Consensus statement on the diagnosis, management, and treatment of angioedema mediated by Bradykinin. Part. II: treatment, follow-up, and special situations

Background: There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema. Aim: To draft a consensus statement on the management and treatment of angioedema mediated by bradykinin in light of currently available scientifi c evidence and the experience of experts. This statement will serve as a guideline to health professionals. Methods: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema, a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientifi c papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor defi ciency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings were held to reach the consensus. Results: Treatment approaches are discussed, and the consensus reached is described. Specifi c situations are addressed, namely, pregnancy, contraception, travelling, blood donation, and organ transplantation. Conclusions: A review of and consensus on treatment of bradykinin-induced angioedema is presentedIntroducción: No existen guías previas españolas sobre el manejo del angioedema mediado por bradicinina. Objetivos: Alcanzar un consenso sobre el manejo y tratamiento del angioedema mediado por bradicinina a la luz de la evidencia científi ca disponible y la experiencia de los expertos, que sirva como guía para los profesionales de la salud. Métodos: SGBA/GEAB, un grupo de trabajo de la SEAIC dirigió el consenso. Se realizó una revisión de los documentos científi cos publicados sobre los diferentes tipos de angioedema mediado por bradicinina [angioedema hereditario o adquirido por defi ciencia de inhibidor de la C1 esterasa, angioedema hereditario relacionado con estrógenos (AEH tipo III, AEH-FXII), angioedema inducido por IECA (inhibidores del enzima convertidor de angiotensina]. Hubo varias reuniones del SGBA/GEAB para alcanzar el consenso. Resultados: Se revisan y discuten los diferentes tratamientos disponibles y se describe el consenso alcanzado. Se abordan situaciones específi cas (embarazo, anticoncepción, viajes, hemodonación, trasplante de órganos). Conclusiones: Se presenta una revisión del tratamiento del angioedema mediado por bradicinina y un consenso sobre su tratamiento en EspañaDr. Teresa Caballero is a researcher with the Hospital La Paz Health Research Institute (IdiPaz) program for promoting research activities (2009

The transcriptional profiling of human in vivo-generated plasma cells identifies selective imbalances in monoclonal gammopathies

Plasma cells (PC) represent the heterogeneous final stage of the B cells (BC) differentiation process. To characterize the transition of BC into PC, transcriptomes from human naïve BC were compared tothose of three functionally-different subsets of human in vivo-generated PC: i) tonsil PC, mainly consisting of early PC; ii) PC released to the blood after a potent booster-immunization (mostly cycling plasmablasts); and, iii) bone marrow CD138 + PCthat represent highly mature PC and include the long-lived PC compartment. This transcriptional transition involves subsets of genes related to key processes for PC maturation: the already knownprotein processing, apoptosis and homeostasis, and of new discovery including histones, macromolecule assembly, zinc-finger transcription factors and neuromodulation. This humanPCsignature is partially reproduced in vitro and is conserved in mouse. Moreover, the present study identifies genes that define PC subtypes (e.g., proliferation-associated genes for circulating PC and transcriptional-related genes for tonsil and bone marrow PC)andproposes someputative transcriptional regulators of the human PC signatures (e.g., OCT/POU, XBP1/CREB,E2F, amongothers). Finally, we also identified a restricted imbalance of the present PC transcriptional program in monoclonal gammopathies that correlated with PC malignancy

The prognostic role of CXCR3 expression by chronic lymphocytic leukemia B cells

Background and Objectives Chemokine receptors are involved in tumor progression and several of these receptors, including CXCR3, are expressed by chronic lymphocytic leukemia (CLL) B cells. This study was aimed to examine a possible relationship between CXCR3 expression in CLL and the clinical evolution of the disease.Design and Methods Using flow activated cell sorting (FACS), we analyzed the level of expression of CXCR3 on blood CLL B cells from 76 consecutive patients. The results were correlated with CD38 expression, IgVH gene status and clinical outcome.Results CXCR3, measured as mean fluorescence intensity (MFI), was unimodally expressed by blood tumor cells at various levels (range, 3.5 to 232.3) but levels within individual patients were remarkably stable over time. Low CXCR3 expression by CLL B cells was strongly associated with Rai disease stages III and IV (

Single-phase five-level multilevel inverter based on a transistors six-pack module

This article introduces a single-phase five-level multilevel inverter based on six switches and two transformers. The proposed converter requires a single dc input source with low voltage. The disposition of switches makes it possible to build the converter with a transistors six-pack module off-the-shelves, traditionally used to build three-phase inverters, which simplifies the manufacturing process. The converter increases the voltage with two transformers; for that reason, it does not require an auxiliary step-up converter. The use of transformers (with the transformer’s turns ratio) allows for using the same topology for several input voltage levels. To verify the operation of the proposed multilevel inverter, a computer-based simulation was performed with PSIM, a software that considers parasitic components. The results show that the proposed converter can work properly

Calibration and simulation of ionization signal and electronics noise in the ICARUS liquid argon time projection chamber

The ICARUS liquid argon time projection chamber (LArTPC) neutrino detector has been taking physics data since 2022 as part of the Short-Baseline Neutrino (SBN) Program. This paper details the equalization of the response to charge in the ICARUS time projection chamber (TPC), as well as data-driven tuning of the simulation of ionization charge signals and electronics noise. The equalization procedure removes non-uniformities in the ICARUS TPC response to charge in space and time. This work leverages the copious number of cosmic ray muons available to ICARUS at the surface. The ionization signal shape simulation applies a novel procedure that tunes the simulation to match what is measured in data. The end result of the equalization procedure and simulation tuning allows for a comparison of charge measurements in ICARUS between Monte Carlo simulation and data, showing good performance with minimal residual bias between the two

Deep-Sequencing Analysis of the Mouse Transcriptome Response to Infection with Brucella melitensis Strains of Differing Virulence

Brucella melitensis is an important zoonotic pathogen that causes brucellosis, a disease that affects sheep, cattle and occasionally humans. B. melitensis strain M5-90, a live attenuated vaccine cultured from B. melitensis strain M28, has been used as an effective tool in the control of brucellosis in goats and sheep in China. However, the molecular changes leading to attenuated virulence and pathogenicity in B. melitensis remain poorly understood. In this study we employed the Illumina Genome Analyzer platform to perform genome-wide digital gene expression (DGE) analysis of mouse peritoneal macrophage responses to B. melitensis infection. Many parallel changes in gene expression profiles were observed in M28- and M5-90-infected macrophages, suggesting that they employ similar survival strategies, notably the induction of anti-inflammatory and antiapoptotic factors. Moreover, 1019 differentially expressed macrophage transcripts were identified 4 h after infection with the different B. melitensis strains, and these differential transcripts notably identified genes involved in the lysosome and mitogen-activated protein kinase (MAPK) pathways. Further analysis employed gene ontology (GO) analysis: high-enrichment GOs identified endocytosis, inflammatory, apoptosis, and transport pathways. Path-Net and Signal-Net analysis highlighted the MAPK pathway as the key regulatory pathway. Moreover, the key differentially expressed genes of the significant pathways were apoptosis-related. These findings demonstrate previously unrecognized changes in gene transcription that are associated with B. melitensis infection of macrophages, and the central signaling pathways identified here merit further investigation. Our data provide new insights into the molecular attenuation mechanism of strain M5-90 and will facilitate the generation of new attenuated vaccine strains with enhanced efficacy

SELNET clinical practice guidelines for bone sarcoma

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context

Meta-analysis of genome-wide association studies for cancer therapy-related cardiovascular dysfunction and functional mapping highlight an intergenic region close to TP63

Cancer therapy-related cardiac dysfunction (CTRCD), which commonly includes left ventricular dysfunction and heart failure, is the main adverse effect of anticancer therapy. In recent years several candidate genes studies and genome-wide association studies have identified common genetic variants associated with CTRCD, but evidence remains limited and few genetic variants are robust. A genome-wide meta-analysis of CTRCD was performed with 852 oncology patients receiving cancer therapy. DNA samples were genotyped and imputed to perform a GWAS meta-analysis for case–control (N = 852 (380 cases and 472 controls) and extreme phenotypes (N = 618 (78 cases and 472 controls) looking for genetic variants that predispose to CTRCD. The results were validated in a replicate cohort of 1,191 oncology patients (245 cases and 946 controls). Functional mapping of the replicated loci was then performed. The meta-analysis showed 9 and 17 loci suggestively associated (P-value –5) with CTRCD in case–control and extreme phenotypes analyses, respectively. The 3q28 locus (rs rs7652759, P = 5.64 × 10–6) in the case–control analysis was the strongest signal, with up to 64 SNPs above the suggestive significance threshold. The rs7652759, an intergenic variant between TPRG1 and TP63 genes, was the only variant validated in the replication cohort (P-value = 0.01). Functional mapping of this significant locus revealed up to 5 new genes potentially involved in the CTRCD. We identified the intergenic region near TP63 as a novel CTRCD susceptibility locus. In the future, the genotyping of these markers could be considered in new CTRCD risk scores to improve preventive strategies in cardio-oncologyThis work was supported by Instituto de Salud Carlos III (ISCIII) –– “Next Generation EU” Funds – Mecanismo de Recuperación y Resiliencia (MRR) (PMP22/00098, PI19/01283, PI18/01242 and PI13/00559). Ph.D. Student Martínez-Campelo L had a Predoctoral Contract for Training in Health Research from Carlos III Health Institut