78 research outputs found
Philadelphia chromosome-negative myeloproliferative chronic neoplasms: is clonal hematopoiesis the main determinant of autoimmune and cardio-vascular manifestations?
No full textIn this article, we reviewed the possible mechanisms linking the clonal hematopoiesis of indeterminate potential (CHIP) to chronic myeloproliferative neoplasms (MPNs), autoimmune diseases (ADs), and cardiovascular diseases (CADs). CHIP is characterized by the presence of clonal mutations with an allelic frequency >2% in the peripheral blood without dysplasia, overt hematological neoplasms, or abnormalities in blood cell count. The prevalence may reach 20% of elderly healthy individuals and is considered a risk factor for myelodysplastic neoplasms and acute leukemia. In MPNs, CHIP is often associated with mutations such as JAK2V617F or DNMT3A, TET2, or ASXL1, which exhibit a 12.1- and 1.7-2-fold increase in CADs. Specifically, JAK2-mutated cells produce excessive cytokines and reactive oxygen species, leading to proinflammatory modifications in the bone marrow microenvironment. Consequently, the likelihood of experiencing thrombosis is influenced by the variant allele frequency (VAF) of the JAK2V617F mutation, which also appears to be correlated with anti-endothelial cell antibodies that sustain thrombosis. However, DNMT3A mutations induce pro-inflammatory T-cell polarization and activate the inflammasome complex, while TET2 downregulation leads to endothelial cell autophagy and inflammatory factor upregulation. As a result, in patients with TET2 and DNMT3A-related CHIP, the inflammasome hyperactivation represents a potential cause of CADs. CHIP also occurs in patients with large and small vessel vasculitis, while ADs are more frequently associated with MPNs. In these diseases, monocytes and neutrophils play a key role in the formation of neutrophil extracellular trap (NET) as well as anti-endothelial cell antibodies, resulting in a final procoagulant effect. ADs, such as systemic lupus erythematosus, psoriasis, and arthritis, are also characterized by an overexpression of the Rho-associated coiled-coil containing protein kinase 2 (ROCK2), a serine/threonine kinase that can hyperactivate the JAK-STAT pathway. Interestingly, hyperactivation of ROCK2 has also been observed in myeloid malignancies, where it promotes the growth and survival of leukemic cells. In summary, the presence of CHIP, with or without neoplasia, can be associated with autoimmune manifestations and thrombosis. In the presence of these manifestations, it is necessary to consider a "disease-modifying therapy" that may either reduce the clonal burden or inhibit the clonally activated JAK pathway
Moderne Klassiker: Die wiedergefundene Zeit: Die Reeditionen von Sitzmöbeln in Deutschland und in Italien und ihre Rezeption
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Impact of Anti-Endothelial Cell Antibodies (AECAs) in Patients with Polycythemia Vera and Thrombosis
No full textPolycythemia vera (PV) causes thrombosis. Erythrocytosis and cell adhesiveness are responsible for thrombosis. JAK2V617F causes inflammation and autoimmunity; however, whether or not autoimmunity or inflammation causes thrombosis has yet to be proven. In 60 PV patients, we analyzed JAK2V671F and its allele burden, autoimmune Th17 cells, interleukin-17 (IL-17), anti-endothelial cell antibodies (AECAs), endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and von Willebrand factor antigen (VWF:Ag). Fifty blood donors were used as the controls. All patients were on phlebotomy-maintaining hematocrit <45% and aspirin. Of the 60 patients, 40 had thrombosis. Those patients with thrombosis had a higher JAK2V617F allele burden than those without thrombosis, andTh17 cells and IL-17 were also higher in patients with thrombosis. Interestingly, we observed a high AECA IgG ELISA ratio (ER) in patients with thrombosis, which was normal in patients without thrombosis. We found high ELAM-1 and ICAM-1 as well as high VWF:Ag in patients with thrombosis compared to patients without thrombosis. AECA-positive sera from patients with thrombosis showed enhanced binding to cytokine-treated HUVEC and a positive antibody-dependent cellular cytotoxicity, suggesting that AECA may contribute to vascular injury. A positive correlation between AECAs, allele burden, and thrombosis was found. These results suggest that autoimmunity may be an additional mechanism in PV thrombogenesis
Adverse Outcome in Non-Severe COVID-19: Potential Diagnostic Coagulation Tests
No full textCOVID-19-associated coagulopathy (CAC) identifies the coagulation changes in coronavirus disease 2019 (COVID-19) and is responsible for thrombosis. CAC has been studied in critical and severe stage COVID-19 disease through tests including the D-Dimer (DD), prothrombin time (PT), thromboplastin partial time (PTT), platelet count, fibrinogen (Fib), and platelet factor 4 (PF4) tests. However, these tests have some limitations. The aim of this study was to identify more accurate warning tests for early recognition of CAC and to prevent its deterioration to disseminated intravascular coagulation (DIC). First, we measured Interleukin-1α (IL-1α) and IL-8, and tissue factor pathway inhibitor (TFPI) as inflammation and endothelial damage markers, respectively. Second, we measured thrombin antithrombin complex (TAT), β-Thromboglobulin (β-TG), and thromboelastometric parameters including clotting time (CT), clot formation time (CFT), clot firmness (MCF), and clot lysis at 30 min (LY-30), as markers of coagulation and platelet activation. This study included 100 non-severe patients with COVID-19 that developed pulmonary embolism (PE) compared to 80 healthy patients. IL-1α and IL-8, and TFPI were higher as well as TAT and β-TG and thromboelastometric parameters, indicating hypercoagulability. If confirmed in other studies, these results could help in predicting the deterioration of non-severe COVID-19 disease, thereby reducing hospitalizations and health costs
Periodic dynamic induction control of wind farms: proving the potential in simulations and wind tunnel experiments
No full textAs wind turbines in a wind farm interact with each other, a control problem arises that has been extensively studied in the literature: how can we optimize the power production of a wind farm as a whole? A traditional approach to this problem is called induction control, in which the power capture of an upstream turbine is lowered for the benefit of downstream machines. In recent simulation studies, an alternative approach, where the induction factor is varied over time, has shown promising results. In this paper, the potential of this dynamic induction control (DIC) approach is further investigated. Only periodic variations, where the input is a sinusoid, are studied. A proof of concept for this periodic DIC approach will be given by the execution of scaled wind tunnel experiments, showing for the first time that this approach can yield power gains in real-world wind farms. Furthermore, the effects on the damage equivalent loads (DEL) of the turbine are evaluated in a simulation environment. These indicate that the increase in DEL on the excited turbine is limited
Erratum: Correction to: Metal and metalloid concentrations in wild mammals from SW Europe: European hedgehog (Erinaceus europaeus) and badger (Meles meles) (Environmental science and pollution research international (2023) 30 56 (118855-118870))
No full textThe correct family name of the 4th author is Míguez-Santiyán
«La aguja fría del deseo»: the sensitive tropology of Margarita Ferreras
No full textLa poesía escrita por mujeres que se produjo desde las postrimerías del Modernismo hasta mediados de los cincuenta se distingue por un subjetivismo copioso y cierto erotismo que procura contradecir el arquetipo femenino de ascendencia romántica y desacreditar el matrimonio en cuanto institución represiva de las exigencias liberales de las mujeres. Propia del clima de emancipación femenina de los años treinta, la incorporación de referencias eróticas en las obras de las poetas del 27 viene a complementar el panorama de libertades que reivindicaban. Con todo, la mayoría de las poetas optan por estrategias estilísticas que insinúan, más o menos directamente, el elemento sensual, parapetándolo detrás de un sistema metafórico complejo, fundamentado en la ambigüedad genérica. Pocas son las que se decantan por un tratamiento franco e inmediato de los impulsos amorosos. Entre estas últimas destaca Margarita Ferreras, otra de las grandes olvidadas de las autoras que operaron en el primer tercio del siglo XX, quien alcanza en Pez en la tierra (1932), su única obra publicada, la cumbre de un erotismo pionero e infrecuente. El poemario, impreso por los Altolaguirre, consta de veintiocho composiciones que destacan por audacia, claridad expresiva y un realismo que puede tildarse de ardoroso. El presente estudio pretende proporcionar un análisis de las soluciones formales adoptadas por Ferreras para vehicular su concepto de erotismo y sensualidad. A través del análisis de algunas composiciones de Pez en la tierra, procuraremos explicar su peculiar uso de la tropología y el simbolismo de los elementos naturales, para luego explayarnos en los recursos metafóricos empleados para poetizar ese erotismo luminoso y atrevido.The poetry written by women that was produced from the end of Modernism to the middle of 1950s is distinguished by copious subjectivism and a certain eroticism that seeks to contradict the feminine archetype of Romanticism and to discredit marriage as an institution that represses the liberal demands of women. The incorporation of erotic references in the poems of the women of the Generation of 27 not only is a characteristic of the climate of female emancipation of the 1930s, but also a complement to the panorama of freedoms that they claimed. However, most poets opt for stylistic strategies that hint, more or less directly, the sensual element, shielding it behind a complex metaphorical system, based on generic ambiguity. Few are those who opt for a frank and immediate treatment of love impulses. Among the latter, Margarita Ferreras, another of the great forgotten of the authors who operated in the first third of the 20th century, stands out, reaching in Pez en la tierra (1932) the summit of a pioneering and infrequent eroticism. The collection of poems, printed by the Altolaguirres, consists of 28 compositions that stand out for their audacity, expressive clarity and a realism that can be called ardent. This study aims to provide an analysis of the formal solutions adopted by the author to convey her concept of eroticism and sensuality. Through the analysis of some compositions of Pez en la tierra, we will try to explain its peculiar use of the tropology and the symbolism of natural elements, to then expand on the metaphorical resources used to poetize that luminous and daring eroticism that we have been talking about, which blind by its calcining power.Aportación realizada en el marco del Proyecto de I+D+I «Género, cuerpo e identidad en las poetas españolas de la primera mitad del siglo XX», dirigido por la Dra. Helena Establier y financiado por el Programa Estatal de Generación del Conocimiento (Ref. PID 2020-113343GB-100)
Peg Interferon alpha-2b (Peg Intron) in Essential Thrombocythemia
No full textIn Essential Thrombocythemia (ET) patients the optimised pharmacokinetics of the weekly administered pegilated Interferons a (IFN) may increase the compliance to a long-lasting IFN treatment. This phase II study has been designed to evaluate in ET patients efficacy, safety and tolerability of a treatment with Peg Interferon a- 2b (Peg Intron, Schering-Plough). The major objective was to measure the Hematological Response rate (HR = PLTs < 500 x 109/L) after one year of treatment with Peg Intron. Since December 2000, in 16 Hematological Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC) the Peg Intron treatment has been started in 90 ET patients, 30 Males and 60 Females, median age 45 years (18-72), pretreated with alkylating agents (8%), Hydroxyurea (47%), IFN alpha (30%), Anagrelide (7%) and antiaggregating drugs (93%). At baseline the patients showed: age over 60 (17%), previous thrombosis (7%), platelet count > 1000 x 109/L (81%), peripheral granulocyte precursors (9%), splenomegaly (22%), mean platelet count 1112 x 109/L, mean Hb level 13.4 g/dl, mean WBC count 9.2 x109/L. The median treatment duration was 45 weeks. The initial very low dose of 25 mg/week was scheduled to be increased to 50, 75 and 100 mg/week if the HR was not reached at weeks 13, 26 and 39 respectively . At weeks 13, 26, 39 and 52 the mean platelet count was decreased to 59%, 48%, 44% and 43% of the baseline respectively, the Hematological Response was obtained in 17%, 50%, 72% and 67% of cases as Intention to treat (ITT), while in the patients really receiving Peg Intron the response was reached in 15/88 pts (17%), 45/84 pts (54%), 57/72 pts (79%) and 43/56 pts (77%) respectively. The increase of Peg Intron dose has been performed at weeks 13, 26 and 39 in 83%, 46% and 29% of patients respectively. Dose reduction and transitory interruption of Peg Intron was registered in 7 (8%) and 10 (11%) pts respectively. A drug withdrawal occurred in 8 patients (1 blastic transformation, 2 patient refusal, 2 neurotoxicity, 1 protocol violation, 1 hypertransaminasemia, 1 thyroid cancer ). The toxicity of Peg Intron was WHO grade III (1 case of leukopenia and 1 case of hypertransaminasemia), WHO grade II (mainly represented by leukopenia (9%) and flu-like syndrome (5%)), WHO grade I (mainly as injection syte inflammmation (44%), flu-like syndrome (31%), leukopenia (28%), hypertransaminasemia (14%) and anemia (9%)). Eight patients showed significant alteration of the laboratory thyroid parameters, in 3 cases requiring Peg Intron dose reduction. These preliminary data show that Peg Intron at low dose (median 50 mg/week) is able to induce the Hematological Response in the majority of ET patients, with acceptable safety and toxicity
Increased risk of recurrent thrombosis in patients with essential thrombocythemia carrying the homozygous JAK2 V617F mutation
No full textEvidence suggests that the JAK2 V617F mutation is associated with an increased risk of first thrombosis in patients with essential thrombocythemia (ET). Whether this mutation is also a risk factor for recurrent thrombosis is currently unknown. To investigate the impact of the JAK2 V617F mutation on the risk of recurrent thrombosis in patients with ET, we carried out a multicentre retrospective cohort study. We recruited 143 patients with previous arterial (64.4%) or venous major thrombosis (34.8%) or both (0.8%); 98 of them (68.5%) carried the mutation. Thrombosis recurred in 43 of the patients (30%); overall, after adjustment for sex, age, presence of vascular risk factors, and treatment after the first thrombosis, the presence of the JAK2 mutation did not predict recurrence (multivariable hazard ratio, HR, 0.88, 95% CI 0.46-1.68). Indeed, the individuals homozygous for the JAK2 V617F (allele burden > 50%) mutation had an increased risk of recurrence in comparison with wild-type patients (HR 6.15, 95% CI 1.51-24.92). In conclusion, a homozygous JAK2 V617F mutation is an independent risk factor for recurrent thrombosis in patients with ET
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