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Splenic marginal zone lymphoma (SMZL) is a mature B-cell neoplasm characterized by rather indolent clinical course. However, nearly one third of patients experience a rapidly progressive disease with a dismal outcome. Despite the characterization of clone geneticsandthe recognition of deregulated immunologic stimulation in the pathogenesis of SMZL, little is known about microenvironment dynamics and their potential biological influence on disease outcome. Here we investigate the effect of stroma-intrinsic features on SMZL disease progression by focusing on the microenvironment of the bone marrow (BM), which represents an elective disease localization endorsing diagnostic and prognostic relevance. We show that the quality of the BM stromal meshwork of SMZL infiltrates correlates with time to progression. In particular, we describe the unfavorable prognostic influence of dense CD40 expression by BM stromal cells, which involves the contribution of CD40 ligand (CD40L)-expressing bystander mast cells infiltrating SMZL BM aggregates. The CD40/CD40L-assisted crosstalk between mesenchymal stromal cells and mast cells populating the SMZL microenvironment finds correlation in p53-/- mice developing SMZL and contributes to the engendering of detrimental proinflammatory conditions. Our study highlights a dynamic interaction, playing between nonneoplastic elements within the SMZL niche, toward disease progression. © 2014 by The American Society of Hematology.

"Amyloidosis associated to hemodialysis is caused by persistently high beta(2)-microglobulin (beta(2)m) serum levels. beta(2)m is an intrinsically amyloidogenic protein whose capacity to assemble into amyloid fibrils in vitro and in vivo is concentration dependent; no beta(2)m genetic variant is known in the human population. We investigated the roles of two evolutionary conserved Trp residues in relation to beta(2)m structure, function and folding/misfolding by means of a combined biophysical and functional approach. We show that Trp60 plays a functional role in promoting the association of beta(2)m in class I major histocompatibility complex; it is exposed to the solvent at the apex of a protein loop in order to accomplish such function. The Trp60 -> Gly mutation has a threefold effect: it stabilizes beta(2)m, inhibits beta(2)m amyloidogenic propensity and weakens the interaction with the class I major histocompatibility complex heavy chain. On the contrary, Trp95 is buried in the beta(2)m core; the Trp95 -> Gly mutation destabilizes the protein, which is unfolded in solution, yielding nonfibrillar beta(2)m aggregates. Trp60 and Trp95 therefore play differential and complementary roles in beta(2)m, being relevant for function (Trp60) and for maintenance of a properly folded structure (Trp95) while affecting in distinct ways the intrinsic propensity of wild-type beta(2)m towards self-aggregation into amyloid fibrils. (c) 2008 Elsevier Ltd. All rights reserved."

CD40 is a member of the growing tumor necrosis factor receptor (TNF-R) family of molecules, and has been shown to play important roles in T cell-mediated B lymphocyte activation. Ligation of B cell CD40 by CD154 expressed on activated T cells stimulates B cell proliferation, differentiation, isotype switching, upregulation of surface molecules contributing to antigen presentation, development of the germinal center, and the humoral memory response. The present review will summarize recent literature data on the various CD40 signalling pathways, which involve both the TNF-R associated factors (TRAFs) and additional signalling proteins, and lead to activation of kinases and transcription factors.

Literature about the impact of infertility and endometriosis on Quality of Life (QoL) is scarce and needs further investigation. Our aim was to deeply investigate the QoL of women with diagnoses of both endometriosis and infertility with failed Assisted Reproductive Treatments (ART). We conducted a concurrent mixed-method study composed of both quantitative and qualitative surveys. The quantitative survey included 22 women who completed the FertiQoL. The qualitative survey included 15 of them who provided written answers to open-ended questions aimed at deeply exploring their QoL. Data were initially analyzed separately and then combined in a meta-matrix. From the quantitative survey emerged that women at higher risk for low QoL were those who have experienced previous spontaneous miscarriages and that the domains of the FertiQoL related to fertility treatment (i.e. increased pain severity, disturbed daily life routine, and dissatisfaction with services) were the most critical. From the Interpretative Phenomenological Analysis (IPA) of qualitative survey, narrations about the physical, relational, social, emotional-cognitive, and behavioural impact of the diseases emerged. Mixed findings showed that the QoL of this population was scarce and that different levels (the inner world, the behaviours, the relational context, and the environmental context) are strictly connected and interact between them in influencing QoL. Multi-level preventive or supportive programs (with specific attention to pain experience, coping strategies, quality of services and governmental support) are required for this population.

Sixty women with a diagnosis of endometriosis (30 with low pain severity - LP; 30 with high pain severity - HP) were evaluated at study entry (T0) and after three months (T1). At T0 they were compared for different psychological dimensions to sixty-two age-paired healthy women (CG). HP group had significantly higher scores on depressive symptomatology, sexual distress, and catastrophizing than CG, and higher scores on worry traits than LP. Metacognitive beliefs predicted sexual distress at T1, over and above pain severity. Pain affects different domains of mental health in this population. Coping strategies, metacognitive beliefs, and worry traits may modulate pain experience and psychological distress.

Objective: Infertility has a severe impact on quality of life and mental health. This condition could be exacerbated by the existence of comorbid medical disease, like endometriosis. The aim of this critical narrative review is the examination of the state of the art about the quality of life and mental health in infertile women with endometriosis. Methods: We performed a rigorous and systematic search for studies on multiple electronic databases. A total of 6 papers were included in the review and were subjected to interpretative and critical narrative synthesis. Results and Discussion: Major findings are resumed in the following points: (a) infertile women with endometriosis when compared to infertile ones without endometriosis show higher depression, stress perception, and anxiety, and lower general quality of life; (b) quality of life specifically related to infertility is similar among women with and without endometriosis and seems to be related to personality and beliefs factors; (c) giving birth to a child is related to better mental quality of life; (d) during assisted reproductive treatment (ART) stimulation, infertile women with endometriosis have a decrease of dysmenorrhea and dyspareunia; (e) satisfaction of ART is related to the number of attempts, treatment accomplishment and pregnancy test outcomes. Clinical implications of these findings and suggestions for future researches were discussed. Conclusion: Concluding, it is crucial to assess the psychological factors related to endometriosis and infertility to reduce the impact of these diseases on quality of life and mental health, provide adequate support to these patients, improve their satisfaction and increase the change to get pregnant.

Objective The impact of pain on quality of life and mental health of women with endometriosis is well known. However, the role that personality traits and coping strategies might have in influencing pain experience is still poorly understood and was the chief purpose of this study. Materials and methods We conducted a mixed-method sequential explanatory study, composed of a quantitative survey followed by qualitative interviews. The first quantitative phase included 162 women with endometriosis who completed a battery of validated questionnaires. After statistical analysis, a semistructured qualitative interview has been developed and conducted with 6 of them, in order to help explain findings obtained in the first phase. Thereafter, both analyses were combined in a metamatrix. Results From the metamatrix, it emerged that acute pain experience, fear of its occurrence, its unpredictability, and control difficulties are the main concerns of women with endometriosis. Worry trait characteristics (ie, the need for control, anticipatory anxiety, intrusive worry thoughts) and maladaptive thoughts such as coping strategies (ie, self-blame, rumination, catastrophizing) were common in this sample and seem to indirectly affect pain experience. Indeed, the unsuccessful struggle in controlling pain reinforces negative thoughts/beliefs and feelings of powerlessness, leading, in turn, to psychological distress and higher pain experience. Discussion From the study emerged a model of onset and maintenance of acute pain in women with endometriosis. Findings have clinical implications for the medical team and psychologists.

The aim of the study was to assess the predictive value of dyspareunia, general chronic pain, and metacognitive beliefs to sexual distress in a sample of women with endometriosis. Ninety-six women (mean age = 34.60 ± 6.44 years) with a diagnosis of endometriosis took part to this cross-sectional study. Sociodemographic and clinical data were collected by means of a structured ad hoc questionnaire. Metacognitive beliefs and sexual distress were assessed by means of the Metacognitions Questionnaire (MCQ30) and the Female Sexual Distress Scale-R (FSDS-r). General chronic pain intensity was collected by means of a Numeric Rating Scale. Data were subjected to Hierarchical logistic regression. We found high percentages of dyspareunia and sexual distress (i.e., 66% and 76%). Findings suggested that dyspareunia and chronic pain did not predict sexual distress, while negative beliefs about worries predicted sexual distress over and above them (p = .040, odd ratio 1.159). In the target population, metacognitive beliefs may have more influence on sexual distress than pain symptomatology.

Objective: To assess quality of life and psychological differences between infertile women with endometriosis and without endometriosis. To investigate predictive role of perfectionism, mindful awareness and beliefs about parenthood to quality of life in a sample of women with fertility problems. Methods: 43 infertile women (22 with endometriosis; 21 without endometriosis) who recurred to Assisted Reproductive Treatments (ARTs) in the last 12 months took part to this cross-sectional study. Sociodemographic and clinical data were collected by means of a structured ad hoc questionnaire. Fertility Quality of Life, Fertility Problem Inventory – Need of parenthood subscale, Obsessive Beliefs Questionnaire – Perfectionism subscale, and Cognitive and Affective Mindfulness Scale – Revised were used to assess target outcomes. Results: Any difference in quality of life and psychological condition was found between infertile women with and without endometriosis. Importance given to parenthood (beta = −.60, p

Aim: This study aimed to investigate which surgery (conservative, radical) is the most effective in improving quality of life and if childbirth after conservative one affects outcomes. Method: 79 women who underwent radical or conservative surgery for severe endometriosis were assessed by means of a semistructured interview and completed the SF-36. Results: Our findings showed that in the whole model of Hierarchical multiple linear regression analyses, surgery group explained significantly 10.7% of variance for bodily pain, 7.2% for general health, and 7.9% for vitality, independently of age and months spent since surgery. Groups of childbirth differed significantly for vitality (p .018, Cohen’s d .939) and role emotional (p .034, Cohen’s d .786). Discussion: Findings suggested that women with endometriosis who underwent radical surgery showed better quality of life in long term, independently of age and time spent since treatment. Moreover, women who gave birth to a child had a better mental quality of life, especially concerning vitality and role limitations due to emotional problems.

Mast cells (MCs) are innate immune cells that exert positive and negative immune modulatory functions capable to enhance or limit the intensity and/or duration of adaptive immune responses. Although MCs are crucial to regulate T cell immunity, their action in the pathogenesis of autoimmune diseases is still debated. Here we demonstrate that MCs play a crucial role in T1D pathogenesis so that their selective depletion in conditional MC knockout NOD mice protects them from the disease. MCs of diabetic NOD mice are overly inflammatory and secrete large amounts of IL-6 that favors differentiation of IL-17-secreting T cells at the site of autoimmunity. Moreover, while MCs of control mice acquire an IL-10 + phenotype upon interaction with FoxP3 + Treg cells, MCs of NOD mice do not undergo this tolerogenic differentiation. Our data indicate that overly inflammatory MCs unable to acquire a tolerogenic IL-10 + phenotype contribute to the pathogenesis of autoimmune T1D. © 2016 Elsevier Inc.