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BACKGROUND: Since the 2000's, plants have been used as bioreactors for the transient production of molecules of interest such as vaccines. To improve protein yield, "amplicon" vectors based on plant viruses are used. These viral constructs, engineered to carry the gene of interest replicate strongly once introduced into the plant cell, allowing significant accumulation of the protein. Here, we evaluated the suitability of the monocot-infecting RNA virus Rice yellow mottle virus (RYMV) as an amplicon vector. The promastigote surface antigen (PSA) of the protozoan Leishmania was considered as a protein of interest due to its vaccine properties against canine leishmaniasis. RESULTS: Since P1 (ORF1) and CP (ORF3) proteins are not strictly necessary for viral replication, ORF1 was deleted and the PSA gene was substituted to ORF3 in the RYMV-based vector. We evaluated its expression in the best described plant bioreactor system, Nicotiana benthamiana which, unlike rice, allows transient transformation by Agrobacterium. Despite not being its natural host, we demonstrated a low level of RYMV-based vector replication in N. benthamiana leaves. Under optimized ratio, we showed that the P19 silencing suppressor in combination with the missing viral CP ORF significantly enhanced RYMV amplicon replication in N. benthamiana. Under these optimized CP/P19 conditions, we showed that the RYMV amplicon replicated autonomously in the infiltrated N. benthamiana cells, but was unable to move out of the infiltrated zones. Finally, we showed that when the RYMV amplicon was expressed under the optimized conditions we set up, it allowed enhanced PSA protein accumulation in N. benthamiana compared to the PSA coding sequence driven by the 35S promoter without amplicon background. CONCLUSION: This work demonstrates that a non-dicot-infecting virus can be used as an amplicon vector for the efficient production of proteins of interest such as PSA in N. benthamiana leaves.
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Vectores Genéticos , Nicotiana , Hojas de la Planta , Nicotiana/genética , Nicotiana/virología , Vectores Genéticos/genética , Hojas de la Planta/virología , Animales , Perros , Antígenos de Protozoos/genética , Antígenos de Protozoos/inmunología , Reactores Biológicos , Plantas Modificadas Genéticamente/genéticaRESUMEN
Introduction : La nécessité de disposer de produits sanguins labiles (PSL) de qualité est un impératif de la transfusion sanguine. Le don de sang n'est pas sans risque pour le donneur. Ce qui soulève la question de la perte de fer par spoliation sanguine. Ce constat a conduit à la réalisation de cette étude dans le but de rechercher l'anémie chez le donneur de sang volontaire jugé apte après évaluation de l'hémoglobine pré-don et d'en déterminer la cause. Patients et méthodes : Il s'agissait d'une étude transversale prospective réalisée au Centre National de Transfusion Sanguine (CNTS) de Libreville. La population d'étude était constituée de donneurs de sang, nouveaux ou anciens, volontaires en bonne santé chez qui les examens suivant ont été réalisés pour le diagnostic de l'anémie et celui de la carence en fer tout en excluant d'autre étiologies: l'hémogramme, le dosage de la Protéine C Réactive (CRP), le fer sérique, la ferritine, l'hepcidine et le test de diagnostic du paludisme (TDR).Résultats : Sur l'ensemble des deux cent quinze volontaires inclus, trente - quatre (15,8%) présentaient une anémie parmi lesquels douze femmes et vingt- deux hommes d'un âge moyen de 32,8 ±8,0. Le nombre de dons effectués était corrélé à la survenue de l'anémie selon le genre et l'âge du donneur. Il en a été de même pour les valeurs de la ferritine, du fer sérique.Conclusion : Le nombre important d'anémie est lié à un seuil bas de l'hémoglobine pré-don. Le caractère microcytaire hypochrome de l'anémie laisse supposer une origine ferriprive.
Introduction: The need to have quality labile blood products (LBP) is an imperative of blood transfusion. Blood donation is not without risk for the donor. This raises the question of the loss of iron by blood spoliation. This finding led to the realization of this study with the aim of looking for anemia in voluntary blood donors deemed suitable after evaluation of the pre-donation hemoglobin and to determine the cause.Patients and methods: This was a prospective cross-sectional study carried out at the National Blood Transfusion Center (CNTS) in Libreville. The study population consisted of blood donors, new or old, healthy volunteers in whom the following examinations were carried out for the diagnosis of anemia and that of iron deficiency while excluding other etiologies: blood count, C-Reactive Protein (CRP), serum iron, ferritin, hepcidin and malaria diagnostic test (RDT). Results: Of the two hundred and fifteen volunteers included, thirty-four (15.8%) presented anemia, including twelve women and twenty-two men with an average age of 32.8 ±8.0. The number of donations made was correlated with the occurrence of anemia according to the sex and age of the donor. It was the same for the values of ferritin, serum iron. Conclusion: The large number of anemia is linked to a low threshold of pre-donation hemoglobin. The hypochromic microcytic character of the anemia suggests an iron deficiency origin.
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Humanos , Masculino , Femenino , Donación de Oocito , Anemia Mielopática , Donantes de Tejidos , Transfusión Sanguínea , Hemoglobina FetalRESUMEN
PURPOSE: To assess the ability of patients with exudative AMD to detect exudative recurrence. Another objective was to assess if self-monitoring, as currently taught, improves this ability. MATERIALS AND METHODS: An observational cross-sectional study was carried out in the ophthalmology center of BeauSoleil clinic in Montpellier between March 1 and April 1 2016. Inclusion criteria were presence of neovascular age related macular degeneration treated with the loading dose of three monthly intravitreal anti-VEGF injections, with at least one injection in the past 12 months and at least one exudative recurrence. All patients underwent a visual acuity measurement with ETDRS charts at 4 meters. A questionnaire assessed familiarity with the Amsler grid and its proper use, performance of and type of self-monitoring at home and the subjective feeling of an exudative recurrence at the visit with a 5-level Likert scale. RESULTS: A total of 94 eyes of 70 patients were included in this study with 69.0 % women and a median (interquartile range) age of 83 (77-96) years. Among them, 81 % performed regular self-monitoring, mostly with environmental Amsler tests (70 %). Only 63 % of the patients knew of the Amsler grid, among which 52 % used it correctly. Sensitivity (95 % confidence interval, 95 % CI) and specificity (95 % CI) of the subjective sensation of exudative recurrence were 0.32 (0.14-0.55) and 0.85 (0.74-0.92), respectively, for the entire population. Sensitivity (95 % CI) and specificity (95 % CI) were 0.33 (0.13-0.59) and 0.85 (0.74-0.93); 0.25 (0.0063-0.81) and 0.82 (0.48-0.98), respectively, in patients performing and not performing self-monitoring. CONCLUSION: Patients' prediction in wet AMD is insufficient in detecting exudative recurrences, even if regular self-monitoring with Amsler grid or environmental Amsler is performed.
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Autoevaluación Diagnóstica , Exudados y Transudados , Degeneración Macular/diagnóstico , Monitoreo Fisiológico , Anciano , Anciano de 80 o más Años , Estudios Transversales , Exudados y Transudados/fisiología , Femenino , Francia , Humanos , Degeneración Macular/patología , Masculino , Monitoreo Fisiológico/métodos , Recurrencia , Autocuidado/métodos , Autoeficacia , Sensibilidad y Especificidad , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/patologíaRESUMEN
Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.
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Daño del ADN , Simulación por Computador , Reparación del ADN , Transferencia Lineal de Energía , Modelos Teóricos , Método de MontecarloRESUMEN
At the European level (CEN/TC386), some efforts are currently devoted to new standards for comparing the efficiency of commercial photocatalytic material/devices in various application fields. Concerning prototype or commercial indoor photocatalytic air purifiers designed for volatile organic compounds (VOC) abatement, the methodology is based on a laboratory airtight chamber. The photocatalytic function is demonstrated by the mineralization of a mixture of five VOCs. Experimental data were obtained for four selected commercial devices and three commercial materials: drop of VOC concentration, but also identification of secondary species (with special attention to formaldehyde), mineralization rates, and Clean Air Delivery Rate (CADR). With two efficient air purifiers, these laboratory experiments were compared to the results in two experimental rooms (35-40 m3) where air pollution was introduced through wooden floor and furniture. The systems' ageing was also studied. The safety of the commercial products was also assessed by the determination of nanoparticle release. Standardized tests are useful to rank photocatalytic air purifiers and passive materials and to discard inefficient ones. A good correlation between the standard experiments and the experimental room experiments was found, even if in the latter case, the concentration of lower weight VOCs drops less quickly than that of heavier VOCs.
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Filtros de Aire , Contaminación del Aire Interior , Catálisis , Proyectos Piloto , Compuestos Orgánicos VolátilesRESUMEN
Since 1st January 2000, the PEDIAB-LR registry has listed new cases of diabetes in children under 16 years of age in the Languedoc-Roussillon region of France, in order to assess the incidence and epidemiological characteristics of children affected by diabetes. At the end of December 2010, 745 children had been registered. The characteristics of these children included an identical proportion of girls and boys, a mean age of 8 years at diagnosis, and a family history of type 1 diabetes in 8.4% of the cases. Inaugural ketoacidosis was observed in 69.5% of the patients and was severe in 23.7% of these cases. To replace intravenous insulin, a two-injection dosing regimen (in the morning and before dinner) was prescribed in 76.5% of cases, multi-injections of basal-bolus in 16%, and subcutaneous insulin infusion (insulin pump therapy) in 7.5% of cases. Between 2000 and 2010, there was no increase in overall incidence. It is noteworthy that age at diagnosis tended to decrease, but this was not statistically significant. In conclusion, the PEDIAB-LR registry is currently the only French registry on diabetes in children, analyzing many factors related to its incidence, such as age at diagnosis and the existence of ketoacidosis.
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Diabetes Mellitus/epidemiología , Adolescente , Niño , Preescolar , Femenino , Francia/epidemiología , Humanos , Incidencia , Lactante , Masculino , Estudios RetrospectivosRESUMEN
A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed.
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Gadolinio , Nanopartículas , Neoplasias/tratamiento farmacológico , Fármacos Sensibilizantes a Radiaciones , Animales , Medios de Contraste , Humanos , Imagen por Resonancia Magnética , Ratones , Modelos Teóricos , Neoplasias/radioterapia , Fármacos Sensibilizantes a Radiaciones/química , SiloxanosRESUMEN
Patient's values and preferences regarding the relative importance of preventing strokes and avoiding bleeding are now recognised to be of great importance in deciding on therapy for the prevention of stroke due to atrial fibrillation (SPAF). We used an iPad questionnaire to determine the minimal clinically important difference (Treatment Threshold) and the maximum number of major bleeding events that a patient would be willing to endure in order to prevent one stroke (Bleeding Ratio) for the initiation of antithrombotic therapy in 172 hospital in-patients with documented non-valvular atrial fibrillation in whom anticoagulant therapy was being considered. Patients expressed strong opinions regarding SPAF. We found that 12% of patients were "medication averse" and were not willing to consider antithrombotic therapy; even if it was 100% effective in preventing strokes. Of those patients who were willing to consider antithrombotic therapy, 42% were identified as "risk averse" and 15% were "risk tolerant". Patients required at least a 0.8% (NNT=125) annual absolute risk reduction and 15% relative risk reduction in the risk of stroke in order to agree to initiate antithrombotic therapy, and patients were willing to endure 4.4 major bleeds in order to prevent one stroke. In conclusion, there was a substantial amount of inter-patient variability, and often extreme differences in opinion regarding tolerance of bleeding risk in the context of stroke prevention in atrial fibrillation. These findings highlight the importance of considering patient preferences when deciding on SPAF therapy.
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Fibrilación Atrial/epidemiología , Actitud Frente a la Salud , Hemorragia/epidemiología , Prioridad del Paciente/estadística & datos numéricos , Accidente Cerebrovascular/epidemiología , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Canadá , Coagulantes/efectos adversos , Coagulantes/uso terapéutico , Sistemas de Apoyo a Decisiones Clínicas , Femenino , Hemorragia/etiología , Humanos , Masculino , Persona de Mediana Edad , Negativa al Tratamiento , Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Encuestas y CuestionariosRESUMEN
In addition to being essential for translation of eukaryotic mRNA, translation initiation factors are also key components of plant-virus interactions. In order to address the involvement of these factors in the infectious cycle of poleroviruses (aphid-transmitted, phloem-limited viruses), the accumulation of three poleroviruses was followed in Arabidopsis thaliana mutant lines impaired in the synthesis of translation initiation factors in the eIF4E and eIF4G families. We found that efficient accumulation of Turnip yellows virus (TuYV) in A. thaliana relies on the presence of eIF (iso)4G1, whereas Beet mild yellowing virus (BMYV) and Beet western yellows virus-USA (BWYV-USA) rely, instead, on eIF4E1. A role for these factors in the infectious processes of TuYV and BMYV was confirmed by direct interaction in yeast between these specific factors and the 5' viral genome-linked protein of the related virus. Although the underlying molecular mechanism is still unknown, this study reveals a totally unforeseen situation in which closely related viruses belonging to the same genus use different translation initiation factors for efficient infection of A. thaliana.
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Arabidopsis/virología , Factor 4E Eucariótico de Iniciación/metabolismo , Factor 4G Eucariótico de Iniciación/metabolismo , Luteoviridae/genética , Enfermedades de las Plantas/virología , Animales , Áfidos/virología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factor 4E Eucariótico de Iniciación/genética , Factor 4G Eucariótico de Iniciación/genética , Interacciones Huésped-Patógeno , Insectos Vectores/virología , Luteoviridae/patogenicidad , Luteoviridae/fisiología , Mutación , Proteínas Recombinantes , Especificidad de la Especie , Técnicas del Sistema de Dos Híbridos , VirulenciaRESUMEN
BACKGROUND, AIM: The aims of the NORMACAT project are: to develop tools and unbiased standardized methods to measure the performance and to validate the safety of new materials and systems integrating photocatalysis, to develop new photocatalytic media with higher efficiency and to give recommendations aimed at improving the tested materials and systems. METHOD: To achieve this objective, it was necessary to design standardized test benches and protocols to assess photocatalytic efficiency of materials or systems used in the treatment of volatile organic compounds (VOCs) and odour under conditions close to applications. The tests are based on the validation of robust analytical methods at the parts per billion by volume level that not only follow the disappearance of the initial VOCs but also identify the secondary species and calculate the mineralization rates. RESULTS: The first results of inter-laboratory closed chamber tests, according to XP B44-013 AFNOR standard, are described. The photocatalytic degradation of mixtures of several defined pollutants under controlled conditions (temperature, relative humidity, initial concentration) was carried out in two independent laboratories with the same photocatalytic device and with various analytical procedures. Comparison of the degradation rate and of the mineralization efficiency allowed the determination of the clean air delivery rate in both cases. Formaldehyde was the only by-product detected during photocatalytic test under standardized experimental conditions. The concentration of transient formaldehyde varied according to the initial VOC concentration. Moreover the photocatalytic reaction rate of formaldehyde in mixture with other pollutants was analysed. It was concluded that formaldehyde concentration did not increase with time. CONCLUSION-PERSPECTIVE: This type of experiment should allow the comparison of the performances of different photoreactors and of photocatalytic media under controlled and reproducible conditions against mixtures of pollutants including formaldehyde.
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Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Restauración y Remediación Ambiental/métodos , Formaldehído/análisis , Compuestos Orgánicos Volátiles/química , Contaminantes Atmosféricos/química , Monitoreo del Ambiente , Restauración y Remediación Ambiental/instrumentación , Procesos FotoquímicosRESUMEN
Soft X-ray induced chemistry of H(2)O, CO and CH(3)OH and the effects of the water and nitric acid hydrate (HNO(3).1.65H(2)O) matrix on the photochemistry of CO and CH(3)OH have been investigated using NEXAFS spectroscopy. For pure H(2)O, CO and CH(3)OH ices, we show that the destruction rates are strongly limited by back reactions, leading to strikingly high survival rates of these molecules upon the harsh irradiation conditions to which they are submitted. We also evidence the interplay between the photochemical reactions of CO and CH(3)OH and those of the matrix. The OH and O radicals released by the photolysis of H(2)O and HNO(3) react with the CO and CH(3)OH and their fragments, considerably reducing the survival rates compared to pure CO and pure CH(3)OH ices, especially in presence of nitric acid, and dramatically enhancing the formation of CO(2) at the expense of CO. Because NEXAFS spectroscopy allows identifying which reactions are important among those possible, it emerges a simple picture of the photochemical routes of CO and CH(3)OH in the H(2)O and HNO(3)/H(2)O environments.
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Monóxido de Carbono/química , Hielo , Metanol/química , Ácido Nítrico/química , Procesos Fotoquímicos , Espectroscopía de Absorción de Rayos XRESUMEN
The enhancement of radiobiological effects by heavy elements is reviewed. As an underlying mechanism, Auger effects have been stressed which can be induced via inner-shell photoabsorption or via excitation and/or ionization by secondary electrons. Latter channel of Auger induction expands the applicability of Auger enhancing phenomena to electron and hadron therapy. After discussion on the required characteristics for radiosensitizers, possibility of nanoparticles of Au or Pt is mentioned since they could be synthesized or modified as ideal radiosensitizers.
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Radiobiología/métodos , Radioterapia/métodos , Animales , Línea Celular , Sistemas de Liberación de Medicamentos , Electrones/uso terapéutico , Humanos , Nanopartículas , Fotones , Plásmidos , Efectos de la Radiación , Fármacos Sensibilizantes a Radiaciones/farmacologíaRESUMEN
A vapor-deposited NH(3) ice film irradiated at 20 K with 150 eV photons has been studied with near-edge x-ray absorption fine structure (NEXAFS) spectroscopy at the nitrogen K-edge. Irradiation leads to the formation of high amounts (12%) of molecular nitrogen N(2), whose concentration as a function of the absorbed energy has been quantified to 0.13 molecule/eV. The stability of N(2) in solid NH(3) has been also studied, showing that N(2) continuously desorbs between 20 and 95 K from the irradiated ammonia ice film. Weak concentrations (<1%) of other photoproducts are also detected. Our NEXAFS simulations show that these features own to NH(2), N(2)H(2), and N(3)(-).
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PURPOSE: This work investigates whether a synergy in cell death induction exists in combining atomic ions irradiation and addition of platinum salts. Such a synergy could be of interest in view of new cancer therapy protocol based on atomic ions--hadrontherapy--with the addition of radiosensitizing agents containing high-Z atoms. The experiment consists in irradiating by fast ions cultured cells previously exposed to dichloroterpyridine Platinum (PtTC) and analyzing cell survival by a colony-forming assay. MATERIALS AND METHODS: Chinese Hamster Ovary (CHO) cells were incubated for six hours in medium containing 350 microM PtTC, and then irradiated by fast ions C(6+) and He(2+), with Linear Energy Transfer (LET) within range 2-70 keV/microm. In some experiments, dimethyl sulfoxide (DMSO) was added to investigate the role of free radicals. The intracellular localization of platinum was determined by Nano Secondary Ion Mass Spectroscopy (Nano-SIMS). RESULTS: For all LET examined, cell death rate is largely enhanced when irradiating in presence of PtTC. At fixed irradiation dose, cell death rate increases with increasing LET, while the platinum relative effect is larger at low LET. CONCLUSION: This finding suggests that hadrontherapy or protontherapy therapeutic index could be improved by combining irradiation procedure with concomitant chemotherapy protocols using platinum salts.
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Carbono , Iones Pesados , Helio , Transferencia Lineal de Energía , Compuestos Organoplatinos , Animales , Células CHO , Supervivencia Celular/fisiología , Supervivencia Celular/efectos de la radiación , Ensayo de Unidades Formadoras de Colonias , Cricetinae , Cricetulus , Dimetilsulfóxido/farmacología , Relación Dosis-Respuesta en la Radiación , Femenino , Radicales Libres/metabolismo , Compuestos Organoplatinos/química , Compuestos Organoplatinos/efectos de la radiación , Compuestos Organoplatinos/uso terapéutico , Dosis de Radiación , Tolerancia a Radiación , Espectrometría de Masa de Ion Secundario , Factores de TiempoRESUMEN
BACKGROUND: Both quality of life (QoL) and comorbidity influence therapy and prognosis of non-small-cell lung cancer (NSCLC). We previously developed a lung cancer disease-specific simplified comorbidity score (SCS) and demonstrated the prognostic impact of this disease-specific instrument. This study aimed at validating the SCS in a prospective bicentric NSCLC population by measuring its relative prognostic determinant impact taking into account well-established variables such as QoL, performance status (PS), Charlson comorbidity index (CCI) and disease stage. PATIENTS AND METHODS: Prognostic values of different pretherapeutic features were tested in univariate and multivariate analyses in a population of 301 NSCLC. RESULTS: Median survival was 17 months. One-third of patients reporting difficulties in their normal daily activities and an overall poor QoL. The following pretreament variables were independent determinants of a shorter overall survival: advanced disease, SCS, Lung Cancer Symptoms Scale global symptoms score, anaemia, hyponatremia, serum alkaline phosphatases level, serum CYFRA 21-1 and serum neuron-specific enolase. CONCLUSION: In this extended validation population, the SCS is more informative than the CCI in predicting NSCLC patient outcome as the former is also more disease specific. Combination of both SCS comorbidity score and LSCC QoL yields a more accurate information that conventional analysis of PS.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Tasa de SupervivenciaRESUMEN
We have developed a novel apparatus that allows us to irradiate nonvolatile organic films of high mass (1-100 microg range) spread out over a large surface area (42 cm(2)) with low energy (kT-100 eV) heavy ions and to quantitatively analyze the film substance via standard biochemical techniques afterwards. Here we discuss the details of the apparatus and method and show that it allows us to measure substantial damage to double stranded DNA molecules (plasmids) and its fundamental subunits induced by heavy ions with unprecedented low energies, i.e., 2.5 eV/amu; these energies correspond to track end energies of stopping ions or secondary ions created along primary ion tracks. We find that hyperthermal Ar(+) ions interacting with plasmid DNA will lead to the formation of single and double strand breaks, as well as fragmentation of nucleosides, which also involve chemical modifications and site specific rupture along the N1-C1 glycosidic bond, resulting in base release. In cells, such localized clustered damage will enhance the severity of DNA strand lesions, thus making them harder to repair.
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Daño del ADN , ADN/química , ADN/efectos de la radiación , Iones Pesados , Aceleradores de Partículas/instrumentación , Disparidad de Par Base/efectos de la radiación , Diseño Asistido por Computadora , ADN/genética , Roturas del ADN , Fragmentación del ADN/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Diseño de Equipo , Análisis de Falla de Equipo , Dosis de Radiación , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
PURPOSE: In order to study the role of the Linear Energy Transfer (LET) of fast atomic ions in platinum-DNA complexes inducing breaks, DNA Plasmids were irradiated by C(6+) and Fe(26+) ions. MATERIAL AND METHODS: DNA Plasmids (pBR322) loaded with different amounts of platinum contained in a terpyridine-platinum molecule (PtTC) were irradiated by C(6+) ions and Fe(26+) ions. The LET values ranged between 13.4 keV/microm and 550 keV/microm. In some experiments, dimethyl sulfoxide (DMSO) was added. RESULTS: In all experiments, a significant increase in DNA strand breaks was observed when platinum was present. The yield of breaks induced per Gray decreased when the LET increased. The yield of single and double strand breaks per plasmid per track increased with the LET, indicating that the number of DNA breaks per Gray was related to the number of tracks through the medium. CONCLUSIONS: These findings show that more DNA breaks are induced by atomic ions when platinum is present. This effect increases for low LET heavy atoms. As DSB induction may induce cell death, these results could open new perspectives with the association of hadrontherapy and chemotherapy. Thus the therapeutic index might be improved by loading the tumour with platinum salts.
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Carbono/química , Aductos de ADN/química , Aductos de ADN/efectos de la radiación , Daño del ADN/efectos de la radiación , Iones Pesados , Hierro/química , Platino (Metal)/química , Relación Dosis-Respuesta en la Radiación , Plásmidos/química , Plásmidos/efectos de la radiación , Platino (Metal)/efectos de la radiación , Dosis de RadiaciónRESUMEN
AIM: Conventional follow-up of type 1 diabetic patients treated with continuous subcutaneous insulin infusion (CSII) was compared with intensive coaching using the Web and the cellular phone network for retrospective data transmission and short message service (SMS). METHODS: Thirty poorly controlled patients (HbA1c 7.5-10%) were enrolled in a bicenter, open-label, randomized, 12-month, two-period, crossover study. After a 1-month run-in period, 15 patients were randomly assigned to receive weekly medical support through SMS based upon weekly review of glucose values, while 15 patients continued to download self-monitored blood glucose (SMBG) values on a weekly basis without receiving SMS. After 6 months, patients crossed over to the alternate sequence for 6 additional months. Visits at the clinic were maintained every 3 months. RESULTS: Patients with long-standing inadequately controlled diabetes (24 +/- 13 years) were included. A non-significant trend to reduction in HbA(1c) (-0.25+/-0.94%, P<0.10) and mean glucose values (-9.2+/-25 mg/dl, P=0.06) during the 6-month SMS sequence was observed as compared with the no-SMS period. No safety issue (hypoglycemia, glucose variability) was reported. Adherence to SMBG was not affected by the trial. Quality of life analysis suggests a significant improvement in DQOL global score, as well as the DQOL satisfaction with life subscale, during the SMS sequence. CONCLUSIONS: Long-term telemedical follow-up of insulin pump-treated patients using a cellular phone-, SMS- and Web-based platform is feasible, safe, does not alter quality of life and associated with a trend toward improved metabolic control.
Asunto(s)
Teléfono Celular/normas , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Sistemas de Infusión de Insulina , Adulto , Glucemia/metabolismo , Capilares , Estudios Cruzados , Diabetes Mellitus Tipo 1/sangre , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/epidemiología , Sistemas de Infusión de Insulina/efectos adversos , Internet , Selección de Paciente , Calidad de Vida , Seguridad , Encuestas y CuestionariosRESUMEN
The changes in the structure and composition of vapor-deposited ice films irradiated at 20 K with soft x-ray photons (3-900 eV) and their subsequent evolution with temperatures between 20 and 150 K have been investigated by near-edge x-ray absorption fine structure spectroscopy (NEXAFS) at the oxygen K edge. We observe the hydroxyl OH, the atomic oxygen O, and the hydroperoxyl HO(2) radicals, as well as the oxygen O(2) and hydrogen peroxide H(2)O(2) molecules in irradiated porous amorphous solid water (p-ASW) and crystalline (I(cryst)) ice films. The evolution of their concentrations with the temperature indicates that HO(2), O(2), and H(2)O(2) result from a simple step reaction fuelled by OH, where O(2) is a product of HO(2) and HO(2) a product of H(2)O(2). The local order of ice is also modified, whatever the initial structure is. The crystalline ice I(cryst) becomes amorphous. The high-density amorphous phase (I(a)h) of ice is observed after irradiation of the p-ASW film, whose initial structure is the normal low-density form of the amorphous ice (I(a)l). The phase I(a)h is thus peculiar to irradiated ice and does not exist in the as-deposited ice films. A new "very high density" amorphous phase-we call I(a)vh-is obtained after warming at 50 K the irradiated p-ASW ice. This phase is stable up to 90 K and partially transforms into crystalline ice at 150 K.