Influence of chronic ocular hypertension on emmetropia: Refractive, structural and functional study in two rat models

Chronic ocular hypertension (OHT) influences on refraction in youth and causes glaucoma in adulthood. However, the origin of the responsible mechanism is unclear. This study analyzes the effect of mild-moderate chronic OHT on refraction and neuroretina (structure and function) in young-adult Long-Evans rats using optical coherence tomography and electroretinography over 24 weeks. Data from 260 eyes were retrospectively analyzed in two cohorts: an ocular normotension (ONT) cohort (20 mmHg), in which OHT was induced either by sclerosing the episcleral veins (ES group) or by injecting microspheres into the anterior chamber. A trend toward emmetropia was found in both cohorts over time, though it was more pronounced in the OHT cohort (p < 0.001), especially in the ES group (p = 0.001) and males. IOP and refraction were negatively correlated at week 24 (p = 0.010). The OHT cohort showed early thickening in outer retinal sectors (p < 0.050) and the retinal nerve fiber layer, which later thinned. Electroretinography demonstrated early supranormal amplitudes and faster latencies that later declined. Chronic OHT accelerates emmetropia in Long–Evans rat eyes towards slowly progressive myopia, with an initial increase in structure and function that reversed over time. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Real-World Multicenter Experience of Immunosuppression Minimization Among 661 Liver Transplant Recipients.

BACKGROUND Long-term morbidity and mortality in liver transplant recipients is frequently secondary to immunosuppression toxicity. However, data are scarce regarding immunosuppression minimization in clinical practice. MATERIAL AND METHODS In this cross-sectional, multicenter study, we reviewed the indications of immunosuppression minimization (defined as tacrolimus levels below 5 ng/mL or cyclosporine levels below 50 ng/mL) among 661 liver transplant recipients, as well as associated factors and the effect on renal function. RESULTS Fifty-three percent of the patients received minimized immunosuppression. The median time from transplantation to minimization was 32 months. The most frequent indications were renal insufficiency (49%), cardiovascular risk (19%), de novo malignancy (8%), and cardiovascular disease (7%). The factors associated with minimization were older age at transplantation, longer post-transplant follow-up, pre-transplant diabetes mellitus and renal dysfunction, and the hospital where the patients were being followed. The patients who were minimized because of renal insufficiency had a significant improvement in renal function (decrease of the median serum creatinine level, from 1.50 to 1.34 mg/dL; P=0.004). Renal function significantly improved in patients minimized for other indications, too. In the long term, glomerular filtration rate significantly decreased in non-minimized patients and remained stable in minimized patients. CONCLUSIONS Immunosuppression minimization is frequently undertaken in long-term liver transplant recipients, mainly for renal insufficiency. Substantial variability exists regarding the use of IS minimization among centers

Chronic glaucoma using biodegradable microspheres to induce intraocular pressure elevation. Six-month follow-up

Background: To compare two prolonged animal models of glaucoma over 24 weeks of follow-up. A novel pre-trabecular model of chronic glaucoma was achieved by injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (10–20 µm) (Ms20/10) into the ocular anterior chamber to progressively increase ocular hypertension (OHT). Methods: Rat right eyes were injected to induce OHT: 50% received a suspension of Ms20/10 in the anterior chamber at 0, 2, 4, 8, 12, 16 and 20 weeks, and the other 50% received a sclerosing episcleral vein injection biweekly (EPIm). Ophthalmological clinical signs, intraocular pressure (IOP), neuroretinal functionality measured by electroretinography (ERG), and structural analysis of the retina, retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) protocols using optical coherence tomography (OCT) and histological exams were performed. Results: Both models showed progressive neuroretinal degeneration (p < 0.05), and contralateral eye affectation. The Ms20/10 model showed a more progressive increase in IOP and better preservation of ocular surface. Although no statistical differences were found between models, the EPIm showed a tendency to produce thicker retinal and thinner GCL thicknesses, slower latency and smaller amplitude as measured using ERG, and more aggressive disturbances in retinal histology. In both models, while the GCL showed the greatest percentage loss of thickness, the RNFL showed the greatest and earliest rate of thickness loss. Conclusions: The intracameral model with biodegradable microspheres resulted more like the conditions observed in humans. It was obtained by a less-aggressive mechanism, which allows for adequate study of the pathology over longer periods. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Caracterización inmunológica de un grupo familiar colombiano con infección por SARS-CoV-2

Introduction: Immunological markers have been described during COVID-19 and persist after recovery. These immune markers are associated with clinical features among SARSCoV-2 infected individuals. Nevertheless, studies reporting a comprehensive analysis of the immune changes occurring during SARS-CoV-2 infection are still limited.Objective: To evaluate the production of proinflammatory cytokines, the antibody response, and the phenotype and function of NK cells and T cells in a Colombian family cluster with SARS-CoV-2 infection.Materials and methods: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. The frequency, phenotype, and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with spike/RdRp peptides) were assessed by flow cytometry. Anti-SARS-CoV-2 antibodies were determined using indirect immunofluorescence and plaque reduction neutralization assay.Results: During COVID-19, we observed a high proinflammatory-cytokine production and a reduced CD56bright-NK cell and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by high IL-10 production. However, during recovery, we observed a bifunctional response characterized by the co-expression of CD107a and granzyme B or perforin.Conclusion: Although the proinflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells couldbe associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and to guide future immunotherapy strategies.Introducción. Se han descrito diferentes marcadores inmunológicos durante la COVID-19, los cuales persisten incluso después de la convalecencia y se asocian con los estadios clínicos de la infección. Sin embargo, aún son pocos los estudios orientados al análisis exhaustivo de las alteraciones del sistema inmunológico en el curso de la infección.Objetivo. Evaluar la producción de citocinas proinflamatorias, la reacción de anticuerpos, y el fenotipo y la función de las células NK y los linfocitos T en una familia colombiana con infección por SARS-CoV-2.Materiales y métodos. Se evaluaron las citocinas proinflamatorias mediante RT-PCR y ELISA; la frecuencia, el fenotipo y la función de las células NK (en cocultivos con células K562) y linfocitos T CD8+ (estimulados con péptidos spike/RdRp) mediante citometría de flujo, y los anticuerpos anti-SARS-CoV-2, mediante inmunofluorescencia indirecta y prueba de neutralización por reducción de placa.Resultados. Durante la COVID-19 hubo una producción elevada de citocinas proinflamatorias, con disminución de las células NK CD56bright y reacción citotóxica. Comparados con los controles sanos, los individuos infectados presentaron con gran frecuencia linfocitos T CD8+ disfuncionales CD38+HLA-DR-. Además, en los linfocitos T CD8+ estimulados con péptidos virales, predominó una reacción monofuncional con gran producción de IL-10 durante la fase aguda y una reacción bifuncional caracterizada por la coexpresión de CD107a y granzima B o perforina durante la convalecencia.Conclusión. Aunque la reacción inflamatoria caracteriza la infección por SARS-CoV-2, hay otras alteraciones fenotípicas y funcionales en células NK y linfocitos T CD8+ que podrían asociarse con la progresión de la infección. Se requieren estudios adicionales para entender estas alteraciones y guiar futuras estrategias de inmunoterapia

Identificación molecular de hongos fitopatógenos de fresa por PCR (ITS Y EF-1α ) y susceptibilidad a bacteriocidas de Bacillus thuringiensis.

La generación de resistencias a fungicidas de algunos hongos residentes del suelo representa un riesgo biológico en la producción de fresa por lo que su identificación permite mejores medidas de control alternas a pesticidas químicos como algunos péptidos de origen bacteriano. Se amplificaron por PCR las secuencias ITS y EF-1α de 14 hongos aislados de muestras de suelo pertenecientes a una huerta dedicada al cultivo de fresa, los cuales fueron identificados por sus características morfológicas dentro de los géneros Aspergillus, Fusarium, Mucor, Penicillium y Trichoderma. El análisis de la secuencias permitieron la identificación de las especies A. Niger, A. calidoustus, F. oxysporum, F. verticillioides, F. sporotrichioides, M. circinelloides, N. fischeri, P. menonorum, P. pinophilium y T. asperellum, comprobando previamente su patogenicidad en fresa. Se determinó la actividad antimicrobiana de las bacteriocinas Morricina, Kurstacina, Kenyacina, Entomocina, Tolworthcina producidas por B. thuringiensis mediante bioensayos de inhibición en pozos y medio líquido corroborando su daño celular por microscopia de fluorescencia. Las 5 bacteriocinas ejercen una actividad inhibitoria sobre todos los aislados del género Fusarium y M. circinelloides evitando la esporulación e inhibiendo su crecimiento comprobando su potencial capacidad como agentes antifúngicos en el biocontrol de hongos en fresa

Variables hormonales y bioquímicas de la densidad mineral ósea y su correlación con hombres jóvenes obesos y no obesos sin diabetes

Introducción: la obesidad se ha asociado con mayor densidad mineral ósea (DMO), sin embargo, recientes estudios reportan que pudiese conllevar incremento de la resorción ósea y, por ende, mayor riesgo de fractura. Metodología: estudio de corte transversal analítico en donde se incluyeron hombres entre 18 y 30 años en quienes se realizaron diversas mediciones hormonales (insulina, testosterona libre y total, IGF-1, estradiol, leptina y adiponectina), bioquímicas (PTOG-glucosa, colesterol total, cHDL, cLDL, proteína C reactiva y HOMA-IR), antropométricas y otras, como composición grasa corporal, DMO y composición mineral ósea. Se evaluaron las diferencias de las variables cuantitativas entre obesos y no obesos mediante una prueba T-student o prueba de Wilcoxon. Para evaluar la correlación de DMO con las demás variables se usó la correlación de Spearman. Finalmente, se realizó un modelo de regresión lineal para predecir la DMO. Resultados: se incluyen 34 obesos y 35 no obesos. En el grupo de no obesos se obtuvo una media de 1,159 +/- 0,08 g/ cm2 de DMO comparado con el grupo de hombres obesos, con una media de 1,311 +/- 0,1 g/cm2 (p = 0,001). Se encontró que la DMO tiene una correlación fuerte con el contenido mineral óseo en los obesos respecto a los no obesos 3412,37 g (+/- 454,01) vs. 2575,96 g (+/-388,04), respectivamente, p <0,001. La adiponectina se correlacionó de forma negativa, aunque sin significancia en los obesos respecto a la densidad mineral ósea (r: -0,1913 y p = 0,27) y de forma débil y no significativa con los no obesos (r: 0,0074 y p = 0,96). Finalmente, se encontró que la presencia de obesidad, grasa total, contenido mineral óseo, insulina basal y HOMA-IR predicen de forma significativa la DMO en un modelo de regresión lineal. Conclusión: la DMO y el contenido mineral óseo son más altos en individuos obesos comparados con individuos no obesos, el índice de masa corporal y variables como insulina predicen la densidad mineral ósea

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study

Background: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. Methods: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. Results: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. Conclusions: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed

Resultados del estudio geológico a escala 1/25.000 del término municipal de Madrid.

Se exponen de forma abreviada los rasgos en cuanto a metodología y conclusiones del estudio geológico a escala 1/25000 realizado en el Municipio de Madrid en los años 1982/83. Las diferentes unidades expresadas en la cartografiase describen en función de las pautas mayores observables en los materiales que forman cada una de ellas, analizándose sus relaciones estratigráficas. El Proyecto «Estudio Geológico a escala 1/25000 del Término Municipal de Madrid ha sido llevado a cabo a lo largo de los años 1982-83 como resultado de la colaboración científica entre diversos organismos de la Administración (Facultad de CC. Geológicas-Universidad Complutense, Instituto Geológico y Minero. Ayuntamiento de Madrid, Instituto de Geología de Madrid-CSIC, y otros). Constituye una de las áreas de actuación definidas dentro del Convenio de Colaboración Técnica y Cultural para el conocimiento de las Características del Suelo y Subsuelo de Madrid», propiciado y patrocinado por el Excmo. Ayuntamiento. La financiación del proyecto especifico de Geología ha sido realizada íntegramente por el IGME, organismo encargado además de su supervisión. El desarrollo del Proyecto tiene un marcado carácter interdisciplinar, fruto del trasvase de información entre los distintos grupos que abarca el Convenio general (aparte de los ya referidos, el SGOP, COPLACO, Laboratorio «José Luis Escario» siendo precisamente uno de los objetivos del trabajo el servir de apoyo a las restantes áreas de investigación. Los estudios geológicos realizados se plasman en un total de siete mapas a escala 1/25000 elaborados según la normativa Magna de cartografía geológica mapas que toman como referencia, aunque en algunos casos no las completan y en otros adosan porciones de hojas adyacentes, las hojas 1/25000 de Madrid, Alcorcón, El Pardo, San Femando de Henares, Pozuelo de Alarcón, Alcobendas y Castillo de Viñuelas

Improving Scientific Knowledge of Mallorca Channel Seamounts (Western Mediterranean) within the Framework of Natura 2000 Network

The scientific exploration of Mallorca Channel seamounts (western Mediterranean) is improving the knowledge of the Ses Olives (SO), Ausias March (AM), and Emile Baudot (EB) seamounts for their inclusion in the Natura 2000 network. The aims are to map and characterize benthic species and habitats by means of a geological and biological multidisciplinary approach: high-resolution acoustics, sediment and rock dredges, beam trawl, bottom trawl, and underwater imagery. Among the seamounts, 15 different morphological features were differentiated, highlighting the presence of 4000 pockmarks, which are seafloor rounded depressions indicators of focused fluid flow escapes, usually gas and/or water, from beneath the seabed sediments. So far, a total of 547 species or taxa have been inventoried, with sponges, fishes, mollusks, and crustaceans the most diverse groups including new taxa and new geographical records. Up to 29 categories of benthic habitats have been found, highlighting those included in the Habitats Directive: maërl beds on the summits of AM and EB, pockmarks around the seamounts and coral reefs in their rocky escarpments as well as fields of Isidella elongata on sedimentary bathyal bottoms. Trawling is the main demersal fishery developed around SO and AM, which are targeted to deep water crustaceans: Parapenaeus longirostris, Nephrops norvegicus, and Aristeus antennatus. This study provides scientific information for the proposal of the Mallorca Channel seamounts as a Site of Community Importance and for its final declaration as a Special Area of Conservation