Development and Role in Therapy of Canakinumab in Adult-Onset Still's Disease

Adult-onset Still's disease (AOSD) is a rare inflammatory disease of unknown etiology typically characterized by episodes of spiking fever, evanescent rash, arthralgia, leukocytosis, and hyperferritinemia. The pivotal role of interleukin (IL)-1 and other pro-inflammatory cytokines gives rise to the development of new targeted therapies. Currently, AOSD patients can benefit from efficient and well tolerated biologic agents, such as IL-1, IL-6, and tumour necrosis factor (TNF)-\u3b1 antagonists. Canakinumab, a human monoclonal anti-IL-1\u3b2 antibody, is indicated for the treatment of different autoinflammatory syndromes in adults, adolescents, and children and it has recently been approved for AOSD treatment. In this article, we summarize the structural and biochemical data describing the molecular interactions between Canakinumab and its target antigen. Some special considerations of the pharmacological properties of Canakinumab are included. We also review the safety, efficacy and tolerability of this drug for the treatment of AOSD

Crystal-induced joint inflammation

L'infiammazione articolare indotta dai microcristalli e tra le piu acute ed intense che e dato conoscere. A supporto di questa affermazione si possono citare le numerose ed autorevoli testimonianze ricevute nei secoli dai personaggi affetti da gotta (1, 2), la piu nota e celebrata artropatia da microcristalli. Proprio sulla particolare capacita di questa malattia di indurre un'infiammazione particolarmente intensa ed essere poi in grado di autolimitarla, almeno durante i primi attacchi, si sono riversate molte attenzioni degli studiosi moderni, i quali hanno cercato di interpretare questo fenomeno con l'ambizione principale di poterlo trasferire ad altri tipi di infiammazione articolare. In effetti, i modelli d'infiammazione indotta dai cristalli di urato monosodico (UMS), di pirofosfato di calcio diidrato (PFCD) e da altri microcristalli di natura calcica, costituiscono un ottimo terreno di applicazione per lo studio della fisiopatologia dell'infiammazione articolare, soprattutto per cio che concerne gli eventi acuti..

Role of omega-3 polyunsaturated fatty acids in diet of patients with rheumatic diseases

The beneficial effects of ω-3 polyunsaturated fatty acids have been widely described in the literature in particular those on cardiovascular system. In the last decade there has been an increased interest in the role of these nutrients in the reduction of articular inflammation as well as in the improvement of clinical symptoms in subjects affected by rheumatic diseases, in particular rheumatoid arthritis (RA). Nutritional supplementation with ω-3 may represent an additional therapy to the traditional pharmacological treatment due to the anti-inflammatory properties which characterize this class of lipids: production of alternative eicosanoids, reduction of inflammatory cytochines, reduction of T-lymphocytes activation, reduction of catabolic enzymes activity. The encouraging results of dietetic therapy based on ω- 3 in RA are leading researchers to test their effectiveness on patients with other rheumatic conditions such as systemic lupus erythematosus and ankylosing spondylitis. Nutritional therapy based on food rich in ω-3 or on supplementation with fish oil capsules, proved to be a valid support to he treatment of chronic inflammatory rheumatic diseases

New horizons in osteoarthritis

Summary Osteoarthritis (OA), also known as degenerative joint disease, is the most frequent chronic musculoskeletal disease and the leading cause of disability in elderly persons. There are currently at least 27 million persons afflicted with OA in the United States, and the annual cost to society in medical care and wage loss is expected to reach nearly $100 billion dollars by 2020, with consequent increased spending on its diagnosis and treatment, side-effect prevention, and loss of productivity. Despite this enormous burden, many aspects of OA are still unknown, with implications not only in terms of diagnosis and assessment but also with regard to therapy. Awareness of this state of affairs has attracted many researchers to this field, making OA one of the most actively studied sectors of rheumatology. Although some clinicians are unaware of recent advances, there is a large body of publications indicating that much has been achieved. Major progress has been made in formulating better definitions of risk factors, in particular in indicating the responsibility of biomechanical and genetic factors, and, with regard to pathogenesis, underlining the role of subchondral bone, cytokines and proteinases. Assessment of OA activity and its progression has been improved with the advent of biomarkers and new imaging procedures, in particular sonography and magnetic resonance imaging (MRI), but also of better clinical instruments, including more reliable patient questionnaires. Information from ongoing studies may improve the to some extent incomplete definition of OA phenotypes. Finally, promising new horizons have been opened up even with regard to the treatment of OA, which is still for the most part unsatisfactory except for surgical replacement therapy. Numerous new substances have been formulated and the findings of trials studying their effects are encouraging, although much has yet to be done

Learning t-doped stabilizer states

In this paper, we present a learning algorithm aimed at learning states obtained from computational basis states by Clifford circuits doped with a finite number t of non-Clifford gates. To tackle this problem, we introduce a novel algebraic framework for t-doped stabilizer states by utilizing tools from stabilizer entropy. Leveraging this new structure, we develop an algorithm that uses sampling from the distribution obtained by squaring expectation values of Pauli operators that can be obtained by Bell sampling on the state and its conjugate in the computational basis. The algorithm requires resources of complexity O(\exp(t)\poly(n)) and exhibits an exponentially small probability of failure.Comment: L.L. and S.O. contributed equally to this wor

Isospectral twirling and quantum chaos

We show that the most important measures of quantum chaos, such as frame potentials, scrambling, Loschmidt echo and out-of-time-order correlators (OTOCs), can be described by the unified framework of the isospectral twirling, namely the Haar average of a k-fold unitary channel. We show that such measures can then always be cast in the form of an expectation value of the isospectral twirling. In literature, quantum chaos is investigated sometimes through the spectrum and some other times through the eigenvectors of the Hamiltonian generating the dynamics. We show that thanks to this technique, we can interpolate smoothly between integrable Hamiltonians and quantum chaotic Hamiltonians. The isospectral twirling of Hamiltonians with eigenvector stabilizer states does not possess chaotic features, unlike those Hamiltonians whose eigenvectors are taken from the Haar measure. As an example, OTOCs obtained with Clifford resources decay to higher values compared with universal resources. By doping Hamiltonians with non-Clifford resources, we show a crossover in the OTOC behavior between a class of integrable models and quantum chaos. Moreover, exploiting random matrix theory, we show that these measures of quantum chaos clearly distinguish the finite time behavior of probes to quantum chaos corresponding to chaotic spectra given by the Gaussian Unitary Ensemble (GUE) from the integrable spectra given by Poisson distribution and the Gaussian Diagonal Ensemble (GDE)

Isospectral twirling and quantum chaos

We show that the most important measures of quantum chaos like frame potentials, scrambling, Loschmidt echo, and out-of-time-order correlators (OTOCs) can be described by the unified framework of the isospectral twirling, namely the Haar average of a $k$-fold unitary channel. We show that such measures can then be always cast in the form of an expectation value of the isospectral twirling. In literature, quantum chaos is investigated sometimes through the spectrum and some other times through the eigenvectors of the Hamiltonian generating the dynamics. We show that, by exploiting random matrix theory, these measures of quantum chaos clearly distinguish the finite time profiles of probes to quantum chaos corresponding to chaotic spectra given by the Gaussian Unitary Ensemble (GUE) from the integrable spectra given by Poisson distribution and the Gaussian Diagonal Ensemble (GDE). On the other hand, we show that the asymptotic values do depend on the eigenvectors of the Hamiltonian. We see that the isospectral twirling of Hamiltonians with eigenvectors stabilizer states does not possess chaotic features, unlike those Hamiltonians whose eigenvectors are taken from the Haar measure. As an example, OTOCs obtained with Clifford resources decay to higher values compared with universal resources. Finally, we show a crossover in the OTOC behavior between a class of integrable models and quantum chaos.Comment: Updated version with several new result

Transitions in entanglement complexity in random quantum circuits by measurements

Random Clifford circuits doped with non Clifford gates exhibit transitions to universal entanglement spectrum statistics [1] and quantum chaotic behavior. In [2] we proved that the injection of Ω(n) non Clifford gates into a n-qubit Clifford circuit drives the transition towards the universal value of the purity fluctuations. In this paper, we show that doping a Clifford circuit with Ω(n) single qubit non Clifford measurements is both necessary and sufficient to drive the transition to universal fluctuations of the purity

Transitions in entanglement complexity in random quantum circuits by measurements

Random Clifford circuits doped with non Clifford gates exhibit transitions to universal entanglement spectrum statistics[1] and quantum chaotic behavior. In [2] we proved that the injection of $O(n)$ non Clifford gates into a $n$-qubit Clifford circuit drives the transition towards the universal value of the purity fluctuations. In this paper, we show that doping a Clifford circuit with $O(n)$ single qubit non Clifford measurements is both necessary and sufficient to drive the transition to universal fluctuations of the purity

MREdictor: a two-step dynamic interaction model that accounts for mRNA accessibility and Pumilio binding accurately predicts microRNA targets.

The prediction of pairing between microRNAs (miRNAs) and the miRNA recognition elements (MREs) on mRNAs is expected to be an important tool for understanding gene regulation. Here, we show that mRNAs that contain Pumilio recognition elements (PRE) in the proximity of predicted miRNA-binding sites are more likely to form stable secondary structures within their 3′-UTR, and we demonstrated using a PUM1 and PUM2 double knockdown that Pumilio proteins are general regulators of miRNA accessibility. On the basis of these findings, we developed a computational method for predicting miRNA targets that accounts for the presence of PRE in the proximity of seed-match sequences within poorly accessible structures. Moreover, we implement the miRNA-MRE duplex pairing as a two-step model, which better fits the available structural data. This algorithm, called MREdictor, allows for the identification of miRNA targets in poorly accessible regions and is not restricted to a perfect seed-match; these features are not present in other computational prediction methods