N-aryltetrahydroisoquinoline derivatives as HA-CD44 interaction inhibitors: Design, synthesis, computational studies, and antitumor effect

Hyaluronic acid (HA) plays a crucial role in tumor growth and invasion through its interaction with cluster of differentiation 44 (CD44), a non-kinase transmembrane glycoprotein, among other hyaladherins. CD44 expression is elevated in many solid tumors, and its interaction with HA is associated with cancer and angiogenesis. Despite efforts to inhibit HA-CD44 interaction, there has been limited progress in the development of small molecule inhibitors. As a contribution to this endeavour, we designed and synthesized a series of N-aryltetrahydroisoquinoline derivatives based on existing crystallographic data available for CD44 and HA. Hit 2e was identified within these structures for its antiproliferative effect against two CD44+ cancer cell lines, and two new analogs (5 and 6) were then synthesized and evaluated as CD44-HA inhibitors by applying computational and cell-based CD44 binding studies. Compound 2-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-5-ol (5) has an EC50 value of 0.59 μM against MDA-MB-231 cells and is effective to disrupt the integrity of cancer spheroids and reduce the viability of MDA-MB-231 cells in a dose-dependent manner. These results suggest lead 5 as a promising candidate for further investigation in cancer treatment

The reference site collaborative network of the european innovation partnership on active and healthy ageing

Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs

Reflections about the problems of the ergonomic adaptation of screens to older users

Las diferentes tecnologías de pantallas se están aplicando en la actualidad a nuevos dispositivos de diferentes tipos y tamaños, para los cuales no se han planteado soluciones de Ergonomía Visual. Los productos tecnológicos que compramos deben pasar controles de seguridad, confortabilidad y usabilidad en general, pero también visuales cuando se trata de PVD’s. Una guía o protocolo del diseño ergonómico de PVD’s resultará de gran interés, sobre todo para los usuarios de edad avanzada, que podrán basarse en ella para adaptar el entorno visual a sus necesidades, y para fabricantes de dispositivos, con el fin de proporcionar la adaptación a diferentes necesidades.The different technologies of screens are being applied at present to new devices of different types and sizes, for which solutions of Visual Ergonomics have not considered. The technological products that we bought must pass controls of security, comfortableness and usability in general, but also visual for PVD’s. A guide or protocol of the ergonomic design of PVD’ s will be from great interest, mainly for the users of advanced age, who will be able to base on it to adapt the visual environment to their needs and for manufacturers of devices, in order to provide the adjustment to different needs

Comparativa de características colorimétricas de pantallas

El proceso de calibrado genérico para monitores CRT, conocido por GOG (gain-offset-gamma), relaciona la luminancia relativa Lrk de cada canal-color (R, G, B) y el nivel digital relativo correspondiente NDRk mediante una función de transferencia electro-óptica de tipo potencial. Sin embargo, cuando se usan otros dispositivos de visualización, como una pantalla LCD (Liquid Crystal Display) de un ordenador portátil, un proyector LCD o una pantalla de plasma, la reproducción de los colores se pierde drásticamente: por ejemplo, un gris anaranjado en el monitor CRT se ve más claro, saturado y verdoso al proyectar en una pantalla blanca usando un proyector LCD. Nuestro objetivo es realizar la comparación de diferentes dispositivos de visualización, con el fin de conocer sus características colorimétricas a partir de las curvas de calibrado

Effect of the color of the intraocular lens on optical and visual quality

Purpose: To analyze the optical quality of intraocular lenses (IOL) with an orange (PC440Y) and a yellow (SN60AT) filter, and correlate these results with the visual quality of patients with these implants. Setting: Fisabio Oftalmologνa Mιdica, Valencia, Spain. Design: Randomized prospective study. Materials and Methods: The IOL optical quality was determined using the modulation transfer function (MTF) and the spectral transmission. The visual quality of 87 eyes with cataract (51 with orange filter and 36 with yellow filter) was determined by best corrected visual acuity (BCVA) and contrast sensitivity function (CSF) under photopic and mesopic conditions. To analyze the results, we use a Student′s t-test. Results: Orange lens filtered more of the blue spectrum (cut-off wavelength of 370 nm) than the yellow lens (390 nm). The MTF of the yellow lens was better than the orange lens (average modulation of 0.676 for natural and 0.672 for orange). The patients′ BCVA was 0.02 + 0.10 logMAR for both lenses. The CSF obtained with the yellow lens was slightly better, although without statistically significant differences (P > 0.05). Conclusions: Both lenses are of good optical quality. The patients′ visual quality was similar with both lenses, and optical quality was also similar. The color of the lens does not affect the visual quality of the patient

Corneal Edema after Cataract Surgery

his systematic review investigates the prevalence and underlying causes of corneal edemafollowing cataract surgery employing manual phacoemulsification. A comprehensive search encom-passing databases such as PubMed, Embase, ProQuest, Cochrane Library, and Scopus was conducted,focusing on variables encompassing cataract surgery and corneal edema. Two independent reviewerssystematically extracted pertinent data from 103 articles, consisting of 62 theoretical studies and41 clinical trials. These studies delved into various aspects related to corneal edema after cataractsurgery, including endothelial cell loss, pachymetry measurements, visual performance, surgicaltechniques, supplies, medications, and assessments of endothelial and epithelial barriers. This review,encompassing an extensive analysis of 3060 records, revealed significant correlations between cornealedema and endothelial cell loss during phacoemulsification surgery. Factors such as patient age,cataract grade, and mechanical stress were identified as contributors to endothelial cell loss. Fur-thermore, pachymetry and optical coherence tomography emerged as valuable diagnostic tools forassessing corneal edema. In conclusion, this systematic review underscores the link between cornealedema and endothelial cell loss in manual phacoemulsification cataract surgery. It highlights therelevance of factors like patient demographics and diagnostic modalities. However, further researchis essential to unravel the complexities of refractive changes and the underlying mechanisms.This study was supported by the following foundations: Alcon-FOM-UVEG Cathedra, Foundation of Ophthalmology Medicine, and Universitat de València.Medicin

A rapid method for measuring intraocular lens power in vitro with a focimeter

En este artículo se describe un nuevo método para medir la potencia de la lente intraocular usando un focímetro, una lente oftálmica negativa y una solución salina. Para probar su fiabilidad, se mide la potencia de 58 lentes diferentes y se comparan con la potencia indicada por el fabricante. A pesar de las limitaciones des dispositivo experimental ideado, los resultados muestran una buena correlación entre ambos parámetros

Research in visual optics of the Vision and Colour Group (University of Alicante)

El Grupo de Visión y color de la Universidad de Alicante se creó en el año 2002 a partir de 3 doctores, cuyas tesis doctorales eran afines al campo de las Ciencias de la Visión. Aunque los campos científicos que abarca el grupo son amplios, desde la Ciencia y Tecnología del Color hasta la Ergonomía Visual, durante los últimos años se han realizado trabajos a nivel docente e investigador directamente relacionados con la Óptica Visual y materias afines (Visión Binocular, etc.). Éste es un breve resumen de estos trabajos.The Colour and Vision Group of the University of Alicante was made in 2002 from three doctors, whose PhD works were related with Vision Sciences. Although the scientific interests the group includes are extent, from Colour Technology and Science to Visual Ergonomics, during last years some academic and scientific works have been done directly related to Visual Optics and some affine topics (Binocular Vision, etc). This article is a short summary of these works

Selective Anticancer Therapy Based on a HA-CD44 Interaction Inhibitor Loaded on Polymeric Nanoparticles.

Hyaluronic acid (HA), through its interactions with the cluster of differentiation 44 (CD44), acts as a potent modulator of the tumor microenvironment, creating a wide range of extracellular stimuli for tumor growth, angiogenesis, invasion, and metastasis. An innovative antitumor treatment strategy based on the development of a nanodevice for selective release of an inhibitor of the HA-CD44 interaction is presented. Computational analysis was performed to evaluate the interaction of the designed tetrahydroisoquinoline-ketone derivative (JE22) with CD44 binding site. Cell viability, efficiency, and selectivity of drug release under acidic conditions together with CD44 binding capacity, effect on cell migration, and apoptotic activity were successfully evaluated. Remarkably, the conjugation of this CD44 inhibitor to the nanodevice generated a reduction of the dosis required to achieve a significant therapeutic effect

The components of adult astigmatism and their age-related changes

Purpose: To study the corneal and internal astigmatism and the age-related changes underlying the known refractive shift with-the-rule (WTR) towards against-the-rule (ATR) astigmatism. Methods: Refractive and corneal biometry data were collected for a total of 1195 healthy Caucasian subjects, recruited by ophthalmological centres across Europe. After conversion of refractive and corneal surface astigmatism to power vectors J 0 and J 45 , the total corneal and internal astigmatism were calculated. Results: Both refractive power vectors had leptokurtic distributions with a narrow peak at zero, and a broader, secondary distribution at its base, corresponding to eyes without balanced components. This may be fitted with a bigaussian function (J 0 : r² = 0.87; J 45 : r² = 0.98). Statistically significant changes in these distributions are seen with age: for refractive J 0 the narrow peak shortens progressively, while the broad peak shifts positive from to negative values, corresponding to increased astigmatism and a shift from with-the-rule towards against-the-rule. For J 45 the narrow peak shortens with age as well, while the broad peak flattens. These changes in refractive J 0 result from statistically significant negative shifts in both the corneal and internal components with age (Kruskal-Wallis, p < 0.05). Conclusion: In young participants corneal and internal astigmatism partially cancel each other out. This balance between both is gradually lost after age 50, leading to larger amounts of refractive astigmatism, as well as a reorientation of the axis. Given the small amplitude of these changes, they are unlikely to have repercussions for long term stability toric cataract or refractive surgery outcomesMedicin