Testing drug release from medicated contact lenses: the missing link to predict in vivo performance

Contact lenses (CLs) offer a wide variety of advantages as ocular drug-releasing platforms, but the feasibility of medicated CL development is constrained by numerous scientific, technological, and regulatory challenges. One main difficulty is the setting of release rate specifications for each drug, since at present there are no standardized in vitro release models that can appropriately predict the performance of drug-eluting CLs once placed onto the eye. CL-adapted release tests may provide knowledge on how the drug release pattern should perform in vivo to trigger and maintain the therapeutic effects for both anterior and posterior ocular tissues. Moreover, in vitro release tests are valuable tools for quality assessment during production and to investigate the effect of a change in composition or process variables. This review aims to shed light on biorelevant ways of evaluating in vitro drug release from CLs and the feasibility of establishing in vitro-in vivo correlations (IVIVC) to predict in vivo performance. First, general guidelines and Pharmacopeia release tests for topical ophthalmic formulations as well as in vitro release tests implemented for drug-CLs in the last two decades are analyzed. Then, development of an appropriate method to investigate IVIVC is attempted from the few papers simultaneously reporting in vitro release profiles and either in vivo release or therapeutic response. Finally, key points to be considered for in vitro testing drug release from a medicated CL are suggested to pave the way to the clinical arenaThis project is funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions grant agreement N° 813440 (ORBITAL–Ocular Research by Integrated Training And Learning). The work was also partially supported by MCIN [PID2020-113881RB-I00/AEI/10.13039/501100011033] Spain, Xunta de Galicia [ED431C 2020/17], and FEDERS

Validation of the index for inclusion questionnaire for parents of non-university education students

The perspective from the parents of non-university students is essential in determining inclusive education in a school. The Index of Inclusion is one of the most widely used self-assessment tools and strategies to help teaching teams self-assess their political cultures and practices from the perspective of the values and principles of educational inclusion worldwide. For this reason, the present study intends to show evidence of validity of the Index for Inclusion questionnaire for parents of non-university education students, in a quantitative way, through a confirmatory factor analysis (CFA). In this study, 108 fathers and 500 mothers took part, aged between 21 and 62 years (M = 43.59; SD = 6.64), whose children belonged to educational institutions throughout Spain. The results revealed adequate adjustment rates, showing invariant structure with respect to sex. The Index for Inclusion for families of non-university education students was shown to be a robust and adequate psychometric instrument to assess the degree of development of inclusive education in educational institutions from the perspective of the parents of said student body. The family is a basic pillar in the education of children and a reference for them. In addition, parents of non-university education students are configured as fundamental participatory elements of the child’s educational institution thus; making the family a fundamental element that favors inclusive education. Precisely because of all this, the future administration of this questionnaire (to the parents of these students) is recommended

SuDS efficiency during the start-up period under Mediterranean climatic conditions

[EN] This paper presents the performance of a number of sustainable drainage systems (SuDS) in the city of Xàtiva in the Valencia Region of Spain relatively soon after their construction. The systems studied comprise two roadside swales, one detention basin receiving runoff from one of the swales and one green roof to a school. The SuDS were installed under an EU LIFEþ project intended to demonstrate their practicability, application, and behavior under Mediterranean rainfall conditions. Most of the systems installed were in new developments but the green roof was retrofitted to a school within Xàtiva, which is a dense urban area. Full flow monitoring was undertaken and spot samples were taken to give a preliminary assessment of water quality performance. The early results presented in the paper demonstrate the effectiveness of the systems under typical Mediterranean conditions, which comprise intense rainfall from September to December and little or no precipitation at other times of the year. It is concluded that SuDS can be effectively introduced in the Mediterranean region of Spain.The research described in this paper has been carried out under the Life+ program research project "AQUAVAL Sustainable Urban Water Management Plans, promoting SUDS and considering climate change, in the province of Valencia" (Life08ENV/E/000099), supported by ERDF funding of the European Union.Perales Momparler, S.; Hernández Crespo, C.; Vallés Morán, FJ.; Martín Monerris, M.; Andrés Doménech, I.; Andreu Álvarez, J.; Jefferies, C. (2014). SuDS efficiency during the start-up period under Mediterranean climatic conditions. CLEAN - Soil, Air, Water. 42(2):178-186. doi:10.1002/clen.201300164S178186422Boletin Oficial del Estado 2012Czemiel Berndtsson, J. (2010). Green roof performance towards management of runoff water quantity and quality: A review. Ecological Engineering, 36(4), 351-360. doi:10.1016/j.ecoleng.2009.12.014Davis, A. P., Stagge, J. H., Jamil, E., & Kim, H. (2012). Hydraulic performance of grass swales for managing highway runoff. Water Research, 46(20), 6775-6786. doi:10.1016/j.watres.2011.10.017Casal-Campos, A., Jefferies, C., & Perales Momparler, S. (2012). Selecting SUDS in the Valencia Region of Spain. Water Practice and Technology, 7(1). doi:10.2166/wpt.2012.001Gomez-Ullate, E., Castillo-Lopez, E., Castro-Fresno, D., & Bayon, J. R. (2010). Analysis and Contrast of Different Pervious Pavements for Management of Storm-Water in a Parking Area in Northern Spain. Water Resources Management, 25(6), 1525-1535. doi:10.1007/s11269-010-9758-xCastro-Fresno, D., Andrés-Valeri, V., Sañudo-Fontaneda, L., & Rodriguez-Hernandez, J. (2013). Sustainable Drainage Practices in Spain, Specially Focused on Pervious Pavements. Water, 5(1), 67-93. doi:10.3390/w5010067Rowe, D. B. (2011). Green roofs as a means of pollution abatement. Environmental Pollution, 159(8-9), 2100-2110. doi:10.1016/j.envpol.2010.10.029Deletic, A. (2001). Modelling of water and sediment transport over grassed areas. Journal of Hydrology, 248(1-4), 168-182. doi:10.1016/s0022-1694(01)00403-6Stagge, J. H., Davis, A. P., Jamil, E., & Kim, H. (2012). Performance of grass swales for improving water quality from highway runoff. Water Research, 46(20), 6731-6742. doi:10.1016/j.watres.2012.02.037Kim, L.-H., Zoh, K.-D., Jeong, S., Kayhanian, M., & Stenstrom, M. K. (2006). Estimating Pollutant Mass Accumulation on Highways during Dry Periods. Journal of Environmental Engineering, 132(9), 985-993. doi:10.1061/(asce)0733-9372(2006)132:9(985)Brodie, I. M., & Dunn, P. K. (2010). Commonality of rainfall variables influencing suspended solids concentrations in storm runoff from three different urban impervious surfaces. Journal of Hydrology, 387(3-4), 202-211. doi:10.1016/j.jhydrol.2010.04.008Zuo, X., Fu, D., Li, H., & Singh, R. P. (2011). Distribution Characteristics of Pollutants and Their Mutual Influence in Highway Runoff. CLEAN - Soil, Air, Water, 39(10), 956-963. doi:10.1002/clen.201000422Sansalone, J. J., Koran, J. M., Smithson, J. A., & Buchberger, S. G. (1998). Physical Characteristics of Urban Roadway Solids Transported during Rain Events. Journal of Environmental Engineering, 124(5), 427-440. doi:10.1061/(asce)0733-9372(1998)124:5(427)Sansalone, J. J., & Cristina, C. M. (2004). First Flush Concepts for Suspended and Dissolved Solids in Small Impervious Watersheds. Journal of Environmental Engineering, 130(11), 1301-1314. doi:10.1061/(asce)0733-9372(2004)130:11(1301)BERNDTSSON, J., EMILSSON, T., & BENGTSSON, L. (2006). The influence of extensive vegetated roofs on runoff water quality. Science of The Total Environment, 355(1-3), 48-63. doi:10.1016/j.scitotenv.2005.02.035Vijayaraghavan, K., Joshi, U. M., & Balasubramanian, R. (2012). A field study to evaluate runoff quality from green roofs. Water Research, 46(4), 1337-1345. doi:10.1016/j.watres.2011.12.05

The role of monitoring sustainable drainage systems for promoting transition towards regenerative urban built environments: a case study in the Valencian region, Spain

[EN] Sustainable drainage systems are an alternative and holistic approach to conventional urban stormwater management that use and enhance natural processes to mimic pre-development hydrology, adding a number of well-recognized, although not so often quantified benefits. However, transitions towards regenerative urban built environments that widely incorporate sustainable drainage systems are "per se" innovative journeys that encounter barriers which include the limited evidence on the performance of these systems which, in many countries, are still unknown to professionals and decision makers. A further important barrier is the frequently poor interaction among stakeholders; key items such as sustainable drainage systems provide collective benefits which also demand collective efforts. With the aim of overcoming such innovation-driven barriers, six showcase projects (including rain gardens acting as infiltration basins, swales and a green roof) to demonstrate the feasibility and suitability of sustainable drainage systems were developed and/or retrofitted in two cities of the Valencian region of Spain as a part of an European project, and their performance was monitored for a year. The data acquired, after being fully analyzed and presented to a group of key regional stakeholders, is proving to be a valuable promoter of the desired transition (for instance in influencing the support to SuDS in recent regional legislation). This paper presents detailed data on how these urban ecological drainage infrastructure elements reduce runoff (peak flows and volumes) and improve its quality, contributing to the goal of healthier and livable cities. The data show that the pilots have good hydraulic performance under a typical Mediterranean climate and also provided water quality benefits. Furthermore, it shows how engagement can contribute to smarter governance in the sense of smoothing the difficulties faced by innovation when being presented, understood, and endorsed by professionals and decision-makers in the field of stormwater management. Finally, activities undertaken in the demonstration sites monitored, show how they have been drivers of innovation and transition towards a new stormwater paradigm in Spain, serving as a reference to other urban areas in the Mediterranean. (C) 2016 Elsevier Ltd. All rights reserved.This research has been conducted as part of the Life+ program project "AQUAVAL: Sustainable Urban Water Management Plans, promoting SUDS and considering climate change, in the province of Valencia" (Life08ENV/E/000099) and the MED program project "E2STORMED: Improvement of energy efficiency in the water cycle by the use of innovative stormwater management in smart Mediterranean cities" (1C-MED12-14), both supported by European Regional Development Fund (ERDF) funding of the European Union.Momparler Perales, S.; Andrés Doménech, I.; Hernández Crespo, C.; Vallés-Morán, FJ.; Martín Monerris, M.; Escuder Bueno, I.; Andreu Álvarez, J. (2017). The role of monitoring sustainable drainage systems for promoting transition towards regenerative urban built environments: a case study in the Valencian region, Spain. Journal of Cleaner Production. 163:113-124. doi:10.1016/j.jclepro.2016.05.153S11312416

In vitro–in vivo correlation of drug release profiles from medicated contact lenses using an in vitro eye blink model

There is still a paucity of information on how in vitro release profiles from drug-loaded contact lenses (CLs) recorded in 3D printed eye models correlate with in vivo profiles. This work aims to evaluate the release profiles of two drug-loaded CLs in a 3D in vitro eye blink model and compare the obtained results with the release in a vial and the drug levels in tear fluid previously obtained from an animal in vivo study. In vitro release in the eye model was tested at two different flow rates (5 and 10 µL/min) and a blink speed of 1 blink/10 s. Model CLs were loaded with two different drugs, hydrophilic pravastatin and hydrophobic resveratrol. The release of both drugs was more sustained and lower in the 3D eye model compared to the in vitro release in vials. Interestingly, both drugs presented similar release patterns in the eye model and in vivo, although the total amount of drugs released in the eye model was significantly lower, especially for resveratrol. Strong correlations between percentages of pravastatin released in the eye model and in vivo were found. These findings suggest that the current 3D printed eye blink model could be a useful tool to measure the release of ophthalmic drugs from medicated CLs. Nevertheless, physiological parameters such as the composition of the tear fluid and eyeball surface, tear flow rates, and temperature should be optimized in further studiesOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This project was funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions grant agreement N° 813440 (ORBITAL–Ocular Research by Integrated Training And Learning). The work was also partially supported by MCIN [PID 2020-113881RB-I00/AEI/10.13039/501100011033], Spain, Xunta de Galicia [ED431C 2020/17], FEDER, and the Hong Kong Special Administrative Region Government and InnoHK. M. Vivero-Lopez acknowledges Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) for a predoctoral research fellowship [ED481A-2019/120]. P. Garg acknowledges the support of the Collaborative Research and Training Experience (CREATE) Program awarded by the Natural Sciences and Engineering Research Council of Canada (NSERC)S

Experimental study of the nature of the 1− and 2− excited state

The nature of the 1− and 2− excited states in 10Be is studied using the 11Be(p, d) transfer reaction in inverse kinematics at 10A MeV at TRIUMF ISAC-II, in particular to assess whether either of them can be considered as an excited halo state. The angular distributions for both states are extracted using deuteron-γ coincidences and analyzed using a transfer model taking into account one-step and two-step processes. A good fit of the angular distributions is obtained considering only the one-step process, whereby an inner p3/2 neutron of 11Be is removed, leaving the halo neutron intact. Higher-order processes however cannot be rejected. The small spectroscopic factors extracted suggest that the structure of both states is not uniquely halo-like, but rather display a more complex configuration mixing cluster and halo structures. Further insights are limited, as this experiment specifically probed the halo-like (but not cluster-like) 11Be(1/2+) ⊗ (ν p3/2 ) −1 configuration in both states.U.S. Department of Energy (DOE): DE-FG03-93ER40789 (Colorado School of Mines), DE-FG02-96ER40978 (Louisiana State), DE-SC0021422 (Michigan State), DE-AC05-00OR22725 (Oak Ridge National Laboratory)The National Nuclear Security Administration a través de los acuerdos de cooperación del DOE de EE. UU.(NNSA) DE-FG52-08NA28552The National Science Foundation PHY-1811815 (Michigan State)Ministerio español de Ciencia e Innovación y fondos FEDER. RTI2018-098117-B-C21 y PGC2018-096994-BC21Agencia Española de Investigación (AEI). PID2019-104714GB-C2

Phosphorylcholine-Based Contact Lenses for Sustained Release of Resveratrol: Design, Antioxidant and Antimicrobial Performances, and In Vivo Behavior

Design of advanced contact lenses (CLs) demands materials that are safe and comfortable for the wearers and that preserve the normal eye microbiota, avoiding chronic inflammation and biofilm development. This work aimed to combine the natural antibiofouling phosphorylcholine and the antioxidant and prebiotic resveratrol as integral components of CLs that may have the additional performance of preventing oxidative-stress related eye diseases. Different from previous uses of 2-methacryloyloxyethyl phosphorylcholine (MPC) as coating, we explored the feasibility of adding MPC at high proportions as a comonomer of 2-hydroxyethyl methacrylate (HEMA)-based hydrogels while still allowing for the loading of the hydrophobic resveratrol. Homogeneous distribution of MPC along the hydrogel depth (confirmed by Raman spectroscopy) notably increased solvent uptake and the proportion of free water while it decreased Young’s modulus. Relevantly, MPC did not hinder the uptake of resveratrol by CLs (>10 mg/g), which indeed showed network/water partition coefficients of >100. Protocols for CLs sterilization and loading of resveratrol under aseptic conditions were implemented, and the effects of tear proteins on resveratrol release rate were investigated. CLs sustained resveratrol release for more than 24 h in vitro, and sorption of albumin onto the hydrogel, although attenuated by MPC, slowed down the release. The combination of MPC and resveratrol reduced P. aeruginosa and S. aureus growth as tested in a novel hydrogel disk-agar interface biofilm growth setup. The developed CLs showed excellent anti-inflammatory properties and biocompatibility in in ovo and rabbit tests and provided higher and more prolonged levels of resveratrol in tear fluid, which favored resveratrol biodistribution in anterior and posterior eye segments compared to eye drops. Correlations between the release profiles of resveratrol in vitro and in vivo were assessed. Relevantly, the CLs preserved the antioxidant properties of resveratrol during the entire 8 h of wearing. In sum, CLs prepared with high proportion in MPC may help address safety and comfort requirements while having drug releasing capabilitiesThe authors are grateful to Mabel Loza and Cristina Val García, from BioFarma Research Group (USC GI-1685), for their help in the UPLC experiment, and to Luis Díaz-Gómez for advice in the anti-inflammatory tests. M.V.-L. acknowledges Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria) for a predoctoral research fellowship [Grant ED481A-2019/120]. A.F.P.-d.-M. is an ESR of the European Union’s Horizon 2020 research and innovation program under Marie Skłodowska-Curie Actions Grant Agreement 813440 (ORBITAL-Ocular Research by Integrated Training and Learning)S

Validation of the Lasher and Faulkender Anxiety about Aging Scale (AAS) for the Spanish Context

Increased longevity has led to concerns and fears among the population about the inexorable process of ageing. This process causes individuals to become more anxious about the physical and psychosocial changes caused by the passage of time. However, there are currently no scales in the Spanish context that analyse ageing. Therefore, the aim of the present study is to validate the Anxiety about Aging scale to the Spanish context. In the present study, 594 subjects between 25 and 64 years old participated. Both exploratory and confirmatory factor analyses were used. The results revealed that the factor structure of the questionnaire shows adequate psychometric properties, showing a four-factor factor structure

Prevention of ventilator-associated pneumonia: the multimodal approach of the spanish ICU pneumonia zero program.

Objectives: The “Pneumonia Zero” project is a nationwide multimodal intervention based on the simultaneous implementation of a comprehensive evidence-based bundle measures to prevent ventilator-associated pneumonia in critically ill patients admitted to the ICU. Design: Prospective, interventional, and multicenter study. Setting: A total of 181 ICUs throughout Spain. Patients: All patients admitted for more than 24 hours to the participating ICUs between April 1, 2011, and December 31, 2012. Intervention: Ten ventilator-associated pneumonia prevention measures were implemented (seven were mandatory and three highly recommended). The database of the National ICU-Acquired Infections Surveillance Study (Estudio Nacional de Vigilancia de Infecciones Nosocomiales [ENVIN]) was used for data collection. Ventilator-associated pneumonia rate was expressed as incidence density per 1,000 ventilator days. Ventilator-associated pneumonia rates from the incorporation of the ICUs to the project, every 3 months, were compared with data of the ENVIN registry (April–June 2010) as the baseline period. Ventilator-associated pneumonia rates were adjusted by characteristics of the hospital, including size, type (public or private), and teaching (postgraduate) or university-affiliated (undergraduate) status. Measurements and Main Results: The 181 participating ICUs accounted for 75% of all ICUs in Spain. In a total of 171,237 ICU admissions, an artificial airway was present on 505,802 days (50.0% of days of stay in the ICU). A total of 3,474 ventilator-associated pneumonia episodes were diagnosed in 3,186 patients. The adjusted ventilator-associated pneumonia incidence density rate decreased from 9.83 (95% CI, 8.42–11.48) per 1,000 ventilator days in the baseline period to 4.34 (95% CI, 3.22–5.84) after 19–21 months of participation. Conclusions: Implementation of the bundle measures included in the “Pneumonia Zero” project resulted in a significant reduction of more than 50% of the incidence of ventilator-associated pneumonia in Spanish ICUs. This reduction was sustained 21 months after implementation