Adjusting the Operational Potential Window as a Tool for Prolonging the Durability of Carbon-Supported Pt-Alloy Nanoparticles as Oxygen Reduction Reaction Electrocatalysts.

A current trend in the investigation of state-of-the-art Pt-alloys as proton exchange membrane fuel cell (PEMFC) electrocatalysts is to study their long-term stability as a bottleneck for their full commercialization. Although many parameters have been appropriately addressed, there are still certain issues that must be considered. Here, the stability of an experimental Pt-Co/C electrocatalyst is investigated by high-temperature accelerated degradation tests (HT-ADTs) in a high-temperature disk electrode (HT-DE) setup, allowing the imitation of close-to-real operational conditions in terms of temperature (60 °C). Although the US Department of Energy (DoE) protocol has been chosen as the basis of the study (30,000 trapezoidal wave cycling steps between 0.6 and 0.95 VRHE with a 3 s hold time at both the lower potential limit (LPL) and the upper potential limit (UPL)), this works demonstrates that limiting both the LPL and UPL (from 0.6-0.95 to 0.7-0.85 VRHE) can dramatically reduce the degradation rate of state-of-the-art Pt-alloy electrocatalysts. This has been additionally confirmed with the use of an electrochemical flow cell coupled to inductively coupled plasma mass spectrometry (EFC-ICP-MS), which enables real-time monitoring of the dissolution mechanisms of Pt and Co. In line with the HT-DE methodology observations, a dramatic decrease in the total dissolution of Pt and Co has once again been observed upon narrowing the potential window to 0.7-0.85 VRHE rather than 0.6-0.95 VRHE. Additionally, the effect of the potential hold time at both LPL and UPL on metal dissolution has also been investigated. The findings demonstrate that the dissolution rate of both metals is proportional to the hold time at UPL regardless of the applied potential window, whereas the hold time at the LPL does not appear to be as detrimental to the stability of metals.

One-year prediction of cognitive decline following cognitive-stimulation from real-world data.

Clinical evidence based on real-world data (RWD) is accumulating exponentially providing larger sample sizes available, which demand novel methods to deal with the enhanced heterogeneity of the data. Here, we used RWD to assess the prediction of cognitive decline in a large heterogeneous sample of participants being enrolled with cognitive stimulation, a phenomenon that is of great interest to clinicians but that is riddled with difficulties and limitations. More precisely, from a multitude of neuropsychological Training Materials (TMs), we asked whether was possible to accurately predict an individual's cognitive decline one year after being tested. In particular, we performed longitudinal modelling of the scores obtained from 215 different tests, grouped into 29 cognitive domains, a total of 124,610 instances from 7902 participants (40% male, 46% female, 14% not indicated), each performing an average of 16 tests. Employing a machine learning approach based on ROC analysis and cross-validation techniques to overcome overfitting, we show that different TMs belonging to several cognitive domains can accurately predict cognitive decline, while other domains perform poorly, suggesting that the ability to predict decline one year later is not specific to any particular domain, but is rather widely distributed across domains. Moreover, when addressing the same problem between individuals with a common diagnosed label, we found that some domains had more accurate classification for conditions such as Parkinson's disease and Down syndrome, whereas they are less accurate for Alzheimer's disease or multiple sclerosis. Future research should combine similar approaches to ours with standard neuropsychological measurements to enhance interpretability and the possibility of generalizing across different cohorts.

Alternative and facile production pathway towards obtaining high surface area PtCo/C intermetallic catalysts for improved PEM fuel cell performance.

The design of catalysts with stable and finely dispersed platinum or platinum alloy nanoparticles on the carbon support is key in controlling the performance of proton exchange membrane (PEM) fuel cells. In the present work, an intermetallic PtCo/C catalyst is synthesized via double-passivation galvanic displacement. TEM and XRD confirm a significantly narrowed particle size distribution for the catalyst particles compared to commercial benchmark catalysts (Umicore PtCo/C). Only about 10% of the mass fraction of PtCo particles show a diameter larger than 8 nm, whereas this is up to or even more than 35% for the reference systems. This directly results in a considerable increase in electrochemically active surface area (96 m2 g-1 vs. >70 m2 g-1), which confirms the more efficient usage of precious catalyst metal in the novel catalyst. Single-cell tests validate this finding by improved PEM fuel cell performance. Reducing the cathode catalyst loading from 0.4 mg cm-2 to 0.25 mg cm-2 resulted in a power density drop at an application-relevant 0.7 V of only 4% for the novel catalyst, compared to the 10% and 20% for the commercial benchmarks reference catalysts.

High-Performance Polyurethane Nanocomposite Membranes Containing Cellulose Nanocrystals for Protein Separation.

With the aim of exploring new materials and properties, we report the synthesis of a thermoplastic chain extended polyurethane membrane, with superior strength and toughness, obtained by incorporating two different concentrations of reactive cellulose nanocrystals (CNC) for potential use in kidney dialysis. Membrane nanocomposites were prepared by the phase inversion method and their structure and properties were determined. These materials were prepared from a polyurethane (PU) yielded from poly(1,4 butylene adipate) as a soft segment diol, isophorone diisocyanate (IPDI) and hexamethylenediamine (HMDA) as isocyanate and chain extender, respectively (hard segment), filled with 1 or 2% w/w CNC. Membrane preparation was made by the phase inversion method using N,N-dimethylformamide as solvent and water as nonsolvent, and subjected to dead-end microfiltration. Membranes were evaluated by their pure water flux, water content, hydraulic resistance and protein rejection. Polymers and nanocomposites were characterized by scanning electronic and optical microscopy, differential scanning calorimetry, infrared spectroscopy, strain stress testing and 13C solid state nuclear magnetic resonance. The most remarkable effects observed by the addition of CNCs are (i) a substantial increment in Young's modulus to twenty-two times compared with the neat PU and (ii) a marked increase in pure water flux up to sixty times, for sample containing 1% (w/w) of CNC. We found that nanofiller has a strong affinity to soft segment diol, which crystallizes in the presence of CNCs, developing both superior mechanical and pure water flow properties, compared to neat PU. The presence of nanofiller also modifies PU intermolecular interactions and consequently the nature of membrane pores.

Pharmacokinetics and biodistribution of amikacin encapsulated in carrier erythrocytes.

OBJECTIVES: To study the changes in the pharmacokinetics and tissue distribution of the aminoglycoside amikacin in rats using amikacin carrier erythrocytes as a delivery system. METHODS: Amikacin-loaded erythrocytes were obtained using a hypotonic dialysis method. The pharmacokinetic and tissue distribution of amikacin were studied in three groups of rats receiving intravenous amikacin in saline solution, amikacin-loaded erythrocytes and amikacin-loaded erythrocytes treated with glutaraldehyde. Pharmacokinetic analysis was accomplished using model-independent methods. RESULTS: Administration of the antibiotic using carrier erythrocytes elicited a sustained release effect, with an increase in the plasma half-life and in the area under the curve of the antibiotic. The tissue pharmacokinetics of amikacin using carrier erythrocytes in comparison with a control group revealed an accumulation of the antibiotic in specific tissues such as the liver and spleen, a similar pharmacokinetics in the lung and moderate changes in the pharmacokinetics in the kidney. Studies of tissue concentrations after the injection of glutaraldehyde-treated loaded erythrocytes demonstrated important changes in organs of the reticulo-endothelial system (RES) in comparison with the results observed for standard carrier erythrocytes, higher levels being observed in the liver whereas spleen levels decreased. CONCLUSIONS: The administration of amikacin in loaded erythrocytes in rats leads to significant changes in the pharmacokinetic behaviour of the antibiotic, a greater accumulation being observed in RES organs such as liver and spleen. This shows that loaded erythrocytes are potentially useful for the delivery of antibiotics in phagocytic cells located in the RES.

Validation and clinical evaluation of a UHPLC method with fluorescence detector for plasma quantification of doxorubicin and doxorubicinol in haematological patients.

A rapid and simple UHPLC-fluorescence detection method for the quantification of doxorubicin and its main metabolite, doxorubicinol, in human plasma has been developed. The method was also validated for its application in therapeutic drug monitoring, a clinical approach used in the optimization of oncologic treatments. Following a single protein precipitation step, chromatographic separation was achieved using a C18 column (50mm×2.10mm, particle size 1.7µm) at 50°C with a mobile phase consisting of water (containing 0.4% triethylamine and 0.4% orthophosphoric acid)/acetonitrile (77:23, v/v). Flow rate was 0.50mL/min and fluorescence detection with an excitation wavelength of 470nm and an emission wavelength of 548nm was used. The method met the specifications of linearity, selectivity, sensitivity, accuracy, precision and stability of the FDA and EMA guidelines for the validation of bioanalytical methods. Linearity for the drug (8-3000ng/mL) and the metabolite (3-150ng/mL) was observed (R(2)>0.992) and the maximum intra-day and inter-day precision coefficients of variation were less than 14% for both. The lower limits of quantification were 8 and 3ng/mL for doxorubicin and doxorubicinol, respectively. The method was successfully applied to the quantify plasma concentrations of doxorubicin and doxorubicinol in 33 patients diagnosed with haematological malignancies in which broad ranges for drug (8.3-2766.0ng/mL) and metabolite (4.8-104.9ng/mL) levels were measured adequately.

Pulmonary versus systemic delivery of levofloxacin. The isolated lung of the rat as experimental approach for assessing pulmonary inhalation.

The present work was aimed to compare levofloxacin pulmonary disposition after systemic or inhalatory delivery and to evaluate the influence of respiratory pattern on lung distribution. An experimental model of the isolated lung of the rat was used. Twenty-four Wistar rats were distributed in four groups receiving levofloxacin under different experimental conditions including systemic or pulmonary delivery and higher or lower respiratory frequency with lower or higher tidal volume, respectively. Levofloxacin (500 microg) was administered as a bolus injection or by inhalation. Lung tissue samples as well as efferent and broncoalveolar fluid were collected. Quantification of levofloxacin levels in all samples was performed by a high-performance liquid chromatography (HPLC) technique. Pulmonary distribution coefficient of levofloxacin after systemic delivery showed mean values of 1.19+/-0.13 and 3.34+/-0.61 ml/g for each respiratory pattern assayed. The partition coefficients estimated from simultaneous drug level in lung tissue and efferent fluid (EF) are in agreement with the above values. Comparison of systemic and pulmonary administration reveals statistical significant differences between partition coefficients showing much higher values for the latter route (8.01+/-5.53 versus 2.86+/-1.35). In conclusion, inhalation compared to systemic administration improves levofloxacin access to the lung tissue; the experimental approach used here to assess the pulmonary drug disposition may be a useful model for biopharmaceutical studies of inhaled therapeutics.

Patología médica y simbolismo en la obra de Durero / Medical pathology and symbolism in the Durer's art work

Durante varios siglos la observación de obras de arte bajo la perspectiva médica ha ocupado la atención de académicos y estudiosos del arte y la medicina, con sorprendentes hallazgos en ambos campos e implicaciones semiológicas que consideran los modelos de enfermedad y los temas patológicos en la pintura o en la escultura, como una nueva corriente denominada Arte social, nunca desprovista de la opción estética.En particular, las hipótesis sobre la deformidad constante de los dedos en las obras de Alberto Durero constituyen un modelo de análisis que conduce a establecer pautas de estudio médico en el arte. ¿Licencia de autor? ¿Camptodactilia o clinodactilia en los modelos? ¿La propia enfermedad ocupacional plasmada en sus obras? ¿Simbolismo religioso en una era de dominio de la Iglesia amenazada por movimientos reformistas? La presente investigación busca respuesta a esos interrogantes.

Diseno de un Esquema Simplificado para la Deteccion, Evaluacion, Manejo y Seguimiento del Paciente Hipertenso en Caldas

La hipertension escencial es un problema que afecta entre el 15 y el 20%de la poblacion Mundial, esta asociada a altas cifras de Morbimortalidad actuando como factor de riesgo en enfermedad cerebro vascular, enfermedad coronaria,insuficiencia cardiaca y renal principalmente.Esta consideracion motivo el interes del Departamento de Medicina Interna de la Facultad de Medicina de la Universidad de Caldas en la creacion de una linea de investigacion sobre el tema. La fase 1 de esta linea consistio en la revision bibliografica y el diseno teorico de un esquema de diagnostico, evaluacion, manejo y seguimiento de pacientes que se aplicara inicialmente en las consultas perifericas que dependen del Hospital Universitario de Caldas. Pretendemos probar la eficacia de la terapeutica recomendada y conocer mediante la aplicacion de un modelo de historia clinica precodificada, las caracteristicas de nuestra poblacion hipertensa. Actualmente estamos iniciando la fase 2 que corresponde al desarrollo operativo del esquema y se elaboran los proyectos de fases 3 y 4 que van a evaluar el Plan por grupos de edad..