Cytokine polymorphisms influence treatment outcomes in SLE patients treated with antimalarial drugs

Antimalarial agents have been widely used as disease-modifying antirheumatic drugs in the treatment of systemic lupus erythematosus (SLE) and other rheumatological diseases, although their mechanism of action has not yet been fully defined. It is known, however, that effective response to treatment is variable among patients. Thus, the identification of genetic predictors of treatment response would provide valuable information for therapeutic intervention. The aim of the present study was to analyze the effect of antimalarial treatment on tumor necrosis factor (TNF)α serum levels and evaluate the possible influence of TNFα and IL-10 functional genetic polymorphisms on the response to antimalarial drugs. To this end, TNFα serum levels were quantified in 171 SLE patients and 215 healthy controls by ELISA techniques and polymorphisms at positions -1,082 and -308 of the IL-10 and TNFα gene promoterswere determined by PCR amplification followed by hybridization with fluorescent-labeled allele-specific probes in 192 SLE patients and 343 matched controls. Data were related to clinical features and treatment at the time of sampling and during the course of the disease. Results showed a significantly higher amount of serum TNFα in the entire SLE population compared with controls. However, TNFα serum levels correlated negatively with the use of antimalarial treatment during at least three months before sampling. Patients under single or combined treatment with these drugs had TNFα serum levels similar to healthy controls, whereas untreated patients and those under corticosteroid or immunosuppressive therapies had increased amounts of this cytokine. This suggests, however, that antimalarial-mediated inhibition of TNFα was only significant in patients who were genetically high TNFα or low IL-10 producers. In addition, evaluation of SLE patients administered antimalarial drugs for three or more years who did not require any other specific SLE treatment indicates that patients with the combined genotype low IL-10/high TNFα are the best responders to antimalarial therapy, developing mild disease with a good course under this treatment. In conclusion, we proposed that an antimalarial-mediated downregulation of TNFα levels in SLE patients is influenced by polymorphisms at IL-10 and TNFα promoters. Our results may thus find important clinical application through the identification of patients who are the most likely to benefit from antimalarial therapy

Escuelas secundarias parroquiales en barrios precarios: Segregación residencial e inclusión educativa

Se presentan los resultados de un estudio de caso en dos escuelas parroquiales de barrios precarios de Buenos Aires cuyo objetivo fue analizar la interrelación entre segregación residencial, segmentación educativa e inclusión socioeducativa. Los datos se relevaron a través de un cuestionario sobre el perfil sociodemográfico y otro sobre el axiológico de los alumnos; se recurrió asimismo a entrevistas a directivos y a los proyectos educativos de ambas escuelas. El análisis de los datos evidenció vulnerabilidad socioeconómica de los alumnos agravada por habitar en espacios segregados de la ciudad y la participación en circuitos escolares de baja calidad. Se muestra asimismo que las visiones, motivaciones y propuestas educativas de ambas escuelas constituyen un capital cultural muy relevante para los estudiantes quienes, según los datos del cuestionario axiológico, manifiestan dos dimensiones descendidas: reconocimiento social y liderazgo. Se concluye en la necesidad de un ajuste curricular situado y focalizado en los alumnos

Caracterización de capacidades nacionales de respuesta a emergencias en sanidad animal y protección vegetal

Esta guía pretende poner a disposición de los países un método que les ayude a determinar su grado de preparación en caso de una emergencia sanitaria o fitosanitaria. Los resultados pueden ser utilizados para identificar las fortalezas y debilidades, definir qué es necesario mejorar áreas, seguimiento de los logros, modernizar los procedimientos y preparar proyectos para el fortalecimiento institucional.This guide aims to provide countries with a method to help them determine their level of preparedness in the event of a sanitary or phytosanitary emergency. The results can be used to identify strengths and weaknesses, define what areas need to be improved, monitor achievements, modernize procedures and prepare projects for institutional strengthening

Manual para la utilización y conservación de variedades locales de cultivo, frutales y leñosas

Consejería de Agricultura y Pesca de la Junta de Andalucía 92162/

Dynamic profiles and predictive values of some biochemical and haematological quantities in COVID-19 inpatients

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in some hospitalized patients has shown some important alterations in laboratory tests. The aim of this study was to establish the most relevant quantities associated with the worst prognosis related to COVID-19. Materials and methods: This was a descriptive, longitudinal, observational and retrospective study, in a cohort of 845 adult inpatients from Bellvitge University Hospital (L'Hospitalet de Llobregat, Barcelona, Spain). A multivariate regression analysis was carried out in demographic, clinical and laboratory data, comparing survivors (SURV) and non-survivors (no-SURV). A receiver operating characteristic analysis was also carried out to establish the cut-off point for poor prognostic with better specificity and sensibility. Dynamic changes in clinical laboratory measurements were tracked from day 1 to day 28 after the onset of symptoms. Results: During their hospital stay, 18% of the patients died. Age, kidney disease, creatinine (CREA), lactate-dehydrogenase (LD), C-reactive-protein (CRP) and lymphocyte (LYM) concentration showed the strongest independent associations with the risk of death in the multivariate regression analysis. Established cut-off values for poor prognosis for CREA, LD, CRP and LYM concentrations were 75.0 mu mol/L, 320 U/L, 80.9 mg/L and 0.69 x10(9)/L. Dynamic profile of laboratory findings, were in agreement with the consequences of organ damage and tissue destruction. Conclusions: Age, kidney disease, CREA, LD, CRP and LYM concentrations in COVID-19 patients from the southern region of Catalonia provide important information for their prognosis. Measurement of LD has demonstrated to be very good indicator of poor prognosis at initial evaluation because of its stability over time

Importance of Timely Treatment Initiation in Infantile-Onset Pompe Disease, a Single-Centre Experience

Abstract Classic infantile Pompe disease (IPD) is a rare lysosomal storage disorder characterized by severe hypertrophic cardiomyopathy and profound muscle weakness. Without treatment, death occurs within the first 2 years of life. Although enzyme replacement therapy (ERT) with alglucosidase alfa has improved survival, treatment outcome is not good in many cases and is largely dependent on age at initiation. The objective of the study was (a) to analyse the different stages in the diagnosis and specific treatment initiation procedure in IPD patients, and (b) to compare clinical and biochemical outcomes depending on age at ERT initiation (<1 month of age vs. <3 months of age). Here, we show satisfactory clinical and biochemical outcomes in two IPD patients after early treatment initiation before 3 months of life with immunomodulatory therapy in the ERT-naïve setting, with a high ERT dose from the beginning. Despite the overall good evolution, the patient who initiated treatment <1 month of life presented even better outcomes than the patient who started treatment <3 months of life, with an earlier normalization of hypertrophic cardiomyopathy, along with CK normalization, highlighting the importance of early treatment initiation in this progressive disease before irreversible muscle damage has occurred.This work was partially funded by the Basque Department of Education (IT1281-19)

MixInYeast: A Multicenter Study on Mixed Yeast Infections

Invasive candidiasis remains one of the most prevalent systemic mycoses, and several studies have documented the presence of mixed yeast (MY) infections. Here, we describe the epidemiology, clinical, and microbiological characteristics of MY infections causing invasive candidiasis in a multicenter prospective study. Thirty-four centers from 14 countries participated. Samples were collected in each center between April to September 2018, and they were sent to a reference center to confirm identification by sequencing methods and to perform antifungal susceptibility testing, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A total of 6895 yeast cultures were identified and MY occurred in 150 cases (2.2%). Europe accounted for the highest number of centers, with an overall MY rate of 4.2% (118 out of 2840 yeast cultures). Of 122 MY cases, the most frequent combinations were Candida albicans/C. glabrata (42, 34.4%), C. albicans/C. parapsilosis (17, 14%), and C. glabrata/C. tropicalis (8, 6.5%). All Candida isolates were susceptible to amphotericin B, 6.4% were fluconazole-resistant, and two isolates (1.6%) were echinocandin-resistant. Accurate identification of the species involved in MY infections is essential to guide treatment decisions

ViDa1: The Development and Validation of a New Questionnaire for Measuring Health-Related Quality of Life in Patients with Type 1 Diabetes

IGTPAltres ajuts: Funding was provided by the Canarian Agency for Research,Innovation and Information Society (ACIISI) (DA predoctoralfellowship TESIS20120050) and the V Guido Ruffino Grantfor Research in Therapeutic Education for Diabetes (SpanishDiabetes Society 2015)This study describes the development of a new questionnaire to measure health-related quality of life (HRQoL) in patients with type 1 diabetes (the ViDa1 questionnaire) and provides information on its psychometric properties. For its development, open interviews with patients took place and topics relevant to patients' HRQoL were identified and items were generated. Qualitative analysis of items, expert review, and refinement of the questionnaire followed. A pilot study (N = 150) was conducted to explore the underlying structure of the 40-item ViDa1 questionnaire. A Principal Component Analysis (PCA) was performed and six of the items that did not load on any of the factors were eliminated. The results supported a four-dimensional structure for ViDa1, the dimensions being Interference of diabetes in everyday life, Self-care, Well-being, and Worry about the disease. Subsequently, the PCA was repeated in a larger sample (N = 578) with the reduced 34-item version of the questionnaire, and a Confirmatory Factor Analysis (CFA) was performed (N = 428). Overall fit indices obtained presented adequate values which supported the four-factor model initially proposed [(2(df =554) = 2601.93) (p < 0.001); Root Mean Square Error of Approximation = 0.060 (CI = 0.056 −0.064)]. As regards reliability, the four dimensions of the ViDa1 demonstrated good internal consistency, with Cronbach's alphas ranging between 0.71 and 0.86. Evidence of convergent-discriminant validity in the form of high correlations with another specific HRQoL questionnaire for diabetes and low correlations with other constructs such as self-efficacy, anxiety, and depression were presented. The ViDa1 also discriminated between different aspects of clinical interest such as type of insulin treatment, presence of chronic complications, and glycemic control, temporal stability, and sensitivity to change after an intervention. In conclusion, the ViDa1 questionnaire presents adequate psychometric properties and may represent a good alternative for the evaluation of HRQoL in type 1 diabetes