A randomized study of nutritional supplementation in patients with unilateral wet age-related macular degeneration

The purpose of this study is evaluate the efficacy and safety of medicinal products con-taining the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, random-ized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.63 (95% CI -0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Leaf water potential and sap flow as indicators of water stress in Crimson ‘seedless’ grapevines under different irrigation strategies

Vitis vinifera L. cv. Crimson Seedless is a late season red table grape developed in 1989, with a high market value and increasingly cultivated under protected environments to extend the availability of seedless table grapes into the late fall. The purpose of this work was to evaluate leaf water potential and sap flow as indicators of water stress in Crimson Seedless vines under standard and reduced irrigation strategy, consisting of 70 % of the standard irrigation depth. Additionally, two sub-treatments were applied, consisting of normal irrigation throughout the growing season and a short irrigation induced stress period between veraison and harvest. Leaf water potential measurements coherently signaled crop-available water variations caused by different irrigation treatments, suggesting that this plant-based method can be reliably used to identify water-stress conditions. The use of sap flow density data to establish a ratio based on a reference ‘well irrigated vine’ and less irrigated vines can potentially be used to signal differences in the transpiration rates, which may be suitable for improving irrigation management strategies while preventing undesirable levels of water stress. Although all four irrigation strategies resulted in the production of quality table grapes, significant differences (p ≤ 0.05) were found in both berry weight and sugar content between the standard irrigation and reduced irrigation treatments. Reduced irrigation increased slightly the average berry size as well as sugar content and technical maturity index. The 2-week irrigation stress period had a negative effect on these parameters

Apparatus Development for the Measurement of the Thermal Conductivity of Geothermal Backfill Materials

This paper describes the design, construction, validation, and calibration of a thermal conductivity measuring apparatus for geothermal backfill materials in the range from 0.13–2.80 W/m·K. The developed apparatus is based on the Transient Hot Wire (THW) method whose mathematical basis is the Infinite Linear Source (ILS) model. The apparatus consists of a nichrome hot wire, an adjustable direct current power supply, a temperature sensor (K-type thermocouple), and a datalogger. For the validation and calibration of the developed apparatus, four standard samples have been used with a known thermal conductivity, to 3.0 W/m·K. Furthermore, the thermal conductivity of four geothermal backfill materials of common use (bentonite, neat cement, cement–sand mortar, and cement–bentonite mortar) has been measured using both the developed apparatus and a commercial meter

Review Article Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. Age-Related Macular Degeneration: Socioeconomic Burden and Limitations of Current Therapies 1.1. General Introduction. Age-related macular degeneration (AMD) is one of the leading causes of vision loss and the most common cause (almost epidemic) of blindness in industrialized countries. It is the first source of legal blindness (visual acuity < 20/200) in Europe and mainly affects people over the age of 50 affecting about 30 million people worldwide. The dramatic loss of autonomy and life quality associated with AMD [1, 2] leads to increased costs for healthcare and long-term care. AMD is multifactorial but clearly age-related pathology. The number of affected people is expected to double by the year 2020 as a result of ageing of the world's population. Even, in developed countries, AMD is gaining attention due to increased life expectancy and improved visual care facilities Limitations of Current Therapies in Clinical Use. Traditional therapeutic products targeting degenerative diseases have largely focused on palliative forms of treatment that mainly ameliorate or control the symptoms of a disease without addressing the underlying biological cause. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options span a broad range of therapeutic approaches, including thermal laser photocoagulation, surgical approaches (excision, displacement, or transplantation), and new treatments targeting the choroidal neovascularization (CNV) component and its pathogenic cascade, such as verteporfin with photodynamic therapy (vPDT) and more recently antivascular endothelial growth factor (VEGF) therapies [10]. Intermediate and Advanced AMD Prevention. In addition to the intake of vitamin and minerals supplements described by the two AREDS studies, stopping smoking and a healthy diet are strongly recommended. Wet/Vascular AMD Treatments Laser Photocoagulation and Photodynamic Therapy. Treatment strategies for the neovascular form of AMD had been focused several years ago on the prevention of further progress of the CNV either with laser photocoagulation for extrafoveal CNV Anti-VEGF Therapy. Vascular endothelial growth factor (VEGF-A) is the most potent promoter of angiogenesis and its role in the pathogenesis of neovascular AMD is well recognized In minimally classic/occult trial of the anti-VEGF antibody ranibizumab in the treatment of neovascular agerelated macular degeneration (MARINA) study, patients receiving the 0.5 mg dose of ranibizumab experienced a 21.4 letter improvement compared with sham injections, and in ANCHOR, they demonstrated a 20.5 letter improvement compared with those receiving photodynamic therapy Although anti-VEGF injections have largely improve the visual outcomes of late neovascular AMD, the risk of visual decline and disease activity persists, and the need for anti-VEGF treatment continues in a substantial portion of patients. The long-time results observed after seven years in the SEVEN-UP cohort may reflect the inexorable nature of this chronic disease even in the face of treatment. In this study, 98% of the study eyes were detected to have macular atrophy which mainly involved the fovea, as indicated by definite decreased autofluorescence. Decreased visual acuity in late neovascular AMD may be associated with macular atrophy and the presence of intraretinal or subretinal fluid Anti-VEGF agents with a higher affinity for VEGF molecule, such as aflibercept (Eylea), offer another option Journal of Ophthalmology 3 Preapproval clinical trials showed benefits and side effects that were similar to those of Ranibizumab. Similar to Ranibizumab, aflibercept binds to all VEGF isoforms (A, B, and C) with a 10-fold higher affinity than Ranibizumab for VEGF Combined Therapy. PDT in combination with anti-VEGF and steroids is currently used as a second-line therapy in patients not responding to monotherapy with anti-VEGF agents or in whom the treatment burden of monthly injections is too great. Combination therapy with anti-VEGF therapy and ionizing radiation offers another option to reduce treatment frequency. Radiation was never widely adopted because it did not provide a significant, reproducible effect on visual acuity, while difficulty delivering targeted doses led to complications in some patients Results of the phase 3 choroidal neovascularization secondary to AMD treated with beta radiation epiretinal therapy trial, which compared epiretinal brachytherapy plus ranibizumab with ranibizumab alone, found that the combination was not noninferior to monotherapy with ranibizumab Ranibizumab efficacy as sole therapy and in combination with PDT has been evaluated in several trials and 6-month results indicate visual acuity improved by 12.8 letters with few drug-related side effects like transient inflammation ([35], Genentech press release: phase III study shows that Lucentis improved vision compared to Visudyne in patients with wet age-related macular degeneration). Nonvascular AMD. Currently, there are no treatments available for nonvascular AMD Surgery. Proof-of-principle for the replacement of RPE cells has been provided by several experimental surgical procedures for treating AMD However, it yields only temporary recovery of vision; the large retinotomies associated with this procedure have high complication rates Socioeconomic Burden. The emotional and economic burden of AMD is often underrecognized. The prevalence of neovascular AMD (NV-AMD), which accounts for 90% of AMD-related severe visual impairment, increases exponentially with age In contrast to other age-related eye diseases like cataracts that are largely solved by current therapies, the visual prognosis for most patients with AMD is poor and the late stages of both wet and dry AMD are usually associated with severe visual loss, which has profound effects on overall quality of life. The shortages in executing ordinary tasks are also extended to their psychological functioning, as evidenced by patients with AMD reporting greater emotional distress than visually intact peers Without treatment, the neovascular form of AMD often leads not only to severe loss of vision but also to considerable associated economic burden The economic impact of AMD on society is expected to increase in the near future as population age and the prevalence of AMD increase. With new AMD therapies, healthcare decision makers will require reliable quantitative data on AMD-related resource utilization to evaluate alternatives, as the ones suggested in the present review. The mean annual direct vision-related medical cost was reviewed by Cruess et al. and estimated to range from 2153C per patient in the UK to 4390C per patient in Canada. The mean direct nonvision related medical cost was estimated to range from 597C (11% of the total cost) in the UK to 1657C (21% of the total cost) in Canada. The annual societal costs estimated in 2004 for bilateral NV-AMD were C1.3 billion in Germany, C624 million in France, C511 million in the UK, C311 million in Canada, and C268 million in Spain. The mean annual cost per bilateral NV-AMD patient ranged from C5300 to 12 445, of which direct vision-related medical costs accounted for 23-63% of the total cost. These estimates are higher than those of two previous prospective studies There are extensive data that emphasize the need for new treatments for AMD that will prevent vision loss and progression to blindness in order to lessen the ensuing economic burden Cell Therapy in AMD: Perspectives and Limitations It has now been almost 40 years since Gouras and colleagues Even though cell transplantation has failed in the past, the successful transplantation in animal models suggests that theoretically cell transplantation has the potential to be a significant treatment for AMD. The failure of cell transplantation to improve vision in AMD patients is part of the result of the lack of knowledge of the factors that Journal of Ophthalmology 5 underlay development and progression of AMD. However, there is enough knowledge about AMD to be able to construct a theoretical framework necessary to eventually achieve restoration of vision by cell transplantation. In general, the approach has been to transplant autologous or homologous cell suspensions or autologous peripheral retina choroid-BM-RPE explants without taking into account the status of the patient's retina. In considering the status of the retina, two characteristics of the disease must be taken into account, namely, the severity and the factors underlying the disease. For this discussion, we will assume that the severity of the disease and loss of vision does not follow a gradient but instead is segregated into three independent phases. Specifically, initially, phase 1: RPE cells in the macular region are intact or reversibly damaged and vision loss is the result of the reversible loss of some function(s) by RPE cells and/or loss of communication between RPE cells and photoreceptors. Later, phase 2: RPE cells in the macular region are degenerated or irreversibly damaged but the photoreceptors are intact or reversibly damaged and loss of vision is the result of nonfunctional RPE cells in the macular region. Finally, phase 3: both RPE cells in the macular region and photoreceptors are degenerated or irreversibly damaged and loss of vision is due to lack of both RPE cells and photoreceptors. As for the factors underlying the disease, numerous studies have indicated that the CNV associated with neovascular AMD results from the lack of the proper balance between angiogenic (VEGF) and antiangiogenic factors (pigment epithelial derived factor, PEDF) In the eye, RPE cells are the principal source of PEDF, a neuroprotective and cytoprotective factor and a potent inhibitor of VEGF Based on the overexpression of VEGF, intravitreal administration of anti-VEGF monoclonal antibodies (Avastin or Lucentis) has become standard therapy for neovascular AMD with approximately 30% of patients gaining 3 or more lines of visual acuity and stabilization in 90% of patients It was thought that transplantation of RPE cells to the subretinal space would be a better and more permanent treatment for AMD. However, transplantation of RPE or IPE cell suspensions could not be an effective treatment for AMD since normal RPE cells would not supply the increased levels of PEDF necessary to inhibit the augmented VEGF and possibly necessary levels of growth factors required to protect photoreceptors from degenerations. An appropriate treatment for phase 1 neovascular AMD, in which RPE cells and photoreceptors are intact or reversibly damaged, would be the transplantation of genetically modified, autologous pigment epithelial (RPE or IPE) cells that would produce increased levels of VEGF inhibitor, such as PEDF and/or endostatin. In addition, the gene for the inhibitor of VEGF should be integrated into the host cell genome, such that the synthesis and secretion of the augmented PEDF would be for the life of the patient. Cell transplantation for the treatment of phase 2 neovascular AMD, in which RPE cells are degenerated but the photoreceptors are functional, will require genetically modified, autologous, PEDF and/or endostatin-transfected pigment epithelial cells transplanted as a monolayer on a biocompatible substratum that supports RPE cell functions. A biocompatible substratum is necessary since cell suspensions transplanted to the subretinal space of AMD patients do not attach and form a monolayer [87] because the aged BM, especially neovascular AMD BM, is altered and does not appear to support good attachment and survival of pigment cells Phase 3 of the disease, in which both RPE cells and photoreceptors are degenerated or nonfunctional, will require the manufacture and transplantation of a complex structure that encompasses a biocompatible substratum upon which autologous, PEDF, and/or endostatin transfected pigment epithelial cells are allowed to form a monolayer; the monolayer is then overlaid with photoreceptor precursor cells. In animal models of retinal degeneration, transplanted photoreceptors integrate into the host retina and improve function Photoreceptor precursor can be selected from iPS cells derived from the patient's fibroblasts. A number of methods have been devised to reprogram fibroblasts and induce iPS cells The essential goal of cell transplantation in neovascular AMD, when the RPE and photoreceptors are intact or reversibly damaged, is the effective inhibition of blood vessel invasion of the subretinal space and restoration of RPE and photoreceptor functions. For such purpose, the addition of the PEDF gene to the transplanted cells should affect blood vessel inhibition and restore RPE and photoreceptor functionality. It will be critical that the PEDF gene be integrated into the host genome so that its activity will last for the life of the patient. For such purpose, the Sleeping Beauty (SB100X) transposon system is ideal as the gene delivery system since it is highly efficient, similar to retroviral vectors, but without the associated side effects. The SB100X system delivers genetic material into a target cell genome resulting in robust and stable expression of the transgene For later stages of neovascular AMD and GA, it may be necessary to introduce into the cells to be transplanted not only the PEDF gene, but also other neuroprotective genes, such as CNTF and IGF1 to engender a neurogenic supportive environment. Before cell transplantation can become a routine procedure, it will be necessary to develop methodologies to identify the stage of degeneration of RPE cells and photoreceptors in AMD patients and transplant cell in an appropriate genetically modified and proper architecture. Tissue Engineering in AMD: Materials, Scaffolds, and Material-Cell Interactions Another challenge of cell therapy is the lack of cell engraftment and survival in the host tissue after implantation. Therefore, the need arises where this is assisted by artificial supports, known as scaffolds, which are structured biocompatible materials that mimic the host tissue. As described above, different cell types have been tested for treating AMD, including RPE, IPE, retinal progenitor cells (RPC), photoreceptor, and stem cells Material and Improved Biomaterial Surfaces. Control over surface chemistry is essential to regulate the interaction between cells and scaffolds. A traditional strategy to improve cell adhesion on biomaterials has been the immobilization of proteins on the surface via incubation. Thus, collagen, fibronectin, vitronectin, laminin, and other ECM proteins were directly bound to the surface, allowing cells to anchor onto them Recent strategies in biomaterials development aim at the combination of increased hydrophilicity and minimized unspecific protein adsorption and cell adhesion, with the ability to permit selective cell binding by the incorporation of cell adhesion motifs. Such techniques have been developed for flat model substrates but remain challenging for biomaterials and three-dimensional structures. One promising one-step technique for the generation of nonwoven textile sheets with basal-membrane like structure and functionalization, with large potential as artificial BM, has recently been introduce

Anales de Edafología y Fisiología Vegetal Tomo 13

Variaciones de los límites de Atterberg en materiales arcillosos de estructura laminar, en función del catión de saturación, por Angel Hoyos de Castro y Mercedes García Muñoz.--Estudio mineralógico y tecnológico de un grupo de tierras de moldeo, por Antonio García Verduch y Manuel Muñoz Taboadela.--Determinación de los iones oxalato por colorimetría indirecta y su aplicación a la determinación de pequeñas cantidades de calcio, por F. Burriel-Martí, J. Ramirez-Muñoz y E. Femández-Caldas.--Acerca de los suelos tropicales, por Paul Schaufclberger.--El diagnóstico de la situación mineral de los cultivos, por M. l. Candela y W. A. Forster.--Caracterización y propiedades de una vermiculita de Badajoz, por F. González, Fca. Tristán de Chaves y M. Chaves.--Estudio mineralógico de algunas rocas sedimentarias, por José García Vicente y Mª del Carmen Sánchez Calvo.--Contribución al conocimiento de los tardígrados de España. Estudio sistemático-ecológico, por F. Mihelcic.--Los minerales de la arcilla : su identificación y relaciones con la Ciencia del Suelo, por Robert C. Mackenzie.--Estudio mineralógico y técnico de algunas tierras de moldeo españolas. I. Identificación mineralógica de la fracción aglomerante, por Vicente Aleixandre Ferrandis, Jaime Robndo Olave y Julia Mª González Peña.--Geofogía de Valencia. l. El Terciario de La Cañada, por P. J. J. Alonso Pasma! y B. García Rodrigo.--Determinación cuantitativa de los aminoácidos por cromatografía ascendente sobre papel, por R. Díaz Cadavieco.--AIteraciones de la superficie de bentonitas homoiónicas por tratamiento térmico. l. Capacidad de cambio y rehidratación, por Angel Hoyos y Julio RodriguezAlteraciones de la superficie de bentonitas homoiónicas por tratamiento térmico. ll. Imbibición, por Angel Hoyos y Julio Rodríguez.--Sobre el análisis espectrográfico en la determinación simultánea de los cationes de cambio en suelos. l. por F. Burriel Martí, S. Jimenez Gómez y C. Alvarez Herrero.--Análisis foliar. l. Aplicación del análisis químico de la hoja y del método de diagnosis visual a la investigación de deficiencia, minerales en relación con los suelos de cultivo, por R. Dios Vidal y J. Mª Albareda Herrera.--Estudio de las formas de fósforo presentes en una serie de suelos, por V. Hernando y M. Losada.--Determinación de yeso en suelos, por J. M. Albareda, V. Hernando y G. Bilbao.--Estudio mineralógico y técnico de algunas tierras de moldeo españolas. II. Estudio de la resistencia a la compresión en verde; por Vicente Aleixandre y Jaime Robredo.--Los arenales costeros de Galicia. I. La ría de Lage por Isidro Parga-Pondal y Josefina Pérez Mateos.--Sobre el método de la Paleoedafología, por W. L. Kübiena.--Contribución al estudio de las reacciones en estado sólido entre el ortosilicato de circonio y el óxido de calcio, por D. A. Estrada.--Análisis foliar. II. El concepto de diagnosis foliar aplicado al control bioquímico de la nutrición de maíz y patatas en una edad fisiológica determinada, por R. Dios Vidal y J. Mª Albareda Herrara.--Influencia de los azúcares en el cultivo in vitro de raíces aisladas de berenjena, por María Bausá Alcalde.--Identificación en el microscopio electrónico de algunas arcillas y caolines españoles, por Vicente Aleixaudre Ferrandis y Julia Mª González Peña.--La península de Anaga y estudio de algunos arenales del litoral de Tenerife (Islas Canarias), por Josefina Pérez Mateos y Manel Martel Sangil.--Clave para la clasificación de los tipos de suelos tropicales, por P. Schaufelberger.--Paralización de la podredumbre del tubérculo de patata durante su período de germinación, por Román Vicente.-- Nota sobre la aditividad de algunas propiedades en mezclas de caolín y bentonita, por Angel Hoyos de Castro y Julio Rodríguez Martínez.--Estudio del pH en suelos de distintas características, por Valentín Hernando y Pilar Sanchez-Conde.--Sobre la determinación espectrofotométrica de fósforo con amidol, por F. Capitán García y F. Martínez Alvarez.--Propiedades termodinámicas del cambio iónico, por E. Gutiérrez Rios y l. Cano Ruiz.--Influencia de la vegetación en la composición del humus. Suelos bajo Quercus ilex y bajo Pinus pinea. El Pardo (Madrid), por José Mª Albareda, Narcisa Martín Retortillo y Mariano Claver.-- Experiencias con fetilizantes en suelos gallegos. l. Acción combinada de los fertilizantes orgánicos y minerales sobre la producción · y el contenido de "proteína en maíces híbridos, por Ramón Dios, Benito Sánchez yMaría Ameijeiras.--Determinación del B. en el suelo por vía espectroquímica, por A. Rodríguez Pérez.--Electroforesis sobre papel de filtro. por R. Díaz CadaviecoPeer reviewe