En este artículo hemos analizado las distintas concepciones de necesidades en el segmento de población de más de 65 años, pudiendo afirmar que si bien este grupo de población tiene necesidades ...comunes al resto de los grupos de edad, también es posible que necesite otra serie de bienes y servicios que le diferencien de otros segmentos de población. Tratamos de resaltar cómo el factor tiempo influye en los hábitos de consumo de las personas mayores, ya que éstas han vivido momentos o situaciones diferentes derivados de la edad, siendo el resultado final del total de los momentos vividos y de la situación personal en que vive a cada momento. Por último, se trata de ver cómo los efectos de la generación a la que pertenecen, así como los diferentes ciclos de vida familiar, influyen en su posición hacia el consumo, haciendo énfasis en que cada vez se trata de un segmento más numeroso de consumidores mayores. /// In this article we have made an analysis of the various ideas of needs experienced in the population segment that covers those over the age of 65, and we can confirm that although this population group has the same needs as all other age groups, it is also possible that they may need another series of goods and services that differentiate them from other population segments. Our aim is to highlight the way in which the time factor affects the consumer habits of the elderly, since they have lived through different times or situations for reasons of their age, the end result being the sum of the times lived through and the personal situation of each individual at any given moment in time. Lastly, an attempt is made to see how the effects of the generation they belong to, as well as the various family life cycles, have an influence on their situation regarding consumer habits; emphasis is placed on the fact that this segment contains an ever-increasing number of elderly consumers.
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BFBNIB, NMLJ, NUK, PNG, UL, UM, UPUK
Objective
To assess the clinical relevance of increased circulating cytokines in patients with giant cell arteritis (GCA) after long‐term followup.
Methods
We performed a cross‐sectional evaluation ...of 54 patients with biopsy‐proven GCA prospectively followed for a median of 5.4 years (range 4–10.5 years). GCA‐related complications, vascular events, relapses, current prednisone dose, time required to achieve a maintenance prednisone dosage <10 mg/day, cumulated prednisone at that point, and adverse effects during followup were recorded. Serum interleukin‐6 (IL‐6) and tumor necrosis factor α (TNFα) were determined by immunoassay.
Results
All patients were in clinical remission. Both cytokines were significantly higher in patients than in controls (mean ± SD 21 ± 35 versus 5 ± 11 pg/ml; P < 0.001 for IL‐6 and mean ± SD 32 ± 14 versus 16 ± 9 pg/ml; P < 0.001 for TNFα). No differences were found in patients with or without GCA‐related complications or vascular events during followup. Circulating cytokines were significantly higher in patients who had experienced relapses (mean ± SD 25 ± 39 versus 10 ± 11 pg/ml; P = 0.04 for IL‐6 and mean ± SD 34 ± 15 versus 25 ± 11 pg/ml; P = 0.042 for TNFα). IL‐6 was significantly higher in patients still requiring prednisone (mean ± SD 29 ± 45 versus 13 ± 17 pg/ml; P = 0.008), and TNFα correlated with cumulated prednisone dose (r = 0.292, P = 0.04). No significant relationship was found between elevated cytokines and prednisone adverse effects or patients' quality of life.
Conclusion
Circulating TNFα and IL‐6 may persist elevated in GCA patients after long‐term followup and remain higher in patients who have experienced more relapsing disease. However, in this patient cohort, elevated circulating cytokines were not associated with increased frequency of GCA complications, vascular events, or treatment‐related side effects.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
CD226 costimulatory signals strongly promote Th1 differentiation enhancing IFN
γ
production by naïve T cells. We recently reported that knockdown of CD226 on human T cells resulted in a decrease in ...T-bet and IFN
γ
expression. However, the role of CD226 on Th2 and Th17 cells remains unknown. Here, we found that CD226 and its ligand CD155 were decreased on Th2-polarized naïve T cells whereas both were highly expressed under Th17 conditions. Most IFN
γ
and IL-17 producing cells expressed high levels of CD226 but production of IL-13 did not correlate with CD226 expression. CD226 knockdown by lentiviral transduction resulted in increased STAT-6 phosphorylation, enhanced GATA3 expression and consequently higher production of IL-4 and IL-13. Under Th17 conditions, CD226-depleted cells showed slightly impaired IL-17 secretion suggesting that CD226 partially contributes to IL-17 production but is dispensable for Th17 cell generation. In line with these results, CD226 blockade with neutralizing antibodies efficiently inhibited T cell activation, proliferation and production of IFN
γ
and IL-17 whereas IL-13 secretion remained functional. Taken together, our results establish an important role for CD226 in differentially regulating the pro-inflammatory (Th1/Th17)/anti-inflammatory (Th2) balance, suggesting that the CD226/CD155 interaction could potentially be targeted in therapeutic approaches to human autoimmune diseases.
Introduction: Multiple myeloma (MM) is considered an incurable disease. Best results are obtained with autologous stem cell transplantation (ASCT). The achievement of complete remission (CR) is the ...crucial step for a prolonged survival. Unfortunately, even with the use of new regimens, the vast majority of patients will ultimately relapse. In fact, with conventional chemotherapy, ASCT or allogeneic stem-cell transplantation (alloSCT), only 1‰, 10% and 15%, respectively are alive and in continued CR beyond 10 years in the best circumstances. The aim of the present research was to evaluate the proportion of patients in long-term CR after stem-cell transplantation, describing the different aspects related to minimal residual disease (MRD) and immunological correlative studies.
Methods: We analyzed the medical records of 160 patients who underwent single melphalan-based ASCT from March 31th 1994 to December 31th 2010, allowing at least 5 years of follow up from diagnosis (median follow-up of 8 years), as well as 58 patients who had received an alloSCT over a 28-year period.
Bone marrow (BM) samples from the alive CR patients beyond 5 years were analyzed to assess MRD using multiparameter flow cytometry (MFC) with Euroflow 8-color consensus panel. Serum free-light chains (FLC) and immunoglobulin heavy/light chains (HLC) (The Binding Site) were assayed by immunonephelometry. A whole-body PET/CT (Siemens) was also performed to evaluate extramedullary and bone disease. Furthermore, a detailed panel of surface cell markers by MFC was also developed to evaluate B, T and NK cell compartments, among other immune cell subpopulations in BM and/or peripheral blood.
Results: Twenty patients (20/160; 12.5%) were alive and in continuous CR after ASCT beyond 5 years; nine (5.7%) remained in CR for more than 10 years. In the alloSCT group, 6 out 58 patients (10.3%) were in CR beyond 5 years (3 of them for more than 10 years). Remarkably, two patients were in CR after 20 and 28 years after ASCT and alloSCT, respectively.
Fourteen long survivors after ASCT (70%) had received maintenance therapy. These regimens were mainly interferon (8 patients), followed by thalidomide (3) or thalidomide plus bortezomib (3).
None patient showed increased uptake of FDG by PET/CT suspicious of MM activity, neither in bone lesions nor previous plasmacytomas. However, in the vast majority of patients (16/22; 72.7%) there were stable lytic lesions, usually with sclerotic borders. Unspecific findings, particularly lymph nodes with unspecific FDG uptake, were described in 28.6%.
Fourteen out of 20 patients after ASCT (70%) and 2 after alloSCT (33.3%) showed oligoclonal bands (OB) in serum and/or urine, differents from the original monoclonal paraprotein by immunofixation. Among the 22 evaluated patients, all but 2 were negative by MFC for MRD in BM. These two patients were in stable CR, with evidence of OB in serum, considering the clone found unrelated to the original one. The aberrant plasma cell population (CD38+/++, CD56+, CD27-, CD19-, CD45-, CD81-, CD117+) was found to a frequency of 0.09% and 0.004% BM cells. Other 4 patients showed a population of plasma cells with some aberrant markers expression; two of them also showed OB.
All patients showed normal serum FLC ratio except one patient after alloSCT. Levels of IgG and IgA HLC were also normal, except in one patient each. Six patients had higher IgM HLC ratio than normal, all of them showing OB.
We also investigated whether T cell clonal expansion could be also involved. Indeed, patients with OB showed a higher diversity of TCR Vb over-represented, preferentially 13.1 and 17, suggesting a potential oligoclonal expansion of the T cell response. Characterization of TCR repertoire of the long survivors also indicated a higher involvement of the CD8+ compared to CD4+ T cells. In BM, the expression of the co-inhibitory receptor PD-1 on CD8+ T cells was elevated in active MM compared to MGUS and long survivors suggesting that exhausted PD1+CD8+ T cells increase in active MM and recover to normal levels in long survivors.
Conclusions: There are a small proportion of long-term survivors after SCT in MM. MRD studies are negatives, but some false positives could be observed by MFC when OB are present. PET invariably showed metabolic CR with stable bone lesions. Our results support that oligoclonal humoral and cellular responses may play an important role in the disease control over the years.
No relevant conflicts of interest to declare.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Although there is a broad consensus on the use of statistical procedures for mediation analysis in psychological research, the interpretation of the effect of mediation is highly ...controversial because of the potential violation of the assumptions required in application, most of which are ignored in practice. Method: This paper summarises two currently independent procedures for mediation analysis, the classical/ SEM and causal inference/CI approaches, together with the statistical assumptions required to estimate unbiased mediation effects, in particular the existence of omitted variables or confounders. A simulation study was run to test whether violating the assumptions changes the estimation of mediating effects. Results: The simulation study showed a significant overestimation of mediation effects with latent confounders. Conclusions: We recommend expanding the classical with the causal inference approach, which generalises the results of the first approach to mediation using a common estimation method and incorporates new tools to evaluate the statistical assumptions. To achieve this goal, we compare the distinguishing features of recently developed software programs in R, SAS, SPSS, STATA and Mplus. Keywords: Classical mediation approach, causal inference mediation approach, statistical mediation analysis, sensibility analysis. Antecedentes: aunque existe un amplio consenso en el uso de los procedimientos estadisticos para el analisis de la mediacion en la investigacion psicologica, la interpretacion del efecto de mediacion resulta muy controvertida debido al potencial incumplimiento de los supuestos que requiere su aplicacion, la mayoria de los cuales son ignorados en la practica. Metodo: se resumen los procedimientos actualmente vigentes para el analisis de mediacion desde los enfoques clasico y de la inferencia causal, junto con los supuestos estadisticos para estimar efectos de mediacion no sesgados, en particular la existencia de variables omitidas o confundidores, y se utiliza un estudio de simulacion para determinar si la violacion de los supuestos puede cambiar la estimacion del efecto de mediacion. Resultados: el estudio de simulacion mostro una sobreestimacion importante del efecto de mediacion en presencia de confundidores latentes. Conclusiones: se recomienda complementar el enfoque clasico con el enfoque de la inferencia causal, que generaliza los resultados del primer enfoque al analisis de la mediacion e incorpora nuevas herramientas para evaluar sus supuestos estadisticos. Para alcanzar tal objetivo se comparan las caracteristicas distintivas de los programas de software recientemente desarrollados en R, SAS, SPSS y Mplus. Palabras clave: enfoque clasico para la mediacion, enfoque de la inferencia causal para la mediacion, analisis de la mediacion estadistica, analisis de la sensibilidad.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives: Immunoparesis (IP) is a risk factor associated with an unfavourable outcome in several plasma cell disorders. It has been suggested that its presence in light-chain (AL) amyloidosis could ...be associated with worse prognosis. However, the relevance of IP after treatment has not been evaluated to date. The aim of this study was to determine the prognostic impact of IP at diagnosis and one year after treatment onset in patients with AL amyloidosis.
Methods: The clinical records of 69 patients with AL amyloidosis treated at a single institution from January 2006 to January 2016 were included in the study.
Results: IP was observed in 27.5% of patients at diagnosis. The presence of IP was associated with a lower probability to achieve very good partial response or better after first-line treatment (37.8% versus 62.2%; p = .04). However, only in the group of patients treated with autologous stem cell transplantation (ASCT), the presence of IP resulted in a shorter progression-free survival (PFS) (30.2 months versus not reached NR; p = .02) but not in overall survival (OS). Persistence of IP at one year after treatment onset was identified in only four (9.8%) of the 41 evaluable patients. In the ASCT group, the absence of IP at one year after treatment onset resulted in a longer median PFS and OS (NR versus 22.6 months; p = .006; and NR versus 35.2 months; p < .001; respectively). In the multivariate analysis, the absence of IP at one year after treatment onset was independently associated with longer survival.
Conclusion: IP at diagnosis has a negative impact on survival while its absence at one year after treatment is an independent marker for long-term survival.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Foxp3
+
T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. ...Here we identified Foxp3
+
T cells expressing the co-inhibitory molecule TIGIT as a distinct Treg cell subset that specifically suppresses pro-inflammatory T helper 1 (Th1) and Th17 cell, but not Th2 cell responses. Transcriptional profiling characterized TIGIT
+
Treg cells as an activated Treg subset with high expression of Treg signature genes. Ligation of TIGIT on Treg cells induced expression of the effector molecule fibrinogen-like protein 2 (Fgl2), which promoted Treg cell-mediated suppression of T effector cell proliferation. In addition, Fgl2 was necessary to prevent suppression of Th2 cell cytokine production in a model of allergic airway inflammation. TIGIT expression therefore identifies a Treg cell subset that demonstrates selectivity for suppression of Th1 and Th17 cell but not Th2 cell responses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Entre los muchos temas relacionados con la vejez, el relativo a la situación económica o al bienestar económico de nuestros mayores, está adquiriendo una gran relevancia, ya que condicionará las ...formas y estilos de vida de una cada vez más importante segmento de nuestra población, no solo desde el punto de vista cuantitativo (hoy en día representan sobre el 15,35% del total de la población), sino también desde el nivel cualitativo; cada vez se llega a la vejez en mejores condiciones de todo tipo y presumiblemente con un mejor nivel adquisitivo, lo que hace mover un importante volumen de dinero en la economía española.
Severino Aznar, sociólogo y experto en política social, le tocó vivir en una época marcada por grandes transformaciones en todas las áreas de la incipiente sociedad del siglo XX. Católico y con ...profunda vocación formó parte del movimiento denominado el “catolicismo social”, cuyo precursor fue el padre San Vicente de Paul. Su preocupación constante y todos sus esfuerzos se concentraron en la lucha por los derechos de las clases más desfavorecidas inspirado siempre en la doctrina social católica. Director General del Instituto Nacional de Previsión (con el gobierno de Franco), y director del Instituto Balmes de Sociología, cuyo órgano de expresión fue la Revista Internacional de Sociología. Es en esta revista donde se encuadran la mayoría de sus trabajos referentes al ámbito de la demografía y al de la Sociología de Familia. Su prolífera obra es escasamente reconocida en el panorama de la Sociología española, pero se puede considerar a este autor como un precursor de los estudios sobre Sociología de la Familia en España. Sus obras sobre este tema se han visto recientemente compiladas en el libro “La institución social de la familia vista por un demógrafo (2008), publicado por el Centro de Investigaciones Sociológicas.
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