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

A Flexible Robotic Depalletizing System for Supermarket Logistics

Depalletizing robotic systems are commonly deployed to automatize and speed-up parts of logistic processes. Despite this, the necessity to adapt the preexisting logistic processes to the automatic systems often impairs the application of such robotic solutions to small business realities like supermarkets. In this work we propose a robotic depalletizing system designed to be easily integrated into supermarket logistic processes. The system has to schedule, monitor and adapt the depalletizing process considering both on-line perceptual information given by non-invasive sensors and constraints provided by the high-level management system or by a supervising user. We describe the overall system discussing two case studies in the context of a supermarket logistic process. We show how the proposed system can manage multiple depalletizing strategies and multiple logistic requests

A Reconfigurable Gripper for Robotic Autonomous Depalletizing in Supermarket Logistics

Automatic depalletizing is becoming a practice widely applied in warehouses to automatize and speed-up logistics. On the other hand, the necessity to adapt the preexisting logistic lines to a custom automatic system can be a limit for the application of robotic solutions into smaller facilities like supermarkets. In this work, we tackle this issue by proposing a flexible and adaptive gripper for robotic depalletizing. The gripper is designed to be assembled on the end-tip of an industrial robotic arm. A novel patent-pending mechanism allows grasping boxes and products from both the upper and the lateral side enabling the depalletizing of boxes with complex shape. Moreover, the gripper is reconfigurable with five actuated degrees of freedom, that are automatically controlled using the embedded sensors to adapt grasping to different shapes and weights

RGB-D Recognition and Localization of Cases for Robotic Depalletizing in Supermarkets

Integrating a robotic system into the depalletizing process of a supermarket demands a high level of autonomy, based on strong perceptive capabilities. This letter presents a system for detection, recognition, and localization of heterogeneous cases in a depalletizing robotic cell, using a single RGB-D camera. Such a system integrates apriori information on the content of the pallet with data from the RGB-D camera, exploiting a sequence of 2D and 3D model-based computer-vision algorithms. The effectiveness of the proposed methodology is assessed in an experiment where multiple cases and pallet configurations are considered. Finally, a complete depalletizing process is shown

Acute respiratory muscle unloading improves time-to-exhaustion during moderate- and heavy-intensity cycling in obese adolescent males

Obesity significantly impairs breathing during exercise. The aim was to determine, in male obese adolescents (OB), the effects of acute respiratory muscle unloading, obtained by switching the inspired gas from ambient air (AIR) to a normoxic helium + oxygen gas mixture (HeO2) (AIR \u2192 HeO2) during moderate [below gas exchange threshold (GET)] and heavy [above GET] constant work rate cycling. Ten OB [age 16.0 \ub1 2.0\ua0years (mean \ub1 SD); body mass index (BMI) 38.9 \ub1 6.1\ua0kg/m2] and ten normal-weight age-matched controls (CTRL) inspired AIR for the entire exercise task, or underwent AIR \u2192 HeO2 when they were approaching volitional exhaustion. In OB time to exhaustion (TTE) significantly increased in AIR \u2192 HeO2 vs. AIR during moderate [1524 \ub1 480\ua0s vs. 1308 \ub1 408 (P = 0.024)] and during heavy [570 \ub1 306\ua0s vs. 408 \ub1 150 (P = 0.0154)] exercise. During moderate exercise all CTRL completed the 40-min task. During heavy exercise no significant differences were observed in CTRL for TTE (582 \ub1 348\ua0s [AIR \u2192 HeO2] vs. 588 \ub1 252 [AIR]). In OB, but not in CTRL, acute unloading of respiratory muscles increased TTE during both moderate- and heavy-exercise. In OB, but not in CTRL, respiratory factors limit exercise tolerance during both moderate and heavy exercise

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

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

Clinical‐epidemiological aspects of the Monkeypox 2022 epidemic: a multicenter study by the Italian SIDeMaST Group of Sexually Transmitted, Infectious and Tropical Diseases

Dear Editor,In spring 2022, an increase of monkeypox (mpox) cases was reported in Europe. Mpox is a zoonotic virus of the Poxviridae family, is endemic in the Congo Basin and just few cases outside Africa were reported before 2022. Its cutaneous presentation is similar to smallpox, usually preceded by a prodromal phase of fever, lymphadenopathy, headache and asthenia. Infection can occur through various means, including skin-to-skin contact, respiratory droplets or contact with fomites. The new outbreak is unique due to the increased human-to-human transmission, without an animal reservoir, particularly among men who have sex with men (MSM). As of February 13, 2023, 85.860 confirmed cases have been reported in 110 countries