Objective
To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)–associated uveitis.
Methods
We conducted a multicenter study of patients with ...JIA‐associated uveitis that was refractory to conventional immunosuppressive drugs and anti–tumor necrosis factor (anti‐TNF) agents.
Results
We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 range 1–5), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 μm to 259.1 ± 39.5 μm after 6 months of TCZ (P = 0.012). The best‐corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow‐up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient.
Conclusion
TCZ appears to be a useful therapy for severe refractory JIA‐associated uveitis.
Nanoscale heterostructures of covalent intermetallics should give birth to a wide range of interface-driven physical and chemical properties. Such a level of design however remains unattainable for ...most of these compounds, due to the difficulty to reach a crystalline order of covalent bonds at the moderate temperatures required for colloidal chemistry. Herein, we design heterostructured cobalt silicide nanoparticles to trigger magnetic and catalytic properties in silicon-based materials. Our strategy consists in controlling the diffusion of cobalt atoms into silicon nanoparticles, by reacting these particles in molten salts. By adjusting the temperature, we tune the conversion of the initial silicon particles toward homogeneous CoSi nanoparticles and core–shell nanoparticles made of a CoSi shell and a silicon-rich core. The increased interface-to-volume ratio of the CoSi component in the core–shell particles yields distinct properties compared to the bulk and homogeneous nanoparticles. First, the core–shell particles exhibit increased ferromagnetism, despite the bulk diamagnetic properties of cobalt monosilicide. Second, the core–shell nanoparticles act as efficient precatalysts for alkaline water oxidation, where the nanostructure is converted in situ into a layered cobalt silicon oxide/(oxy)hydroxide with high and stable oxygen evolution reaction (OER) electrocatalytic activity. This work demonstrates a route to design heterostructured nanocrystals of covalent intermetallic compounds and shows that these new structures exhibit very rich, yet poorly explored, interface-based physical properties and reactivity.
Objective To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants.Design Prospective cohort study with estimates of ...relative risk adjusted for sex, age, years of university education, total energy intake, body mass index, physical activity, sedentary habits, smoking, family history of diabetes, and personal history of hypertension.Setting Spanish university department.Participants 13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years.Main outcome measures Dietary habits assessed at baseline with a validated 136 item food frequency questionnaire and scored on a nine point index. New cases of diabetes confirmed through medical reports and an additional detailed questionnaire posted to those who self reported a new diagnosis of diabetes by a doctor during follow-up. Confirmed cases of type 2 diabetes.Results Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes. The incidence rate ratios adjusted for sex and age were 0.41 (95% confidence interval 0.19 to 0.87) for those with moderate adherence (score 3-6) and 0.17 (0.04 to 0.75) for those with the highest adherence (score 7-9) compared with those with low adherence (score <3). In the fully adjusted analyses the results were similar. A two point increase in the score was associated with a 35% relative reduction in the risk of diabetes (incidence rate ratio 0.65, 0.44 to 0.95), with a significant inverse linear trend (P=0.04) in the multivariate analysis.Conclusion Adherence to a Mediterranean diet is associated with a reduced risk of diabetes.
• The tree of life is highly reticulate, with the history of population divergence emerging from populations of gene phylogenies that reflect histories of introgression, lineage sorting and ...divergence. In this study, we investigate global patterns of oak diversity and test the hypothesis that there are regions of the oak genome that are broadly informative about phylogeny.
• We utilize fossil data and restriction-site associated DNA sequencing (RAD-seq) for 632 individuals representing nearly 250 Quercus species to infer a time-calibrated phylogeny of the world’s oaks. We use a reversible-jump Markov chain Monte Carlo method to reconstruct shifts in lineage diversification rates, accounting for among-clade sampling biases. We then map the > 20 000 RAD-seq loci back to an annotated oak genome and investigate genomic distribution of introgression and phylogenetic support across the phylogeny.
• Oak lineages have diversified among geographic regions, followed by ecological divergence within regions, in the Americas and Eurasia. Roughly 60% of oak diversity traces back to four clades that experienced increases in net diversification, probably in response to climatic transitions or ecological opportunity.
• The strong support for the phylogeny contrasts with high genomic heterogeneity in phylogenetic signal and introgression. Oaks are phylogenomic mosaics, and their diversity may in fact depend on the gene flow that shapes the oak genome.
To assess the possible interactions between the dorsolateral periaqueductal gray matter (dlPAG) and the different domains of the nucleus ambiguus (nA), we have examined the pattern of double-staining ...c-Fos/FoxP2 protein immunoreactivity (c-Fos-ir/FoxP2-ir) and tyrosine hydroxylase (TH) throughout the rostrocaudal extent of nA in spontaneously breathing anaesthetised male Sprague–Dawley rats during dlPAG electrical stimulation. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in the somatas of the loose (
p
< 0.05) and compact formation (
p
< 0.01) within the nA and confirmed the expression of FoxP2 bilaterally in all the domains within the nA. A second group of experiments was made to examine the importance of the dlPAG in modulating the laryngeal response evoked after electrical or chemical (glutamate) dlPAG stimulations. Both electrical and chemical stimulations evoked a significant decrease in laryngeal resistance (subglottal pressure) (
p
< 0.001) accompanied with an increase in respiratory rate together with a pressor and tachycardic response. The results of our study contribute to new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity.
Bone Regeneration represents a clinical need, related to bone defects such as congenital anomalies, trauma with bone loss, and/or some pathologies such as cysts or tumors This is why a polymeric ...biomaterial that mimics the osteogenic composition and structure represents a high potential to face this problem. The method of obtaining these materials was first to prepare a stabilized hydrogel by means of physical bonds and then to make use of the lyophilization technique to obtain the 3D porous scaffolds with temperature conditions of −58 °C and pressure of 1 Pa for 16 h. The physicochemical and bioactive properties of the scaffolds were studied. FTIR and TGA results confirm the presence of the initial components in the 3d matrix of the scaffold. The scaffolds exhibited a morphology with pore size and interconnectivity that promote good cell viability. Together, the cell viability and proliferation test, Alamar Blue
TM
and the differentiation test: alizarin staining, showed the ability of physically stabilized scaffolds to proliferate and differentiate swine dental pulp stem cell (DPSCs) followed by mineralization. Therefore, the Cs-PCL-PVA-HA scaffold stabilized by physical bonds has characteristics that suggest great utility for future complementary in vitro tests and in vivo studies on bone defects. Likewise, this biomaterial was enhanced with the addition of HA, providing a scaffold with osteoconductive properties necessary for good regeneration of bone tissue.
Graphical abstract
Inflammatory bowel diseases (IBDs) are associated with uncontrolled innate and adaptive immunity against normal constituents, including commensal bacteria and microbial products. Mesenchymal stem ...cells (MSCs) suppress effector T cell responses and have beneficial effects in various immune disorders. This work investigates the therapeutic effects of human adipose-derived MSCs (hASCs) in various models of IBD and sepsis.
Acute and chronic colitis was induced in mice with dextran sulfate sodium. Sepsis was induced by caecal ligation and puncture or by endotoxin injection. Colitic and septic mice were treated intraperitoneally with hASCs or murine ASCs, and diverse disease clinical signs and mortality were determined. The levels of various inflammatory cytokines and chemokines, T helper 1(Th1)-type response and generation of regulatory T cells (Treg) were determined in affected organs.
Systemic infusion of ASCs significantly ameliorated the clinical and histopathological severity of colitis, abrogating weight loss, diarrhoea and inflammation, and increasing survival. The therapeutic effect was associated with downregulation of the Th1-driven inflammatory responses. ASCs decreased a wide panel of inflammatory cytokines and chemokines and increased interleukin 10 (IL10), acting on macrophages. hASCs also impaired Th1 cell activation in both colonic mucosa and draining lymph nodes. The induction of IL10-secreting Treg was partially involved in the therapeutic effect of hASCs. Moreover, ASCs protected from severe sepsis by reducing the infiltration of inflammatory cells in various target organs and by downregulating the production of various inflammatory mediators.
hASCs emerge as key regulators of immune/inflammatory responses in vivo and as attractive candidates for cell-based treatments for IBD and sepsis.
In recent years, the variety and volume of data acquired by modern analytical instruments in order to conduct a better authentication of food has dramatically increased. Several pattern recognition ...tools have been developed to deal with the large volume and complexity of available trial data. The most widely used methods are principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), soft independent modelling by class analogy (SIMCA), k-nearest neighbours (kNN), parallel factor analysis (PARAFAC), and multivariate curve resolution-alternating least squares (MCR-ALS). Nevertheless, there are alternative data treatment methods, such as support vector machine (SVM), classification and regression tree (CART) and random forest (RF), that show a great potential and more advantages compared to conventional ones. In this paper, we explain the background of these methods and review and discuss the reported studies in which these three methods have been applied in the area of food quality and authenticity. In addition, we clarify the technical terminology used in this particular area of research.
Display omitted
•Alternative machine learning methods to perform the authentication of foods are described•Chemometric multivariate tools are similar to data mining methods•The terms used in different work areas are discussed and defined•RF and SVM methods provide better results than the traditional chemometrics in the food quality field
Biochar constitutes a promising support material for the formulation of controlled-release fertilizers (CRFs). In this study we evaluated the effect of different polymeric materials as encapsulating ...agents to control nitrogen (N) leaching from biochar based CRFs. Nitrogen impregnation onto biochar was performed in a batch reactor using urea as N source. The resulting product was encapsulated by using sodium alginate (SA), cellulose acetate (CA) and ethyl cellulose (EC). Leaching potential was studied in planted and unplanted soil columns, monitoring nitrate, nitrite, ammonium and urea concentrations. After 90days, plants were removed from the soil columns and plant yield was evaluated. It was observed that the ammonium concentration in leachates presented a maximum concentration for all treatments at day 22. The highest concentration of N in the leachates was the nitrate form. The crop yield was negatively affected by all developed CRFs using biochar compared with the traditional fertilization.
•Polymeric coating materials retard N leaching from biochar based fertilizers.•N-species concentration in leachates depends on polymeric materials nature.•Biochar did influence N release in the tested fertilizers.
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