In Vitro and in Vivo Evaluation of Novel Cross-Linked Saccharide Based Polymers as Bile Acid Sequestrants

Bile acid sequestrants (BAS) represent a therapeutic approach for the management of hypercholesterolemia that relies on the cationic polymeric nature of BAS to selectively bind negatively charged bile acids. We hypothesized that the cross-linking of β-cyclodextrin (β-CD) and saccharides such as starch or dextrin with divinyl sulfone (DVS) yields homo- and hetero-polymeric materials with the ability to trap sterols. Our hypothesis was put to test by synthesizing a library of 22 polymers that were screened to evaluate their capability to sequester both cholesterol (CHOL) and cholic and deoxycholic acids (CA and DCA). Three polymers synthesized in high yield were identified as promising. Two were neutral hetero-polymers of β-CD and starch or dextrin and the third was a weakly cationic homo-polymer of starch, highlighting the importance of the cavity effect. They were tested in hypercholesterolemic male Wistar rats and their ability to regulate hypercholesterolemia was similar to that for the reference BAS cholestyramine, but with two additional advantages: (i) they normalized the TG level and (ii) they did not increase the creatinine level. Neither hepatotoxicity nor kidney injury was detected, further supporting them as therapeutical candidates to manage hypercholesterolemia.Financial Support was provided by Universidad de Granada in the frame of the Granada Research of Excellence Initiative on BioHealth (GREIB)

Clinical Significance of Langerhans Cells in Squamous Cell Carcinoma of the Larynx

Langerhans cells (LCs) may be involved in the immunosurveillance against tumors as antigen-presenting cells. Our objective has been to determine the relevance of LC in progression of larynx squamous cell carcinomas and their relationship with different subpopulations of tumor-infiltrating cells. LCs were investigated by immunohistochemical methods using anti-CD1 antibody. LCs were detected in most of the primary tumors studied (44 out of 50) and also in metastases (6 out of 10) and recurrences (2 out of 3), but we did not find any statistical association between number of LCs and clinical-pathological parameters or survival. However, the number of LCs was increased in patients with evident infiltration of lymphocytes, mainly cytotoxic T cells. We can conclude that although LCs did not show clinical utility as prognostic marker, they may play a role in releasing an active immune response in larynx carcinomas, according to their ability to present antigens to sensitized T cells

La nueva teoría social en hispanoamérica. Introducción a la teoría de sistemas constructivista

El propósito de esta obra es responder al creciente interés en ciencias sociales por libros en lengua española sobre la Teoría de Sistemas Constructivista. Las tres preguntas que frecuentemente se hacen a esta teoría son: qué significan sus conceptos, cuál es su metodología y cómo se puede llevar a la práctica una investigación tal. Con respecto a la primera pregunta, es posible afirmar que hay mayor claridad en su respuesta que en las dos preguntas siguientes. Un investigador neófito no ocuparía la palabra claridad, pero debería reconocer que está disponible una mayor cantidad de bibliografía teórica sobre el asunto, que sobre sus variantes metodológicas o de aplicación en estudios. En nuestra experiencia académica, hay dos tipos de aprendices de la teoría de sistemas constructivista: aquellos que son instruidos por un profesor y aquellos que se aproximan de manera autodidacta. Quienes más sufren los rigores de la teoría son estos últimos, aunque los otros tienen el apoyo emocional de sus maestros cuando entran en la típica desesperación inicial. Lo anterior siempre nos ha llevado a pensar que la enseñanza universitaria es vital para lograr dar una respuesta con fundamentos, y atractiva, a las mencionadas tres preguntas frecuentes sobre la teoría de sistemas constructivista

Click to learn, learn to click: undergraduate synthetic organic chemistry experiments

The optimization of an undergraduate experiment for Organic Chemistry students is described to explore the concept of click chemistry. The preparation of a terminal fluorescent alkyne and an organic azide is reported consisting of simple steps. These are employed in the Cu(I)-catalized azide-alkyne cycloaddition to obtain a novel molecule containing a triazole ring whose characterization allows the students to practice a variety of techniques: NMR (1H, 13C, COSY and HSQC), melting point, thin layer chromatography, IR, fluorescence spectroscopy and mass spectrometry to confirm the structure of their obtained product. An alternative methodology in a one-pot reaction is also explored and a full laboratory manual provided.FQM-208. GlycoChemBio: Glycochemistry and Bioconjugatio

The influence of sensor placement on in-situ ultrasound wave velocity measurement.

Ultrasound wave velocity was measured in 30 pieces of Spanish Scots pine (Pinus sylvestris L.), 90 x 140 mm in cross-section and 4 m long. Five different sensor placement arrangements were used: end to end (V0), face to opposite face, edge to opposite edge, face to same face and edge to same edge. The pieces were successively shortened to 3, 2 and 1 m, in order to obtain these velocities and their ratios to reference value V0 for different lengths and angles with respect to the piece axis for the crossed measurements. The velocity obtained in crossed measurements is lower than V0. A correction coefficient for crossed velocities is proposed, depending on the angle, to adjust them to the V0 benchmark. The velocities measured on a surface, are also lower than V0, and their ratio with respect to V0 is close to 0.97 for distances equal to or greater than 18 times the depth of the beam

Antimicrobial Defined Daily Dose in Neonatal Population: Validation in the Clinical Practice

Antimicrobial consumption; Daily-defined dosage; Neonatal antimicrobial prescriptionConsum d'antimicrobians; Dosi diària definida; Prescripció antimicrobiana neonatalConsumo de antimicrobianos; Dosis diaria definida; Prescripción antimicrobiana neonatalBackground: Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population. Methods: The validation of the neonatal DDD, Phase II of the research project, was carried out through a descriptive observational study. Periodic cut-offs were performed to collect antimicrobial prescriptions of neonates admitted to the neonatology and intensive care units of nine Spanish hospitals. The data collected included demographic variables (gestational age, postnatal age, weight and sex), antimicrobial dose, frequency and route of administration. The selection of the optimal DDD value takes into account power value, magnitude obtained from the differences in the DDD, statistical significance obtained by the Wilcoxon test and degree of agreement in the stipulated doses. Results: Set of 904 prescriptions were collected and finally 860 were analysed based on the established criteria. The antimicrobials were mostly prescribed in the intensive care unit (63.1%). 32 different antimicrobials were collected, and intravenous administration was the most commonly used route. Neonatal DDD were defined for 11 different antimicrobials. A potency > 80% was obtained in 7 antibiotics. The 57.1% of the selected DDD correspond to phase I and 21.4% from phase II. Conclusion: DDD validation has been achieved for the majority of intravenously administered antimicrobials used in clinical practice in the neonatal population. This will make it possible to have an indicator that will be used globally to estimate the consumption of antimicrobials in this population, thus confirming its usefulness and applicability.M.M.-T. received financial support from the Subprograma Río Hortega, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain (CM21/00115). The project has been carried out without financial funding but is supported by the Spanish Society of Hospital Pharmacy (SEFH), the Working Group on Pharmaceutical Care in Infectious Diseases of the SEFH (Afinf) and Spanish working group on paediatric pharmacy of the SEFH (gefp)

Respuesta de tres cultivares de maíz a la inoculación con Azospirillum brasilense bajo cuatro diferentes dosis de nitrógeno

En el municipio de Huamuxtitlán, estado de Guerrero, México, se evaluó la respuesta de los materiales de maíz VS-535, H-507 y criollo veracruzano en las dosis de 0, 30, 60 y 90 kg de nitrógeno ha-1, con y sin Azospirillum brasilense. En el sintético VS- 535 se registró el mayor rendimiento de grano (5.23 t ha-1). En las dosis de 0, 30, 60 y 90 kg de N ha-1 se registraron 4.38, 4.36, 4.81 y 4.93 t ha-1, respectivamente. La diferencia entre aplicar o no Azospirillum brasilense (promedio sobre los factores A, B y repeticiones) fue de 1.47 t ha-1 y de dos días en el ciclo biológico del cultivo.En el municipio de Huamuxtitlán, estado de Guerrero, México, se evaluó la respuesta de los materiales de maíz VS-535, H-507 y criollo veracruzano en las dosis de 0, 30, 60 y 90 kg de nitrógeno ha-1, con y sin Azospirillum brasilense. En el sintético VS535 se registró el mayor rendimiento de grano (5.23 t ha-1). En las dosis de 0, 30, 60 y 90 kg de N ha-1 se registraron 4.38, 4.36, 4.81 y 4.93 t ha-1, respectivamente. La diferencia entre aplicar o no Azospirillum brasilense (promedio sobre los factores A, B y repeticiones) fue de 1.47 t ha-1 y de dos días en el ciclo biológico del cultivo

Deep Prototypical-Parts Ease Morphological Kidney Stone Identification and are Competitively Robust to Photometric Perturbations

Identifying the type of kidney stones can allow urologists to determine their cause of formation, improving the prescription of appropriate treatments to diminish future relapses. Currently, the associated ex-vivo diagnosis (known as Morpho-constitutional Analysis, MCA) is time-consuming, expensive and requires a great deal of experience, as it requires a visual analysis component that is highly operator dependant. Recently, machine learning methods have been developed for in-vivo endoscopic stone recognition. Deep Learning (DL) based methods outperform non-DL methods in terms of accuracy but lack explainability. Despite this trade-off, when it comes to making high-stakes decisions, it's important to prioritize understandable Computer-Aided Diagnosis (CADx) that suggests a course of action based on reasonable evidence, rather than a model prescribing a course of action. In this proposal, we learn Prototypical Parts (PPs) per kidney stone subtype, which are used by the DL model to generate an output classification. Using PPs in the classification task enables case-based reasoning explanations for such output, thus making the model interpretable. In addition, we modify global visual characteristics to describe their relevance to the PPs and the sensitivity of our model's performance. With this, we provide explanations with additional information at the sample, class and model levels in contrast to previous works. Although our implementation's average accuracy is lower than state-of-the-art (SOTA) non-interpretable DL models by 1.5 %, our models perform 2.8% better on perturbed images with a lower standard deviation, without adversarial training. Thus, Learning PPs has the potential to create more robust DL models.Comment: This paper has been accepted at the LatinX in Computer Vision Research Workshop at CVPR2023 as a full paper and it will appear on the CVPR proceeding

Improved Kidney Stone Recognition Through Attention and Multi-View Feature Fusion Strategies

This contribution presents a deep learning method for the extraction and fusion of information relating to kidney stone fragments acquired from different viewpoints of the endoscope. Surface and section fragment images are jointly used during the training of the classifier to improve the discrimination power of the features by adding attention layers at the end of each convolutional block. This approach is specifically designed to mimic the morpho-constitutional analysis performed in ex-vivo by biologists to visually identify kidney stones by inspecting both views. The addition of attention mechanisms to the backbone improved the results of single view extraction backbones by 4% on average. Moreover, in comparison to the state-of-the-art, the fusion of the deep features improved the overall results up to 11% in terms of kidney stone classification accuracy.Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl