Intravitreal anti-VEGF therapy for choroidal neovascularisation secondary to pathological myopia: 4-year outcome

OBJECTIVE: To report the visual outcome after 4-year follow-up in a series of highly myopic eyes with choroidal neovascularisation (CNV) treated with antivascular endothelial growth factor (anti-VEGF) drugs. METHODS: A retrospective, non-randomised, multicentre, consecutive, interventional case series study was performed. 92 highly myopic eyes with subfoveal CNV were treated with intravitreal injection (IVI) of anti-VEGF. The initial protocol (1 vs 3 injections) was dictated by surgeons' preferences and followed by an as-needed monthly regime. Best-corrected visual acuity (BCVA) was evaluated at baseline and then monthly. The primary aim was to analyse BCVA changes. The effect of age, spherical equivalent (SE) and treating drug were evaluated as secondary objectives. RESULTS: The mean age of the patients was 57 years (SD 14, range 30-93). The mean number of letters read was 46.1 (SD 16.8, range 5-70) at baseline, 55.5 (SD 18.6, range 10-85) at 12 months, 50.1 (SD 20.1, range 5-82) at 24 months, 54.2 (SD 21.9, range 2-85) at 36 months and 53.1 (SD 22.5, range 1-83) at 48 months (p=0.000, initial vs 12, 24 and 36 months; p=0.01 initial vs 48 months; Student t test for paired data). The mean total number of IVI was 4.9 (SD 5.4, range 1-29). SE and treating drug had no influence on the final visual outcome and number of injections required. CONCLUSIONS: Intravitreal bevacizumab and ranibizumab are effective therapies and show similar clinical effects in highly myopic CNV. Visual acuity gain is maintained at 4-year follow-up

Fatty Acid Profile and Bioactivity from Annona hypoglauca Seeds Oil

Plants from Annona (Annonaceae) genus are present in tropical regions, where they have economic and medicinal potential. Information on the fatty acids profile and bioactivity from seed oil of Annona species are incipient. The objective of this work was to investigate Annona hypoglauca seeds oil in terms of its yield, composition and biological activity (acetylcholinesterase enzyme inhibition, bactericidal and fungicidal activity). Fatty acids profiles were determined by Gas Chromatography equipped with Flame Ionization Detector. Oil yield reached about 15% and the major constituents detected were ω-9 oleic acid (42.65%) and ω-6 linoleic acid (29.63%). A. hypoglauca oil was potent for acetylcholinesterase inhibition (79.55%), and presented high and selective bioactivity against Candida albicans.Keywords: Annona hypoglauca, ω-9 Oleic Acid, ω-6 Linoleic Acid, Acetylcholinesterase, Candida albican

PELIGROSIDAD A LOS MOVIMIENTOS DE LADERA EN LA VERTIENTE MERIDIONAL DE SIERRA NEVADA (GRANADA) A PARTIR DE LA ESTIMACIÓN MULTI-TÉCNICA DE LA ACTIVIDAD

El presente trabajo aborda la cartografía de la susceptibilidad y la peligrosidad a los movimientos de ladera, en un ambiente montañoso, con información limitada sobre su actividad. El análisis y validación de la susceptibilidad se realizada mediante un modelo elaborado a partir del ModelBuilder™ de ArcGIS basado en el Método de la Matriz en un SIG. Dicho modelo necesita una cartografía previa de los movimientos, un MDE y un análisis discriminante de los factores determinantes de la estabilidad. Los datos del análisis reflejan que el 15% de la zona estudiada muestra una susceptibilidad a los movimientos de moderada a muy alta que, a su vez, coincide con lugares donde se encuentran la mayoría de las infraestructuras públicas de la región. Además, los valores registrados en la validación mediante el grado de ajuste están por encima del 83% para las zonas de susceptibilidad alta y muy alta. Estas zonas que presentan un mayor grado de susceptibilidad y, por tanto, una mayor exposición potencial al riesgo, son las seleccionadas para el análisis detallado de la peligrosidad. El principal problema, que, por otra parte, suele ser generalizado en este tipo de áreas para la estimación de la frecuencia con la que se suceden movimientos de ladera, es la falta de información sobre su ocurrencia. Por tanto, y con el objetivo de obtener la mayor información posible, los datos relativos a la actividad de los movimientos se extraen de diversas fuentes y técnicas, de forma que interactivamente solventen sus correspondientes limitaciones. Estos datos se extraen de una documentación previa, tanto en prensa como bibliografía específica, donde se presentan trabajos sobre DInSAR, fotogrametría aérea y LIDAR, y TLS. Además, se realiza de forma específica un análisis dendrogeomorfológico de árboles en movimientos de ladera y se revisa la ortofotografía aérea histórica de la zona de estudio. Posteriormente, con los datos de actividad, se realiza un análisis de los factores desencadenantes, que refleja que los movimientos de ladera están relacionados con episodios de precipitaciones intensas y prolongadas, y no tanto con la actividad sísmica del área. Por último, de forma indirecta, se estima la peligrosidad de la zona de estudio a los movimientos de ladera, asociando los resultados obtenidos de actividad con los factores desencadenantes; esto es, con periodos de precipitaciones intensas. Así, se establece un periodo de retorno que se extrapola a toda el área, con la asunción de que los grandes deslizamientos se generan o reactivan, conjuntamente con movimientos superficiales, tras periodos lluviosos intensos y prolongados, y que las lluvias torrenciales generan movimientos de ladera superficiales tipo flujo y desprendimientos. Los resultados obtenidos indican que la frecuencia con la que se generan los movimientos es de 5 años para los flujos superficiales y desprendimientos (F=0,2), y de 18 años para los deslizamientos y movimientos complejos (F=0,06). La zona, en términos generales, presenta determinados sectores con susceptibilidad moderada a muy alta, sin embargo la peligrosidad a los movimientos de ladera es de moderada a muy baja. En términos de probabilidad temporal, los flujos y desprendimientos son los movimientos con mayor peligrosidad

The Calcitonin and Glucocorticoids Combination: Mechanistic Insights into Their Class-Effect Synergy in Experimental Arthritis

PMCID: PMC3564948This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Recovery of early meteorological records from Extremadura region (SW Iberia): The ''CliPastExtrem'' (v1.0) database

In this work, we provide instrumental meteorological data recovered for the Extremadura region (interior SW Iberia), from 1826 to mid-20th century. Meteorological variables such as air temperature, atmospheric pressure, precipitation, wind direction and humidity, among others, were retrieved. In total, more than 750 000 instrumental data in 157 meteorological series belonging to 131 different locations throughout Extremadura were rescued. It must be noted that daily resolution data constitutes 80% of the database. This great effort of digitization and data collection has been carried out with the aim of contributing to a significant expansion of the length of the databases with meteorological information in this region. Therefore, this database will provide a better understanding of climate variability, trends and extreme events of the Extremadura region

Assessment of Chemical Inhibitor Addition to Improve the Gas Production from Biowaste

The coexistence of sulphate-reducing bacteria and methanogenic archaea in the reactors during the anaerobic digestion from sulphate-containing waste could favor the accumulation of sulfide on the biogas, and therefore reduce its quality. In this study, the effect of sulphate-reducing bacteria inhibitor (MoO−2 4 ) addition in a two phase system from sulphate-containing municipal solid waste to improve the quality of the biogas has been investigated. The results showed that although SRB and sulphide production decreased, the use of inhibitor was not effective to improve the anaerobic digestion in a two phase system from sulphate-containing waste, since a significant decrease on biogas and organic matter removal were observed. Before MoO−2 4 addition the average values of volatile solid were around 12 g/kg, after 5 days of inhibitor use, those values did exceed to 28 g/kg. Molybdate caused acidification in the reactor and it was according to decrease in the pH values. In relation to microbial consortia, the effect of inhibitor was a decrease in Bacteria (44%; 60% in sulphate-reducing bacteria) and Archaea (38%) population

Artificial intelligence prediction of the effect of rehabilitation in whiplash associated disorder.

The active cervical range of motion (aROM) is assessed by clinicians to inform their decision-making. Even with the ability of neck motion to discriminate injured from non-injured subjects, the mechanisms to explain recovery or persistence of WAD remain unclear. There are few studies of ROM examinations with precision tools using kinematics as predictive factors of recovery rate. The present paper will evaluate the performance of an artificial neural network (ANN) using kinematic variables to predict the overall change of aROM after a period of rehabilitation in WAD patients. To achieve this goal the neck kinematics of a cohort of 1082 WAD patients (55.1% females), with mean age 37.68 (SD 12.88) years old, from across Spain were used. Prediction variables were the kinematics recorded by the EBI® 5 in routine biomechanical assessments of these patients. These include normalized ROM, speed to peak and ROM coefficient of variation. The improvement of aROM was represented by the Neck Functional Holistic Analysis Score (NFHAS). A supervised multi-layer feed-forward ANN was created to predict the change in NFHAS. The selected architecture of the ANN showed a mean squared error of 308.07-272.75 confidence interval for a 95% in the Monte Carlo cross validation. The performance of the ANN was tested with a subsample of patients not used in the training. This comparison resulted in a medium correlation with R = 0.5. The trained neural network to predict the expected difference in NFHAS between baseline and follow up showed modest results. While the overall performance is moderately correlated, the error of this prediction is still too large to use the method in clinical practice. The addition of other clinically relevant factors could further improve prediction performance

The methylation status of the embryonic limb skeletal progenitors determines their cell fate in chicken

Digits shape is sculpted by interdigital programmed cell death during limb development. Here, we show that DNA breakage in the periphery of 5-methylcytosine nuclei foci of interdigital precursors precedes cell death. These cells showed higher genome instability than the digit-forming precursors when exposed to X-ray irradiation or local bone morphogenetic protein (BMP) treatments. Regional but not global DNA methylation differences were found between both progenitors. DNA-Methyl-Transferases (DNMTs) including DNMT1, DNMT3B and, to a lesser extent, DNMT3A, exhibited well-defined expression patterns in regions destined to degenerate, as the interdigital tissue and the prospective joint regions. Dnmt3b functional experiments revealed an inverse regulation of cell death and cartilage differentiation, by transcriptional regulation of key genes including Sox9, Scleraxis, p21 and Bak1, via differential methylation of CpG islands across their promoters. Our findings point to a regulation of cell death versus chondrogenesis of limb skeletal precursors based on epigenetic mechanisms.We thank Prof. Miguel Lafarga for helpful comments and advice. We thank Dr Jose E Gomez-Arozamena for helping us with the irradiation experiments. We are grateful to Montse Fernandez Calderon, Susana Dawalibi, and Sonia Perez Mantecon, for excellent technical assistance. This work was supported by a Grant (BFU2017–84046-P) from the Spanish Science and Innovation Ministry to JAM. C.S.F is recipient of a FPI grant (BES-2015–074267)

Transforming growth factor beta signaling: The master sculptor of fingers

Transforming growth factor beta (TGF?) constitutes a large and evolutionarily conserved superfamily of secreted factors that play essential roles in embryonic development, cancer, tissue regeneration, and human degenerative pathology. Studies of this signaling cascade in the regulation of cellular and tissue changes in the three-dimensional context of a developing embryo have notably advanced in the understanding of the action mechanism of these growth factors. In this review, we address the role of TGF? signaling in the developing limb, focusing on its essential function in the morphogenesis of the autopod. As we discuss in this work, modern mouse genetic experiments together with more classical embryological approaches in chick embryos, provided very valuable information concerning the role of TGF? and Activin family members in the morphogenesis of the digits of tetrapods, including the formation of phalanxes, digital tendons, and interphalangeal joints. We emphasize the importance of the Activin and TGF? proteins as digit inducing factors and their critical interaction with the BMP signaling to sculpt the hand and foot morphology