Blocking IL-17: A Promising Strategy in the Treatment of Systemic Rheumatic Diseases

Systemic rheumatic diseases are a heterogeneous group of autoimmune disorders that affect the connective tissue, characterized by the involvement of multiple organs, leading to disability, organ failure and premature mortality. Despite the advances in recent years, the therapeutic options for these diseases are still limited and some patients do not respond to the current treatments. Interleukin-17 (IL-17) is a cytokine essential in the defense against extracellular bacteria and fungi. Disruption of IL-17 homeostasis has been associated with the development and progression of rheumatic diseases, and the approval of different biological therapies targeting IL-17 for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) has highlighted the key role of this cytokine. IL-17 has been also implicated in the pathogenesis of systemic rheumatic diseases, including systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and systemic sclerosis (SSc). The aim of this review is to summarize and discuss the most recent findings about the pathogenic role of IL-17 in systemic rheumatic and its potential use as a therapeutic option

Cost-Effectiveness Analysis of Apixaban Versus Edoxaban in Patients with Atrial Fibrillation for Stroke Prevention

OBJECTIVE: Our objective was to assess the cost effectiveness of apixaban versus edoxaban in the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) in Spain. METHODS: We customized a Markov model with ten health states to estimate the lifetime economic and clinical outcomes in 6-week cycles. The efficacy (clinical event rates per 100 patient-years) and safety data were derived from a pairwise indirect treatment comparison. The analysis was conducted from both the national health service (NHS) and societal perspectives, and included pharmaceutical costs (retail price plus value-added tax (VAT) and applicable national deductions) according to daily dosages (apixaban 10 mg (5 mg twice daily (bid)) and edoxaban 60 or 30 mg) and complications and disease-management costs, obtained from national databases. Utilities for quality-adjusted life-year (QALY) calculations reflected EuroQoL 5-Dimension scores in patients with AF. An annual discount rate of 3% was applied for costs (euro, year 2019 values) and outcomes. RESULTS: In a 1000-patient cohort, apixaban 5 mg bid versus edoxaban 60 mg could avoid five strokes, six major bleedings and 29 clinically relevant non-major bleedings (CRNMBs). Compared with edoxaban 30 mg, apixaban could avoid 21 strokes and two SEs. An increase in bleedings was observed with apixaban (seven haemorrhagic strokes, 48 major bleedings and 17 CRNMBs). Apixaban yielded 0.04 additional QALYs compared with edoxaban 60 mg or 30 mg. Incremental costs/QALY were euro9639.33 and euro354.22 for apixaban versus edoxaban 60 mg and edoxaban 30 mg, respectively, from the NHS perspective and euro7756.62 for apixaban versus edoxaban 60 mg from the societal perspective. Apixaban was dominant versus edoxaban 30 mg from the societal perspective. Sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: This study suggests that apixaban 5 mg bid is a cost-effective alternative to edoxaban for stroke prevention in the AF population in Spain

Enhanced solar anti-neutrino flux in random magnetic fields

We discuss the impact of the recent KamLAND constraint on the solar anti-neutrino flux on the analysis of solar neutrino data in the presence of Majorana neutrino transition magnetic moments and solar magnetic fields. We consider different stationary solar magnetic field models, both regular and random, highlighting the strong enhancement in the anti-neutrino production rates that characterize turbulent solar magnetic field models. Moreover, we show that for such magnetic fields inside the Sun, one can constrain the intrinsic neutrino magnetic moment down to the level of mu_nu lessthan few times 10^-12 x mu_B irrespective of details of the underlying turbulence model. This limit is more stringent than all current experimental sensitivities, and similar to the most stringent bounds obtained from stellar cooling. We also comment on the robustness of this limit and show that at most it might be weakened by one order of magnitude, under very unlikely circumstances.Comment: 25 pages, 5 figures; final version to appear in Phys. Rev.

Neutrino conversions in random magnetic fields and ν~e\tilde{\nu}_e from the Sun

The magnetic field in the convective zone of the Sun has a random small-scale component with the r.m.s. value substantially exceeding the strength of a regular large-scale field. For two Majorana neutrino flavors $\times$ two helicities in the presence of a neutrino transition magnetic moment and nonzero neutrino mixing we analyze the displacement of the allowed ($\Delta m^2- \sin^22\theta$)-parameter region reconciled for the SuperKamiokande(SK) and radiochemical (GALLEX, SAGE, Homestake) experiments in dependence on the r.m.s. magnetic field value $b$, or more precisely, on a value $\mu b$ assuming the transition magnetic moment $\mu = 10^{-11}\mu_B$. In contrast to RSFP in regular magnetic fields we find an effective production of electron antineutrinos in the Sun even for small neutrino mixing through cascade conversions $\nu_{eL}\to \nu_{\mu L}\to \tilde{\nu}_{eR}$, $\nu_{eL}\to \nu_{\mu R}\to \tilde{\nu}_{eR}$ in a random magnetic field that would be a signature of the Majorana nature of neutrino if $\tilde{\nu}_{eR}$ will be registered. Basing on the present SK bound on electron antineutrinos we have also found an excluded area in the same $\Delta m^2,~\sin^22\theta$-plane and revealed a strong sensitivity to the random magnetic field correlation length $L_0$.Comment: LaTex 36 pages including 14 PostScript figure

Thermal Background Corrections to the Neutrino Electromagnetic Vertex in Models with Charged Scalar Bosons

We calculate the correction to the neutrino electromagnetic vertex due to background of electrons in a large class of models, as the supersymmetric model with explicit breaking of R-parity, where charged scalar bosons couple to leptons and which are able to provide an astrophysically interesting value for the neutrino magnetic (electric) moment, $\mu_\nu\sim 10^{-12}\:\mu_B$. We show that the medium contribution to the chirality flipping magnetic (electric) dipole moment is not significant, however a new chirality flipping, but helicity conserving, term arises. It signals the presence of ${\cal CP}$ and ${\cal CPT}$ asymmetries in the medium and is associated to the longitudinal photon and therefore disappears in the vacuum. We estimate the contribution of this new term to the rate of the plasmon decay process $\gamma_{pl}\rightarrow \nu\nu$ in the core of degenerate stars, showing that it can be comparable with the contribution coming from the vacuum magnetic (dipole) moment. We also calculate the correction to the effective potential of a propagating neutrino in presence of a magnetic field due to a chirality preserving contribution to the diagonal magnetic moment from the medium. This contribution is identical for particles and antiparticles and so need not to vanish for Majorana neutrinos.Comment: DFPD 93/TH/75, SISSA 93/183/A preprint, 25 pages + 4 figures available by e-mail reques

Explicit solution for a Gaussian wave packet impinging on a square barrier

The collision of a quantum Gaussian wave packet with a square barrier is solved explicitly in terms of known functions. The obtained formula is suitable for performing fast calculations or asymptotic analysis. It also provides physical insight since the description of different regimes and collision phenomena typically requires only some of the terms.Comment: To be published in J. Phys.

Cell wall components and pectin esterification levels as markers of proliferation and differentiation events during pollen development and pollen embryogenesis in Capsicum annuum L.

Plant cell walls and their polymers are regulated during plant development, but the specific roles of their molecular components are still unclear, as well as the functional meaning of wall changes in different cell types and processes. In this work the in situ analysis of the distribution of different cell wall components was performed during two developmental programmes, gametophytic pollen development, which is a differentiation process, and stress-induced pollen embryogenesis, which involves proliferation followed by differentiation processes. The changes in cell wall polymers were compared with a system of plant cell proliferation and differentiation, the root apical meristem. The analysis was also carried out during the first stages of zygotic embryogenesis. Specific antibodies recognizing the major cell wall polymers, xyloglucan (XG) and the rhamnogalacturonan II (RGII) pectin domain, and antibodies against high- and low-methyl-esterified pectins were used for both dot-blot and immunolocalization with light and electron microscopy. The results showed differences in the distribution pattern of these molecular complexes, as well as in the proportion of esterified and non-esterified pectins in the two pollen developmental pathways. Highly esterified pectins were characteristics of proliferation, whereas high levels of the non-esterified pectins, XG and RGII were abundant in walls of differentiating cells. Distribution patterns similar to those of pollen embryos were found in zygotic embryos. The wall changes reported are characteristic of proliferation and differentiation events as markers of these processes that take place during pollen development and embryogenesis

A snapshot of cancer-associated thromboembolic disease in 2018-2019: First data from the TESEO prospective registry

BACKGROUND: The ever-growing complexity of cancer-associated thrombosis (CAT), with new antineoplastic drugs and anticoagulants, distinctive characteristics, and decisions with low levels of evidence, justifies this registry. METHOD: TESEO is a prospective registry promoted by the Spanish Society of Medical Oncology to which 34 centers contribute cases. It seeks to provide an epidemiological description of CAT in Spain. RESULTS: Participants (N=939) with CAT diagnosed between July 2018 and December 2019 were recruited. Most subjects had advanced colon (21.4%), non-small cell lung (19.2%), and breast (11.1%) cancers, treated with dual-agent chemotherapy (28.4%), monochemotherapy (14.4%), or immune checkpoint inhibitors (3.6%). Half (51%) were unsuspected events, albeit only 57.1% were truly asymptomatic. Pulmonary embolism (PE) was recorded in 571 (58.3%); in 120/571 (21.0%), there was a concurrent deep venous thromboembolism (VTE). Most initially received low molecular weight heparin (89.7%). Suspected and unsuspected VTE had an OS rate of 9.9 (95% CI, 7.3-non-computable) and 14.4 months (95% CI, 12.6-non-computable) (p=0.00038). Six-month survival was 80.9%, 55.9%, and 55.5% for unsuspected PE, unsuspected PE admitted for another reason, and suspected PE, respectively (p<0.0001). The 12-month cumulative incidence of venous rethrombosis was 7.1% (95% CI, 4.7-10.2) in stage IV vs 3.0% (95% CI, 0.9-7.1) in stages I-III. The 12-month cumulative incidence of major/clinically relevant bleeding was 9.6% (95% CI, 6.1-14.0) in the presence of risk factors. CONCLUSION: CAT continues to be a relevant problem in the era of immunotherapy and targeted therapies. The initial TESEO data highlight the evolution of CAT, with new agents and thrombotic risk factors