PND30 Cost Analysis of Glatiramer Acetate Versus Fingolimod for the Treatment of Patients With Relapsing-Remitting Multiple Sclerosis in Spain

BACKGROUND: Fingolimod is an innovative drug with a significant budget impact in the treatment of MS in Spain. The aim of this study was to calculate the direct cost comparison of glatiramer acetate and fingolimod for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS) in Spain. METHODS: A cost analysis model was developed to compare glatiramer acetate and fingolimod, based on a 1-year time horizon. In addition to the pharmacological costs, resource use was estimated for glatiramer acetate (1 hour of training with nursing staff in self-injection techniques for subcutaneous administration) and fingolimod (vaccination for varicella-zoster virus in 5% of patients, 3 complete blood counts per year, 3 ophthalmology visits for prevention of macular edema, 3 transaminase tests to monitor liver function, and cardiovascular monitoring consisting of 1 ECG before the first fingolimod dose and at 6 hours; 1 day outpatients-hospital visit for cardiological monitoring during 6 hours on the day of the first fingolimod dose, with follow-up of blood pressure and heart rate every hour). The pharmacological costs were calculated based on the ex-factory price of the drugs evaluated, using the doses recommended in the respective Summary of Products Characteristics (SmPC). Total invoicing volume was discounted by 7.5%, as laid down in Spanish Royal Decree 8/2010. Unit costs were obtained from the e-Salud database and the drug catalog. Costs in the model are expressed in €2012. RESULTS: The cost of annual treatment was €9,439.42 for glatiramer acetate and €19,602.18 for fingolimod, yielding a cost difference of €10,162.76. Assuming a fixed budget of €100,000.00, approximately 10 patients could be treated with glatiramer acetate, compared to 5 with fingolimod. CONCLUSIONS: Fingolimod therapy requires twice the investment as glatiramer acetate

Learning Mineralogy in a virtual didactic environment

Las colecciones de minerales de las universidades constituyen un valioso patrimonio geológico mueble, aunque suelen tener un uso limitado como material didáctico en las sesiones de prácticas. Los sistemas de comunicación digitales a través de internet permiten utilizar nuevos entornos didácticos virtuales y ofrecer un acceso universal a las colecciones, de modo dinámico e interactivo, proporcionando múltiples niveles de información sobre los minerales. En esta ponencia se pretende comunicar la metodología y los resultados de un proyecto de innovación docente para la creación del Museo Virtual de Mineralogía de la Universidad de Huelva, al objeto de promover la aplicación de recursos multimedia que estimulan un aprendizaje más autónomo y una mayor participación en las actividades grupales. La web se diseñó mediante una estructura hipertextual, considerando los requerimientos y características de los usuarios potenciales, con textos vinculados a bases de datos mineralógicas multimedia. El Museo Virtual de Mineralogía es un paso más en el proceso de adaptación a las TICs, para afrontar los retos que plantea el nuevo modelo educativo de enseñanza-aprendizaje y, al mismo tiempo, proyecta de forma novedosa y universal la acción formativa y divulgadora del patrimonio mineralógico, pues tiene la ventaja de permitir el acceso remoto a cualquier cibernauta interesado en sus contenidos digitales, a cualquier hora y desde cualquier lugar del mundo.The university mineral collections are a valuable geological heritage despite having a limited use as a didactic material in the practical sessions. The digital media allow the use of new virtual learning environment and offer a global access to the collections in a dynamic and interactive way, thus allowing different dimensions of information on the Science of Minerals. This presentation aims to communicate the methodology and results of a teaching innovation project conducted at the University of Huelva for the creation of a virtual museum of Mineralogy. The web technology has been used as the main tool to promote the application of multimedia resources that encourage a more independent learning and more engagement in group activities. A website has been developed through a basic hypertext structure in order to complement and globalise training and disseminative actions. The design of the web took into account the requirements of the potential users allowing an easy access to the digital contents, including links to multimedia mineralogical databases. The virtual museum of Mineralogy is a further step in the process of integrating the new information and communications technology to tackle the challenges that the modern educational system of teaching and learning brings. Furthermore, the university mineral collection is disseminated to a wide and diversified audience given that the virtual museum allows the remote access to any web user interested in their digital contents, at any time and anywhere in the world

High-trhoughput screening of cytochrome C novel partners chlamydomonas ReindhartII

Comunicaciones a congreso

Histone chaperone activity of Arabidopsis thaliana NRP1 is blocked by cytochrome c

Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone chaperone-mediated nucleosome disassembly/reassembly is essential for DNA to be accessible to repair machinery. However, little is known about the specific role and modulation of histone chaperones in the context of DNA damage in plants. Here, the histone chaperone NRP1, which is closely related to human SET/TAF-I, was found to exhibit nucleosome assembly activity in vitro and to accumulate in the chromatin of Arabidopsis thaliana after DNA breaks. In addition, this work establishes that NRP1 binds to cytochrome c, thereby preventing the former from binding to histones. Since NRP1 interacts with cytochrome c at its earmuff domain, that is, its histone-binding domain, cytochrome c thus competes with core histones and hampers the activity of NRP1 as a histone chaperone. Altogether, the results obtained indicate that the underlying molecular mechanisms in nucleosome disassembly/reassembly are highly conserved throughout evolution, as inferred from the similar inhibition of plant NRP1 and human SET/TAF-I by cytochrome c during DNA damage response

Current challenges in chronic bronchial infection in patients with chronic obstructive pulmonary disease

Currently, chronic obstructive pulmonary disease (COPD) patients and their physicians face a number of significant clinical challenges, one of which is the high degree of uncertainty related to chronic bronchial infection (CBI). By reviewing the current literature, several challenges can be identified, which should be considered as goals for research. One of these is to establish the bases for identifying the biological and clinical implications of the presence of potentially pathogenic microorganisms in the airways that should be more clearly elucidated according to the COPD phenotype. Another urgent area of research is the role of long-term preventive antibiotics. Clinical trials need to be carried out with inhaled antibiotic therapy to help clarify the profile of those antibiotics. The role of inhaled corticosteroids in patients with COPD and CBI needs to be studied to instruct the clinical management of these patients. Finally, it should be explored and confirmed whether a suitable antimicrobial treatment during exacerbations may contribute to breaking the vicious circle of CBI in COPD. The present review addresses the current state of the art in these areas to provide evidence which will enable us to progressively plan better healthcare for these patients

Spatial distribution of pyrogenic carbon in Iberian topsoils estimated by chemometric analysis of infrared spectra

Understanding the global carbon (C) cycle is critical to accurately model feedbacks between climate and soil. Thus, many climate change studies focused on soil organic carbon (SOC) stock changes. Pyrogenic carbon (PyC) is one of the most stable fractions of soil organic matter (SOM). Accurate maps based on measured PyC contents are required to facilitate future soil management decisions and soil-climate feedback modelling. However, consistent measurements that cover large areas are rare. Therefore, this study aimed to map the PyC content and stock of the Iberian Peninsula, which covers contrasting climatic zones and has long-term data on wildfire occurrence. A partial least square (PLS) regression using the mid-infrared spectra (1800–400 cm−1) was applied to a dataset composed of 2961 soil samples from the Iberian component of the LUCAS 2009 database. The values of PyC for LUCAS points were modelled to obtain a map of topsoil PyC by a random forest (RF) approach using 36 auxiliary variables. The results were validated through comparison with documented historical wildfire activity and anthropogenic energy production. A strong relationship was found between these sources and the distribution of PyC. Our study estimates that the accumulated PyC in Iberian Peninsula soils comprises between 3.09 and 20.39% of total organic carbon (TOC) in the topsoil. Forests have higher PyC contents than grasslands, followed by agricultural soils. The incidence of recurrent wildfires also has a notable influence on PyC contents. This study shows the potential of estimating PyC with a single, rapid, low cost, chemometric method using new or archived soil spectra, and has the ability to improve soil-climate feedback modelling. It also offers a possible tool for measuring, reporting and verifying soil C stocks, which is likely to be important moving forward if soils are used as sinks for C sequestration

The role of Epstein-Barr virus in adults with bronchiectasis : A prospective cohort study

Epstein-Barr virus (EBV) is implicated in the progression of chronic obstructive pulmonary disease. We aimed to determine whether EBV correlates with bronchiectasis severity, exacerbations, and progression. We collected induced sputum in healthy controls and spontaneous sputum at 3-6-month intervals and onset of exacerbations in bronchiectasis patients between March 2017 and October 2018. EBV DNA was detected with quantitative polymerase chain reaction. We collected 442 sputum samples from 108 bronchiectasis patients and 50 induced sputum samples from 50 healthy controls. When stable, bronchiectasis patients yielded higher detection rates of EBV DNA (48.1% vs 20.0%; P =.001), but not viral loads (mean log load, 4.45 vs 4.76; P =.266), compared with controls; 64.9% of patients yielded consistent detection status between 2 consecutive stable visits. Neither detection rate (40.8% vs 48.1%; P =.393) nor load (mean log load, 4.34 vs 4.45; P =.580) differed between the onset of exacerbations and stable visits, nor between exacerbations and convalescence. Neither detection status nor viral loads correlated with bronchiectasis severity. EBV loads correlated negatively with sputum interleukin-1β (P =.002), CXC motif chemokine-8 (P =.008), and tumor necrosis factor-α levels (P =.005). Patients initially detected with, or repeatedly detected with, EBV DNA had significantly faster lung function decline and shorter time to next exacerbations (both P .05). The EBV strains detected in bronchiectasis patients were phylogenetically homologous. Patients with detection of EBV DNA have a shorter time to bronchiectasis exacerbations. EBV may contribute to bronchiectasis progression

Análisis del peso vivo y la ganancia media diaria de peso en tres genotipos caprinos en el semiárido de Formosa

The aim of this study was to compare the live weight and average daily weight gain (DWG) of 538 kids in Laguna Yema, Formosa, considering three breeds (173 Criollos Formoseños -CF-, 207 Boer, and 156 Anglo-Nubian -AN-), sex (243 males and 293 females), and birth type (BT) (129 singles and 407 twins) under similar management conditions. Adjusted live weight (ALW) and DWG at birth, 30, 60, 90, 180, and 365 days were evaluated. Descriptive and comparative statistics between breeds, sex, and BT were determined by ANOVA and Tukey’s test (p<0,05). The mean ALW (DWG) values were at birth 2.60 kg; 30 days 6.49 kg (128 g d-1); 60 days 9.67 kg (104 g d-1); 90 days 11.30 kg (54 g d-1); 180 days 17.98 kg (72 g d-1); and 365 days 25.39 kg (44 g d-1). Up to 60 days, CF and AN showed lower ALW than Boer, with no differences at 90 days. At 180 days, AN and Boer outperformed CF, and at 365 days, Boer again stood out with higher ALW. Regarding DWG, Boer was superior <60 days and between 180-365 days, while CF and AN surpassed Boer between 60-180 days. According to sex, ALW and DWG were equal, except at 180 days (males > females). For BT, values favored singles, except for ALW at one year and DWG at 180 days. Consequently, Boer is recommended for suckling kids or heavy wethers, while AN and CF are more suitable for intermediate animals. The lack of sex-based differences allows for the sale of females at any time. By one year of age, BT becomes less relevant, which benefits replacement strategies and supports selection for prolificacy in long-cycle systems. In short-cycle systems, additional treatment is recommended for animals from multiple births.El objetivo del estudio fue comparar el peso vivo y ganancia diaria de peso (GDP) de 538 cabritos en Laguna Yema, Formosa, considerando tres razas (173 Criollos Formoseños -CF-, 207 Boer y 156 Anglo Nubian -AN-), sexo (243 machos y 293 hembras) y tipo de parto (TP) (129 simples y 407 dobles), bajo similares condiciones de manejo. Se evaluó peso al nacimiento y el peso vivo ajustado (PVA) y la GDP a 30, 60, 90, 180 y 365 días. Se determinaron estadísticos descriptivos y comparativos entre razas, sexo y TP mediante ANOVA y test de Tukey (p<0,05). Las medias de PVA (GDP) fueron: nacimiento 2,60 kg; 30 días 6,49 kg (128 g d-1); 60 días 9,67 kg (104 g d-1); 90 días 11,30 kg (54 g d-1); 180 días 17,98 kg (72 g d-1) y 365 días 25,39 kg (44 g d-1). Hasta los 60 días, CF y AN mostraron PVA menores que Boer, sin diferencias a los 90 días. A los 180 días, AN y Boer superaron a CF, y a los 365 días, Boer volvió a destacarse con mayores PVA. En GDP, Boer fue superior <60 días y entre 180-365 días, mientras que CF y AN superaron a Boer entre 60-180 días. Según el sexo, el PVA y GDP fue igual, excepto a los 180 días (machos > hembras). Según TP, se observaron valores a favor de los simples, salvo en PVA al año y en GDP a los 180 días. Por tanto, Boer es ideal para cabritos lechales o capones pesados; AN y CF, para intermedios. No hubo diferencias según sexo. Al año de vida, el tipo de parto pierde relevancia, lo cual es positivo para la reposición y potencia la selección por prolificidad en sistemas largos. En sistemas cortos, se recomienda un tratamiento adicional para animales muy prolíficos

Inhibition of the PP2A activity by the histone chaperone ANP32B is long-range allosterically regulated by respiratory cytochrome c

Repair of injured DNA relies on nucleosome dismantling by histone chaperones and de-phosphorylation events carried out by Protein Phosphatase 2A (PP2A). Typical histone chaperones are the Acidic leucine-rich Nuclear Phosphoprotein 32 family (ANP32) members, e.g. ANP32A, which is also a well-known PP2A inhibitor (a.k.a. I1PP2A). Here we report the novel interaction between the endogenous family member B—so-called ANP32B—and endogenous cytochrome c in cells undergoing camptothecin-induced DNA damage. Soon after DNA lesions but prior to caspase cascade activation, the hemeprotein translocates to the nucleus to target the Low Complexity Acidic Region (LCAR) of ANP32B; in a similar way, our group recently reported that the hemeprotein targets the acidic domain of SET/Template Activating Factor-Iß (SET/TAF-Iß), which is another histone chaperone and PP2A inhibitor (a.k.a. I2PP2A). The nucleosome assembly activity of ANP32B is indeed unaffected by cytochrome c binding. Like ANP32A, ANP32B inhibits PP2A activity and is thus herein referred to as I3PP2A. Our data demonstrates that ANP32B-dependent inhibition of PP2A is regulated by respiratory cytochrome c, which induces long-distance allosteric changes in the structured N-terminal domain of ANP32B upon binding to the C-terminal LCAR. In agreement with the reported role of PP2A in the DNA damage response, we propose a model wherein cytochrome c is translocated from the mitochondria into the nucleus upon DNA damage to modulate PP2A activity via its interaction with ANP32B. © 2021 The Author(s

Functional characterization of the evolutionarily divergent fern plastocyanin

De functie van eiwitten die betrokken zijn bij insulinewerking en glucose hemeostrase en de rol van genetische varianten hierin bij de ontwikkeling van type 2 diabete