Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis.

Objective Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. Methods Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. Results A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (PFDR=5.07E-03, OR=1.48, CI 95%=1.14-1.92 and PFDR=3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. Conclusion Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies

Efficacy, Safety and Cost-Effectiveness of Methotrexate, Adalimumab or Their Combination in Non-infectious Non-anterior Uveitis: A Protocol for a Multicentre, Randomised, Parallel Three Arms, Active-Controlled, Phase III Open Label With Blinded Outcome Assessment Study

[Abstract] Introduction: Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet. Methods and analysis: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects’ subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers. Ethics and dissemination: The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation. Trial registration number: 2020-000130-18; NCT04798755.This work was supported by the Instituto de Salud Carlos III, grant number [ICI19/00020]. Sponsor: Fundación para la Investigacion Biomédica del Hospital Clínico San Carlos. Executive Committee: Administrative and executive arm of the clinical trial, providing overall oversight for the study and making decisions on day-to-day operational issues (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Spanish Clinical Trial Network (Amanda López Picado), and 5 Site Directors (these seats will be rotatory, with changes every 6 months months)); Data Coordinating and Analysis Committee: Supervising data collection,management and quality control, designing the statistical analysis plan, performing unmasked data analysis and preparing interim and final reports for the Data Security Monitoring Board and the Executy Committee (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Spanish Clinical Trial Network (Amanda López Picado) and Ester Carreño); Biobank and Biomarker Identification Committee (Maintaining an up-to-date manual of operations for blood extraction, processing and storage, and monitoring procedures adherence, supervising biological sample collection, sample shipment coordination, coordinating the phamacogenetic and proteomic analysis (Study Coordinator (Luis Rodriguez-Rodriguez), a representative from the Instituto de Salud Carlos III Biobank Platform (Elena Molino), a representative the Instituto de Investigación Biomédica de A Coruña, a representative from, the Data Coordinating and Analysis Committee); Data Security Monitoring Committee (PierGiogio Neri, Andrew Dick, Loreto Carmona

Validation of UVEDAI: An Index for Evaluating the Level of Inflammatory Activity in Uveitis

Introduction Uveitis is the inflammation of the middle layer of the eye, the uvea, and is a major cause of blindness. None of the instruments used in clinical practice are, in themselves, sufficient to evaluate the course of uveitis. Therefore, it is necessary to develop instruments enabling standardized measurement of inflammatory activity. We developed a composite disease activity index for patients with uveitis known as UVEDAI, which considers the overall activity of the eye. The objective of this study was to validate the composite index of ocular inflammation, UVEDAI. Methods A multicenter cross-sectional study involving eight Spanish tertiary hospitals. Sixty-two patients aged ≥ 18 years with acute uveitis were recruited. Participants gave informed consent before participating in the study. A full ophthalmological examination was performed by two ophthalmologists to determine inflammatory activity: one used the UVEDAI score and the other used clinical judgment. The ophthalmologists did not share their findings with each other to avoid introducing bias into the analysis. Construct validity was established by means of factor analysis. The criterion validity of the index was determined using an ordinal multivariate regression model, in which the dependent variable was the degree of uveal inflammation (mild, moderate, or high/severe). Cut-off points were determined for the UVEDAI and for the receiver operating characteristic (ROC) curves. Results Sixty-two patients were included. Total variance with the three components accounted for 80.32% of the construct validity. Each of the three components identified one type of eye involvement. The discriminatory capacity of UVEDAI was 0.867 (95% CI 0.778; 0.955 p < 0.001) for mild versus moderate–high and 0.946 (95% CI 0.879; 1.000 p < 0.001) for high versus mild–moderate. Conclusions The variables included in UVEDAI enable ocular inflammatory activity to be described with a high degree of accuracy. The index may be used to evaluate and classify this activity with considerable discriminatory power.We would like to acknowledge the support of Abbvie: this study was conducted with an unrestricted grant from Abbvie. The Spanish Society of Rheumatology is the sponser and funder of this study and the journal's Rapid Service Fee, and has participated in the study design; in the analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The corresponding author had full access to all study data and had final responsibility for the decision to submit the manuscript for publication

Development of an activity disease score in patients with uveitis (UVEDAI)

To develop a disease activity index for patients with uveitis (UVEDAI) encompassing the relevant domains of disease activity considered important among experts in this field. The steps for designing UVEDAI were: (a) Defining the construct and establishing the domains through a formal judgment of experts, (b) A two-round Delphi study with a panel of 15 experts to determine the relevant items, (c) Selection of items: A logistic regression model was developed that set ocular inflammatory activity as the dependent variable. The construct "uveitis inflammatory activity" was defined as any intraocular inflammation that included external structures (cornea) in addition to uvea. Seven domains and 15 items were identified: best-corrected visual acuity, inflammation of the anterior chamber (anterior chamber cells, hypopyon, the presence of fibrin, active posterior keratic precipitates and iris nodules), intraocular pressure, inflammation of the vitreous cavity (vitreous haze, snowballs and snowbanks), central macular edema, inflammation of the posterior pole (the presence and number of choroidal/retinal lesions, vascular inflammation and papillitis), and global assessment from both (patient and physician). From all the variables studied in the multivariate model, anterior chamber cell grade, vitreous haze, central macular edema, inflammatory vessel sheathing, papillitis, choroidal/retinal lesions and patient evaluation were included in UVEDAI. UVEDAI is an index designed to assess the global ocular inflammatory activity in patients with uveitis. It might prove worthwhile to motorize the activity of this extraarticular manifestation of some rheumatic diseases

FATTY ACIDS, a-TOCOFEROL AND L-CARNITINE: THEIR RELATIONSHIPS IN TURBOT (Scophthalmus maxímus L. GROWTH: FIRST RESULTS.

The effect that the administration of diets rich in essential fattyacids has on growth in weight of turbot (S. maxímus), contrasted with non-enriched diets supplemented with a-tocoferol, and at two different levels of administration of l-carnitine has be en studied. The weight of individual s corresponding to the different levels of treatment is analysed using MANOVA of repeated measures, resulting in significant differences between the different treatments, with p<O.OOl. An evaluation is made of the efficiency of each of the different treatments with respect to growth and body content in fat and protein

The production of ammonia in mass cultures of the rotifer, Brachionus plicatilis O. F. Müller, feeding on bread yeast

The production of ammonia in mass cultures of the rotifer, B.plicatilis,fed with different concentrations of bread yeast and temperatures are compared w i th that of the rotifer initially inoculated with algae culture.The levels of ammonia remained low in the last ones when the algae cells were still present They increased when the cells had been ingered by the rotifers. Nevertheless,the rotifer population initial1y inocu1ated in a1- gae culture always show a better growth than the ones fed on1y with bread yeast.This fact seems to be independent of the ammo- nia concentration in the culture water

EFFECT ON GROWTH AND MUSCLE CONTENTS OF TURBOT (Scophthalmus maximus) USING DIETS WITH DIFFERENT LEVELS OF FAT, TOCOPHEROL AND L-CARNITINE.

This work studies growth in weight of 10 groups of turbot (S. maximus) fed on a diet in which fat, ó-tocopherol or L-Carnitine have been incorporated, or in other cases a combination of the these. Significant differences between the groups were found, which were determined through a MANOVA with a design of repeated measurements, being p<O.OOl for all groups. Those which presented higher growth ingested a dose of 300 mg of l-Carnitine and those presenting lower growth ingested fat (16% of dry food), without any other factors added. The protein and lipid content analyses in carcass and liver showa difference of fat accumulation, with values varying from 7 to 20% of humid weight for those treated with l-Carnitine, ó-tocopherol, and fat respectively according to treatment

First results obtained about the contents in lipid, protein, water, ash and free fatty-acids, in same species of sea-fish most commonly used in feeding in aquaculture

In this report; we introduce the first results obtained about the contents in Lipid, Protein, Water, and Ash of the following species: Bogue (Boops boops,L.), Horse mackerel (Trachurus trachurus,L.), Mackerel (Scomber scombrus, L.), Blue whiting (Micromesistius poutassou, R.). In Spain, these species are basicaly used as much for their fresh consumption as for the production of fodder and flour for Aquaculture At the same time, the contents in free fatty acids of the same species in different periods of cold conservation are introduced.A cette comunication nous presentons les premiers resultés obtenues du contenue de grases, proteines, humedité et cendres du suivantes species: Bogue (Boops boops, L.), Chinchard (Trachurus trachurus, L.), Maquereau (Scomber scombrus, L.) et Poutassou (Micromesistius poutassou,R.). Cettes espéces sont fondamentellement employees en Spagne autant pour son employee domestique comme pour la production de aliments et farines pour l'acuiculture. Au meme temps ont presente le contenue en acides grases libres des memes espéces en diferents periodes de conservation au froid

Posibilidades de la Acuicultura en el litoral de Cantabria

Se presentan una parte de los resultados obtenidos durante la realización del proyecto citado, y llevado a cabo durante los años 1984 a 1987 como primer proyecto realizado tras la firma del primer Convenio de Colaboración IEO- Diputación de Cantabria. Los datos que se han recuperado aunque parciales, se exponen por la utilidad que pudieran tener daos los años en que fueron realizados. El estudio está encaminado principalmente a las Rías de Santoña y de San Vicente de la Barquera, aunque se aportan algunos datos sobre la bahía de Santander. El hecho de no aportar mas sobre esta ría es que es motivo de estudio en otras publicaciones. Se abordan los siguientes parámetros, de utilidad principalmente para el cultivo de moluscos, dado que para la instalación de cultivo de peces en aguas de costa mas abierta, requerirían en su caso de estudios particulares: Turbidez (Secchi);Profundidad;T aire;T agua;pH;salinidad;Oxígeno;Saturación de oxígeno;Nitrito;Amonio;Fosfato;Clorofila “a”;Granulometría Estos datos se presentan como un punto de referencia, dados los años en que fueron efectuados. Desgraciadamente por diversas circunstancias, se extraviaron algunos informes y sólo se puede aportar una parte de ellos Se presentan también los datos de la primera experiencia en Cantabria sobre crecimiento de almeja japonesa (Ruditapes phillipinarum) en comparación con almeja fina (Venerupis decussata) en la Ría de san Vicente de la Barquera

Growth of turbot (Scophthalmus maximus L.) from 1 to 3,000 g in the north of Spain

Growth of Turbot from 1 y. to 3000 g. is related in this paper. Groups of fish were fed on semihumid food. Gompertz's and Bertalanffy's equations were applied for growth in weight and length respectively. Parameters such as food conversion index and specific growth rate, as well as condition factor were calculated.Growth is presented as a curve-line for different intervals