Predictive Factors of the Use of Rituximab and Belimumab in Spanish Lupus Patients.

Objectives: To analyze the characteristics and the predictive factors of the use of rituximab and belimumab in daily practice in patients from the inception cohort Registro Español de Lupus (RELES). Material and methods: The study included 518 patients. We considered patients treated with biologics who received at least one dose of rituximab or belimumab, and possible indications of those manifestations registered at the same time or in the previous 2 months of the start of the therapy. Results: In our cohort, 37 (7%) patients received at least one biological treatment. Rituximab was prescribed in 26 patients and belimumab in 11. Rituximab was mainly prescribed for hemolytic anemia or thrombocytopenia (11 patients, 42%), lupus nephritis and neuropsychiatric lupus (5 patients each, 19%). Belimumab was mostly used for arthritis (8 patients, 73%). In the univariate analysis, the predictive factors at diagnosis for the use of biologic therapy were younger age (p = 0.022), a higher SLEDAI (p = 0.001) and the presence of psychosis (p = 0.011), organic mental syndrome (SOCA) (p = 0.006), hemolytic anemia (p = 0.001), or thrombocytopenia (p = 0.01). In the multivariant model, only younger age, psychosis, and hemolytic anemia were independent predictors of the use of biologics. Conclusions: Rituximab is usually given to patients with hematological, neuropsychiatric and renal involvement and belimumab for arthritis. Psychosis, hemolytic anemia and age at the diagnosis of lupus were independent predictive factors of the use of biological agents. Their global effects are beneficial, with a significant reduction in SLE activity and a low rate of side effects.

Multidisciplinary approach to the study of large-format oil paintings.

Cultural heritage has become a keystone for comprehending our society, as it represents and reflects our origins, passions, beliefs and traditions. Furthermore, it provides fundamental information about specific temporary spaces, materials' availability, technology, artist's intention, and site weather conditions. Our aim was to develop a multidisciplinary approach with a main focus on investigating two Italian large-format paintings located in highly diverse environments such as the National Theater of Costa Rica. We monitored environmental conditions and quantified fungal aerial spores. Then, we determined regions of possible biodeterioration with the software MicroorganismPattern and used the software PigmentArrangement to elucidate the apparent colour of the paintings based on distribution and arrangement of the pigment crystals. Finally, we characterized eight genera of calcareous nannofossils found in the ground layers of the artwork. The former Men's Canteen at the National Theater of Costa Rica presented a mean air temperature of 23.5 [Formula: see text]C, a relative humidity of 72.7% and a concentration of CO[Formula: see text] of 570 ppm. The fungal aerial concentration was 1776 spores/m[Formula: see text]. The software MicroorganismPattern identified 32 sampling regions, out of which 11 were positive for microbial contamination. The software PigmentArrangement determined that the blue crystals (ultramarine pigment) had the shortest distances between themselves (29 [Formula: see text]m). Finally, the nanofossils identified enabled us to restrict the age of the material to a biostratigraphic interval ranging from Coniacian to Maastricthian ages. By using a multidisciplinary approach we were able to explore the diptych, suggest a set of minimally invasive perspectives in tropical environments to be used worldwide and obtain key information about the artist's artistic process, materials used along with better understand its state of conservation.

Photocatalytic properties of Cu-containing ZnO nanoparticles and their antifungal activity against agriculture-pathogenic fungus.

In this work, nanoparticles (NPs) of ZnO, ZnO with Cu incorporated at 2 and 30 wt%, and CuO were prepared by the hydrothermal method. X-ray diffraction pattern (DRX) analysis showed that ZnO with high Cu incorporation (30 wt%) generates the formation of a composite oxide (ZnO/CuO), while X-ray photoelectron spectroscopy (XPS) of the Cu (2 wt%) sample indicated that Cu is incorporated as a dopant (ZnO/Cu2%). The samples with Cu incorporated had enhanced visible light absorption. Methyl orange (MO) dye was used to perform photocatalytic tests under UV radiation. The antifungal activity of the NPs was tested against four agricultural phytopathogenic fungi: Neofusicoccum arbuti, Alternaria alternata, Fusarium solani, and Colletotrichum gloeosporioides. The ZnO/Cu2% nanoparticles showed adequate photocatalytic and high antifungal activity in comparison to pure oxides and the composite sample.

Pregnancy loss in beef cattle: A meta-analysis.

Pregnancy loss in beef cattle causes both management and economic challenges to a producer. A meta-analysis was conducted to quantify reproductive failures that occur during fertilization, early embryonic development, and late embryonic/early fetal development periods of gestation in beef cattle. The meta-analysis included more than 56,000 diagnostic records in 159 studies from 48 papers with 12 studies included in fertilization and pre- blastocyst loss analysis (FERT; days 1-7 of gestation), 107 in early embryo (EEM; days 7-32), and 40 in late embryo/early fetal period (LEF; days 32-100) analysis. Although fertilization rates are reportedly high in beef cattle, significant developmental failure occurs within the first 7 days of gestation. Approximately 28.4 % of embryos will not develop past day 7 of gestation with most embryonic losses occurring before day 4. By the conclusion of the first month of gestation, 47.9 % of cows submitted to a single insemination at day 0 will not be pregnant. Overall, LEF between days 32-60 and 100 was 5.8 %. Bos indicus animals had greater (P = 0.001) EEM compared to Bos taurus, but there was no difference (P = 0.39) for the LEF period between subspecies. Primiparous cows had greater EEM (P = 0.002) compared to nulliparous heifers and multiparous cows; and nulliparous heifers had a greater LEF compared to primiparous and multiparous cows (P = 0.048). Collectively, these cumulative findings provide a baseline assessment of pregnancy loss specific to beef cattle.

Aqueous-phase synthesis of nanoparticles of copper/copper oxides and their antifungal effect against Fusarium oxysporum.

Different copper based-materials have been used for controlling some fungal and bacterial pathogens. However, the antifungal activity of the copper-based materials depends on different parameters, such as the crystal phase, synthesis route, and size of the particles. Herein a facile route synthesis method of Cu/CuxO-NPs was achieved through the aqueous phase. The influence of NaBH4 concentration on the phase composition was studied. The synthesized Cu/CuxO-NPs were characterized by X-Ray diffraction (XRD), Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering. Five Cu/CuxO-NPs with different phase composition and nanoparticle size were obtained. The antifungal activity of the synthesized Cu/CuxO-NPs was studied in vitro against Fusarium oxysporum. The results indicate that a high percent of inhibition of radial growth (IGR) was obtained with NPs, which have a higher proportion of Cu2O phase and relatively smaller size particles. Furthermore, hypha morphology, membrane damage and production of reactive oxygen species (ROS) was evaluated with SEM and confocal microscopy.

Impact of the GK-1 adjuvant on peritoneal macrophages gene expression and phagocytosis.

PURPOSE: The synthetic peptide GK-1 potentiates protective immunity elicited by the influenza vaccine in mice. In order to understand its adjuvant properties, this study was designed to determine the impact of GK-1 on gene expression and phagocytosis of peritoneal macrophages (PMa). METHODS: Increased gene expression of chemokines involved in leukocyte recruitment and of pro-inflammatory mediators was detected by microarray analysis of control and GK-1 treated PMa macrophages. The expression profile was subsequently confirmed by Multiplex Immunoassays analysis to measure cytokines levels, flow cytometer to describe M1/M2 surface markers and an assay to evaluate their phagocytic activity. RESULTS: Treatment of PMa with GK-1 results in development to the classically activated M1 functional macrophage subpopulation with increased expression of the CCL3 and CXCLO2 chemokines, IL-6 and TNF-α proinflammatory cytokines with a concomitant increase in the levels of NO, accompanied by the expression of modulatory factors that downregulate the inflammatory phenotype. GK-1 treated PMa significantly increased their phagocytic activity. CONCLUSION: GK-1 classical activated with enhanced phagocitic capacity may underlie in the increased specific immunity induced when concomitant administered with other antigens.

Pollinator Preferences for Floral Volatiles Emitted by Dimorphic Anthers of a Buzz-Pollinated Herb.

Floral scents attract pollinators to plant rewards; in nectarless flowers, pollen grains are the only reward. Thus, pollen not only fertilizes ovules, but also feeds pollinators. This dilemma is resolved by specialization of anthers (i.e., heteranthery): feeding anthers that feed pollinators and pollinating anthers for fertilization. We hypothesized that the chemical composition of floral volatiles differs between the two types of anther and influences pollination preference for feeding anthers. We used Solanum rostratum as a study model because its heterantherous flowers produce a floral scent that suggests a close association with their pollinators. The main aim of this study was to determine the chemical composition of the two types of anther and to investigate how they influence foraging behaviour of pollinators. To characterize this composition, we used solid phase microextraction and hexane extraction followed by gas chromatography-mass spectrometry. We registered 12 volatile compounds in S. rostratum floral extracts, mainly aromatic and sesquiterpene compounds. The proportion of these compounds differed between feeding and pollinating anthers. Some of these compounds were probably emitted by osmophores located in both anther types. Also, we used electroantennography to investigate Melipona solani antennal response to floral volatiles. The M. solani antennae are receptive to the highest floral extract dose tested. Finally, we conducted two behavioural bioassays to test bee attraction for each type of floral extract: a) multiple-choice in a feeding arena using M. solani and b) Y-olfactometer bioassay using Bombus impatiens. Both bee species preferred feeding anthers in bioassays. In conclusion, heteranthery involves chemical differentiation (i.e., proportion of volatiles compounds) in anther specialization that influences bee preference for feeding anthers over pollinating anthers.

Downstream valorization and comprehensive two-dimensional liquid chromatography-based chemical characterization of bioactives from black chokeberries (Aronia melanocarpa) pomace.

In this work, a new alternative for the downstream processing and valorization of black chokeberry pomace (Aronia melanocarpa) which could be potentially coupled to a biorefinery process is proposed. This alternative is based on the application of pressurized liquid extraction (PLE) to the residue obtained after the supercritical fluid extraction of the berry pomace. An experimental design is employed to study and optimize the most relevant extraction conditions in order to attain extracts with high extraction yields, total phenols content and antioxidant activity. Moreover, the PLE extracts were characterized by using a new method based on the application of comprehensive two-dimensional liquid chromatography in order to correlate their activity with their chemical composition. Thanks to the use of this powerful analytical tool, 61 compounds could be separated being possible the tentative identification of different anthocyanins, proanthocyanidins, flavonoids and phenolic acids. By using the optimized PLE approach (using pressurized 46% ethanol in water at 165°C containing 1.8% formic acid), extracts with high total phenols content (236.6mg GAE g-1 extract) and high antioxidant activities (4.35mmol TE g-1 extract and EC50 5.92µgmL-1) could be obtained with high yields (72.5%).

Registry of the Spanish Network for Systemic Sclerosis: Survival, Prognostic Factors, and Causes of Death.

Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan-Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors.

Miocarditis y enfermedad de Still del adulto / Myocarditis and adult onset still disease

No disponible

Anti-ribosomal P antibodies are associated with elevated circulating IFNα and IL-10 levels in systemic lupus erythematosus patients.

OBJECTIVE: The objective of this paper is to analyze the relationship of anti-protein ribosomal P (RibP) antibodies with circulating levels of IFNα, TNFα, IFNγ, IL-17 and IL-10 in SLE. Disease activity and other systemic lupus erythematosus (SLE) features were also analyzed. METHODS: Anti-RibP and other SLE-related antinuclear antibodies (ANA) were determined by fluoro-enzyme immunoassay in the sera of 107 SLE patients. Circulating cytokines were quantified by flow cytometry (IFNα, IL-10 and IL-17) or ELISA (TNFα and IFNγ). RESULTS: Anti-RibP-positive patients (14.9%) displayed significantly higher serum levels of IFNα (p = 0.023) and IL-10 (p = 0.016) than their negative counterparts. This cytokine upregulation was independent of the presence of other ANA even though, in our patient cohort, anti-dsDNA was found to be associated with anti-RibP (OR, CI 95%: 6.03, 1.32-27.93, p = 0.021) and to correlate with IL-10 levels (r = 0.204, p = 0.036). In fact, patients positive for anti-RibP but negative for anti-dsDNA exhibited the highest amounts of both IL-10 and IFN-α that were not related to disease activity since these patients showed lower SLEDAI than patients also positive for anti-dsDNA (p = 0.018). Anti-RibP positivity was also associated with early diagnosis, hypocomplementemia and leukopenia. CONCLUSIONS: Presence of anti-RibP was found to be related to increased serum IFNα and IL-10 levels independently of both antibody status and disease activity.

Influence of the IL17A locus in giant cell arteritis susceptibility.

OBJECTIVE: Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes. METHODS: We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed. RESULTS: In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10(-05)). CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.

Mating system in Mexican populations of the annual herb Solanum rostratum Dunal (Solanaceae).

Traditionally, annual colonising species are expected to have high rates of self-fertilisation, although recent theoretical and empirical studies have shown that cross-fertilisation can be selected for under heterogeneous pollination environments. Solanum rostratum is a self-compatible annual herb that colonises disturbed habitats. Despite the lack of physiological mechanisms to prevent self-fertilisation, pollen transfer between individuals is expected to be favoured because of its complex floral morphology. In previous studies of S. rostratum it has been shown that anther dimorphism within flowers results in precise pollen placement on the pollinator's body, and the presence of mirror-image floral morphs within plants promotes outcrossing in experimental arrays. However, the mating system of natural populations of S. rostratum has never been assessed, and thus whether it is predominantly selfing or outcrossing remains unknown. We hypothesise that floral and inflorescence morphology of S. rostratum should facilitate cross-fertilisation, making it a predominantly outcrossing despite its lack of a self-incompatibility system. To test this hypothesis, we estimated outcrossing rates by genotyping 700 individuals at 13 microsatellite loci, sampled from four populations across a 690-km transect in the species' native range. We found that populations had mean outcrossing rates of 0.70 ± 0.03, with multiple sires contributing to paternity of each progeny array (average effective number of sires = 8.97 ± 0.57). This indicates that natural populations S. rostratum have relatively high levels of outcrossing, probably facilitated by its floral and inflorescence morphology. We speculate that partial selfing in this species may be an unavoidable consequence of displaying multiple flowers at the same time (geitonogamy), as well as the result of self-pollen transfer by illegitimate visitors.