An Innovative Polymeric Platform for Controlled and Localized Drug Delivery.

Precision medicine aims to optimize pharmacological treatments by considering patients' genetic, phenotypic, and environmental factors, enabling dosages personalized to the individual. To address challenges associated with oral and injectable administration approaches, implantable drug delivery systems have been developed. These systems overcome issues like patient adherence, bioavailability, and first-pass metabolism. Utilizing new combinations of biodegradable polymers, the proposed solution, a Polymeric Controlled Release System (PCRS), allows minimally invasive placement and controlled drug administration over several weeks. This study's objective was to show that the PCRS exhibits a linear biphasic controlled release profile, which would indicate potential as an effective treatment vehicle for cervical malignancies. An injection mold technique was developed for batch manufacturing of devices, and in vitro experiments demonstrated that the device's geometry and surface area could be varied to achieve various drug release profiles. This study's results motivate additional development of the PCRS to treat cervical cancer, as well as other malignancies, such as lung, testicular, and ovarian cancers.

Impact of augmented renal clearance on the pharmacokinetics of linezolid: Advantages of continuous infusion from a pharmacokinetic/pharmacodynamic perspective.

OBJECTIVES: The aim of this study was to assess the influence of renal function, in particular the presence of augmented renal clearance (ARC), on the pharmacokinetics of linezolid in critically ill patients. The effect of continuous infusion on the probability of therapeutic success from a pharmacokinetic/pharmacodynamic (PK/PD) perspective was also evaluated. METHODS: Seventeen patients received linezolid (600 mg every 12 h) as a 30-min infusion and 26 as a continuous infusion (50 mg/h). The PK parameters were calculated and the probability of PK/PD target attainment (PTA) was estimated by Monte Carlo simulation (MCS) for different doses administered by intermittent (600 mg every 12 h or 600 mg every 8 h) or continuous infusion (50 mg/h or 75 mg/h). RESULTS: In patients without ARC, the standard dose was adequate to attain the PK/PD target. However, linezolid clearance was significantly higher in ARC patients, leading to sub-therapeutic concentrations. Continuous infusion (50 mg/h) provided concentrations ≥2 mg/l in 70% of the ARC patients. MCS revealed that concentrations ≥2 mg/l would be reached in >90% of patients receiving 75 mg/h. CONCLUSIONS: ARC increases linezolid clearance and leads to a high risk of underexposure with the standard dose. Continuous infusion increases the PTA, but an infusion rate of 75 mg/h should be considered to ensure concentrations ≥2 mg/ml.

Endometriosis colónica que simula tumor carcinoide cecal / Colonic endometriosis mimicking a caecal carcinoid tumour

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Priming effects in the recognition of simple and complex words and pseudowords / Efectos de anticipación en el reconocimiento de palabras y pseudopalabras simples y complejas

Whether morphological processing of complex words occurs beyond orthographic processing is a matter of intense debate. In this study, morphological processing is examined by presenting complex words (brujería -> brujo - witchcraft -> witch), as well as simple (brujaña->brujo) and complex pseudowords (brujanza ->brujo), as primes in three masked lexical decision tasks. In the first experiment, the three experimental conditions facilitated word recognition in comparison to the control condition, but no differences emerged between them. Given the importance of the surface frequency effect observed, a second experiment was conducted. The results fully replicate those observed in the first one, but this time with low frequency targets. In the third experiment, vowels were removed from the stems of primes to reduce the orthographic overlap between primes and targets and, therefore, the influence of the embedded stem effect. The results show facilitative effects only for complex words. However, paired comparisons show no differences between experimental conditions. The overall results show the central role played by the processing of stems in visual word recognition and are explained in terms of current models of morphological processing

La cuestión de si el procesamiento morfológico ocurre más allá del mero procesamiento ortográfico continúa siendo objeto de intenso debate. En este estudio se examina el procesamiento morfológico en tres experimentos de decisión léxica con anticipador enmascarado presentando como anticipadores palabras complejas (brujería -> brujo - witchcraft -> witch), así como pseudopalabras simples (brujaña ->brujo) y pseudopalabras complejas (brujanza ->brujo). En el primer experimento, las tres condiciones experimentales facilitaron el reconocimiento en comparación con la condición de control, pero sin mostrar diferencias entre ellas. Debido a la importancia del efecto observado de la frecuencia de palabra se llevó a cabo un segundo experimento. En él se emplearon únicamente estímulos de baja frecuencia, pero los resultados fueron idénticos a los del primer experimento. En el tercer experimento se eliminaron las vocales de los anticipadores para reducir el solapamiento ortográfico entre anticipador y objetivo y, consecuentemente, la influencia del efecto de repetición de la base. Los resultados mostraron efectos facilitadores solo para las palabras complejas. Sin embargo, las comparaciones por pares no mostraron diferencias entre las condiciones experimentales. Los resultados obtenidos suponen en conjunto un rol muy destacado para el procesamiento de las bases en el reconocimiento léxico y son explicados a la luz de los modelos teóricos actuales sobre procesamiento morfológico

Written Type and Token Frequency Measures of Fifty Spanish Derivational Morphemes.

Several databases of written language exist in Spanish that manage important information on the lexical and sublexical characteristics of words. However, there is no database with information on the productivity and frequency of use of derivational suffixes: sublexical units with an essential role in the formation of orthographic representations and lexical access. This work examines these two measures, known as type and token frequencies, for a series of 50 derivational suffixes and their corresponding orthographic endings. Derivational suffixes are differentiated from orthographic endings by eliminating pseudoaffixed words from the list of orthographic endings (cerveza [beer] is a simple word despite its ending in -eza). We provide separate data for child and adult populations, using two databases commonly accessed by psycholinguists conducting research in Spanish. We describe the filtering process used to obtain descriptive data that will provide information for future research on token and type frequencies of morphemes. This database is an important development for researchers focusing on the role of morphology in lexical acquisition and access.

The suffix priming effect: Further evidence for an early morpho-orthographic segmentation process independent of its semantic content.

This work presents the results of a masked lexical decision experiment in which we explore the morphological parsing of Spanish suffixed or pseudosuffixed words through the suffix priming effect. Priming the bases or pseudobases with their suffixed or pseudosuffixed forms is the standard process in experiments aimed at understanding the processes underlying morphological parsing in visual word recognition with masked priming lexical decision (e.g., darkness-DARK; corner-CORN). We, however, compare the effect of suffix priming on the lexical decision of suffixed (ero-JORNALERO) and pseudosuffixed words (ero-CORDERO), as well as the effect of orthographic priming on nonsuffixed words (eba-PRUEBA). The results show that in the case of suffixed and pseudosuffixed words, related primes (ero-JORNALERO; ero-CORDERO) significantly accelerated response latencies in comparison to unrelated primes (ista-JORNALERO; ura-CORDERO), while for simple words there was no facilitation from the orthographically related prime in comparison to the unrelated prime (eba-PRUEBA; afo-PRUEBA). These results are consistent with the so-called morpho-orthographic segmentation process in the course of visual word recognition, which might also be independent of orthographic and purely semantic factors. Our results also support the view that morphological parsing takes place regardless of whether a stem is present in a word. These results complement findings from studies dealing with CORNER- and BROTHEL-like stimuli.

Written type and token frequency measures of fifty Spanish derivational morphemes

Several databases of written language exist in Spanish that manage important information on the lexical and sublexical characteristics of words. However, there is no database with information on the productivity and frequency of use of derivational suffixes: sublexical units with an essential role in the formation of orthographic representations and lexical access. This work examines these two measures, known as type and token frequencies, for a series of 50 derivational suffixes and their corresponding orthographic endings. Derivational suffixes are differentiated from orthographic endings by eliminating pseudoaffixed words from the list of orthographic endings (cerveza [beer] is a simple word despite its ending in -eza). We provide separate data for child and adult populations, using two databases commonly accessed by psycholinguists conducting research in Spanish. We describe the filtering process used to obtain descriptive data that will provide information for future research on token and type frequencies of morphemes. This database is an important development for researchers focusing on the role of morphology in lexical acquisition and access (AU)

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The role of derivative suffix productivity in the visual word recognition of complex words / El papel de la productividad de los sufijos derivativos en el reconocimiento visual de palabras complejas

In this article we present two lexical decision experiments that examine the role of base frequency and of derivative suffix productivity in visual recognition of Spanish words. In the first experiment we find that complex words with productive derivative suffixes result in lower response times than those with unproductive derivative suffixes. There is no significant effect for base frequency, however. In experiment two, the same procedure was undertaken with pseudowords, showing that when they are composed by productive derivative suffixes they take longer to be rejected than when they are composed by unproductive derivative suffixes. Again, the role of base frequency fails to reach significance. These results endorse the view that derivative suffixes have a relevant role in visual recognition of complex words. According to our results, derivative suffixes create the conditions for taking a lexical candidate as a legal lexical entry and therefore they contribute decisively to the lexical decision (AU)

En este artículo presentamos dos experimentos de decisión léxica que examinan el rol de las variables de frecuencia de base y de la productividad de los sufijos derivativos en el reconocimiento visual de las palabras. En el primer experimento encontramos que las palabras complejas con sufijos derivativos productivos tardan menos tiempo en ser respondidas que aquellas otras con sufijos derivativos improductivos. Se observa también la falta de significación para la frecuencia de base. En el experimento dos se lleva a cabo la misma metodología pero con pseudopalabras, mostrando que cuando éstas están compuestas por sufijos derivativos productivos tardan más tiempo en ser rechazadas que cuando están compuestas por sufijos derivativos improductivos. De nuevo la variable de frecuencia de base no alcanza valor significativo. Estos resultados respaldan la visión de que los sufijos derivativos tienen un rol relevante en el reconocimiento visual de las palabras complejas. De acuerdo a nuestros resultados, los sufijos derivativos crean las condiciones para tomar un candidato como una entrada léxica legal y por lo tanto contribuyen decisivamente a la decisión léxica. Estos resultados se interpretan finalmente a la luz de estudios previos centrados en las mismas variables (AU)

The effect of family size on spanish simple and complex words.

This study presents the results of three experiments in which the Family Size (FS) effect is explored. The first experiment is carried out with no prime on simple words. The second and third experiments are carried out with morphological priming on complex words. In the first experiment a facilitatory effect of FS is observed: high FS targets produced faster responses than low FS targets. However, an inhibitory effect of Stem-FS is observed in the second experiment: low Stem-FS targets produced faster responses than high Stem-FS targets. In the third experiment a facilitatory effect is observed when the Affix-FS is manipulated: high Affix-FS targets produced faster responses than low Affix-FS targets. Overall data confirms that the effect of FS plays an important role in lexical access in Spanish. The results also show that the effect of FS is modulated by the lexical nature of the prime (lexical or sublexical) and by the number of candidates activated. Finally, it is suggested that the nonwords employed were decisive in obtaining the results mentioned.

Ultrasonically enhanced extraction of bioactive principles from Quillaja Saponaria Molina.

A study of ultrasonic enhancement in the extraction of bioactive principles from Quillaja Saponaria Molina (Quillay) is presented. The effects influencing the extraction process were studied through a two-level factorial design. The effects considered in the experimental design were: granulometry, extraction time, acoustic Power, raw matter/solvent ratio (concentration) and acoustic impedance. It was found that for aqueous extraction the main factors affecting the ultrasonically-assisted process were: granulometry, raw matter/solvent ratio and extraction time. The extraction ratio was increased by Ultrasonics effect and a reduction in extraction time was verified without any influence in the product quality. In addition the process can be carried out at lower temperatures than the conventional method. As the process developed uses chips from the branches of trees, and not only the bark, this research contributes to make the saponin exploitation process a sustainable industry.

Fluorine-18 fluorodeoxyglucose PET in the preoperative staging of colorectal cancer.

INTRODUCTION: In patients with colorectal cancer (CC), preoperative evaluation and staging should focus on techniques that might alter the preoperative or intraoperative surgical plan. Conventional imaging methods (CT, MRI) have low accuracy for identifying the depth of tumour infiltration and have limited ability to detect regional lymph node involvement. The aim of this study was to evaluate the utility of FDG-PET in the initial staging of patients with CC in comparison with conventional staging methods and to determine its impact on therapeutic management. METHODS: One hundred and four patients with a diagnosis of CC (53 males and 51 females; mean age 66.76+/-12.36 years), selected prospectively, were studied for staging using a standard procedure (CT) and FDG-PET. When possible, the reference method was histology. RESULTS: In 14 patients, surgery was contraindicated by FDG-PET owing to the extent of disease (only 6/14 suspected by CT). FDG-PET revealed four synchronous tumours. For N staging, both procedures showed a relatively high specificity but a low diagnostic accuracy (PET 56%, CT 60%) and sensitivity (PET 21%, CT 25%). For M assessment, diagnostic accuracy was 92% for FDG-PET and 87% for CT. FDG-PET results led to modification of the therapy approach in 50% of patients with unresectable disease. FDG-PET findings were important, revealing unknown disease in 19.2%, changing the staging in 13.46% and modifying the scope of surgery in 11.54% (with a change in the therapeutic approach in 17.85% of those patients with rectal cancer). CONCLUSION: Compared with conventional techniques, FDG-PET appears to be useful in pre-surgical staging of CC, revealing unsuspected disease and impacting on the treatment approach.

Modeling of yeast metabolism and process dynamics in batch fermentation.

Much is known about yeast metabolism and the kinetics of industrial batch fermentation processes. In this study, however, we provide the first tool to evaluate the dynamic interaction that exists between them. A stoichiometric model, using wine fermentation as a case study, was constructed to simulate batch cultures of Saccharomyces cerevisiae. Five differential equations describe the evolution of the main metabolites and biomass in the fermentation tank, while a set of underdetermined linear algebraic equations models the pseudo-steady-state microbial metabolism. Specific links between process variables and the reaction rates of metabolic pathways represent microorganism adaptation to environmental changes in the culture. Adaptation requirements to changes in the environment, optimal growth, and homeostasis were set as the physiological objectives. A linear programming routine was used to define optimal metabolic mass flux distribution at each instant throughout the process. The kinetics of the process arise from the dynamic interaction between the environment and metabolic flux distribution. The model assessed the effect of nitrogen starvation and ethanol toxicity in wine fermentation and it was able to simulate fermentation profiles qualitatively, while experimental fermentation yields were reproduced successfully as well.