Janus kinase inhibitors: a new tool for the treatment of axial spondyloarthritis

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease involving the spine, peripheral joints, and entheses. This condition causes stiffness, pain, and significant limitation of movement. In recent years, several effective therapies have become available based on the use of biologics that selectively block cytokines involved in the pathogenesis of the disease, such as tumor necrosis factor-α (TNFα), interleukin (IL)-17, and IL-23. However, a significant number of patients show an inadequate response to treatment. Over 10 years ago, small synthetic molecules capable of blocking the activity of Janus kinases (JAK) were introduced in the therapy of rheumatoid arthritis. Subsequently, their indication extended to the treatment of other inflammatory rheumatic diseases. The purpose of this review is to discuss the efficacy and safety of these molecules in axSpA therapy

Advances in the pathogenesis and treatment of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the development of effective targeted therapies, that hold out hope for personalized therapy. However, the new drugs available to date are still an adjunct to conventional therapy, which is known to be toxic in the short and long term. The purpose of this review is to summarize recent advances in understanding the pathogenesis of the disease and discuss the results obtained from the use of new targeted drugs, with a look at future therapies that may be used in the absence of the current standard of care or may even cure this serious systemic autoimmune disease

Flux creep in Bi2Sr2CaCu2O8(sub +x) single crystals

The results of a magnetic study on a Bi2Sr2CaCu2O(8+x) single crystal are reported. Low field susceptibility (dc and ac), magnetization cycles and time dependent measurements were performed. With increasing the temperature the irreversible regime of the magnetization cycles is rapidly restricted to low fields, showing that the critical current J(sub c) becomes strongly field dependent well below T(sub c). At 2.4 K the critical current in zero field, determined from the remanent magnetization by using the Bean formula for the critical state, is J(sub c) = 2 10(exp 5) A/sq cm. The temperature dependence of J(sub c) is satisfactorily described by the phenomenological law J(sub c) = J(sub c) (0) (1 - T/T(sub c) (sup n), with n = 8. The time decay of the zero field cooled magnetization and of the remanent magnetization was studied at different temperatures for different magnetic fields. The time decay was found to be logarithmic in both cases, at least at low temperatures. At T = 4.2 K for a field of 10 kOe applied parallel to the c axis, the average pinning energy, determined by using the flux creep model, is U(sub o) = 0.010 eV

Excitation of the l=3 diocotron mode in a pure electron plasma by means of a rotating electric field

The l=3 diocotron mode in an electron plasma confined in a Malmberg–Penning trap has been resonantly excited by means of a rotating electric field applied on an azimuthally four-sectored electrode. The experimental observations are interpreted with a theory based on the linearization of the drift-Poisson equations and by means of two-dimensional particle-in-cell simulations. The experimental technique presented in this paper is able to selectively excite different diocotron perturbations and can be efficiently used for electron or positron plasma control and manipulation

Coherence properties and diagnostics of betatron radiation emitted by an externally-injected electron beam propagating in a plasma channel

A 3-dimensional time-domain simulation of X-ray produced by a laser wakefield accelerated electron beam was performed in order to know its properties like intensity, spectrum, divergence and coherence. Particular attention was paid to the coherence around the acceleration axis. The broad spectrum of betatron radiation (1–10 keV) leads to a short coherence length. Nevertheless we observe that under particular detection condition the spatial coherence has a characteristic enlargement. We give a simplified interpretation of this effect in terms of phase shift of the electric field on a virtual detector. Moreover we describe a near field scattering technique to characterize the betatron radiation. This diagnostics will be used to map the transverse spatio-temporal coherence of X-ray radiation in the laser wakefield accelerator under development at Frascati National Laboratories (LNF)

Diocotron modulation in an electron plasma through continuous radio-frequency excitation

The application of a radio-frequency (RF) excitation to any electrode of a Penning-Malmberg trap may result in significant electron heating and ionization of the residual gas with the formation of a plasma column when the RF frequency is of the order or larger than the typical axial bounce frequencies of few-eV electrons. The use of a quadrupolar excitation can induce additional phenomena, like formation of dense, narrow-cross section columns which exhibit an m\u3b8 = 1 diocotron mode, i.e., a rotation of their center around the trap axis. A series of experiments is presented and discussed showing that the continuous application of such excitation causes a dramatic perturbation of the plasma equilibrium also involving continuous production and loss of particles in the trapping region. In particular, the growth of the first diocotron mode is suppressed even in the presence of ion resonance and resistive instability and the mode exhibits steady-state or underdamped amplitude and frequency modulations, typically in the Hertz range

Excitation of the l=2 diocotron mode with a resistive load

The resistive wall instability of the l=2 diocotron mode in a pure electron plasma has been investigated with a systematic variation of the parameters of the external impedance connected to a pair of sectored electrodes. The measured growth rate is well described by a linear perturbation theory of the two-dimensional drift-Poisson system

ERAP1 and ERAP2 Haplotypes Influence Suboptimal HLA-B*27:05-Restricted Anti-Viral CD8+ T Cell Responses Cross-Reactive to Self-Epitopes

The human leukocyte antigen (HLA)-B*27 family of alleles is strongly associated with ankylosing spondylitis (AS), a chronic inflammatory disorder affecting the axial and peripheral joints, yet some HLA-B*27 variants not associated with AS have been shown. Since no major differences in the ligandome of associated compared to not-associated alleles have emerged, a plausible hypothesis is that the quantity rather than the quality of the presented epitopes makes the difference. In addition, the Endoplasmic Reticulum AminoPeptidases (ERAPs) 1 and 2, playing a crucial role in shaping the HLA class I epitopes, act as strong AS susceptibility factors, suggesting that an altered peptidome might be responsible for the activation of pathogenic CD8+ T cells. In this context, we have previously singled out a B*27:05-restricted CD8+ T cell response against pEBNA3A (RPPIFIRRL), an EBV peptide lacking the B*27 classic binding motif. Here, we show that a specific ERAP1/2 haplotype negatively correlates with such response in B*27:05 subjects. Moreover, we prove that the B*27:05 allele successfully presents peptides with the same suboptimal N-terminal RP motif, including the self-peptide, pDYNEIN (RPPIFGDFL). Overall, this study underscores the cooperation between the HLA-B*27 and ERAP1/2 allelic variants in defining CD8+ T cell reactivity to suboptimal viral and self-B*27 peptides and prompts further investigation of the B*27:05 peptidome composition

Spontaneous corneal melting in pregnancy: a case report

<p>Abstract</p> <p>Background</p> <p>To report a case of spontaneous corneal melting in pregnancy. We reviewed the literature on corneal melting and the effect of pregnancy on cornea and collagen containing tissues.</p> <p>Case presentation</p> <p>A 29-year-old woman who underwent radial keratotomy in both eyes followed by trabeculectomy in her left eye developed corneal melting in the same eye, in her seventh month of pregnancy. Despite screening, no infectious or immune mediated condition could be identified. She was managed conservatively with cyanoacrylate glue, bandage contact lens, lubricants and antibiotics.</p> <p>Conclusion</p> <p>It may not always be possible to find the underlying cause of corneal melting but the more common underlying causes should be ruled out by proper investigations. Pregnancy with its host of hormonal changes could potentially have some effect on corneal collagen leading to corneal melting in compromised corneas.</p