Influence of Atg5 Mutation in SLE Depends on Functional IL-10 Genotype

Increasing evidence supports the involvement of autophagy in the etiopathology of autoimmune diseases. Despite the identification of autophagy-related protein (Atg)-5 as one of the susceptibility loci in systemic Lupus erythematosus (SLE), the consequences of the carriage of these mutations for patients remain unclear. The present work analyzed the association of Atg5 rs573775 single nucleotide polymorphism (SNP) with SLE susceptibility, IFNα, TNFα and IL-10 serum levels, and clinical features, in 115 patients and 170 healthy individuals. Patients who where carriers of the rs573775 T* minor allele presented lower IFNα levels than those with the wild genotype, whereas the opposite result was detected for IL-10. Thus, since IL-10 production was regulated by rs1800896 polymorphisms, we evaluated the effect of this Atg5 mutation in genetically high and low IL-10 producers. Interestingly, we found that the rs573775 T* allele was a risk factor for SLE in carriers of the high IL-10 producer genotype, but not among genetically low producers. Moreover, IL-10 genotype influences SLE features in patients presenting the Atg5 mutated allele. Specifically, carriage of the rs573775 T* allele led to IL-10 upregulation, reduced IFNα and TNFα production and a low frequency of cytopenia in patients with the high IL-10 producer genotype, whereas patients with the same Atg5 allele that were low IL-10 producers presented reduced amounts of all these cytokines, had a lower prevalence of anti-dsDNA antibodies and the latest onset age. In conclusion, the Atg5 rs573775 T* allele seems to influence SLE susceptibility, cytokine production and disease features depending on other factors such as functional IL-10 genotype

Anti-High-Density Lipoprotein Antibodies and Antioxidant Dysfunction in Immune-Driven Diseases

This work was supported by European Union FEDER funds and “Fondo de Investigación Sanitaria” (FIS, PI12/00523 and PI16/0011; ISCIII, Spain). JR-C is supported by a postdoctoral contract from the “Juan de la Cierva” program (FJCI-2015-23849; MICINN, Spain)

Non-esterified fatty acids profiling in rheumatoid arthritis: Associations with clinical features and Th1 response

Since lipid compounds are known to modulate the function of CD4+ T-cells and macrophages, we hypothesize that altered levels of serum non-esterified fatty acids (NEFA) may underlie rheumatoid arthritis (RA) pathogenesis.Serum levels of NEFA (palmitic, stearic, palmitoleic, oleic, linoleic, γ-linoleic, arachidonic -AA-, linolenic, eicosapentaenoic -EPA- and docosahexaenoic -DHA-) were quantified by LC-MS/MS after methyl-tert-butylether (MTBE)-extraction in 124 RA patients and 56 healthy controls (HC). CD4+ phenotype was studied by flow cytometry. TNFα, IL-8, VEGF, GM-CSF, IFNγ, IL-17, CCL2, CXCL10, leptin and resistin serum levels were quantified by immunoassays. The effect of FA on IFNγ production by PBMC was evaluated in vitro.Lower levels of palmitic (p<0.0001), palmitoleic (p = 0.002), oleic (p = 0.010), arachidonic (p = 0.027), EPA (p<0.0001) and DHA (p<0.0001) were found in RA patients, some NEFA being altered at onset. Cluster analysis identified a NEFA profile (hallmarked by increased stearic and decreased EPA and DHA) overrepresented in RA patients compared to HC (p = 0.002), being associated with clinical features (RF, shared epitope and erosions), increased IFNγ expression in CD4+ T-cells (p = 0.002) and a Th1-enriched serum milieu (IFNγ, CCL2 and CXCL10, all p<0.005). In vitro assays demonstrated that imbalanced FA could underlie IFNγ production by CD4+ T-cells. Finally, changes on NEFA levels were associated with clinical response upon TNFα-blockade.An altered NEFA profile can be found in RA patients associated with clinical characteristics of aggressive disease and enhanced Th1 response. These results support the relevance of lipidomic studies in RA and provide a rationale for new therapeutic targets

Technology: a strategic imperative for successful retailers

This author accepted manuscript is deposited under a Creative Commons Attribution Non-commercial 4.0 International (CC BY-NC) licence. This means that anyone may distribute, adapt, and build upon the work for non-commercial purposes, subject to full attribution. If you wish to use this manuscript for commercial purposes, please contact [email protected]: In the aftermath of the COVID-19 pandemic, technology is rewriting the way consumers shop as well as the retail operating models. In this context, investment in new technologies is a strategic imperative for retailers striving to remain relevant and profitable. Using Kahn's Retail Success Matrix as the conceptual framework, the aim of the study is to propose a classification of emerging technologies based on their potential for sustaining retailers' competitive strategies. Design/methodology/approach: Following an initial qualitative study based on in-depth interviews and focus groups with 20 retail managers, the authors collected survey data from a sample of 168 retail and technology professionals. To achieve the research objectives, content, descriptive and multiple correspondence factor analyses were carried out. Findings: The data analyses result on a map that plots the technological solutions that retail experts identify as enablers of four key competitive strategies: product superiority, enhanced customer experience, frictionless shopping experience and operational excellence. Practical implications: This research work provides valuable insight into how retail companies can capitalise on technology to create or reinforce their competitive positioning. The framework acts as a guide for retail companies to assess their technology priorities. Originality/value: This exploratory empirical study is the result of a collaboration between academic researchers and retail professionals. Thus, it addresses challenges experienced by key stakeholders. The encompassing classification enables a better understanding of the impact of technology on retailers' competitive positioning.This work was supported by the Spanish Ministry of Science and Innovation (Funding Agency #1) under Grant PID2020-113561RB-I00. This study benefited from the Professorship Excellence Program in accordance with the multi-year agreement signed by the Government of Madrid and the Autonomous University of Madrid (Line #3)

Estrategias y posicionamiento competitivo de las empresas minoristas españolas

Se analizan las estrategias competitivas de las principales empresas minoristas españolas a partir de la Matriz de Khan, identificando las principales estrategias seguidas. Se contrastan estas estrategias con el posicionamiento obtenido mediante una muestra de directivos de empresas del sector y con el derivado de una muestra de consumidores, analizándose las diferencias entre las percepciones de ambos y verificándose la utilidad de esta Matriz para explicar el posicionamiento de las empresas minoristas

Calidad de vida de los profesionales en el modelo de gestión clínica de Asturias

ResumenObjetivoAnalizar la calidad de vida profesional en el modelo de gestión clínica de Asturias y comprobar si hay diferencias en los centros donde el modelo lleva implantado más tiempo o en función del ámbito asistencial (atención primaria o especializada).MétodosSe aplicó el CVP-35 (35 preguntas), anónimo y autocumplimentado, con tres preguntas adicionales. Se realizó un análisis descriptivo, univariado y bivariado, de las preguntas por separado y según las subescalas «Apoyo directivo» (AD), «Cargas de trabajo» (CT) y «Motivación intrínseca» (MI), siendo las principales variables independientes el ámbito asistencial y el tiempo como unidad o área de gestión clínica.ResultadosDe la población de estudio, 2572 profesionales, respondieron 1395 (54%) (el 67% en primaria y 51% en especializada). El 87% llevaba 5 años o más en su puesto. Para el 33% era su primer año en gestión clínica. El ítem con mayor puntuación fue la capacitación para el trabajo (8,39±1,42) y el más bajo los conflictos con los compañeros (3,23±2,2). Primaria obtiene resultados más altos en AD y calidad de vida en el trabajo, y especializada en CT. Respecto a la gestión clínica, las mejores puntuaciones se obtienen en las de 3 años y las peores en las de primer año. Las diferencias son especialmente favorables a la gestión clínica en especializada: las que más tiempo llevan perciben menos CT y más MI y calidad de vida.ConclusionesLlevar más tiempo en el modelo de gestión clínica se asocia con mejores percepciones en la calidad de vida profesional, sobre todo en atención especializada.AbstractObjectiveTo evaluate professional quality of life in our clinical governance model by comparing differences according to the time since the model's implementation (1-3 years) and the setting (primary or hospital care).MethodsA cross-sectional descriptive study was performed. The 35-item, anonymous, self-administered Professional Quality of Life Questionnaire, with three additional questions, was applied. A minimum sample size for each clinical governance unit/area (CGU/CGA) was calculated. Descriptive, univariate and bivariate analyses were performed using the 35 items separately. The subscales of «management support», «workload» and «intrinsic motivation» were used as dependant variables, and the setting and time since implementation of the CGU/CGA as independent variables.ResultsOf the study population of 2572 professionals, 1395 (54%) responded (67% in primary care and 51% in hospital care). A total of 87% had been working for 5 years or more in their positions. Thirty-three percent had worked for less than a year in clinical governance. The item with the highest score was job training (8.39±1.42) and that with the lowest was conflicts with peers (3.23±2.2). Primary healthcare professionals showed better results in management support and quality of life at work and hospital professionals in workload. The clinical governance model obtained the best scores at 3 years and the worst at 1 year. These differences were especially favorable for clinical governance in hospitals: professionals working longer perceived a lower workload and more intrinsic motivation and quality of life.ConclusionsA longer time working in the clinical governance model was associated with better perception of professional quality of life, especially in hospital care

Barreras de cambio y confianza: impacto sobre las recomendaciones boca-oído en el entorno online

El objetivo del presente trabajo es contribuir al estudio de los factores que favorecen una de las manifestaciones más interesantes de la lealtad: las recomendaciones favorables a terceros. Para ello se ha elegido como contexto de análisis el sector de las agencias de viaje virtuales. En dicho entorno y, a diferencia de las investigaciones existentes hasta la fecha en el entorno on-line, se evalúa el papel que tienen las barreras de cambio en la estabilización de las relaciones entre la empresa y sus clientes, distinguiendo dentro de las mismas dos componentes en función de su naturaleza: barreras de cambio positivas y barreras de cambio negativas. Se comprueba la influencia directa de dichas barreras de cambio sobre la comunicación interpersonal, así como su contribución a la capacidad explicativa de una de las variables clave en el marketing de relaciones: la confianza. Las implicaciones empresariales que se derivan de los resultados obtenidos en la investigación empírica facilitan la reflexión a las empresas que operan en la Red sobre estrategias adecuadas que permitan obtener una cartera de clientes estables que lleven a cabo recomendaciones positivas a terceros.In the services sector positive word-of-mouth is regarded as one of the most important consumer behavior for firms Thus, one of the most important questions within services marketing is the analysis of the factors influencing this variable, with a view to strengthening it.The current article attempts to extend previous research by testing the effects of customer trust and two types of switching barriers – negative and positive – on the most relevant manifestation of attitudinal loyalty (positive recommendations) in an online environment: virtual travel agencies. To this end, a total of 480 online customers were surveyed. The hypotheses were tested using structural linear equations through EQS version 6.1a for Windows. The distinction between negative and positive switching barriers is important to draw theoretical and managerial implications