Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra.

Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36-a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs-a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool.

Foot and Soccer Referees': A Pilot Study Searching "Performance" Throughout Prevention.

Soccer refereeing is a "not-conventional" sport in which aerobic workload is prevalent. Along the years, several studies have attempted to define best markers of referees' performance. Many studies focused their attention on field tests and their relationship with aerobic power. Instead, in this study, starting by a medical assessment satisfying the FIFA 11+ criteria for injuries prevention, we have investigated the foot of soccer referees and we have also wanted to find possible and/or unexpected improvements in performance. As performance marker, we have used the referral field test for soccer referees that is internationally validated and known as Yo-Yo test (YYiR1). While standardized foot posture index (FPI) questionnaire was used for screening foot referees conditions (40 young, all men by sex, with mean age 23.47 ± 4.36). Analyzing collected data, we have demonstrated by means of Read-Cressie Chi square test that neutral FPI is an important favor item affecting YYiR1 results. Further studies will be necessary in order to confirm our pilot investigation.

Antibiotic sensitivities of coagulase-negative staphylococci and Staphylococcus aureus in hip and knee periprosthetic joint infections: does this differ if patients meet the International Consensus Meeting Criteria?

INTRODUCTION: Coagulase-negative staphylococci (CoNS) are the main pathogens responsible for prosthetic joint infections (PJIs). As normal inhabitants of human skin, it is often difficult to define if they are contaminants, or if they have an active role in initiating infection. This study aims to evaluate differences in CoNS organisms (Staphylococcus hominis, Staphylococcus capitis, Staphylococcus haemolyticus, Staphylococcus warneri) and Staphylococcus aureus in terms of isolation rate and antimicrobial susceptibility from patients who met the International Consensus Meeting (ICM) criteria for PJIs and those who did not. METHODS: Staphylococci isolates from January 2014 to December 2015 retrieved from patients undergoing revision joint arthroplasty were classified in accordance with criteria established by the ICM of Philadelphia. RESULTS: As per the consensus classification, 50 CoNS and 39 S. aureus infections were recognized as pathogens, while 16 CoNS and four S. aureus were considered as contaminants. Frequency of isolation of S. aureus was significantly higher in infected patients than in those without infection, while no significant differences were observed among CoNS. Resistance to levofloxacin, erythromycin, gentamicin trimethoprim/sulfamethoxazole, and rifampicin was significantly more frequent in S. haemolyticus than in the other species, as well as resistance to erythromycin and gentamicin in S. hominis. In comparison to S. aureus, CoNS were significantly more resistant to daptomycin and gentamicin and more susceptible to rifampicin. CONCLUSION: CoNS, other than Staphylococcus epidermidis, are frequently isolated from PJIs, and their infective role and antimicrobial susceptibility need to be assessed on an individual patient basis. S. haemolyticus seems to emerge as responsible for PJI in a large volume of patients, and its role needs to be further investigated, also considering its pattern of resistance.