Immunologic Storm Simulating Systemic Lupus Erythematosus Following Parvovirus B19 Infection

Background: The appearance of symptoms compatible with systemic autoimmune diseases has been described in relation to several viral infections like HIV, cytomegalovirus and especially PVB19, depending on the evolution of the immunological condition of the host and their age. We present a young immunocompetent male patient, with clinical manifestations simulating systemic lupus erythematosus (SLE) with important activation of cytokines. Methods: For quantification of the different cytokines in plasma, a commercially available multiplex bead immunoassay, based on the Luminex platform (Cat # HSCYTO-60SK-08, Milliplex® MAP High Sensitivity, Millipore), was used according to the manufacturer’s instructions. All samples were run in duplicate and the data (mean fluorescence intensity) were analyzed using a Luminex reader. The mean concentration was calculated using a standard curve. Results: The clinical evolution was favourable without the need for any specific treatment, showing complete recovery after two months. Whilst the symptoms and viral charge were disappearing, the anti-DNA continued to increase and we demonstrate important activation of IL-10, IL-6 and TNFα cytokines as a result of a hyperstimulating response by an immunocompetent hyperfunctional system, which persists after clinical improvement. We should emphasize the behaviour of two cytokines: IL-12p70 and IL-2, which showed opposite tendencies. Conclusions: Viral infections, especially PVB19, can produce or simulate several autoimmune diseases as a hyperstimulation response from an immunocompetent hyperfunctional system. Consequently, a persistent increase of autoantobodies and important activation of cytokines, even after clinical improvement and seroconversion, can be demonstrated

Assessment of the influence of the elastic properties of rail vehicle suspensions on safety, ride quality and track fatigue

A sensitivity analysis has been performed to assess the influence of the elastic properties of railway vehicle suspensions on the vehicle dynamic behaviour. To do this, 144 dynamic simulations were performed modifying, one at a time, the stiffness and damping coefficients, of the primary and secondary suspensions. Three values were assigned to each parameter, corresponding to the percentiles 10, 50 and 90 of a data set stored in a database of railway vehicles.After processing the results of these simulations, the analyzed parameters were sorted by increasing influence. It was also found which of these parameters could be estimated with a lesser degree of accuracy in future simulations without appreciably affecting the simulation results. In general terms, it was concluded that the highest influences were found for the longitudinal stiffness and the lateral stiffness of the primary suspension, and the lowest influences for the vertical stiffness and the vertical damping of the primary suspension, with the parameters of the secondary suspension showing intermediate influences between them

Anti-inflammatory and regenerative effects of MKARE® Eggshell Membrane: An in vitro osteoarthritis model and placebo-controlled clinical study

[EN]MKARE®, a 100% natural ingredient derived from fresh eggshell membrane (ESM), has a rich composition in bioactive compounds like collagen, hyaluronic acid, and elastin. These components are beneficial for managing osteoarthritis (OA) due to their anti-inflammatory and regenerative properties. Highlighting the significance of freshness, our research has shown that the effectiveness of MKARE® is higher than that of other commercial products based on ESM that have been stored for several days at room temperature, losing their bioactive compounds. This study explores the MKARE® anti-inflammatory capacity through an in vitro and clinical analyses, demonstrating its ability to alleviate OA symptoms and improve joint health. This underscores the crucial role of freshness in optimizing the therapeutic benefits.S

El Porfiriato

1 archivo PDF (229 páginas)Debate sobre el Porfiriato desde una perspectiva crítica y analítica de la historia y el diseño para mostrar lo más actual de la reflexión histórica y que, al mismo tiempo, sea útil para la generación de nuevos conocimientos, propósito fundamental para la formación de futuras generaciones de estudiosos e investigadores sobre la historia nacional y la historia del diseño

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias. A Randomized Trial.

Background: The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. Objective: To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. Design: Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136) Setting: Spanish colorectal cancer screening program. Participants: 3213 persons with a positive fecal immunochemical test. Intervention: Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. Measurements: Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. Results: The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. Limitations: The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. Conclusion: Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. Primary Funding Source: Medtronic

Tradición y vanguardia: utilización de recursos electrónicos para la enseñanza de la poesía anglo-norteamericana

Memoria ID12-0020. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2012-2013

Ensayo de una tipología de las cuencas mediterráneas del proyecto GUADALMED siguiendo las directrices de la Directiva Marco del Agua

RESUMEN Utilizando la propuesta de tipología de ríos de la Directiva Marco del Agua en su anexo 2 se realiza un ensayo tipológico de los puntos de muestreo del proyecto GUADALMED. Según el sistema A, se presentan 16 ecotipos, lo que se juzga poco adecuado para la gestión de los mismos y sin una base ecológica que lo justifique. De acuerdo con la selección previa hecha por los miembros del grupo GUADALMED para 5 de estos ecotipos no habría estaciones de referencia. Con algunas variables medidas en los puntos de muestreo y otras de tipo geológico e hidromorfológico, se realiza un ensayo tipológico usando el sistema B. El método implica un análisis de la correlación entre variables, un cluster de las estaciones utilizando el método K-means y un análisis discriminante de cuáles son las variables que distinguen estos grupos. El estudio da como resultado la caracterización de 6 ecotipos que sin embargo, a juicio de los miembros del proyecto GUADALMED, no recogen la variedad de tipos de ríos mediterráneos. Valorando cualitativamente parámetros no introducidos (por falta de datos) en el análisis K-means, se propone una tipología provisional en 9 grupos. Un análisis de las comunidades de macroinvertebrados (a nivel taxonómico de familia) revela un grado importante de coherencia entre las familias asociadas a cada tipo y sus preferencias ecológicas conocidas. ABSTRACT A preliminary analysis was conducted of the river types in the GUADALMED project using the river typology proposed in the Water Framework Directive (WFD) in its annex 2. Using System A, 16 different types were found, a number too high for water management purposes and such typology lacks a supportive ecological basis. For 5 of these 16 ecotypes, no reference stations exist. Reference stations were selected a priori in project GUADALMED for each of the 12 basins sampled. An ecotypological analysis was performed using System B of the WFD using several variables measured during the study, and other variables obtained from maps or data bases (e.g., geology). The method included the analysis of the calibration between variables, the clustering of stations by the K-means method and a discriminant analysis. The latter revealed which factors were distinctive of each group. Six ecotypes were established for the GUADALMED study sites. These, however, do not include all the mediterranean-type streams of the region. This is mainly due to the absence in the data base of some important features of streams in the data base such as temporality or the dependence of flow on the presence of karstic aquifers, attribute

Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response

BackgroundEpstein–Barr virus (EBV) and human herpesvirus 6 (HHV-6) have been associated with multiple sclerosis (MS). Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing forms of MS. In the preclinical Theiler’s murine encephalitis virus model of MS, the drug demonstrated an increased rate of viral clearance versus the vehicle placebo. Furthermore, teriflunomide inhibits lytic EBV infection in vitro.Objective1. To evaluate the humoral response against EBV and HHV-6 prior to teriflunomide treatment and 6 months later. 2. To correlate the variation in the humoral response against EBV and HHV-6 with the clinical and radiological response after 24 months of treatment with teriflunomide. 3. To analyze the utility of different demographic, clinical, radiological, and environmental data to identify early biomarkers of response to teriflunomide.MethodsA total of 101 MS patients (62 women; mean age: 43.4 years) with one serum prior to teriflunomide onset and another serum sample 6 months later were recruited. A total of 80 had been treated for at least 24 months, 13 had stopped teriflunomide before 24 months, and 8 were currently under teriflunomide therapy but with less than 24 months of follow-up. We analyzed the levels of the viral antibodies titers abovementioned in serum samples with ELISA commercial kits, and the levels of serum neurofilament light chain (Nf-L).ResultsAntiviral antibody titers decreased for EBNA-1 IgG (74.3%), VCA IgG (69%), HHV-6 IgG (60.4%), and HHV-6 IgM (73.3%) after 6 months of teriflunomide. VCA IgG titers at baseline correlated with Nf-L levels measured at the same time (r = 0.221; p = 0.028) and 6 months later (r = 0.240; p = 0.017). We found that higher EBNA-1 titers (p = 0.001) and a higher age (p = 0.04) at baseline were associated with NEDA-3 conditions. Thus, 77.8% of patients with EBNA-1 >23.0 AU and >42.8 years (P50 values) were NEDA-3.ConclusionTreatment with teriflunomide was associated with a reduction of the levels of IgG antibody titers against EBV and HHV-6. Furthermore, higher EBNA-1 IgG titers prior to teriflunomide initiation were associated with a better clinical response

Update of the list of QPS‐recommended biological agents intentionally added to food or feed as notified to EFSA 15: suitability of taxonomic units notified to EFSA until September 2021

[EN]The qualified presumption of safety (QPS) approach was developed to provide a generic pre-evaluation of the safety of biological agents. The QPS approach is based on an assessment of published data for each agent, with respect to its taxonomic identity, the body of relevant knowledge and safety concerns. Safety concerns are, where possible, confirmed at the species/strain or product level and reflected by ‘qualifications’. The QPS list was updated in relation to the revised taxonomy of the genus Bacillus, to synonyms of yeast species and for the qualifications ‘absence of resistance to antimycotics’ and ‘only for production purposes’. Lactobacillus cellobiosus has been reclassified as Limosilactobacillus fermentum. In the period covered by this statement, no new information was found that would change the status of previously recommended QPS taxonomic units (TU)s. Of the 70 microorganisms notified to EFSA, 64 were not evaluated: 11 filamentous fungi, one oomycete, one Clostridium butyricum, one Enterococcus faecium, five Escherichia coli, one Streptomyces sp., one Bacillus nakamurai and 43 TUs that already had a QPS status. Six notifications, corresponding to six TUs were evaluated: Paenibacillus lentus was reassessed because an update was requested for the current mandate. Enterococcus lactis synonym Enterococcus xinjiangensis, Aurantiochytrium mangrovei synonym Schizochytrium mangrovei, Schizochytrium aggregatum, Chlamydomonas reinhardtii synonym Chlamydomonas smithii and Haematococcus lacustris synonym Haematococcus pluvialis were assessed for the first time. The following TUs were not recommended for QPS status: P. lentus due to a limited body of knowledge, E. lactis synonym E. xinjiangensis due to potential safety concerns, A. mangrovei synonym S. mangrovei, S. aggregatum and C. reinhardtii synonym C. smithii, due to lack of a body of knowledge on its occurrence in the food and feed chain. H. lacustris synonym H. pluvialis is recommended for QPS status with the qualification ‘for production purposes only’.S

Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care : a pragmatic, randomised, non-inferiority clinical trial (OB12)

The trial was financed by Ministerio de Sanidad y Consumo Español through their call for independent clinical research, Orden Ministerial SAS/2377, 2010 (EC10-115, EC10-116, EC10-117, EC10-119, EC10-122); CAIBER—Spanish Clinical Research Network, Instituto de Salud Carlos III (ISCIII) (CAI08/010044); and Gerencia Asistencial de Atención Primaria de Madrid. This study is also supported by the Spanish Clinical Research Network (SCReN), funded by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, project number PT13/0002/0007, within the National Research Program I+D+I 2013-2016 and co-funded with European Union ERDF funds (European Regional Development Fund). This project received a grant for the translation and publication of this article from the Foundation for Biomedical Research and Innovation in Primary Care (FIIBAP) Call 2017 for grants to promote research programs.Objectives To compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency. Design Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain). Participants 283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm. Interventions The IM arm received 1 mg VB12 on alternate days in weeks 1–2, 1 mg/week in weeks 3–8 and 1 mg/month in weeks 9–52. The oral arm received 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. Main outcomes Serum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction. Results The follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%; the differences in this percentage between the oral and IM arm were −0.7% (133 out of 135 vs 129 out of 130; 95% CI: −3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: −1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were −6.3% (103 out of 112 vs 115 out of 117; 95% CI: −11.9 to −0.1; p=0.025) and −6.8% (103 out of 140 vs 115 out of 143; 95% CI: −16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>−10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route. Conclusions Oral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low.Publisher PDFPeer reviewe