the stellar initial mass function (IMF), which describes the distribution of stellar masses when the population formed, and knowledge of it is critical to almost every aspect of galaxy evolution. More than 50 years after the first IMF determination, no consensus has emerged on whether it is universal among different types of galaxies. Previous studies indicated that the IMF and the dark matter fraction in galaxy centres cannot both be universal, but they could not convincingly discriminate between the two possibilities. Only recently were indications found that massive elliptical galaxies may not have the same IMF as the Milky Way. Here we report a study of the two-dimensional stellar kinematics for the large representative ATLAS(3D) sample of nearby early-type galaxies spanning two orders of magnitude in stellar mass, using detailed dynamical models. We find a strong systematic variation in IMF in early-type galaxies as a function of their stellar mass-to-light ratios, producing differences of a factor of up to three in galactic stellar mass. This implies that a galaxy's IMF depends intimately on the galaxy's formation history.
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Reinforcing biodegradable polymers with phosphate-based glass fibres (PGF) is of interest for bone repair and regeneration. In addition to increasing the mechanical properties, PGF can also release bioinorganics, as they are water soluble, a property that may be controllably translated into a fully degradable composite. Herein, the effect of Si and Fe on the solubility of calcium-containing phosphate-based glasses (PG) in the system (50P(2)O(5)-40CaO-(10-x)SiO(2)-xFe(2)O(3), where x=0, 5 and 10 mol.%) were investigated. On replacing SiO(2) with Fe(2)O(3), there was an increase in the glass transition temperature and density of the PG, suggesting greater crosslinking of the phosphate chains. This significantly reduced the dissolution rates of degradation and ion release. Two PG formulations, 50P(2)O(5)-40CaO-10Fe(2)O(3) (Fe10) and 50P(2)O(5)-40CaO-5Fe(2)O(3)-5SiO(2) (Fe5Si5), were melt drawn into fibres and randomly incorporated into polycaprolactone (PCL). Initially, the flexural strength and modulus significantly increased with PGF incorporation. In deionized water, PCL-Fe(5)Si(5) displayed a significantly greater weight loss and ion release compared with PCL-Fe10. In simulated body fluid, brushite was formed only on the surface of PCL-Fe(5)Si(5). Dynamic mechanical analysis in phosphate buffered saline (PBS) at 37°C revealed that the PCL-Fe10 storage modulus (E') was unchanged up to day 7, whereas the onset of PCL-Fe(5)Si(5)E' decrease occurred at day 4. At longer-term ageing in PBS, PCL-Fe(5)Si(5) flexural strength and modulus decreased significantly. MC3T3-E1 preosteoblasts seeded onto PCL-PGF grew up to day 7 in culture. PGF can be used to control the properties of biodegradable composites for potential application as bone fracture fixation devices.
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Sustitutos de Huesos/farmacología , Fosfatos de Calcio/farmacología , Vidrio/química , Hierro/farmacología , Poliésteres/farmacología , Silicio/farmacología , Animales , Líquidos Corporales/química , Adhesión Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Análisis Diferencial Térmico , Concentración de Iones de Hidrógeno/efectos de los fármacos , Iones , Ensayo de Materiales , Ratones , Microscopía Electrónica de Rastreo , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Temperatura , Factores de Tiempo , Agua/químicaRESUMEN
Hip resurfacing (HR) is a highly attractive option for young and active patients. Some surgeons have advocated cementing the metaphyseal stem of the femoral component to improve fixation and survivorship of HR. However, extending component fixation to the metaphysis may promote femoral head strain shielding, which in turn may reduce survival of the femoral component. Replacing the metallic metaphyseal stem by a composite material with bone-matching properties could help to alleviate this phenomenon. This study uses finite element analysis to examine the strain state in the femoral head for three types of implant fixation: an unfixed metallic stem, an osseointegrated biomimetic stem and a cemented metallic stem. Bone remodeling is also simulated to evaluate long-term bone resorption due to strain shielding. Results show that the unfixed stem causes strain shielding in the femoral head, and that cementing the stem increases strain shielding. The biomimetic stem does not eliminate the strain shielding effect, but reduces it significantly versus the metallic cemented version. The current finite element study suggests that an osseointegrated metaphyseal stem made of biomimetic material in hip resurfacing implants could become an interesting alternative when fixation extension is desired.
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Artroplastia de Reemplazo de Cadera , Materiales Biomiméticos , Remodelación Ósea , Análisis de Elementos Finitos , Fenómenos Mecánicos , Metales , Anisotropía , Carbono , Fibra de Carbono , Humanos , Estrés MecánicoRESUMEN
Total hip arthroplasty (THA) enjoys excellent rates of success in older patients, but younger patients are still at risk of aseptic loosening and bone resorption from stress shielding. One solution to the stress shielding problem is to use a hip stem with mechanical properties matching those of cortical bone. The objective of the present study was to investigate numerically the biomechanical performance of such a biomimetic hip stem based on a hydroxyapatite (HA)-coated carbon fibre composite. A finite element model (FEM) of the biomimetic stem was constructed. Contact elements were studied to model the bone-implant interface in a non-osseointegrated and osseointegrated state in the best way. Three static load cases representing slow walking, stair climbing, and gait in a healthy individual were considered. Stress shielding and bone-implant interface micromotions were evaluated and compared with the results of a similar FEM based on titanium alloy (Ti-6Al-4V). The composite stems allowed for reduced stress shielding when compared with a traditional Ti-6Al-4V stem. Micromotions were slightly higher with the composite stem, but remained below 40 microm on most of the HA-coated surface. It is concluded that a biomimetic composite stem might offer a better compromise between stress shielding and micromotions than the Ti-6Al-4V stem with the same external geometry.
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Materiales Biocompatibles/química , Materiales Biomiméticos , Carbono/química , Prótesis de Cadera , Modelos Biológicos , Fenómenos Biomecánicos , Fibra de Carbono , Simulación por Computador , Cabeza Femoral/anatomía & histología , Cabeza Femoral/fisiología , Humanos , Oseointegración , Estrés MecánicoRESUMEN
Allantoic cysts are a somewhat rare entity. They are identifiable on antenatal ultrasound examination but are not easily distinguishable from pseudocysts, which are often associated with a poor prognosis. Their etiology remains obscure and obstructive uropathies have been proposed to be one of the underlying mechanisms. We report on a case in which both allantoic cysts and a patent urachus were detected antenatally and turned out to be associated with posterior urethral valves (PUV). The cysts were first seen in the early second trimester, with a full fetal bladder and patent urachus. They disappeared by the 29(th) week. During the subsequent sonographic examinations, the bladder was emptying regularly. The kidneys remained normal throughout the pregnancy. It is hypothesized that the increased pressure within the urinary tract kept the urachus patent, led to the formation of allantoic cysts and, later, to their perforation; this allowed the fetus to empty his bladder and kept him from the usual complications of PUV. This case emphasizes the importance of detection and characterization of umbilical cord cysts on antenatal ultasound examination and suggests that obstructive uropathies should be included in the differential diagnosis of umbilical cord cyst communicating with the fetal bladder.
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Quiste del Uraco/diagnóstico por imagen , Uretra/anomalías , Enfermedades Uretrales/diagnóstico por imagen , Enfermedades de la Vejiga Urinaria/diagnóstico por imagen , Adulto , Alantoides/diagnóstico por imagen , Femenino , Humanos , Riñón/diagnóstico por imagen , Riñón/embriología , Masculino , Embarazo , Ultrasonografía Prenatal , Quiste del Uraco/embriología , Uretra/diagnóstico por imagen , Enfermedades Uretrales/embriología , Enfermedades de la Vejiga Urinaria/embriologíaRESUMEN
Bioengineering approaches have been intensively applied to create small diameter vascular grafts using artificial materials. However, a fully successful, high performing and anti-thrombogenic structure has not been achieved yet. In this study, we have designed and fabricated a novel non-woven fibrous vascular graft with biomechanical properties closely resembling those of native vessels. Vascular cell growth, preservation of cell phenotype, retention of vasoactive properties, as well as the effect of gelatin coating on the cellular interaction with the scaffolds under static and shear stress conditions were investigated. The non-woven fibrous scaffolds were made from melt blown polyethylene terephthalate fiber webs stacked by means of a consolidation technique. The scaffold variables were fiber diameter distribution and the number of consolidated web stacks. SEM analysis confirmed various fiber diameter and pore size ranges corresponding to the different conditions. The scaffolds showed burst pressure values of â¼1500 mmHg and compliance (8.4 ± 1.0 × 10(-2) % mmHg(-1) ) very similar to those of native arteries (â¼8 × 10(-2) % mmHg(-1) ). The structure with the smallest fiber diameter range (1-5 µm) and pore size range (1-20 µm) was the most suitable for the growth of human brain endothelial cells and aortic smooth muscle cells. The cells maintained their specific cell phenotype, expressed collagen and elastin and produced cAMP in response to α-calcitonin gene-related peptide. However, under shear stress conditions (0.9 dyne cm(-2) ), only 30% of the cells were retained in both uncoated and gelatin-coated scaffolds indicating the need for improving the cell retention capacity of these structures, which is our future research direction. This study indicates that the biomechanical and biocompatible properties of this novel vascular scaffold are promising for the development of a vascular graft with similar characteristics to those of native vessels.
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Materiales Biocompatibles/química , Tereftalatos Polietilenos/química , Andamios del Tejido/química , Materiales Biocompatibles/metabolismo , Adhesión Celular/fisiología , Técnicas de Cultivo de Célula , Células Cultivadas , Circulación Cerebrovascular , Células Endoteliales/citología , Hemodinámica , Humanos , Ensayo de Materiales , Tereftalatos Polietilenos/metabolismo , Estrés MecánicoRESUMEN
Gene transfer into muscle cells is a key issue in biomedical research. Indeed, it is important for the development of new therapy for many genetic disorders affecting this tissue and for the use of muscle tissue as a secretion platform of therapeutic proteins. Electrotransfer is a promising method to achieve gene expression in muscles. However, this method can lead to some tissue damage especially on pathologic muscles. Therefore there is a need for the development of new and less deleterious methods. Triblock copolymers as pluronic L64 are starting to be used to improve gene transfer mediated by several agents into muscle tissue. Their mechanism of action is still under investigation. The combination of electrotransfer and triblock copolymers, in allowing softening electric field conditions leading to efficient DNA transfection, could potentially represent a milder and more secure transfection method. In the present study, we addressed the possible synergy that could be obtained by combining the copolymer triblock L64 and electroporation. We have found that a pre-treatment of cells with L64 could improve the transfection efficiency. This pre-treatment was shown to increase cell viability and this is partly responsible for the improvement of transfection efficiency. We have then labelled the plasmid DNA and the pluronic L64 in order to gain some insights into the mechanism of transfection of the combined physical and chemical methods. These experiences allowed us to exclude an action of L64 either on membrane permeabilization or on DNA/membrane interaction. Using plasmids containing or not binding sequences for NF-κB and an inhibitor of NF-κB pathway activation we have shown that this beneficial effect was rather related to the NF-κB signalling pathway, as it is described for other pluronics. Finally we address here some mechanistic issues on electrically mediated transfection, L64 mediated membrane permeabilization and the combination of both for gene transfer.
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Permeabilidad de la Membrana Celular/efectos de los fármacos , ADN , Portadores de Fármacos/química , Electroporación , Técnicas de Transferencia de Gen , Poloxámero/química , Animales , Células CHO , Supervivencia Celular/efectos de los fármacos , Cricetinae , Cricetulus , ADN/administración & dosificación , ADN/genética , Portadores de Fármacos/farmacología , Genes Reporteros , Luciferasas/genética , Plásmidos , Poloxámero/farmacología , TransfecciónRESUMEN
Bone loss around femoral implants used for THA is a persistent clinical concern. It may be caused by stress shielding, generally attributed to a mismatch in stiffness between the implants and host bone. In this regard, a fatigue resistant, carbon fiber (CF) composite femoral implant with bone-matching stiffness has been developed. This study evaluated the tissue response to the three material components of this implant in normal and textured (blasted with 24 grit alumina) surfaces: the hydroxyapatite (HA) coating, the CF composite and the intermediate crystalline HA particulate composite layer to bond to the HA coating (blended). Sprague-Dawley rats underwent bilateral femoral implantation each receiving two rod-like implants. Bone apposition to the HA (37%) and textured Ti (41%) implants was not significantly different. Bone apposition to the untextured CF (14%) and blended (19%) implants and polished Ti (8%) implants was significantly lower. Bone apposition to the textured CF (9%) and blended (11%) implants was lower (but not statistically from the as received or untextured counterparts). Nearly all sections from femurs containing CF implants presented CF debris. There was no evidence of localized bone loss or any strong immune response associated with any of the implant materials. All materials were well tolerated with minimal inflammation despite the presence of particulate debris. The high degree of bone apposition to the HA-coated composite implants and the lack of short-term inflammation and adverse tissue response to the three material implant component support continued evaluation of this composite technology for use in THA.
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Materiales Biocompatibles Revestidos/metabolismo , Durapatita/metabolismo , Fémur/cirugía , Implantes Experimentales , Animales , Artroplastia de Reemplazo de Cadera , Materiales Biocompatibles Revestidos/química , Durapatita/química , Fémur/patología , Humanos , Masculino , Ensayo de Materiales , Ratas , Ratas Sprague-DawleyRESUMEN
In cemented total hip arthroplasty (THA), porosity plays a major role in the fatigue failure of bone cement. Stem preheating procedure is known to reduce the stem/cement interfacial porosity. In the literature, no information is available about the effect of such procedure on cement bulk porosity. This study helps to find out if stem preheating can have a beneficial effect on bulk porosity, thus enhancing long-term bone cement integrity. A simplified experimental model of a stem/cement/bone construct of a cemented THA is designed to reproduce the mechanical boundary conditions of polymerizing cement. Effect of stem preheating and polymethylmethacrylate prechilling and mixing method (hand mixed and vacuum mixed) on cement porosity are investigated. Bulk porosity is analysed within three zones across the cement mantle in terms of pore number, pore area, and mean pore size. The results demonstrate that bulk cement porosity is strongly influenced by stem preheating, cement precooling as well as cement composition and mixing method. Stem preheating procedure displaces the porosity away from stem/cement interface toward bone; consequently reducing the pore area within the zone near the stem and increasing it in the middle and bone/cement zone. The most pronounced beneficial effect of stem preheating before implantation is visible for vacuum mixed procedure as the cement contains few pores of very small size (<100 µm). However, if stem is preheated, cement precooling should be avoided as it could counteract the beneficial effect of reduced porosity inside cement mantle.
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Artroplastia de Reemplazo de Cadera/métodos , Cementos para Huesos/química , Calor , Polimetil Metacrilato/uso terapéutico , Técnicas de Laboratorio Clínico , VacioRESUMEN
It is well known that interstitials affect the mechanical properties of titanium and titanium alloys. Their effects on the fatigue properties of titanium foams have not, however, been documented in the literature. This paper presents the effect of the oxygen content on the static and dynamic compression properties of titanium foams. Increasing the oxygen content from 0.24 to 0.51 wt% O in solution significantly increases the yield strength and reduces the ductility of the foams. However, the fatigue limit is not significantly affected by the oxygen content and falls within the 92 MPa +/- 12 MPa range for all specimens investigated in this study. During cyclic loading, deformation is initially coming from cumulative creep followed by the formation of microcracks. The coalescence of these microcracks is responsible for the rupture of the specimens. Fracture surfaces of the specimens having lower oxygen content show a more ductile aspect than the specimens having higher oxygen content.
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Oxígeno/química , Titanio/química , Aleaciones/química , Fuerza Compresiva , Ensayo de Materiales , Metales/química , Microscopía Electrónica de Rastreo/métodos , Equipo Ortopédico , Porosidad , Polvos , Presión , Soluciones , Propiedades de Superficie , Temperatura , Resistencia a la TracciónRESUMEN
A novel composite femoral stem has been developed to match cortical stiffness and achieve fixation by osseointegration with the primary goal to reduce cortical bone loss associated with stress shielding. The femoral stem consists of three distinct material layers: the first is a long carbon fiber (CF) in a polyamide 12 (PA12) polymer matrix (PA12/CF); the second is a PA12/HA (hydroxyapatite) interface; and the third is a plasma-sprayed coating of HA. In vitro studies with MG63 cells indicated that the HA surface supported improved proliferation and differentiation of osteoblast-like cells as determined by alkaline phosphatase activity and osteocalcin production when compared with Ti-6Al-4V (Ti64). In vivo studies comparing the composite and Ti64 rods in the rabbit femur demonstrated significantly higher bone apposition to the composite than Ti64 rods. The results of this study indicate that the invasion of surrounding bone cells and thus osteointegration together with its bone-matching mechanical properties make the PA12/CF/HA stem a promising hip replacement candidate.