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Abstract Hearing loss is the most common sensory defect in humans, affecting normal communication. In most cases, hearing loss is a multifactorial disorder caused by both genetic and environmental factors, but single‐gene mutations can lead to syndromic or non‐syndromic hearing loss. Monoallelic variants in ACTG1, coding for gamma (γ)‐actin, are associated with classical Baraitser‐Winter Syndrome type 2 (BRWS2, nonsyndromic deafness, and a variety of clinical presentations not fitting the original BRWS2 description or nonsyndromic deafness. Here two unrelated patients with ACTG1 variants are reported, having severe hearing loss as a common phenotype but with different clinical presentations, supporting the extreme variability of ACTG1‐related disorders.

Changes in bottom and pore water oxygenation over glacial – interglacial cycles have influenced the ocean's capacity to store particulate organic carbon regardless of its source, either the marine primary productivity or the continent-to-ocean transfer of terrestrial organic matter. In the Philippine Sea, east off Taiwan, despite being currently oligotrophic, the enhanced East Asian Winter Monsoon during the Last Glacial Maximum and the Heinrich Stadial 1 might have altered the nutrient budget in surface waters by providing nutrients from the Eurasian loess dust and deepening the vertical mixing, bringing nutrients from the nutrient-enriched Kuroshio Current subsurface waters to the surface. During the deglaciation, previous studies also suggest an overall weakening of the marine biological pump during the Heinrich Stadial 1, and the rise in sea level is expected to have led to a global significant decline in the ability of continents to bury their particulate organic carbon in marine sediments. However, changes in the continent-ocean transfer of terrestrial organic matter and on the marine biological pump around Taiwan remain poorly constrained.In the present study, we have thus aimed to reconstruct bottom – pore water oxygenation, past marine primary productivity and continental-ocean transfer of terrestrial particulate organic carbon to the ocean since the end of the Last Glacial Maximum, in order to better constrain the ability of marine sediments to capture atmospheric carbon over the past 20,000 years. To this end, sediment core MD18-3523 has been recovered from a levee of Hoping Canyon, north-east of Taiwan, in the Ryukyu forearc basin. The reconstructions were made possible by the application of multivariate statistics and transfer functions on benthic foraminiferal assemblages, by the measurement of total organic carbon concentration and by the investigation of chemical element ratios obtained from X-ray fluorescence (XRF).We observed a transition across the Bølling–Allerød and the Younger Dryas from suboxic-dysoxic bottom – pore waters during Heinrich Stadial 1 to oxic-suboxic during the Holocene, and revealed an increase in marine primary productivity during Heinrich Stadial 1 in all probability due to intensified East Asian Winter Monsoon winds. We have also identified periods of enhanced terrestrial particulate organic carbon transfer to the ocean driven by short-lived extreme events, most likely typhoons, during the Bølling–Allerød, at the beginning of the Early Holocene and the end of the Late Holocene, when the typhoon dynamics affecting Taiwan were intensified. Overall, these findings suggest an enhanced marine biological pump during the Heinrich Stadial 1 and an efficient carbon turbidity pump during the Bølling–Allerød, the Early and Late Holocene, contrasting with the western coast of Taiwan.

Scientific discovery can be aided when data are shared following the principles of findability, accessibility, interoperability, reusability (FAIR) data (Wilkinson et al., 2016). Recent discussions in the palaeoclimate literature have focussed on defining the ideal database format for storing data and associated metadata. Here, we highlight an often overlooked primary process in widespread adoption of FAIR data, namely the systematic creation of machine readable data at source (i.e. at the field and laboratory level). We detail a file naming and structuring method that was used at LSCE to store data in text file format in a way that is machine-readable, and also human-friendly to persons of all levels of computer proficiency, thus encouraging the adoption of a machine-readable ethos at the very start of a project. Thanks to the relative simplicity of downcore palaeoclimate data, we demonstrate the power of this simple but powerful file format to function as a basic database in itself: we provide a Matlab-based GUI tool that allows users to search and visualise isotope data by sediment core location and species type, against either depth or age. We share the database format here so that other laboratories might consider developing a similar approach depending on their own needs and requirements.

Abstract A 27 m core collected on the sea floor near Juan de Nova island at 1,909 m depth in the SW Indian Ocean preserves a high‐resolution record of carbonate sediment export to the deep sea over the past 1 Myr. Core chronology was established using calcareous nannofossil biostratigraphy and benthic foraminiferal δ18O. Throughout the core, preserved highstand intervals (MIS 1, 5, 7, 9, 11, 13, 15, 23 and 25) are marked by an increase in the aragonite content within the sediment. Aragonite is likely sourced from the nearby Juan de Nova carbonate platform ca 10 km to the south, and is interpreted as resulting from flooding of the platform top. Platform inundation allows carbonate muds to be winnowed from their original shallow‐water environment of deposition, suspended in the water column, and redeposited onto the proximal slopes and within the basin. Sharp increases in aragonite content at the beginning of each highstand interval can be used to estimate the approximate sea‐level range when platform flooding occurred; results show that the depth of the platform top has likely changed little over the past 1 Myr due to balanced aggradation and subsidence. Previously hypothesized large‐scale aragonite dissolution cycles are evidenced by a disproportionally low aragonite increase during MIS 11. This study provides a new, exceptionally long record of highstand shedding, expanding the known occurrences of the process to the southern Indian Ocean and supporting its importance as a globally significant depositional mechanism that impacts deep‐sea stratigraphic records.

Fetal programming by exposure to high-energy diets increases the susceptibility to type 2 diabetes mellitus (T2DM2) in the offspring. Glucose imbalance during fetal programming might be associated to still unknown selective lipid species and their characterization might be beneficial for T2DM diagnosis and treatment. We aim to characterize the effect of the lipid specie, C24:0 ceramide, on glucose imbalance and metabolic impairment in cellular and murine models. A lipidomic analysis identified accumulation of C24:0 ceramide in plasma of offspring rats exposed to high-energy diets during fetal programing, as well as in obese-T2DM subjects. In vitro experiments in 3T3L-1, hMSC and HUH7 cells and in in vivo models of Wistar rats and C57BL/6 mice demonstrated that C24:0 ceramide disrupted glucose balance, and differentiation and lipid accumulation in adipocytes, whereas promoted liver steatosis. Mechanistically, C24:0 ceramide impaired mitochondrial fatty acid oxidation in adipocytes and hepatic cells, tentatively by favoring reactive oxygen species accumulation and calcium overload in the mitochondria; and also, activates endoplasmic reticulum (ER) stress in hepatocytes. We propose that C24:0 ceramide accumulation in the offspring followed a prenatal diet exposure, impair lipid allocation into adipocytes and enhances liver steatosis associated to mitochondrial dysfunction and ER stress, leading to glucose imbalance.

We combine consistently dated benthic carbon isotopic records distributed over the entire Atlantic Ocean with numerical simulations performed by a glacial configuration of the Norwegian Earth System Model with active ocean biogeochemistry, in order to interpret the observed Cibicides δ13C changes at the stadial-interstadial transition corresponding to the end of Heinrich Stadial 4 (HS4) in terms of ocean circulation and remineralization changes. We show that the marked increase in Cibicides δ13C observed at the end of HS4 between ~2000 and 4200 m in the Atlantic can be explained by changes in nutrient concentrations as simulated by the model in response to the halting of freshwater input in the high latitude glacial North Atlantic. Our model results show that this Cibicides δ13C signal is associated with changes in the ratio of southern-sourced (SSW) versus northern-sourced (NSW) water masses at the core sites, whereby SSW is replaced by NSW as a consequence of the resumption of deep water formation in the northern North Atlantic and Nordic Seas after the freshwater input is halted. Our results further suggest that the contribution of ocean circulation changes to this signal increases from ~40 % at 2000 m to ~80 % at 4000 m. Below ~4200 m, the model shows little ocean circulation change but an increase in remineralization across the transition marking the end of HS4. The simulated lower remineralization during stadials than interstadials is particularly pronounced in deep subantarctic sites, in agreement with the decrease in the export production of carbon to the deep Southern Ocean during stadials found in previous studies. [ABSTRACT FROM AUTHOR]

The present study is a systematic review of the research on family functioning in families who have a child with a rare disease. The research was carried out using the databases Pubmed, EBSCO, and Google Scholar, following PRISMA guidelines. After applying the inclusion and exclusion criteria to the 460 articles initially found, a total of 49 articles made up the final sample. The following topics regarding family functioning were identified: impact of diagnosis; caregiver’s role and responsibilities; family functioning; impact on the emotional sphere; effects on marital and social life; coping strategies; family, and care and health system. The results of this study may provide justification for considering factors associated with family functioning when diagnosing a rare disease and deciding on treatment.

Introduction: This study analysed the psychometric properties of the Spanish version of the Pediatric Quality of Life Questionnaire Family Impact Module (PedsQL FIM) in the Argentinian population. Patients and Methods: The sample included 232 caregivers, of who 108 were parents of children with chronic diseases (mean, 9.54; standard deviation [SD], 4.43) and 124 parents of children in the general population (mean, 12.37; SD, 4.6). Results: We assessed the validity of the instrument with the known-groups method, finding significant differences between the case and control groups in the overall and subscale scores (P < .01). We also assessed test validity by means of exploratory factor analysis, which yielded an 8-factor model that explained 74.03% of the variance. We assessed reliability with the Cronbach alpha and found a high internal consistency (α = 0.95). Conclusion: The PedsQL module proved to be a valid and reliable tool to assess the impact of a chronic paediatric condition on caregiver quality of life and family functioning. Resumen: Introducción: Este trabajo analiza las propiedades psicométricas de la versión en castellano del Cuestionario de Calidad de Vida Pediátrica Módulo de Impacto Familiar (PedsQL FIM) en población argentina. Pacientes y Métodos: Se obtuvo una muestra de 232 cuidadores, 108 de niños con enfermedades crónicas (M = 9,54, DE = 4,43) y 124 de niños de población general (M = 12,37, DE = 4,6). Resultados: La validez del instrumento se estudió a través del método de grupos contrastados, encontrando diferencias significativas en la escala total y subdimensiones de la escala (p

Food patterns are deteriorating and, consequently, not meeting nutritional recommendations. Learning about the adherence to a diet is crucial for understanding children’s dietary habits. The objective of the present analysis was to assess the degree of compliance with the ALINFA nutritional intervention and the effectiveness of adherence groups, and to evaluate potential baseline factors predicting a higher adherence to the intervention. A total of 44 children aged 6 to 12 years-old participated in the eight-week intervention. A two-week dietary plan was specifically designed, providing participants with food products, ready-to-eat dishes, and recipes. An intake of 75% of calories of the prescribed diet was defined to divide the participants into high- and low-adherence groups (HA/LA, respectively). From the 44 participants, 24 showed a LA to the intervention, whereas 20 of them were in the HA group. Diet quality improved in both groups (p < 0.001), mainly by increasing cereals and nuts, and reducing pastries. A decrease in BMI z-score was observed (LA: p < 0.001; HA: p = 0.021). Fat mass (p = 0.002), LDL-c (p = 0.036), and CRP (p = 0.023) reductions were only achieved in the HA group, whereas leptin decreased only in the LA group (p = 0.046). All participants ameliorated their dietary habits, but those with better diet quality at baseline experienced greater enhancements in their nutritional status.

Mentalization isconsidered as an enriching and useful clinical competence in the training of psychologists, especially clinical ones. The objective was to analyze the mentalization capacity in psychology students and to identify if there were significant differences according to in which year of study they are in —first, third and fifth year. The sample consisted of 169 university students who responded to the instruments: Mentalization Scale (Ments) and Mentalization Questionnaire (MZQ). The results of the study showed significant differences according to the degree of advancement of the career in two dimensions of mentalization, psychic equivalence and the regulation of affect. That is, it is observed that the students who are more advanced in the career obtained better levels of mentalization, in 2 of the 7 evaluated dimensions of mentalization, although the results must be considered in relation to the limitations of the scales. Conclusions: It is worth emphasizing that the results in relation to the other dimension did not obtain significant differences throughout the career. Given that psychotherapeutic treatment and its effectiveness are linked to the quality of relationships with the other, it is important to consider the possibility of its development during university training and at the beginning of the profession. The present study represents a significant contribution, since it allows raising the possibility of training in mentalization as part of undergraduate training in psychology

Genetic counseling is a complex process when working with rare diseases. It requires the accompaniment of different health professionals trained in the subject. Most published articles agree that psychologists should work from a psychoeducational model that offers information and support, being able to clearly transfer the knowledge that genetics and genomics offer to promote the health and well-being of those people diagnosed with a rare disease and their families. The aim of this review is to clarify on the approach that psychologists take regarding the complexity of having a rare diagnosis.

Los niños que padecen enfermedades genéticas son una población vulnerable para desarrollar problemas de salud mental. La fisura labiopalatina (FLAP) es una anomalía congénita de tipo estructural. Objetivo: Estudiar el impacto a nivel familiar del diagnóstico de FLAP. Metodología: Alcance descriptivo, de diseño mixto y corte transversal. Se construyó un cuestionario autoadministrado compuesto por un consentimiento informado, un cuestionario de datos sociodemográficos, el Child Behavior CheckList y preguntas abiertas. El muestreo fue intencional y la muestra fue de 42 casos. Resultados: El diagnóstico de una fisura labio palatina es una experiencia difícil en los padres, quienes viven este momento de manera negativa, con tristeza y miedo. Los niños en edad preescolar con diagnóstico de fisura labiopalatina son una población en riesgo de desarrollar trastornos psicopatológicos, mayormente de tipo externalizantes.

Globally, we are failing to meet numerous nutritional, health, and environmental targets linked to food. Defining food composition in its full chemical and quantitative diversity is central to data-driven decision making for supporting nutrition and sustainable diets. “Foodomics”—the application of omics-technology to characterize and quantify biomolecules to improve wellbeing—has the potential to comprehensively elucidate what is in food, how this composition varies across the food system, and how diet composition as an ensemble of foods guides outcomes for nutrition, health, and sustainability. Here, we outline: (i) challenges of evaluating food composition; (ii) state-of-the-art omics technology and innovations for the analysis of food; and (iii) application of foodomics as a complementary data-driven approach to revolutionize nutrition and sustainable diets. Featuring efforts of the Periodic Table of Food Initiative, a participatory effort to create a globally shared foodomics platform, we conclude with recommendations to accelerate foodomics in ways that strengthen the capacity of scientists and benefit all people.

Overweight and obesity are present in about three-quarters of the adult population in Mexico. The inflammatory mechanisms subjacent to visceral white adipose tissue are accountable for the initiation and development of cardiometabolic alterations, including type 2 diabetes. Lifestyle changes are pillars within its therapeutics and, thus, current dietary modifications should include not only hypocaloric prescriptions with balanced macronutrient intake, preferably by increasing the amount of whole grains, fruits, vegetables, nuts and legumes, but in concomitance, bioactive substances, such as anthocyanins, have been correlated with lower incidence of this disease.

The rabbit skin irritation test has been the standard for evaluating the irritation potential of chemicals; however, alternative methods that do not use animal testing are actively encouraged. Reconstructed human epidermis (RhE) models mimic the biochemical and physiological properties of the human epidermis and can be used as an alternative method. On RhE methods, the metabolic activity of RhE models is used to predict skin irritation, with a reduction in metabolic activity indicating a reduced number of viable cells and linking cell death to skin irritation processes. However, new challenges have emerged as the use of RhE models increases, including the need for non-invasive and marker-free methodologies to assess cellular states. Electrochemical impedance spectroscopy (EIS) is one such methodology that can meet these requirements. In this study, our results showed that EIS can differentiate between irritant and non-irritant chemicals, with a significant increase in the capacitance values observed in the irritant samples. A ROC curve analysis showed that the prediction method based on EIS met OECD TG 439 requirements at all time points and had 95% within-laboratory reproducibility. Comparison with the MTT viability assay showed that prediction using EIS achieved higher sensitivity, specificity, and accuracy. These results suggest that EIS could potentially replace animal testing in the evaluation of irritation potential and could be a valuable addition to in vitro testing strategies.

This study proposes a method to prepare autologous bio-based fibrin glue (FG) for use in ophthalmic surgery. FGs containing three fibrinogen concentrations and a thrombin concentrate were prepared using human blood from five donors (FG1: physiological fibrinogen concentration; FG2 and FG3: concentrated fibrinogen). The adhesion strength was tested, and the clinical safety and efficacy were studied in rabbit eyes in conjunctival surgery. A commercial FG was used as a control. From each donor, 2 mL of FG was prepared, containing 1 mL of 3.49 ± 0.78 (FG1), 17.74 ± 4.66 (FG2), or 47.46 ± 9.36 mg/mL (FG3) of fibrinogen and 1 mL of 2248.12 ± 604.20 UI/mL of thrombin. The average adhesion strength increased with the fibrinogen concentration, from 1.49 ± 0.39 kPa (FG1) to 3.14 ± 1.09 kPa (FG3). FG1 showed poor results when used for autograft adhesion. In contrast, the conjunctival autografts were successfully grafted using FG2 and FG3, revealing equivalent adhesion properties compared with commercial FG, but with less inflammation. In conclusion, FGs could be prepared on demand within minutes from small volumes of human blood, using a method that results in FGs which exhibit good adhesion capacity and are also safe and effective in a preclinical study.

Introducción: La convivencia con una condición genética es compleja y puede resultar limitante para el adolescente. Esta situación constituye un estresor y un factor de riesgo para la salud mental tanto del paciente como de su familia. Objetivo: Estudiar los niveles de adaptación psicológica y alfabetización genética en adolescentes con enfermedades genéticas, residentes en Argentina. Métodos: Alcance descriptivo correlacional, de diseño cuantitativo y corte transversal. El protocolo administrado consistió en un consentimiento informado, un cuestionario de datos socio-demográficos, y los instrumentos Genetic Health Literacy Screening Tool (REAL G) y Psychological Adaptation Scale (PAS). El muestreo fue intencional y la muestra fue de 68 casos. Resultados: El REAL G indicó bajos niveles de de alfabetización genética en todos sus componentes (decodificación, familiaridad, comprensión, aritmética). En cuanto a la adaptación psicológica, se encontró una M=4,02 (DE= 0.8) para la escala general y puntuaciones elevadas para todas las dimensiones. Conclusión: Los adolescentes diagnosticados con enfermedades genéticas en Argentina poseen un buen nivel de adaptación psicológica a su enfermedad, a pesar de tener bajos niveles de alfabetización genética.

Introducción: Los niños que padecen enfermedades genéticas son una población vulnerable para desarrollar problemas de salud mental. La fisura labiopalatina (FLAP) es una anomalía congénita de tipo estructural. Objetivo: Estudiar el impacto a nivel familiar del diagnóstico de FLAP. Métodos: Alcance descriptivo, de diseño mixto y corte transversal. Se construyó un cuestionario autoadministrado compuesto por un consentimiento informado, un cuestionario de datos sociodemográficos, el Child Behavior Checklist y preguntas abiertas. El muestreo fue intencional y la muestra fue de 50 casos. Resultados: El CBCL 1.5-5 indicó una media de M=53.60 (DE 23,53) en la escala general de problemas comportamentales y emocionales, M=14,86 para la escala internalizante, y de M=19.04 para la externalizante. Conclusión: El diagnóstico de una fisura labio palatina es una experiencia difícil en los padres, quienes viven este momento de manera negativa, con tristeza y miedo. Los niños en edad preescolar con diagnóstico de fisura labiopalatina son una población en riesgo de desarrollar trastornos psicopatológicos, mayormente de tipo externalizantes.

Abstract Fruit is a key component of a healthy diet. However, it is still not clear whether some classes of fruit may be more beneficial than others and whether all individuals whatever their age, gender, health status, genotype, or gut microbiota composition respond in the same way to fruit consumption. Such questions require further observational and intervention studies in which the intake of a specific fruit can be precisely assessed at the population and individual levels. Within the Food Biomarker Alliance Project (FoodBAll Project) under the Joint Programming Initiative “A Healthy Diet for a Healthy Life”, an ambitious action was undertaken aiming at reviewing existent literature in a systematic way to identify validated and promising biomarkers of intake for all major food groups, including fruits. This paper belongs to a series of reviews following the same BFIRev protocol and is focusing on biomarkers of pome and stone fruit intake. Selected candidate biomarkers extracted from the literature search went through a validation process specifically developed for food intake biomarkers.

Diabetes Mellitus is a highly prevalent disease in Mexico and in the world, among whose complications is diabetic neuropathy. DN is a group of disorders that present signs and/or symptoms of peripheral nerve dysfunction and have different clinical manifestations in both peripheral neuropathy and autonomic neuropathy. As a part of the mechanisms by which DN develops, oxidative stress and inflammation have been described. Cocoa is a plant origin product which includes around 300 components and through different studies, it has been suggested that cocoa has different mechanisms of action through which exerts its beneficial effects on health. It has been proposed that cocoa has hypoglycemic, lipid-lowering, antioxidant and anti-inflammatory effects, and thus, potentially have a beneficial direct or indirect effect on diabetic neuropathy. Specially in preclinical studies, the anti-inflammatory and anti-nociceptive effect of cocoa has been evaluated through different mechanisms of action. However, most of the studies presented concerning this complication, are in vitro or preclinical studies, so there is still a great area of opportunity regarding the use of cocoa on diabetic neuropathy.

Among several requirements for the manufacture of Advanced Therapy Medicinal Products (ATMP) are: following the guidelines of a pharmaceutical quality system, complying with Good Manufacturing Practice (GMP) and access to a cleanroom fulfilling strict environmental conditions (Class A work area and Class B environment). This makes ATMP expensive. Moreover, the production of many of these therapeutic products may also be unprofitable, as in most cases their use is limited to a few patients and to a single batch per manufacturing unit. To reduce costs, ATMP may be produced in a scaled-down system isolated from the external environment (isolator), allowing for placement of this facility in a Class D environment, which is much more permissive and less costly. In this work, we confirm that it is possible to manufacture bioengineered corneal epithelium inside an isolator while fulfilling all the safety assurance standards at an affordable cost for patients. This small-scale ultra-clean working environment complies with GMP guidelines and could be a solution for the high costs associated with conventional cleanroom ATMP production.

El objetivo del presente estudio fue avanzar en la metodología clínica y de investigación relativa a la evaluación psicopatológica poniendo a prueba la generalización internacional de un modelo de ocho síndromes derivado de evaluaciones de personas allegadas a adultos sobre los problemas emocionales, sociales y de pensamiento y conducta de dichos adultos. Informantes allegados a los adultos calificaron a 8.582 residentes de 18 países con edades comprendidas entre 18 y 59 años con el Adult Behavior Checklist(ABCL). Mediante un análisis factorial confirmatorio se examinó el ajuste del modelo de ocho síndromes a las puntuaciones provenientes de cada país. El índice primario de ajuste del modelo (RMSEA) mostró un buen ajuste del modelo en todos los países, mientras que índices secundarios (Comparative Fit Index Tucker-Lewis Index) mostraron un ajuste de aceptable a bueno en 17 países. Se obtuvieron cargas factoriales robustas para los distintos países e ítems. De los 5.007 parámetros estimados, cuatro (0,08 %) se encontraban fuera de rango. No obstante, los intervalos de confianza del 95% comprendían el espacio admisible, indicando que la desviación de los cuatro parámetros podría deberse a fluctuaciones en el muestreo. Los hallazgos coinciden con la evidencia previa existente sobre la generalización del modelo de ocho síndromes obtenida de autoinformes realizados en 28 sociedades. Además, los resultados indican que el modelo es adecuado para operacionalizar fenotipos de la psicopatología del adulto a partir de evaluaciones de múltiples informantes en diversas sociedades.

El presente artículo tiene como objetivo principal informar acerca de las características psicométricas y los datos normativos de la Adaptación Argentina de la Escala de Autoeficacia General (EAG) de Jerusalem y Schwarzer (1992) a fin de poder contar con evidencias de validez y fiabilidad que permitan su uso idóneo en tareas de investigación. Incluye 10 ítemes con escalamiento tipo Likert de 4 puntos. La autoeficacia refiere a la percepción de los individuos para manejar adecuadamente una amplia gama de estresores de la vida cotidiana. Se analizaron los datos obtenidos de 292 sujetos, residentes en la Ciudad de Buenos Aires y alrededores (República Argentina). Se llevó a cabo un Análisis de Componentes Principales y se observó que, si bien emergen dos factores que explican el 44% de la variancia, el mayor porcentaje lo explica el primer factor con un 33%. En cuanto a la fiabilidad, los resultados indican una apropiada consistencia interna de los ítemes (¿ = .76) y, en relación a otras evidencias de validez, se obtuvieron correlaciones significativas con estrategias de afrontamiento al estrés de planeamiento (r = .459; p < .001) y actividad (r = .393; p < .001) y con medidas de locus de control externo (r = -.293; p < .001). Asimismo, se registraron diferencias en cuanto al sexo y la edad. En resumen, los resultados obtenidos indican evidencias de fiabilidad en términos de consistencia interna y de la validez de las puntuaciones obtenidas mediante la administración de la versión local de la EAG a residentes de Buenos Aires.

Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane. Human corneal endothelial cells were cultured from corneal rims after corneal penetrating keratoplasty and type I collagen was isolated from remnant cancellous bone chips. Isolated type I collagen was analyzed by western blot, liquid chromatography -mass spectrometry and quantified using the exponentially modified protein abundance index. Later on, collagen solution was casted at room temperature obtaining an optically transparent and mechanically manageable membrane that supports the growth of human and rabbit corneal endothelial cells which expressed characteristic markers of corneal endothelium: zonula ocluddens-1 and Na+/K+ ATPase. To evaluate the therapeutic efficiency of our artificial endothelial grafts, human purified type I collagen membranes cultured with rabbit corneal endothelial cells were transplanted in New Zealand white rabbits that were kept under a minimal immunosuppression regimen. Transplanted corneas maintained transparency for as long as 6 weeks without obvious edema or immune rejection and maintaining the same endothelial markers that in a healthy cornea. In conclusion, it is possible to develop an artificial human corneal endothelial graft using remnant tissues that are not employed in transplant procedures. This artificial endothelial graft can restore the integrality of corneal endothelium in an experimental model of endothelial dysfunction. This strategy could supply extra endothelial tissue and compensate the deficit of cadaveric grafts for corneal endothelial transplantation.