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The aim of this study was to identify single-nucleotide polymorphisms (SNPs) in bone remodeling-related genes associated with disease severity and bone mineral density (BMD) in early arthritis (EA) patients. For this purpose, the genotyping of 552 SNPs located in gene regions of semaphorins 4b, 4d, 4f, DKK1, 2 and 3, sclerostin, OPG, RANK and RANKL was performed using Immunochip from Illumina Inc. in 268 patients from the Princesa Early Arthritis Register Longitudinal (PEARL) study. Measurements of BMD and disease activity were chosen as outcome variables to select SNPs of interest. The relationships of SNPs with the BMD of the forearm, lumbar spine and hip (Hologic-4500 QDR) were analyzed by linear regression adjusted for age, sex, body mass index and presence of anti-citrullinated peptide antibodies (ACPAs). The association of each SNP with activity variables was analyzed by linear regression, logistic regression or ordered logistic regression according to the variable, and multivariate models were adjusted for potentially confounding variables, such as age, sex and presence of ACPAs. These analyses showed that four SNPs located in the genes coding for RANK (TNFRSF11A) and OPG (TNFRSF11B) were significantly associated with clinical variables of severity. SNP rs1805034 located in exon 6 of TNFRSF11A, which causes a non-synonymous (A/V) mutation, showed significant association with BMD and therefore may be considered as a possible biomarker of severity in RA patients. SNPs in the OPG gene showed an association with serum OPG levels and predicted disease activity after two years of follow-up. [ABSTRACT FROM AUTHOR]

This article discusses a study which examined the toxicity of different Photobacterium damselae subspecies damselae strains isolated from cultured diseased fish. The study conducted in vivo and in vitro assays using bacterial cultures and their extracellular products (ECPs). It also made a comparison of the enzymatic activities of the products with their cyto toxicity in fish and mammalian cell lines. The study suggested the relationship of the virulence of the strain with the hemolytic activity or with the production of the toxin damselysin.

Background and Purpose: According to the latest European guidelines, discontinuation of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP MAb) may be considered after 12-18 months of treatment. However, some patients may worsen after discontinuation. In this study, we assessed the response following treatment resumption., Methods: This was a prospective study conducted in 14 Headache Units in Spain. We included patients with response to anti-CGRP MAb with clinical worsening after withdrawal and resumption of treatment. Numbers of monthly migraine days (MMD) and monthly headache days (MHD) were obtained at four time points: before starting anti-CGRP MAb (T-baseline); last month of first treatment period (T-suspension); month of restart due to worsening (T-worsening); and 3 months after resumption (T-reintroduction). The response rate to resumption was calculated. Possible differences among periods were analysed according to MMD and MHD., Results: A total of 360 patients, 82% women, with a median (interquartile range [IQR]) age at migraine onset of 18 (12) years. The median (IQR) MHD at T-baseline was 20 (13) and MMD was 5 (6); at T-suspension, the median (IQR) MHD was 5 (6) and MMD was 4 (5); at T-worsening, the median (IQR) MHD was 16 (13) and MMD was 12 (6); and at T-reintroduction, the median (IQR) MHD was 8 (8) and MHD was 5 (5). In the second period of treatment, a 50% response rate was achieved by 57.4% of patients in MHD and 65.8% in MMD. Multivariate models showed significant differences in MHD between the third month after reintroduction and last month before suspension of first treatment period (p < 0.001)., Conclusion: The results suggest that anti-CGRP MAb therapy is effective after reintroduction. However, 3 months after resumption, one third of the sample reached the same improvement as after the first treatment period., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity., Materials and Methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed., Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 ( HMOX1 ; T/T genotype OR 9.9 p  < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p  = 0.04 and T/T genotype OR 12.9, p  < 0.0001), and rs713400 (eQTL for TMPRSS2 ; C/T + T/T genotype OR 1.86, p  = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 ( CD69 ; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p  = 0.01), rs2660 ( OAS1 ; A/G genotype OR 0.6, p  = 0.08), rs896 ( VIPR1 ; T/T genotype OR 0.4, p  = 0.02) and rs33980500 ( TRAF3IP2 ; C/T + T/T genotype OR 0.3, p  = 0.01) were associated with lower risk of viremia., Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population., Competing Interests: FA, has been consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Aptatargets, Chemo, FAES, Farmalíder, Ferrer, Galenicum, GlaxoSmithKline, Gilead, Italfarmaco, Janssen-Cilag, Kern, Normon, Novartis, Servier, Teva and Zambon. IG-Á reports grants from Instituto de Salud Carlos III, during the course of the study; personal fees from Lilly and Sanofi; personal fees and non-financial support from BMS; personal fees and non-financial support from Abbvie; research support, personal fees and non-financial support from Roche Laboratories; research support from Gebro Pharma; non-financial support from MSD, Pfizer and Novartis, not related to the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Roy-Vallejo, Fernández de Córdoba-Oñate, Delgado-Wicke, Triguero-Martínez, Montes, Carracedo-Rodríguez, Zurita-Cruz, Marcos-Jiménez, Lamana, Galván-Román, Villapalos García, Zubiaur, Ciudad, Rabes, Sanz, Rodríguez, Villa, Rodríguez, Marcos, Hernando, Díaz-Fernández, Abad, de los Santos, Rodríguez Serrano, García-Vicuña, Suárez Fernández, P. Gomariz, Muñoz-Calleja, Fernández-Ruiz, González-Álvaro Cardeñoso and the PREDINMUN-COVID Group.)

Objective: The physiological response of the synovium to acute mechanical stress has not been extensively studied. This response is interesting in terms of the morphological changes it can cause as any such changes should be taken into account during ultrasound examinations. The purpose of this study was to assess the extent of changes in ultrasound images of the synovial joint in the hands of healthy individuals after controlled mechanical stress., Method: We included 110 healthy volunteers on whom we carried out two ultrasound examinations of the non-dominant hand: one at baseline and the other after controlled handgrip exercise at 70% of the maximum voluntary contraction., Results: The synovitis scores at baseline and after exercise were 0.472±0.798 and 0.772±1.162 t(109)=-3.791, respectively; p < 0.001. We observed no tenosynovitis in 88.2% of the participants at baseline, while after exercise the percentage fell to 70.9%; x2 (1, N=110) =10.0851, p = 0.0014., Conclusion: We conclude that synovitis and tenosynovitis are inducible by physical exercise and are detectable on ultrasound. This should be taken into account during ultrasound examinations for suspicion or follow-up of inflammatory rheumatism.

Objectives: To analyse changes over time in the treatment with disease modifying anti-rheumatic drugs and biological therapies prescribed to patients from an early arthritis register and whether these changes had an impact on their outcome., Methods: This was a longitudinal retrospective 2-year study based on data collected in the PEARL study. The population was clustered in three groups depending on year of symptoms onset (2000-2004, 2005-2009, 2010-2014). Intensity of disease-modifying anti-rheumatic drug treatment was calculated and the percentage of patients receiving biological therapy during the first 2-year follow-up was collected. Disease activity and remission at the end of follow-up, as well as radiological progression were the outcomes analysed. Multivariable analyses were fitted to determine which variables including the three period times were associated with the outcomes., Results: A significant increase in treatment intensity was observed in patients with undifferentiated arthritis, getting closer to that prescribed to patients fulfilling the 1987 RA criteria at the last period studied (2010-2014). This finding was associated with a significantly higher percentage of patients in remission and lower progression of the erosion component of the Sharp van der Heijde score., Conclusions: During the last 15 years, the treatment of patients with early arthritis in our hospital has been progressively increased and it has been associated with significantly better outcomes.

The purpose of this study is to determine the rate of bleeding complications in patient's anticoagulated with acenocoumarol according to the international normalized ratio (INR) coagulation index. A cross-sectional study was performed with 901 charts of patients who underwent arthrocentesis or joint infiltration between 2009 and 2013; the charts were grouped on the basis of having an INR higher or lower than 2.0 (268 and 633, respectively). Comparisons were performed in terms of rates of early or late bleeding complications. A 0.37% rate of early bleeding complications (< 24hours) was observed in the group of patients with INR<2 and 0.99% in the group of patients with INR≥2 (P=.47). Only one case of late complication was presented by bleeding between 24 hours and 30 days, in the group of patients with INR≥2. We conclude that oral anticoagulation with acenocoumarol at terapeutical doses does not increase the risk of bleeding joint punctures., (Copyright © 2014 Elsevier España, S.L.U. All rights reserved.)

Understanding plant-virus coevolution requires wild systems in which there is no human manipulation of either host or virus. To develop such a system, we analysed virus infection in six wild populations of Arabidopsis thaliana in Central Spain. The incidence of five virus species with different life-styles was monitored during four years, and this was analysed in relation to the demography of the host populations. Total virus incidence reached 70 per cent, which suggests a role of virus infection in the population structure and dynamics of the host, under the assumption of a host fitness cost caused by the infection. Maximum incidence occurred at early growth stages, and co-infection with different viruses was frequent, two factors often resulting in increased virulence. Experimental infections under controlled conditions with two isolates of the most prevalent viruses, cauliflower mosaic virus and cucumber mosaic virus, showed that there is genetic variation for virus accumulation, although this depended on the interaction between host and virus genotypes. Comparison of Q(ST)-based genetic differentiations between both host populations with F(ST) genetic differentiation based on putatively neutral markers suggests different selection dynamics for resistance against different virus species or genotypes. Together, these results are compatible with a hypothesis of plant-virus coevolution.