Search

An important part of the preparation and homogenization of the seismic catalog used in the recent seismic hazard assessment study of Spain is the development of relationships among the different scales used to measure earthquake size. The objective is to convert all earthquake size data in the original catalog to a single magnitude scale, the moment magnitude M, in order to have a set of events with an uniform comparable size measurement. These new relationships are based on regression analysis between M and the other units used in the catalog in different epochs. The reduced major axis regression scheme is used, because it is the most suitable method for symmetric treatment of the variables involved in the fits. The new relationships obtained for Spain, M as a function of m; M as a function of m; and M as a function of I, are presented and their applicability limits and accuracy are discussed. The results obtained could have other practical uses in regional seismicity analysis. [ABSTRACT FROM AUTHOR]

Background: Immune dysregulation in individuals with Down syndrome (DS) leads to an increased risk for hospitalization and death due to coronavirus disease 2019 (COVID-19) and may impair the generation of protective immunity after vaccine administration., Methods: The cellular and humoral responses of 55 individuals with DS who received a complete SARS-CoV-2 vaccination regime at 1 to 3 (visit [V 1]) and 6 (V2) months were characterized., Results: SARS-CoV-2-reactive CD4+ and CD8+ T lymphocytes with a predominant Th1 phenotype were observed at V1 and increased at V2. Likewise, an increase in SARS-CoV-2-specific circulating Tfh (cTfh) cells and CD8+ CXCR5+ PD-1hi lymphocytes was already observed at V1 after vaccine administration. Specific immunoglobulin G (IgG) antibodies against SARS-CoV-2 S protein were detected in 96% and 98% of subjects at V1 and V2, respectively, although IgG titers decreased significantly between both time points., Conclusions: Our findings show that DS individuals develop an effective immune response to usual regimes of SARS-CoV-2 vaccination., Competing Interests: Potential conflicts of interest. E. P.-A. reports fees for Advisory Board participation from Pharmamar and AstraZeneca. D. R. d. A. reports grant number 19/00634 from Instituto Carlos III and grant number 2021A/2069 from Fondation Jerome Lejeune; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Universidad Complutense de Madrid (Título propio de experto en bioética clínica), Weill Cornell Medicine-Qatar (Division of Medical Ethics—several courses), Instituto Universitario de Investigación Ortega Y Gasset (Máster oficial en bioética clínica), Escuela Andaluza de Salud Pública (Curso Consultoría Ética Clínica [2022] y Máster en bioética [2021]), and Consejería de Salud, Comunidad De Madrid (Curso Consultoría Ética Clínica [November 2021]). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The immunological synapse (IS) is a superstructure formed during T cell activation at the zone of contact between T cells and dendritic cells (DCs). The IS includes specific molecular components in the T cell and DCs sides that may result in different functionality. Most of the studies on the IS have focused on the T cell side of this structure and, in contrast, the information available on the IS of DCs is sparse. Autophagy is a cellular process involved in the clearance of damaged proteins and organelles via lysosomal degradation. Mitophagy is the selective autophagy of damaged mitochondria. In this study, it is shown that IS formation induces clustering of mitochondria in the IS of DCs and partial depolarization of these organelles. At the IS of the DCs also accumulate autophagy and mitophagy markers, even when the kinase complex mTORC1, an inhibitor of the autophagy, is active. Together the results presented indicate that IS formation induces local clustering of mitochondria and mitophagy, which could be a homeostatic mechanism to control the quality of mitochondria in this region. The data underline the complexity of the regulatory mechanisms operating in the IS of DCs., (Copyright © 2019 by The American Association of Immunologists, Inc.)

Chemokine receptor CCR7 directs mature dendritic cells (mDCs) to secondary lymph nodes where these cells regulate the activation of T cells. CCR7 also promotes survival in mDCs, which is believed to take place largely through Akt-dependent signaling mechanisms. We have analyzed the involvement of the AMP-dependent kinase (AMPK) in the control of CCR7-dependent survival. A pro-apoptotic role for AMPK is suggested by the finding that pharmacological activators induce apoptosis, whereas knocking down of AMPK with siRNA extends mDC survival. Pharmacological activation of AMPK also induces apoptosis of mDCs in the lymph nodes. Stimulation of CCR7 leads to inhibition of AMPK, through phosphorylation of Ser-485, which was mediated by G(i)/Gβγ, but not by Akt or S6K, two kinases that control the phosphorylation of AMPK on Ser-485 in other settings. Using selective pharmacological inhibitors, we show that CCR7-induced phosphorylation of AMPK on Ser-485 is mediated by MEK and ERK. Coimmunoprecipitation analysis and proximity ligation assays indicate that AMPK associates with ERK, but not with MEK. These results suggest that in addition to Akt-dependent signaling mechanisms, CCR7 can also promote survival of mDCs through a novel MEK1/2-ERK1/2-AMPK signaling axis. The data also suggest that AMPK may be a potential target to modulate mDC lifespan and the immune response., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

The incidence of malignant melanoma is increasing worldwide. In Spain, its incidence is increasing faster than any other cancer type, with a 5-year survival rate of about 85%. The impact and characteristics of malignant melanoma in the Spanish population can be ascertained from the national melanoma registry of the Academia Española de Dermatología y Venereología. This review presents consensus group recommendations for the diagnosis, staging and treatment of malignant melanoma in Spain. Incidence and mortality are discussed, as well as evaluation of various prevention and treatment strategies. Prognostic factors, such as BRAF and C-KIT mutations, which are expected to become routine staging procedures over the next few years, are outlined, especially in relation to treatment options. The use of recently approved targeted agents such as ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitor, and vemurafenib, a BRAF inhibitor, in metastatic disease are also discussed.

Although there are multiple methods for analyzing apoptosis in cultured cells, methodologies for analyzing apoptosis in vivo are sparse. In this protocol, we describe how to detect apoptosis of leukocytes in mouse lymph nodes (LNs) via the detection of apoptotic caspases. We have previously used this protocol to study factors that modulate dendritic cell (DC) survival in LNs; however, it can also be used to analyze other leukocytes that migrate to the LNs. DCs labeled with a fluorescent cell tracker are subcutaneously injected in the posterior footpads of mice. Once the labeled DCs reach the popliteal LN (PLN), the animals are intravenously injected with FLIVO, a permeant fluorescent reagent that selectively marks active caspases and consequently apoptotic cells. Explanted PLNs are then examined under a two-photon microscope to look for the presence of apoptotic cells among the DCs injected. The protocol requires 6-6.5 h for preparation and analysis plus an additional 34-40 h to allow apoptosis of the injected DCs in the PLN.

Rationale: To prepare and validate a simple and self-administered questionnaire for the clinical rating of patients with urinary incontinence (UI) for use in the clinical practice., Methods: The questionnaire was prepared based on a review of the literature on urinary incontinence and the views of 7 urodynamic urologists. The initial questionnaire UI-5 included 5 items related to UI symptoms that divided patients into three categories: stress incontinence (UEI), urge incontinence (UUI) or mixed urinary incontinence (MUI). An additional question evaluates the impact of UI type on the quality of life. The of construct validity was analyzed correlating the responses to UI-5 items and the question on quality of life. The area under the ROC curve was calculated for each UI type correlating the UI-5 scores and the results of the urodynamic test. The cut-off values for each scale were determined based on sensitivity (SE) and specificity (SP)., Results: The study included 188 females with UI (73.4% with UEI, 13.3% with UUI and 13.3% with MUI; based on the urodynamics). Only 4.3% patients did not answer some UI-5 items. One item related to the protective material used was excluded as it was not related to UI types, and so the final questionnaire included only 4 items (UI-4). The results show that UI-4 discriminates the different types of incontinence: UEI (SE: 0.69/SP: 0.76; 1 item), UUI (SE: 0.83/SP: 0.65; 2 items), MUI (SE: 0.72/SP: 0.65; 1 item). 100% patients with MUI, 84% with UUI and 59.9% with UEI report some impact on their quality of life., Conclusions: UI-4 is simple, valid and easy to administer, and can be particularly valuable in the clinical rating of UI in settings where urodynamic testing is not easily available such is primary health care.