Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER)

Objectives: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. Methods: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. Results: Mean age (years) ± S.D. at diagnosis was 14.2 ± 2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ± S.D. was 1.27 ± 1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). Conclusions: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

Objective: To assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. Methods: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet =4 ACR-97 SLE criteria and disease onset <18 years old (jSLE), were retrospectively investigated for SI (defined as either the need for hospitalization with antibacterial therapy for a potentially fatal infection or death caused by the infection). Standardized SI rate was calculated per 100 patient years. Patients with and without SI were compared. Bivariate and multivariate logistic and Cox regression models were built to calculate associated factors to SI and relative risks. Results: A total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and =6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2–4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. Conclusions: The risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy

Direct Determination of miR‐21 in Total RNA Extracted from Breast Cancer Samples Using Magnetosensing Platforms and the p19 Viral Protein as Detector Bioreceptor

A novel magnetobiosensing approach for the rapid, sensitive and selective miR‐21 detection is reported involving the use of a specific RNA probe (antimiR‐21), streptavidin‐magnetic beads (Strep‐MBs), the siRNA Binding Protein p19 as detector bioreceptor, and amperometric detection with the H2O2/hydroquinone (HQ) system at disposable screen‐printed carbon electrodes. The magnetosensor exhibited a dynamic range from 1.4 to 10 nM and a detection limit of 4.2 fmol of synthetic target miR‐21 without any amplification step in 75 min. The usefulness of the approach was evaluated by analyzing total RNA (RNAt) extracted from metastatic breast cancer cell lines, human tissues and breast cytologies.Spanish Ministerio de Ciencia e InnovaciónSpanish Ministerio de Economía y CompetitividadComunidad de MadridEuropean CommissionSpanish Ministry of EducationDepto. de Química AnalíticaFac. de Ciencias QuímicasTRUEpu

Amperometric determination of hazelnut traces by means of Express PCR coupled to magnetic beads assembled on disposable DNA sensing scaffolds

A disposable amperometric sensor using magnetic microcarriers has been designed and implemented to be used in combination with the so called Express PCR to detect the presence of hazelnut traces in foodstuffs through the detection of Cor a 9 allergen coding sequence. The developed procedure involves the use of streptavidin-modified magnetic microbeads (Strep-MBs), specific biotinylated capture and detector probes which hybridize with a specific region of the gene encoding the protein Cor a 9, and appropriate primers for PCR amplification. A 50-mer synthetic target DNA or unmodified 100-bp PCR products were selective captured via sandwich hybridization with capture probe modified MBs and biotinylated signaling probes. The resulting biotinylated hybrids were coupled with a commercial streptavidin–peroxidase (Strep-HRP) conjugate and the final modified MBs were magnetically captured onto a screen-printed carbon electrode to perform amperometric detection using the H2O2/HQ system. A LOD of 0.72�pM was obtained for the synthetic target and the applicability studies demonstrated the possibility to detect the denatured PCR amplified samples obtained using only 20�pg of genomic DNA extracted from hazelnut. RSD values obtained, below 10% in all cases, confirmed the good reliability of extraction, amplification and quantification protocols involved in the developed methodology. The strict specificity of the designed primers and selected probes for hazelnut was demonstrated by performing PCR amplification of genomic DNA extracted from different hazelnut varieties and other species of similar families (pistachio, cashew, walnut and tangerine) and analyzing the resultant amplicons by the developed electrochemical sensor. The reliable and sensitive results achieved indicate that Express PCR in conjunction with an electrochemical DNA sensor, used for the first time in this work, provides a suitable sensitive, specific, and cost-effective method for routine food allergens determinations, particularly useful for resource-limited settings. � 2017 Elsevier B.V

Simultaneous detection of two breast cancer-related miRNAs in tumor tissues using p19-based disposable amperometric magnetobiosensing platforms

Los resultados derivados de esta investigación fueron empleados por la Oficina de Transferencia de Resultados de Investigación de la UCM para la elaboración de una noticia con título: 'Un biosensor magnético detecta el cáncer de mama más agresivo'. Además, este artículo fue resaltado en numerosos sitios web, poniendo de manifiesto su indiscutible relevancia. Algunos de los sitios en los que la noticia fue publicaba se incluyen a continuación: https://www.agenciasinc.es/Noticias/Un-biosensor-magnetico-detecta-el-cancer-de-mama-mas-agresivo https://revistalvr.es/un-biosensor-magnetico-detecta-el-cancer-de-mama-mas-agresivo/ https://www.biotechmagazine.es/noticias-biotech/biosensor-magnetico-frente-al-cancer-de-mama/ https://www.infosalus.com/asistencia/noticia-biosensor-detectar-cancer-mama-mas-agresivo-made-in-spain-20150422183529.html https://www.rtve.es/noticias/20150422/biosensor-magnetico-detecta-cancer-mama-mas-agresivo-solo-15-minutos/1134380.shtml https://www.bolsamania.com/noticias/sanidad/disenan-un-biosensor-magnetico-capaz-de-detectar-precozmente-el-cancer-de-mama-mas-agresivo--699233.html http://biotech-spain.com/en/articles/un-biosensor-magn-tico-detecta-el-c-ncer-de-mama-m-s-agresivo/A novel magnetobiosensing approach for the rapid and simultaneous detection of two breast cancer-related miRs (miR-21 and miR-205) is reported. It involves the use of antimiR-21 and antimiR-205 specific probes, chitin-modified magnetic beads (Chitin-MBs), the p19 viral protein as capture bioreceptor and amperometric detection with the H2O2/hydroquinone (HQ) system at dual screen-printed carbon electrodes (SPdCEs). The use of SPdCEs allows the simultaneous independent amperometric readout for each target miR to be measured. The magnetosensor exhibited sensitive and selective detection with dynamic ranges from 2.0 to 10.0nM and detection limits of 0.6nM (6fmol) for both target miRs without any amplification step in less than 2h. The usefulness of the approach was evaluated by detecting the endogenous levels of both target miRs in total RNA (RNAt) extracted from metastatic breast cancer cell lines and human tissues.Spanish Ministerio de Ciencia e InnovaciónSpanish Ministeri de Economía y CompetitividadComunidad de MadridEuropean CommissionSpanish Ministry of EducationDepto. de Química AnalíticaFac. de Ciencias QuímicasTRUEpu

Correlation of fatigue with other disease related and psychosocial factors in patients with rheumatoid arthritis treated with tocilizumab ACT-AXIS study

To assess the hypothesis if tocilizumab (TCZ) is effective on disease activity, and also its effect in fatigue and other clinical and psychological disease-related factors in patients with rheumatoid arthritis (RA) treated with TCZ.A 24-week, multicenter, prospective, observational study in patients with moderate to severe RA receiving TCZ after failure or intolerance to disease-modifying antirheumatic drugs or tumor necrosis factor-alpha was conducted.Of the 122 patients included, 85 were evaluable for effectiveness (85% female, 51.9 +/- 12.5 years, disease duration 8.7 +/- 7.4 years). Mean change in C-reactive protein level from baseline to week 12 was -11.2 +/- 4.0 (P < .001). Mean Disease Activity Index score (DAS28) decreased from 5.5 +/- 1.0 at baseline to 2.7 +/- 1.3 (P < .001) at week 24. Mean change in Functional Assessment of Chronic Illness Therapy score was -5.4 +/- 11.2 points at week 24. Multiple regression analysis showed that the improvement in DAS28, sleep, and depression explained 56% and 47% of fatigue variance at week 12 and 24, respectively.Tocilizumab is effective in reducing disease activity and results in a clinically significant improvement in fatigue, pain, swollen joint count, morning stiffness, sleepiness, depression, and DAS28; the last 3 were specifically identified as factors explaining fatigue variance with the use of TCZ in RA patients

11PS04 is a new chemical entity identified by microRNA-based biosensing with promising therapeutic potential against cancer stem cells

13 p.-5 fig-1 tab.Phenotypic drug discovery must take advantage of the large amount of clinical data currently available. In this sense, the impact of microRNAs (miRs) on human disease and clinical therapeutic responses is becoming increasingly well documented. Accordingly, it might be possible to use miR-based signatures as phenotypic read-outs of pathological status, for example in cancer. Here, we propose to use the information accumulating regarding the biology of miRs from clinical research in the preclinical arena, adapting it to the use of miR biosensors in the earliest steps of drug screening. Thus, we have used an amperometric dual magnetosensor capable of monitoring a miR-21/miR-205 signature to screen for new drugs that restore these miRs to non-tumorigenic levels in cell models of breast cancer and glioblastoma. In this way we have been able to identify a new chemical entity, 11PS04 ((3aR,7aS)-2-(3-propoxyphenyl)-7,7a-dihydro-3aH-pyrano[3,4-d]oxazol-6(4H)-one), the therapeutic potential of which was suggested in mechanistic assays of disease models, including 3D cell culture (oncospheres) and xenografts. These assays highlighted the potential of this compound to attack cancer stem cells, reducing the growth of breast and glioblastoma tumors in vivo. These data demonstrate the enhanced chain of translatability of this strategy, opening up new perspectives for drug-discovery pipelines and highlighting the potential of miR-based electro-analytical sensors as efficient tools in modern drug discovery.This work was supported by grants CTQ2014-52213-R, CTQ2015-64402-C2-1-R and CTQ2015-64402-C2-2-R (Spanish Ministry of Economy and Competitiveness, MINECO), CM S2011/BMED-2353 (Comunidad de Madrid), and FEDER Funds.Peer reviewe

Fitness Trends from around the Globe

Apply It! From this article, the reader should be able to do the following: • Identify top 20 fitness trends for Australia, Brazil, China, Europe, Mexico, Spain, and the United States • Recognize individual and unique fitness trends represented within Australia, Brazil, China, Europe, Mexico, Spain, and the United States © Lippincott Williams &Wilkins