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1.
Environ Res ; 252(Pt 1): 118712, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38548255

RESUMEN

Lead ammunition stands out as one of the most pervasive pollutants affecting wildlife. Its impact on bird populations have spurred efforts for the phase-out of leaded gunshot in several countries, although with varying scopes and applications. Ongoing and future policy changes require data to assess the effectiveness of adopted measures, particularly in the current context of biodiversity loss. Here, we assessed the long-term changes in blood lead (Pb) levels of Egyptian vultures from the Canary Islands, Spain, which have been severely affected by Pb poisoning over the past two decades. During this period, the reduction in hunting pressure and changes in legislation regarding firearms usage for small game hunting likely contributed to a decrease in environmental Pb availability. As anticipated, our results show a reduction in Pb levels, especially after the ban on wild rabbit hunting with shotgun since 2010. This effect was stronger in the preadult fraction of the vulture population. However, we still observed elevated blood Pb levels above the background and clinical thresholds in 5.6% and 1.5% of individuals, respectively. Our results highlight the positive impact of reducing the availability of Pb from ammunition sources on individual health. Nonetheless, the continued use of Pb gunshot remains an important source of poisoning, even lethal, mainly affecting adult individuals. This poses a particular concern for long-lived birds, compounding by potential chronic effects associated with Pb bioaccumulation. Our findings align with recent studies indicating insufficient reductions in Pb levels among European birds of prey, attributed to limited policy changes and their uneven implementation. We anticipated further reductions in Pb levels among Egyptian vultures with expanded restrictions on hunting practices, including a blanket ban on Pb shot usage across all small game species.


Asunto(s)
Especies en Peligro de Extinción , Contaminantes Ambientales , Falconiformes , Plomo , Animales , Plomo/sangre , Falconiformes/sangre , España , Contaminantes Ambientales/sangre , Armas de Fuego/legislación & jurisprudencia , Monitoreo del Ambiente , Intoxicación por Plomo/veterinaria , Intoxicación por Plomo/sangre , Masculino , Femenino
2.
Pharmacol Res ; 169: 105626, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33892092

RESUMEN

Understanding the in vitro biology and behavior of human osteoblasts is crucial for developing research models that reproduce closely the bone structure, its functions, and the cell-cell and cell-matrix interactions that occurs in vivo. Mimicking bone microenvironment is challenging, but necessary, to ensure the clinical translation of novel medicines to treat more reliable different bone pathologies. Currently, bone tissue engineering is moving from 2D cell culture models such as traditional culture, sandwich culture, micro-patterning, and altered substrate stiffness, towards more complex 3D models including spheroids, scaffolds, cell sheets, hydrogels, bioreactors, and microfluidics chips. There are many different factors, such cell line type, cell culture media, substrate roughness and stiffness that need consideration when developing in vitro models as they affect significantly the microenvironment and hence, the final outcome of the in vitro assay. Advanced technologies, such as 3D bioprinting and microfluidics, have allowed the development of more complex structures, bridging the gap between in vitro and in vivo models. In this review, past and current 2D and 3D in vitro models for human osteoblasts will be described in detail, highlighting the culture conditions and outcomes achieved, as well as the challenges and limitations of each model, offering a widen perspective on how these models can closely mimic the bone microenvironment and for which applications have shown more successful results.


Asunto(s)
Huesos/fisiología , Microambiente Celular/fisiología , Osteoblastos/fisiología , Animales , Células Cultivadas , Humanos , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Andamios del Tejido
3.
Chem Soc Rev ; 47(22): 8263-8306, 2018 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-30167621

RESUMEN

Research activities and recent developments in the area of three-dimensional zeolites and their two-dimensional analogues are reviewed. Zeolites are the most important industrial heterogeneous catalysts with numerous applications. However, they suffer from limited pore sizes not allowing penetration of sterically demanding molecules to their channel systems and to active sites. We briefly highlight here the synthesis, properties and catalytic potential of three-dimensional zeolites followed by a discussion of hierarchical zeolites combining micro- and mesoporosity. The final part is devoted to two-dimensional analogues developed recently. Novel bottom-up and top-down synthetic approaches for two-dimensional zeolites, their properties, and catalytic performances are thoroughly discussed in this review.

4.
Genome ; 60(10): 868-873, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28753409

RESUMEN

High-throughput DNA barcoding has become essential in ecology and evolution, but some technical questions still remain. Increasing the number of PCR cycles above the routine 20-30 cycles is a common practice when working with old-type specimens, which provide little amounts of DNA, or when facing annealing issues with the primers. However, increasing the number of cycles can raise the number of artificial mutations due to polymerase errors. In this work, we sequenced 20 COI libraries in the Illumina MiSeq platform. Libraries were prepared with 40, 45, 50, 55, and 60 PCR cycles from four individuals belonging to four species of four genera of cephalopods. We found no relationship between the number of PCR cycles and the number of mutations despite using a nonproofreading polymerase. Moreover, even when using a high number of PCR cycles, the resulting number of mutations was low enough not to be an issue in the context of high-throughput DNA barcoding (but may still remain an issue in DNA metabarcoding due to chimera formation). We conclude that the common practice of increasing the number of PCR cycles should not negatively impact the outcome of a high-throughput DNA barcoding study in terms of the occurrence of point mutations.


Asunto(s)
Cefalópodos/genética , Código de Barras del ADN Taxonómico/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación , Reacción en Cadena de la Polimerasa/métodos , Animales , Cefalópodos/clasificación , Biblioteca de Genes
5.
Photochem Photobiol Sci ; 16(1): 17-23, 2017 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-27898125

RESUMEN

The activity of NaNbO3 and NaTaO3 perovskites for the photocatalytic reduction of CO2 is studied in this work. For this purpose, sodium niobate and tantalate have been prepared using solid-state reactions, extensively characterised by means of powder X-ray diffraction, UV-vis, photoluminescence and Raman spectroscopies and N2 adsorption isotherms, and tested in the gas-phase reduction of CO2 under UV light in a continuous flow photoreactor. NaNbO3 is constituted of an orthorhombically distorted perovskite structure, while a ca. 4.5 : 1 combination of the orthorhombic and monoclinic modifications is found in the tantalate. Both catalysts exhibit interesting intrinsic activities, with the tantalate material giving rise to a slightly higher performance. This is attributed to a compromise situation between electron-hole recombination and the reducing potential of conduction band electrons. In addition, a decrease in the competition of water protons for photogenerated electrons is observed with both catalysts with respect to TiO2.


Asunto(s)
Compuestos de Calcio/química , Dióxido de Carbono/química , Niobio/química , Óxidos/química , Sodio/química , Tantalio/química , Titanio/química , Catálisis , Microscopía Electrónica de Transmisión , Oxidación-Reducción/efectos de la radiación , Espectrofotometría Ultravioleta , Espectrometría Raman , Rayos Ultravioleta , Difracción de Rayos X
6.
Heredity (Edinb) ; 117(2): 94-9, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27118157

RESUMEN

In contrast with the classical population genetics theory that models population structure as discrete panmictic units connected by migration, many populations exhibit heterogeneous spatial gradients in population connectivity across semi-continuous habitats. The historical dynamics of such spatially structured populations can be captured by a spatially explicit coalescent model recently proposed by Etheridge (2008) and Barton et al. (2010a, 2010b) and whereby allelic lineages are distributed in a two-dimensional spatial continuum and move within this continuum based on extinction and coalescent events. Though theoretically rigorous, this model, which we here refer to as the continuum model, has not yet been implemented for demographic inference. To this end, here we introduce and demonstrate a statistical pipeline that couples the coalescent simulator of Kelleher et al. (2014) that simulates genealogies under the continuum model, with an approximate Bayesian computation (ABC) framework for parameter estimation of neighborhood size (that is, the number of locally breeding individuals) and dispersal ability (that is, the distance an offspring can travel within a generation). Using empirically informed simulations and simulation-based ABC cross-validation, we first show that neighborhood size can be accurately estimated. We then apply our pipeline to the South African endemic shrub species Berkheya cuneata to use the resulting estimates of dispersal ability and neighborhood size to infer the average population density of the species. More generally, we show that spatially explicit coalescent models can be successfully integrated into model-based demographic inference.


Asunto(s)
Genética de Población/métodos , Modelos Genéticos , Análisis Espacial , Asteraceae/genética , Teorema de Bayes , Simulación por Computador , Ecosistema , Dispersión de las Plantas , Densidad de Población , Dinámica Poblacional
7.
Phys Chem Chem Phys ; 18(11): 8039-48, 2016 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-26922970

RESUMEN

The barium peroxide-based redox cycle was proposed in the late 1970s as a thermochemical energy storage system. Since then, very little attention has been paid to such redox couples. In this paper, we have revisited the use of reduction-oxidation reactions of the BaO2/BaO system for thermochemical heat storage at high temperatures. Using thermogravimetric analysis, reduction and oxidation reactions were studied in order to find the main limitations associated with each process. Furthermore, the system was evaluated through several charge-discharge stages in order to analyse its possible degradation after repeated cycling. Through differential scanning calorimetry the heat stored and released were also determined. Oxidation reaction, which was found to be slower than reduction, was studied in more detail using isothermal tests. It was observed that the rate-controlling step of BaO oxidation follows zero-order kinetics, although at high temperatures a deviation from Arrhenius behaviour was observed probably due to hindrances to anionic oxygen diffusion caused by the formation of an external layer of BaO2. This redox couple was able to withstand several redox cycles without deactivation, showing reaction conversions close to 100% provided that impurities are previously eliminated through thermal pre-treatment, demonstrating the feasibility of this system for solar thermochemical heat storage.

8.
Opt Express ; 23(23): 29434-48, 2015 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-26698427

RESUMEN

We analyze and model the nonlocal response of ultrathin hyperbolic metasurfaces (HMTSs) by applying an effective medium approach. We show that the intrinsic spatial dispersion in the materials employed to realize the metasurfaces imposes a wavenumber cutoff on the hyperbolic isofrequency contour, inversely proportional to the Fermi velocity, and we compare it with the cutoff arising from the structure granularity. In the particular case of HTMSs implemented by an array of graphene nanostrips, we find that graphene nonlocality can become the dominant mechanism that closes the hyperbolic contour - imposing a wavenumber cutoff at around 300k(0) - in realistic configurations with periodicity L<π/(300k(0)), thus providing a practical design rule to implement HMTSs at THz and infrared frequencies. In contrast, more common plasmonic materials, such as noble metals, operate at much higher frequencies, and therefore their intrinsic nonlocal response is mainly relevant in hyperbolic metasurfaces and metamaterials with periodicity below a few nm, being very weak in practical scenarios. In addition, we investigate how spatial dispersion affects the spontaneous emission rate of emitters located close to HMTSs. Our results establish an upper bound set by nonlocality to the maximum field confinement and light-matter interactions achievable in practical HMTSs, and may find application in the practical development of hyperlenses, sensors and on-chip networks.

9.
Transpl Infect Dis ; 17(2): 221-33, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25652036

RESUMEN

BACKGROUND: Umbilical cord blood transplantation (CBT) is an established alternative source of stem cells in the setting of unrelated transplantation. When compared with other sources, single-unit CBT (sCBT) is associated with a delayed hematologic recovery, which may lead to a higher infection-related mortality (IRM). Co-infusion with the sCBT of CD34+ peripheral blood stem cells from a third-party donor (TPD) (sCBT + TPDCD34+) has been shown to markedly accelerate leukocyte recovery, potentially reducing the IRM. However, to our knowledge, no comparative studies have focused on severe infections and IRM with these 2 sCBT strategies. METHODS: A total of 148 consecutive sCBT (2000-2010, median follow-up 4.5 years) were included in a multicenter retrospective study to analyze the incidence and risk factors of IRM and severe viral and invasive fungal infections (IFIs). Neutrophil engraftment occurred in 90% of sCBT (n = 77) and 94% sCBT + TPDCD34+ (n = 71) recipients at a median of 23 and 12 days post transplantation, respectively (P < 0.01). RESULTS: The 4-year IRM was 24% and 20%, respectively (P = 0.7), with no differences at day +30 (5% and 4%, respectively) and day +100 (10% and 8%, respectively). In multivariate analysis early status of the underlying malignancy, cytomegalovirus (CMV)-seronegative recipient and high CD34+ cell content in the cord blood unit before cryostorage (≥1.4 × 10(5) /kg) were protective of IRM. Among the causes of IRM, bacterial infections and IFIs were more common in sCBT (15% vs. 4%), while CMV disease and parasitic infections were more common in the sCBT + TPDCD34+ cohort (5% vs. 16%). CONCLUSION: These data show that sCBT supported with TPDCD34(+) cells results in much shorter periods of post-transplant leukopenia, but the short- and long-term rates of IRM were comparable to those of sCBT, presumably because immune recovery is equally delayed in both graft types.


Asunto(s)
Infecciones Bacterianas/epidemiología , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Inmunosupresores/uso terapéutico , Leucemia/terapia , Linfoma/terapia , Micosis/epidemiología , Agonistas Mieloablativos/uso terapéutico , Trasplante de Células Madre de Sangre Periférica/métodos , Virosis/epidemiología , Adolescente , Adulto , Antígenos CD34 , Infecciones Bacterianas/mortalidad , Busulfano/uso terapéutico , Estudios de Cohortes , Ciclosporina/uso terapéutico , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Micosis/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tiotepa/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Virosis/mortalidad , Irradiación Corporal Total , Adulto Joven
10.
Exp Appl Acarol ; 67(2): 209-18, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26139533

RESUMEN

Understanding the ecological function of species and the structure of communities is crucial in the study of ecological interactions among species. For this purpose, not only the occurrence of particular species but also their abundance in ecological communities is required. However, abundance quantification of species through morphological characters is often difficult or time/money consuming when dealing with elusive or small taxa. Here we tested the use of next-generation sequencing (NGS) for abundance estimation of two species of feather mites (Proctophyllodes stylifer and Pteronyssoides parinus) under five proportions (16:1, 16:4, 16:16, 16:64, and 16:256 mites) against a mock community composed by Proctophyllodes clavatus and Proctophyllodes sylviae. In all mixtures, we retrieved sequence reads from all species. We found a strong linear relationship between 454 reads and the real proportion of individuals in the mixture for both focal species. The slope for Pr. stylifer was close to one (0.904), and the intercept close to zero (-0.007), thus showing an almost perfect correspondence between real and estimated proportions. The slope for Pt. parinus was 0.351 and the intercept 0.307, showing that while the estimated proportion increased linearly relative to real proportions of individuals in the samples, proportions were overestimated at low real proportions and underestimated at larger ones. Additionally, pyrosequencing replicates from each DNA extraction were highly repeatable (R = 0.920 and 0.972, respectively), showing that the quantification method is highly consistent given a DNA extract. Our study suggests that NGS is a promising tool for abundance estimation of feather mites' communities in birds.


Asunto(s)
Enfermedades de las Aves/parasitología , Código de Barras del ADN Taxonómico/veterinaria , Infestaciones por Ácaros/veterinaria , Ácaros/fisiología , Pájaros Cantores , Animales , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/metabolismo , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Plumas/parasitología , Masculino , Infestaciones por Ácaros/parasitología , Ácaros/genética , Datos de Secuencia Molecular , Análisis de Secuencia de ADN/veterinaria , España , Simbiosis
11.
Ann Oncol ; 25(3): 618-623, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24351403

RESUMEN

BACKGROUND: Ki-67 is increasingly being used as a response biomarker in window of opportunity, pre-surgical trials for breast cancer patients. Since Ki-67 is often higher at surgery than at baseline core biopsy in subjects allocated to placebo, we investigated which factors affected this change. PATIENTS AND METHODS: We retrieved data from 274 patients who received no active treatment in three consecutive pre-surgical trials from a single institution. We assessed the association between changes in Ki-67 from diagnostic biopsy to surgical specimen and the following factors: age, body mass index, tumor prognostic and predictive factors, including immunohistochemical molecular subtype, number and size of biopsy specimens, time from biopsy to surgery, circulating insulin-like growth factor-I, sex hormone-binding globulin and hsCRP. RESULTS: A total of 269 patients with paired measures of Ki-67 at biopsy and surgery were analyzed. Overall, the mean (±SD) change was 2.2 ± 9.2% after a median interval of 41 days (inter-quartile range 33-48). Molecular subtype was the only factor associated with a significant change of Ki-67 (P = 0.004), with a mean absolute increase of 5.3% [95% confidence interval (CI): 2.3-8.3, P = 0.0005] in estrogen receptor-negative HER2-positive tumors (n = 36) and 5.4% (95% CI: 2.9-7.9, P < 0.0001) in triple-negative tumors (n = 78). No significant change in luminal-A (n = 46), luminal-B (n = 85) and luminal-B HER2-positive (n = 24) tumors was observed. CONCLUSIONS: A significant increase in Ki-67 from baseline biopsy to end point surgery in untreated subjects was ascertained in HER2-positive and triple-negative tumors. This biological association suggests a real increase in cancer proliferation, possibly as a result of a biopsy-driven wound healing effect, and should be considered in the design and interpretation of pre-surgical studies. REGISTERED CLINICAL TRIAL NUMBERS: ISRCTN86894592; ISRCTN16493703.


Asunto(s)
Antígeno Ki-67/genética , Tipificación Molecular , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/cirugía , Biomarcadores de Tumor/genética , Biopsia , Índice de Masa Corporal , Proliferación Celular , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina , Terapia Neoadyuvante , Placebos/uso terapéutico , Pronóstico , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Globulina de Unión a Hormona Sexual , Neoplasias de la Mama Triple Negativas/mortalidad
12.
Mol Ecol ; 23(11): 2876-85, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24750181

RESUMEN

It has been suggested that individual behavioural traits influence the potential to successfully colonize new areas. Identifying the genetic basis of behavioural variation in invasive species thus represents an important step towards understanding the evolutionary potential of the invader. Here, we sequenced a candidate region for neophilic/neophobic and activity behaviour - the complete exon 3 of the DRD4 gene - in 100 Yellow-crowned bishops (Euplectes afer) from two invasive populations in Spain and Portugal. The same birds were scored twice for activity behaviour while exposed to novel objects (battery or slice of apple) in captivity. Response to novel objects was repeatable (r = 0.41) within individuals. We identified two synonymous DRD4 SNPs that explained on average between 11% and 15% of the phenotypic variance in both populations, indicating a clear genetic component to the neophilic/neophobic/activity personality axis in this species. This consistently high estimated effect size was mainly due to the repeated measurement design, which excludes part of the within-individual nongenetic variance in the response to different novel objects. We suggest that the alternative alleles of these SNPs are likely introduced from the original population and maintained by weak or antagonistic selection during different stages of the invasion process. The identified genetic variants have not only the potential to serve as genetic markers of the neophobic/neophilic/activity personality axis, but may also help to understand the evolution of behaviour in these invasive bird populations.


Asunto(s)
Conducta Exploratoria , Passeriformes/genética , Personalidad/genética , Receptores de Dopamina D4/genética , Animales , Conducta Animal , Exones , Femenino , Genotipo , Especies Introducidas , Masculino , Datos de Secuencia Molecular , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Portugal , Análisis de Secuencia de ADN , España
13.
Chem Soc Rev ; 42(9): 4004-35, 2013 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-23138888

RESUMEN

Great interest has arisen in the past years in the development of hierarchical zeolites, having at least two levels of porosities. Hierarchical zeolites show an enhanced accessibility, leading to improved catalytic activity in reactions suffering from steric and/or diffusional limitations. Moreover, the secondary porosity offers an ideal space for the deposition of additional active phases and for functionalization with organic moieties. However, the secondary surface represents a discontinuity of the crystalline framework, with a low connectivity and a high concentration of silanols. Consequently, hierarchical zeolites exhibit a less "zeolitic behaviour" than conventional ones in terms of acidity, hydrophobic/hydrophilic character, confinement effects, shape-selectivity and hydrothermal stability. Nevertheless, this secondary surface is far from being amorphous, which provides hierarchical zeolites with a set of novel features. A wide variety of innovative strategies have been developed for generating a secondary porosity in zeolites. In the present review, the different synthetic routes leading to hierarchical zeolites have been classified into five categories: removal of framework atoms, surfactant-assisted procedures, hard-templating, zeolitization of preformed solids and organosilane-based methods. Significant advances have been achieved recently in several of these alternatives. These include desilication, due to its versatility, dual templating with polyquaternary ammonium surfactants and framework reorganization by treatment with surfactant-containing basic solutions. In the last two cases, the materials so prepared show both mesoscopic ordering and zeolitic lattice planes. Likewise, interesting results have been obtained with the incorporation of different types of organosilanes into the zeolite crystallization gels, taking advantage of their high affinity for silicate and aluminosilicate species. Crystallization of organofunctionalized species favours the formation of organic-inorganic composites that, upon calcination, are transformed into hierarchical zeolites. However, in spite of this impressive progress in novel strategies for the preparation of hierarchical zeolites, significant challenges are still ahead. The overall one is the development of methods that are versatile in terms of zeolite structures and compositions, capable of tuning the secondary porosity properties, and being scaled up in a cost-effective way. Recent works have demonstrated that it is possible to scale-up easily the synthesis of hierarchical zeolites by desilication. Economic aspects may become a significant bottleneck for the commercial application of hierarchical zeolites since most of the synthesis strategies so far developed imply the use of more expensive procedures and reagents compared to conventional zeolites. Nevertheless, the use of hierarchical zeolites as efficient catalysts for the production of high value-added compounds could greatly compensate these increased manufacturing costs.


Asunto(s)
Zeolitas/síntesis química , Tamaño de la Partícula , Porosidad , Propiedades de Superficie , Zeolitas/química
14.
Br J Cancer ; 108(8): 1593-601, 2013 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-23579208

RESUMEN

BACKGROUND: The post-surgical management of ductal intraepithelial neoplasia (DIN) of the breast is still a dilemma. Ki-67 labelling index (LI) has been proposed as an independent predictive and prognostic factor in early breast cancer. METHODS: The prognostic and predictive roles of Ki-67 LI were evaluated with a multivariable Cox regression model in a cohort of 1171 consecutive patients operated for DIN in a single institution from 1997 to 2007. RESULTS: Radiotherapy (RT) was protective in subjects with DIN with Ki-67 LI ≥ 14%, whereas no evidence of benefit was seen for Ki-67 LI <14%, irrespective of nuclear grade and presence of necrosis. Notably, the higher the Ki-67 LI, the stronger the effect of RT (P-interaction <0.01). Hormonal therapy (HT) was effective in both Luminal A (adjusted hazard ratio (HR)=0.56 (95% CI, 0.33-0.97)) and Luminal B/Her2neg DIN (HR 0.51 (95% CI, 0.27-0.95)). CONCLUSION: Our data suggest that Ki-67 LI may be a useful prognostic and predictive adjunct in DIN patients. The Ki-67 LI of 14% could be a potential cutoff for better categorising this population of women at increased risk for breast cancer and in which adjuvant treatment (RT, HT) should be differently addressed, independent of histological grade and presence of necrosis.


Asunto(s)
Neoplasias de la Mama/terapia , Carcinoma in Situ/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Intraductal no Infiltrante/terapia , Antígeno Ki-67/metabolismo , Adulto , Anciano , Antineoplásicos Hormonales/administración & dosificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Carcinoma in Situ/metabolismo , Carcinoma in Situ/radioterapia , Carcinoma in Situ/cirugía , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirugía , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/radioterapia , Carcinoma Intraductal no Infiltrante/cirugía , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Estudios Retrospectivos , Tamoxifeno/administración & dosificación
15.
Br J Cancer ; 109(11): 2792-7, 2013 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-24157825

RESUMEN

BACKGROUND: Metformin has been associated with antitumour activity in breast cancer (BC) but its mechanism remains unclear. We determined whether metformin induced a modulation of apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) overall and by insulin resistance status in a presurgical trial. METHODS: Apoptosis was analysed in core biopsies and in surgical samples from 100 non-diabetic BC patients participating in a randomised trial of metformin vs placebo given for 4 weeks before surgery. RESULTS: Eighty-seven subjects (45 on metformin and 42 on placebo) were assessable for TUNEL measurement at both time points. TUNEL levels at surgery were higher than that at baseline core biopsy (P<0.0001), although no difference between arms was noted (metformin arm: median difference surgery-biopsy levels +4%, interquartile range (IQR): 2-12; placebo arm: +2%, IQR: 0-8, P=0.2). Ki67 labelling index and TUNEL levels were directly correlated both at baseline and surgery (Spearman's r=0.51, P<0.0001). In the 59 women without insulin resistance (HOMA index<2.8) ,there was a higher level of TUNEL at surgery on metformin vs placebo (median difference on metformin +4%, IQR: 2-14 vs +2%, IQR: 0-7 on placebo), whereas an opposite trend was found in the 28 women with insulin resistance (median difference on metformin +2%, IQR: 0-6, vs +5%, IQR: 0-15 on placebo, P-interaction=0.1). CONCLUSION: Overall, we found no significant modulation of apoptosis by metformin, although there was a trend to a different effect according to insulin resistance status, with a pattern resembling Ki67 changes. Apoptosis was significantly higher in the surgical specimens compared with baseline biopsy and was directly correlated with Ki67. Our findings provide additional evidence for a dual effect of metformin on BC growth according to insulin resistance status.


Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Periodo Preoperatorio , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Terapia Combinada , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Antígeno Ki-67/análisis , Persona de Mediana Edad , Terapia Neoadyuvante , Placebos
16.
Ann Oncol ; 24(7): 1859-1866, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23532115

RESUMEN

BACKGROUND: Postsurgical treatment of ductal intraepithelial neoplasia (DIN) with standard doses of tamoxifen has not reached a consensus yet. Given positive results of low-dose tamoxifen on breast cancer biomarkers modulation, we analyzed a large cohort of DIN patients treated with low-dose tamoxifen or no treatment as per institutional guidelines. PATIENTS AND METHODS: All consecutive women operated on at the European Institute of Oncology for estrogen receptor (ER)-positive DIN (474 treated with low-dose tamoxifen and 509 untreated patients) were followed up for a median of 7 years. RESULTS: Compared with untreated patients, a significant 30% reduction in breast cancer risk was observed on low-dose tamoxifen with an adjusted hazard ratio (HR) = 0.70 [95% confidence interval (CI) 0.51-0.94], with a greater benefit in postmenopausal (HR = 0.57; 95% CI 0.34-0.94) than in premenopausal women (HR = 0.79; 95% CI 0.54-1.17). Treated patients with ER and progesterone receptor (PgR) >50% DIN had a lower incidence of breast events than untreated ones (HR = 0.61; 95% CI 0.40-0.94), whereas no protective effect has been observed in patients with ER or PgR <50% DIN. Drug discontinuation resulted in a doubled risk of recurrence in premenopausal women only (HR = 1.95; 95% CI 0.98-3.89). No excess of endometrial cancer occurred. CONCLUSIONS: Low-dose tamoxifen is a promising and safe strategy for highly endocrine responsive DIN. Treatment adherence is crucial in premenopausal women. A definitive trial is ongoing.


Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma in Situ/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Tamoxifeno/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Quimioterapia Adyuvante , Ensayos Clínicos como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Mastectomía Segmentaria , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estudios Retrospectivos , Resultado del Tratamiento
17.
Ann Oncol ; 24(11): 2753-60, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23864098

RESUMEN

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Terapia de Reemplazo de Hormonas/efectos adversos , Tamoxifeno/administración & dosificación , Neoplasias de la Mama/patología , Climaterio/efectos de los fármacos , Cálculo de Dosificación de Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Posmenopausia , Tamoxifeno/efectos adversos
18.
J Evol Biol ; 26(7): 1445-57, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23638705

RESUMEN

Ornaments displayed by females have often been denied evolutionary interest due to their frequently reduced expression relative to males, habitually attributed to a genetic correlation between the sexes. We estimated annual and lifetime reproductive success of female pied flycatchers (Ficedula hypoleuca) and applied capture-mark-recapture models to analyse annual survival rates in relation to the patterns of expression (absence/presence) of an ornament displayed by all males and a fraction of females. Overall, the likelihood of expressing the ornament increased nonlinearly with female age and was due to within-individual variation, not to the selective appearance or disappearance of ornament-related expression of phenotypes in the population. Accordingly, expressing the forehead patch in a given year did not influence survival probability. However, those females expressing the ornament at early ages (1-2 years old) enjoyed survival advantages throughout lifetime. Although ornamented females had higher lifetime fecundity and fledging success, their yearly reproductive performance, in terms of fledging productivity, decreased as they aged so that, late in life, ornamented females reared fewer offspring than nonexpressing females of the same age. In addition, both strategies (expressing vs. not expressing the trait) returned similar fitness payoffs in terms of recruited offspring. Our results support the hypothesis that fecundity and survival selection are involved in the displaying of this 'male' ornament by females.


Asunto(s)
Fertilidad , Passeriformes/fisiología , Conducta Sexual Animal , Factores de Edad , Animales , Evolución Biológica , Tamaño de la Nidada , Femenino , Aptitud Física , Selección Genética , España , Sobrevida
19.
Chemosphere ; 339: 139784, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37567278

RESUMEN

Globally increasing concern related to municipal solid waste generation is encouraging research efforts on developing alternative routes to valorize mixed refused wastes. In this way, catalytic pyrolysis is emerging as an interesting and efficient technology due to its great flexibility in terms of feedstock. In the current work, upgrading of a Solid Recovered Fuel (SRF) has been investigated by catalytic pyrolysis over nanocrystalline ZSM-5 zeolite (n-ZSM-5), paying special attention to dechlorination effects due to the high Cl content of the raw waste. Thus, pretreatment of the SRF by water washing and mild thermal processing allows for a significant reduction of the Cl concentration. Regarding the catalytic pyrolysis step, the best conditions correspond with a temperature of 400 °C in the catalyst bed and 0.50 catalyst/SRF mass ratio, which lead to ca. 30 wt% oil yield (rich in aromatic hydrocarbons) together with about 40 wt% gas yield (rich in C3-C4 olefins). Accordingly, these products could find use as raw chemicals or for the production of advanced fuels. In addition, zeolite reutilization has been tested for several cycles, denoting a progressive modification of the products distribution because of coke deposition. However, an almost total recovery of the n-ZSM-5 zeolite catalytic performance is achieved after regeneration by air calcination, affording the production of an oil fraction with a Cl content as low as 40 ppm.


Asunto(s)
Hidrocarburos Aromáticos , Zeolitas , Zeolitas/química , Pirólisis , Temperatura , Catálisis , Calor
20.
Macromol Biosci ; 23(7): e2300066, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37031382

RESUMEN

Synthetic and functional grafts are a great alternative to conventional grafts. They can provide a physical support and the precise signaling for cells to heal damaged tissues. In this study, a novel RGD peptide end-functionalized poly(ethylene glycol)-b-poly(lactic acid)-b-poly(globalide)-b-poly(lactic acid)-b-poly(ethylene glycol) (RGD-PEG-PLA-PGl-PLA-PEG-RGD) is synthetized and used to prepare functional scaffolds. The PGl inner block is obtained by enzymatic ring-opening polymerization of globalide. The outer PLA blocks are obtained by ring-opening polymerization of both, l-lactide or a racemic mixture, initiated by the α-ω-telechelic polymacrolactone. The presence of PGl inner block enhances the toughness of PLA-based scaffolds, with an increase of the elongation at break up to 300% when the longer block of PGl is used. PLA-PGl-PLA copolymer is coupled with α-ω-telechelic PEG diacids by esterification reaction. PEGylation provides hydrophilic scaffolds as the contact angle is reduced from 114° to 74.8°. That difference improves the contact between the scaffolds and the culture media. Moreover, the scaffolds are functionalized with RGD peptides at the surface significantly enhancing the adhesion and proliferation of bone marrow-derived primary mesenchymal stem cells and MC3T3-E1 cell lines in vitro. These results place this multifunctional polymer as a great candidate for the preparation of temporary grafts.


Asunto(s)
Ácido Láctico , Polietilenglicoles , Poliésteres/farmacología , Polímeros , Regeneración Ósea , Oligopéptidos
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