Overexpression of BAG3 (Bcl2-associated athanogene 3) in serum and skin of patients with systemic sclerosis.

OBJECTIVES: BAG3 (Bcl2-associated athanogene3) is able to induce the transformation of cancer-associated fibroblasts to alpha smooth muscle actin (a-SMA) positive (+) myofibroblasts. In systemic sclerosis (SSc), a-SMA+ myofibroblasts also play an important role in the progression of fibrosis in the skin and involved internal organs. The aim of the study was to investigate whether BAG3 is overexpressed in SSc and may be a biomarker of fibrogenesis. METHODS: BAG3 serum levels were measured in 106 patients with SSc, 47 with the limited (lc) and 59 the diffuse (dc) SSc, and in age- and sex-matched healthy controls (HC). BAG3 levels were then compared according to their clinical subset, nailfold video-capillaroscopic (NVC) patterns, interstitial lung disease (ILD, and correlated with modified Rodnan skin score (mRSS) and global disease activity. BAG3 expression was also investigated in skin biopsies of 8 dcSSc patients. RESULTS: BAG3 serum levels were significantly higher in dcSSc (143.3 pg/mL, 95%CI 78-208.5) than in HC (0.68 pg/mL, 95%CI 0.13-1.23), and were significantly higher in patients with late NVC pattern and ILD but did not correlate with disease activity and mRSS. Of note, BAG3 was strongly expressed in the skin biopsies of dcSSc patients. CONCLUSIONS: BAG3 is overexpressed in dcSSc patients and may contribute to skin and organ fibrosis by prompting the transition of fibroblasts into myofibroblasts and increasing their survival. Thus, BAG3 may play an important role in SSc fibrotic pathogenesis and be a potential biomarker of fibrosis. Further research on its role as a therapeutic target is warranted.

Uncovering the Underworld of Axial Spondyloarthritis.

Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.

Promoting the psychological well-being of Italian youth: a pilot study of a high school mental health program.

School is potentially one of the most important and effective agencies for the promotion of mental health. For this reason, in Italy, the Mental Health Department of The National Health Institute has developed an intervention based on a structured handbook. The aim of this intervention is to promote the psychological well-being of the students. In this study, we have evaluated the efficacy of this intervention through a quasi-experimental study design of four classes (two were control) of secondary education, including 79 students aged 14 to 16 years (15.35 ± 0.68). Assessments were administered before and after the intervention. The results showed improvement in perceived self-efficacy (p ≤ .001), emotional coping (p = .003), and overall well-being (p < .05). The students' perception of usefulness was also increased (p < .05); the intervention successfully promoted the idea of life as a continuous process of learning, in change and growth (p < .05). The intervention was effective despite some limitations described by authors related to a lack of involvement of relatives and the team teachers, as well as the absence of homework; however, the adoption of a program promoting life skills, problem solving, and goal definition training is recommended with the use of a revised handbook.

Pyoderma gangrenosum following anti-TNF therapy in chronic recurrent multifocal osteomyelitis: drug reaction or cutaneous manifestation of the disease? A critical review on the topic with an emblematic case report.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, clinically characterized by chronic and recurrent episodes of osteoarticular inflammation, that generally presents in children and adolescents. From a dermatological point-of-view, CMRO can be associated with skin rashes mainly including psoriasis, palmoplantar pustulosis and acne. Pyoderma gangrenosum (PG) is a rare immune-mediated inflammatory skin disease classified within the spectrum of neutrophilic dermatoses that, in some cases, has been reported as cutaneous manifestation in CMRO patients. This paper presents a 16-year female patient diagnosed with CMRO, who presented PG lesions located on the lower leg, that arose after the administration of the tumour necrosis factor (TNF)-α inhibitor adalimumab. Cases of PG have been reported in patients being treated with certain medications, including TNF-α antagonists, leading to classified them in a setting aptly termed "drug-induced PG." In this paper, we discuss the co-occurrence of PG and CRMO, in the light of recent evidence on the pathogenesis of both diseases and giving ample space to a literature review on drug induced PG. In our case, it is plausible that PG could be considered a cutaneous manifestation of CRMO, although the mechanisms underlying this intriguingly relationship remain to be fully unraveled.

Tocilizumab in Juvenile Idiopathic Arthritis Associated Uveitis, a Narrative Review.

Juvenile idiopathic arthritis (JIA) associated uveitis (JIA-U) is the most common extra-articular manifestation of JIA, affecting 10-15% of patients, especially in oligoarticular JIA where its course may be faint. Therefore, JIA-U is one of the most challenging pediatric uveitis, associated with major ocular morbidity and possibly leading to irreversible structural ocular damage and to vision-threatening complications. Adequate management is crucial for avoiding visual impairment complications. Since the introduction of biologic disease modifying anti-rheumatic drugs (bDMARDS), the visual prognosis of JIA-U has dramatically improved over the decades. Tumor necrosis factor-α (TNF-α) blockers are the most used bDMARDs in treating JIA-U with large evidence of efficacy. However, inadequate response to these agents, either due to intolerance or inefficacy, may be observed, requiring a swap to other classes of immunosuppressive agents, including anti-IL-6, anti-CD20, and, more recently, JAK inhibitors. Tocilizumab is a humanized monoclonal antibody to the interelukin-6 receptor preventing IL-6 from binding to its soluble and membrane-bound receptors. A growing body of literature provides promising results about the efficacy of intravenous and subcutaneous tocilizumab in the treatment of JIA-U. A narrative review of the literature on this topic will improve our knowledge on the potential use of tocilizumab in JIA-U.

Description and impact of a structured psychoeducational and salutogenetic approach (InteGRO) to support the recovery of people with severe mental disorders / Descrizione e impatto di un approccio psicoeducativo strutturato (InteGRO) di salutogenesi per sostenere il percorso di recovery delle persone con disturbo mentale grave

Aim: In mental health services there is an increasing attention to the recovery of people with severe mental illness. Consequently there is a growing literature on this topic focused above-all on the description of excellence paths that often include variables related to the organizational aspects of the service. Less attention is given to specific interventions to foster all the goals that are essential to improve the living conditions, including defining and planning goal, emotional perception, effective communication for negotiation, practical interpersonal and intrapersonal problem-solving. The aim of this paper is to describe an innovative and salutogenetic approach and to illustrate the results of the impact after a year of "active intervention". Methods: We used a "quasi-experiment" design-study with a pre-post assessment without a control group on 21 subjects with schizophrenia or bipolar disorder according to DSM-IV-TR criteria. We used to evaluate Functioning, the primary outcome, the Personal and Social Performance Scale. For the secondary outcome measures we used the Stress-Scale, the Modified Five-Point Test for cognitive flexibility, the APEN/G e APEP/G Scale for perceived self-efficacy, the Integrative Hope Scale, the items "subjective and objective load" of the "Aid received, Needs and Burden" self-filled questionnaire. The clinical assessment was made by the Brief Psychyatric Rating Scale, while we used the Repeatable Battery for the Assessment of Neuropsychological Status. Results: Of the 21 subjects included, 18 completed the assessment. Significant improvements were noted for all variables considered, with particular relevance for Personal and Social Functioning (p<0.001). Predictive variables for this dimension were the level of stress and perceived self-efficacy (p<0.05). Conclusions: The observed data confirm the effectiveness of this innovative approach, above all on Personal and Social Functioning where there has been improvement from two or more marked dysfunction areas to one area.

Promoting Mental Health in Italian Middle and High School: A Pilot Study.

AIM: In Italy, a handbook has been developed based on the principles of cooperative learning, life skills, self-effectiveness, and problem-solving at high school level. Early studies have shown the handbook's effectiveness. It has been hypothesized that the revised handbook could be more effective in middle schools. METHOD: The study design is a "pre- and posttest" that compares the results obtained from 91 students of the high schools with those of the 38 students from middle schools. The assessment was made through "self-reporting" questionnaires of (a) learning skills including problem-solving and (b) perceived self-efficacy in managing emotions, dysfunctional beliefs, and unhealthy behaviours (i.e., drinking/smoking). RESULTS: Significant improvements were observed in both groups with the exceptions of perceived self-efficacy in managing emotions. The improvement of dysfunctional beliefs and the learning of problem-solving skills were better in middle schools. CONCLUSION: The results confirm the authors' hypothesis that the use of this approach is much more promising in middle school.

[Evaluation of the impact of the new version of a handbook to promote psychological wellbeing and emotional intelligence in the schools (students aged 12-15)]. / Valutazione dell'impatto della nuova versione di un manuale per la promozione del benessere psicologico e dell'intelligenza emotiva nelle scuole con studenti di età 12-15 anni.

AIM: A recent study has demonstrated the effectiveness of a structured intervention based on a manual of mental health promotion for students of secondary schools developed by the Istituto Superiore di Sanità based on the "cooperative learning", the "life skills" and "self-efficacy"; unfortunately, the results were less significant than expected. The Authors made changes to the Handbook for Students simplifying the language to allow its use even in middle schools. The present study aims at evaluating the effectiveness of this new version of the manual that includes a notebook. METHODS: A pre-post study design was used with also experimental vs. control group comparison. Five classes were included in the experimental group and five in the control group belonging to 5 different institutes. The efficacy has been established through several self-filled questionnaires to assess improvement of skills (effective communication, goal-setting, problem solving), psychological well-being, perceived self-efficacy in the regulation of negative and positive emotions, irrational believes, and unhealthy lifestyles such as drinking and smoking. RESULTS: Significant improvements were observed in almost all dimensions evaluated with the exception of self-efficacy and irrational believes. Of particular importance were the improvements about skills (effective communication, goal-setting and problem solving), psychological well-being and in some behaviors "at risk" as the frequent involvement in fights and smoking habit. Overall, the improvement was greater than that observed in the first study by the same authors using the manual in the original version. CONCLUSIONS: The observed data confirm the effectiveness of this approach with better results if compared to previous studies because of the use of the new edition of the manual. One of the ingredient of success, in the opinion of the authors, was the use of this manual that includes a notebook that stimulates extracurricular exercises.