Ciprofloxacin in Layered Double Hydroxides: Looking for the Best Synthesis Method.

It is important to develop new methods of release to improve pharmacokinetic parameters of drugs, especially antibiotics, whose plasmatic concentration is determinant to ensure an effective treatment. Layered double hydroxides (LDH) are inorganic and biocompatible materials with high drug intercalation capacity and release properties that can be tuned by controlling the pH value. These materials can be an excellent choice to achieve a sustained release and an optimal drug concentration in plasm. In this work, LDH were synthesized with intercalated ciprofloxacin (CIP) by three different methods: coprecipitation, reconstruction and ion exchange. LDH-CIP complexes were characterized by XRD, TG-DSC, TEM, SEM, FTIR, electrophoretic mobilities, and drug release and dissolution kinetics in NaCl solutions and under physiological conditions. The coprecipitation and reconstruction methods lead to the formation of ill-defined products, whereas the ion exchange method rendered the best intercalation results. CIP release was controlled by dissolution at pH<3 and by desorption and ion exchange at intermediate and high pH. In comparison with a commercial formulation, the LDH-CIP complex prepared by ion exchange presented a slower release profile. The fast dissolution at gastric pH raises the need of developing some type of coating for protecting LDH materials.

Steepest-descent algorithm for simulating plasma-wave caustics via metaplectic geometrical optics.

The design and optimization of radiofrequency-wave systems for fusion applications is often performed using ray-tracing codes, which rely on the geometrical-optics (GO) approximation. However, GO fails at wave cutoffs and caustics. To accurately model the wave behavior in these regions, more advanced and computationally expensive "full-wave" simulations are typically used, but this is not strictly necessary. A new generalized formulation called metaplectic geometrical optics (MGO) has been proposed that reinstates GO near caustics. The MGO framework yields an integral representation of the wavefield that must be evaluated numerically in general. We present an algorithm for computing these integrals using Gauss-Freud quadrature along the steepest-descent contours. Benchmarking is performed on the standard Airy problem, for which the exact solution is known analytically. The numerical MGO solution provided by the new algorithm agrees remarkably well with the exact solution and significantly improves on previously derived analytical approximations of the MGO integral.

Synthesis of Layered Double Hydroxides Intercalated With Drugs for Controlled Release: Successful Intercalation of Ibuprofen and Failed Intercalation of Paracetamol.

This work examines the effect of drug structure and ionization degree on the formation and properties of biocompatible layered double hydroxides (LDH) intercalated with ibuprofen and paracetamol. Ibuprofen (pKa = 5.3) is in its anionic form, whereas paracetamol (pKa 9.4) is only partially ionized at the synthesis pH (9.0), and thus intercalation is expected to be different in the two cases. Chemical analyses, X-ray diffraction, electron microscopy, infrared spectroscopy and thermal analyses were applied to characterize the materials. Dissolution kinetics and drug release kinetics were also investigated, in an ample range of pH (3.0-9.0) in NaCl solutions, and in physiological buffers (1.2, 4.5 and 6.8). All characterization techniques showed that an efficient intercalation of ibuprofen took place, resulting in a material with 30% of its weight corresponding to the drug. On the contrary, all techniques revealed a very poor intercalation of paracetamol (1.2%). The dissolution kinetics of LDHs was highly pH-dependent, being higher as pH decreased. The drug release kinetics, conversely, increased as pH increased. In physiological buffers the release rate depended not only on the pH but also on the type of buffer. This last behavior is useful to control the release in different parts of the digestive system.

Cognitive impairment in heart failure is associated with altered Wnt signaling in the hippocampus.

Age represents the highest risk factor for death due to cardiovascular disease. Heart failure (HF) is the most common cardiovascular disease in elder population and it is associated with cognitive impairment (CI), diminishing learning and memory process affecting life quality and mortality in these patients. In HF, CI has been associated with inadequate O2 supply to the brain; however, an important subset of HF patients displays CI with almost no alteration in cerebral blood flow. Importantly, nothing is known about the pathophysiological mechanisms underpinning CI in HF with no change in brain tissue perfusion. Here, we aimed to study memory performance and learning function in a rodent model of HF that shows no change in blood flow going to the brain. We found that HF rats presented learning impairments and memory loss. In addition, HF rats displayed a decreased level of Wnt/ß-catenin signaling downstream elements in the hippocampus, one pathway implicated largely in aging diseases. Taken together, our results suggest that in HF rats CI is associated with dysfunction of the Wnt/ß-catenin signaling pathway. The mechanisms involved in the alterations of Wnt/ß-catenin signaling in HF and its contribution to the development/maintenance of CI deserves future investigations.

Shifts in the suitable habitat available for brown trout (Salmo trutta L.) under short-term climate change scenarios.

The impact of climate change on the habitat suitability for large brown trout (Salmo trutta L.) was studied in a segment of the Cabriel River (Iberian Peninsula). The future flow and water temperature patterns were simulated at a daily time step with M5 models' trees (NSE of 0.78 and 0.97 respectively) for two short-term scenarios (2011-2040) under the representative concentration pathways (RCP 4.5 and 8.5). An ensemble of five strongly regularized machine learning techniques (generalized additive models, multilayer perceptron ensembles, random forests, support vector machines and fuzzy rule base systems) was used to model the microhabitat suitability (depth, velocity and substrate) during summertime and to evaluate several flows simulated with River2D©. The simulated flow rate and water temperature were combined with the microhabitat assessment to infer bivariate habitat duration curves (BHDCs) under historical conditions and climate change scenarios using either the weighted usable area (WUA) or the Boolean-based suitable area (SA). The forecasts for both scenarios jointly predicted a significant reduction in the flow rate and an increase in water temperature (mean rate of change of ca. -25% and +4% respectively). The five techniques converged on the modelled suitability and habitat preferences; large brown trout selected relatively high flow velocity, large depth and coarse substrate. However, the model developed with support vector machines presented a significantly trimmed output range (max.: 0.38), and thus its predictions were banned from the WUA-based analyses. The BHDCs based on the WUA and the SA broadly matched, indicating an increase in the number of days with less suitable habitat available (WUA and SA) and/or with higher water temperature (trout will endure impoverished environmental conditions ca. 82% of the days). Finally, our results suggested the potential extirpation of the species from the study site during short time spans.

Price and consumption of tobacco in Spain over the period 1965-2000.

Changes in cigarette price have had an appreciable impact on smoking prevalence in several countries. We analysed the price elasticity of demand for cigarettes (effect of price of cigarettes on tobacco consumption) between 1965 and 2000 in Spain. For total consumption of cigarettes, a 1% increase in price is associated with a 0.19% decrease of consumption (price elasticity of -0.19; P<0.01). The real price of blond cigarettes was significantly and inversely associated with blond cigarette consumption: on average, smoking prevalence decreased 1.25% for a 1% increase in the real price of cigarettes (significant price elasticity of -1.25). For black cigarettes we found a lower but still high and significant elasticity of -0.61. There is an inverse relation between price and consumption of cigarettes in Spain, indicating that interventions at the economic level (such as real increases in prices) may have an important public health impact in tobacco control.

Morbilidad, mortalidad y costes sanitarios evitables medianteuna estrategia de tratamiento del tabaquismo en España / The effects of implementing a smoking cessation intervention in Spain on morbidity, mortality and health care costs

Objetivo: Se valoran los efectos que tendría una intervención destinada a reducir el uso de tabaco en la población española de fumadores sobre la morbilidad, la mortalidad y los costes asociados al consumo de tabaco. Método: Se ha adaptado el modelo Health and Economic Consequences of Smoking patrocinado por la OMS y desarrollado por The Lewin Group. La intervención propuesta incluye el acceso a asistencia farmacológica de un 35% de los fumadores que intentan dejar de fumar, y obtienen una tasa global de cesación al año del 7,2%. Las enfermedades estudiadas son: cáncer de pulmón, enfermedad coronaria, enfermedad cerebrovascular, EPOC, asma y bajo peso al nacer. Se estiman los casos de enfermedad y muerte atribuibles al consumo de tabaco evitados y la reducción en el coste sanitario debidos a la intervención, proyectados a 20 años. Resultados: Sin intervención, en el año 1 del modelo 2.136.094 fumadores padecen alguna de las condiciones clínicas atribuibles al consumo de tabaco, el coste asistencial es de 4.286 millones de euros y las muertes atribuibles son 26.537. La intervención propuesta evita 2.613, 9.192, 17.415 y 23.837 casos de enfermedad atribuible al consumo de tabaco en los años 2, 5, 10 y 20 del modelo, respectivamente. Los costes asistenciales acumulados evitados son 3,5 millones de euros en el año 2 y 386 millones de (..) (AU)

Objective: We estimated the effect that a smoking cessation intervention in the Spanish population of smokers would have on smoking-related morbidity, mortality and healthcare costs. Methods: We adopted the model Health and Economic Consequences of Smoking sponsored by the WHO Health Organization and developed by the The Lewin Group. The smoking cessation intervention proposed incluides pharmacological treatment to 35% of smokers who are trying to quit smoking and obtains a quit rate of 7.2%. The diseases studied are: lung cancer, heart disease, stroke, chronic obstructive pulmonary disease, asthma exacerbation, and low birth weight. The smoking-related cases of disease and of averted death and the reduction in healthcare expenditure due to the intervention were estimated. Results: Without intervention, at year 1 of the model, 2,136,094 smokers would be affected by some smoking-related disease; healthcare expenditure would be 4,286 million € and deaths attributable to smoking would total 26,537. The proposed intervention (..) (AU)

[The effects of implementing a smoking cessation intervention in Spain on morbidity, mortality and health care costs]. / Morbilidad, mortalidad y costes sanitarios evitables mediante una estrategia de tratamiento del tabaquismo en España.

OBJECTIVE: We estimated the effect that a smoking cessation intervention in the Spanish population of smokers would have on smoking-related morbidity, mortality and health care costs. METHODS: We adopted the model Health and Economic Consequences of Smoking sponsored by the WHO Health Organization and developed by the The Lewin Group. The smoking cessation intervention proposed includes pharmacological treatment to 35% of smokers who are trying to quit smoking and obtains a quit rate of 7.2%. The diseases studied are: lung cancer, heart disease, stroke, chronic obstructive pulmonary disease, asthma exacerbation, and low birth weight. The smoking-related cases of disease and of averted death and the reduction in health care expenditure due to the intervention were estimated. RESULTS: Without intervention, at year 1 of the model, 2,136,094 smokers would be affected by some smoking-related disease; health care expenditure would be 4,286 million e and deaths attributable to smoking would total 26,537. The proposed intervention would prevent 2,613, 9,192, 17,415 and 23,837 cases of smoking-related disease at years 2, 5, 10 and 20 of the model, respectively. The saving in accumulated health care costs would amount to 3.5 million e at year 2 and 386 million e over 20 years. The accumulated prevented deaths are 284 at year 2 and 9,205 over 20 years. The intervention would save a total of 78,173 life-years by the end of the period considered. CONCLUSIONS: The availability of new effective smoking cessation interventions and the increase in accessibility to such interventions may contribute significantly to reducing morbidity, mortality and health care costs associated with smoking in Spain.

Unobserved heterogeneity and censoring in the demand for health care.

In this paper we estimate a demand for private medical services equation based on the tradition of Grossman's model of demand for health using data for a panel of Spanish households. The econometric specification accounts for the censored nature of the data, which arises from no participation and infrequency of purchases, and the existence of unobserved heterogeneity, which arises from the non-observability of health states. Our evidence suggests that ignoring these features can have a significant impact on the size, sign and significance of the model estimates. The estimates for the participation and consumption processes also suggest that the deduction of expenditures on health care currently applicable in the Spanish tax system are positively associated to income and fertility.

More evidence of the plateau effect: a social perspective.

The purpose of this study was to test the existence of the plateau effect at the social level. The authors tried to confirm the preliminary conclusion that people may not be willing to trade off any longevity to improve the health state of a large number of people if the health states are mild enough. They tested this assumption using the person-tradeoff technique. They also used a parametric approach and a nonparametric approach to study the relationship between individual and social values. Results show the existence of the plateau effect in the context of resource allocation. Furthermore, with the nonparametric approach, a plateau effect in the middle part of the scale was also observed, suggesting that social preference may not be directly predicted from individual utilities. The authors caution against the possible framing effects that may be present in these kinds of questions.