Supporting mentalizing in primary school children: the effects of thoughts in mind project for children (TiM-C) on metacognition, emotion regulation and theory of mind.

Mentalization is a useful ability for social functioning and a crucial aspect of mentalizing is emotion regulation. Literature suggests programmes for children and adults to increase mentalizing abilities useful both for emotional and social competences. For this reason, the issue of how to prompt children's mentalization has started to attract researchers' attention, supporting the importance of the interpersonal dimension for the individual differences in the developmental of mentalization. The TiM (Thoughts in Mind) Project, a training programme based on the explanation of mentalization mechanisms and designed for adults, deals with emotion regulation. Starting from the TiM Project, this study tests the effects of the TiM Child (TiM-C) training programme, over a control training programme, a conversational training designed for the school context, in children attending Year 2 of primary school. We designed a training based on narratives, followed by multiple-choice questions and conversations about mental states. Our results revealed significant improvements over the training period only in the TiM-C Project group for Metacognition, Emotion Regulation Strategies and a Theory of Mind task. As far as the educational implications, our findings suggest that it is possible to enhance mentalization through activities at school by promoting not only the understanding of the relations between mind and emotion, but also metacognitive skills.

The Role of T Cell Immunity in Monoclonal Gammopathy and Multiple Myeloma: From Immunopathogenesis to Novel Therapeutic Approaches.

Multiple Myeloma (MM) is a malignant growth of clonal plasma cells, typically arising from asymptomatic precursor conditions, namely monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Profound immunological dysfunctions and cytokine deregulation are known to characterize the evolution of the disease, allowing immune escape and proliferation of neoplastic plasma cells. In the past decades, several studies have shown that the immune system can recognize MGUS and MM clonal cells, suggesting that anti-myeloma T cell immunity could be harnessed for therapeutic purposes. In line with this notion, chimeric antigen receptor T cell (CAR-T) therapy is emerging as a novel treatment in MM, especially in the relapsed/refractory disease setting. In this review, we focus on the pivotal contribution of T cell impairment in the immunopathogenesis of plasma cell dyscrasias and, in particular, in the disease progression from MGUS to SMM and MM, highlighting the potentials of T cell-based immunotherapeutic approaches in these settings.

Corrigendum: Children's representations of the COVID-19 lockdown and pandemic through drawings.

[This corrects the article DOI: 10.3389/fpsyg.2022.960893.].

Adipose stromal/stem cells assist fat transplantation reducing necrosis and increasing graft performance.

Autologous fat transfer (AFT) is a procedure for adipose tissue (AT) repair after trauma, burns, post-tumor resections and lipodystrophies still negatively impacted by the lack of graft persistence. The reasons behind this poor outcome are unclear and seem to involve damages in either harvested/transplanted mature adipocytes or on their mesenchymal progenitors, namely adipose stromal/stem cells (ASC), and due to post-transplant AT apoptosis and involution. A rabbit subcutaneous AT regeneration model was here developed to first evaluate graft quality at different times after implant focusing on related parameters, such as necrosis and vasculogenesis. Standard AFT was compared with a strategy where purified autologous ASC, combined with hyaluronic acid (HA), assisted AFT. Five million of autologous ex vivo isolated CD29+, CD90+, CD49e+ ASC, loaded into HA, enriched 1 ml of AT generating an early significant protective effect in reducing AFT necrosis and increasing vasculogenesis with a preservation of transplanted AT architecture. This beneficial impact of ASC assisted AFT was then confirmed at three months with a robust lipopreservation and no signs of cellular transformation. By a novel ASC assisted AFT approach we ensure a reduction in early cell death favoring an enduring graft performance possibly for a more stable benefit in patients.

Four amino acids of an insect densovirus capsid determine midgut tropism and virulence.

Densoviruses are insect parvoviruses that are orally infectious for Lepidoptera. To assess the mechanisms underlying their specificity and their virulence, we investigated the role of eight candidate residues in the densovirus capsid. We showed that the substitutions of four amino acids were associated with decreased virulence due to a decreased ability to cross the host midgut epithelium, without an effect on viral replication in other tissues.

The monocytic population in chronic lymphocytic leukemia shows altered composition and deregulation of genes involved in phagocytosis and inflammation.

Macrophages reside in tissues infiltrated by chronic lymphocytic leukemia B cells and the extent of infiltration is associated with adverse prognostic factors. We studied blood monocyte population by flow cytometry and whole-genome microarrays. A mixed lymphocyte reaction was performed to evaluate proliferation of T cells in contact with monocytes from patients and normal donors. Migration and gene modulation in normal monocytes cultured with CLL cells were also evaluated. The absolute number of monocytes increased in chronic lymphocytic leukemia patients compared to the number in normal controls (792 ± 86 cells/µL versus 485 ± 46 cells/µL, P=0.003). Higher numbers of non-classical CD14(+)CD16(++) and Tie-2-expressing monocytes were also detected in patients. Furthermore, we performed a gene expression analysis of monocytes in chronic lymphocytic leukemia patients, showing up-regulation of RAP1GAP and down-regulation of tubulins and CDC42EP3, which would be expected to result in impairment of phagocytosis. We also detected gene alterations such as down-regulation of PTGR2, a reductase able to inactivate prostaglandin E2, indicating immunosuppressive activity. Accordingly, the proliferation of T cells in contact with monocytes from patients was inhibited compared to that of cells in contact with monocytes from normal controls. Finally, normal monocytes in vitro increased migration and up-regulated CD16, RAP1GAP, IL-10, IL-8, MMP9 and down-regulated PTGR2 in response to leukemic cells or conditioned media. In conclusion, altered composition and deregulation of genes involved in phagocytosis and inflammation were found in blood monocytes obtained from chronic lymphocytic leukemia patients, suggesting that leukemia-mediated "education" of immune elements may also include the establishment of a skewed phenotype in the monocyte/macrophage population.

The promotion of mature theory of mind skills in educational settings: a mini-review.

After formal school entry, theory of mind development encounters a blooming period of growth intertwined with social and academic achievements and challenges. Within this framework, in last years researchers have proposed training programs to foster mature ToM skills, but also, to test causal pathways for the role that ToM development may have in broader cognitive and social outcomes. In the current mini-review we examine which training programs have been developed so far to enhance three key aspects of mature ToM skills: second-order false belief reasoning, the ability to put one's own ToM knowledge into use, and the mentalization of thoughts and emotions. We also illustrate effects of these activities on intra- and inter- personal competence. In its conclusion the paper provides considerations of both first achievements of research in this area and gaps to be addressed in future works.

Internalizing and externalizing symptoms in children during the COVID-19 pandemic: a systematic mixed studies review.

Introduction: Given the vulnerability of children during the COVID-19 pandemic, paying close attention to their wellbeing at the time is warranted. The present protocol-based systematic mixed-studies review examines papers published during 2020-2022, focusing on the impact of the COVID-19 pandemic on children's internalizing/externalizing symptoms and the determinants thereof. Method: PROSPERO: CRD42022385284. Five databases were searched and the PRISMA diagram was applied. The inclusion criteria were: papers published in English in peer-reviewed journals; papers published between January 2020 and October 2022 involving children aged 5-13 years; qualitative, quantitative, and mixed studies. The standardized Mixed Method Appraisal Tool protocol was used to appraise the quality of the studies. Results: Thirty-four studies involving 40,976 participants in total were analyzed. Their principal characteristics were tabulated. The results showed that children's internalizing/externalizing symptoms increased during the pandemic, largely as a result of disengagement from play activities and excessive use of the internet. Girls showed more internalizing symptoms and boys more externalizing symptoms. Distress was the strongest parental factor mediating children's internalizing/externalizing symptoms. The quality of the studies was appraised as low (n = 12), medium (n = 12), and high (n = 10). Conclusion: Gender-based interventions should be designed for children and parents. The studies reviewed were cross-sectional, so long-term patterns and outcomes could not be predicted. Future researchers might consider a longitudinal approach to determine the long-term effects of the pandemic on children's internalizing and externalizing symptoms. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022385284, identifier: CRD42022385284.

Teachers during the COVID-19 Era: The Mediation Role Played by Mentalizing Ability on the Relationship between Depressive Symptoms, Anxious Trait, and Job Burnout.

BACKGROUND: The COVID-19 outbreak caused severe changes in school activities over the past two years. Teachers underwent a re-planning of their teaching approaches, shifting from face-to-face teaching formats to remote ones. These challenges resulted in high levels of burnout. The identification of risk/protective factors contributing to burnout is crucial in order to inform intervention programs. Thus, we hypothesized a mediation role of teachers' mentalizing ability (processing of emotions, a component of mentalized affectivity) on the relationship between depression, anxiety, and depersonalization (burnout dimension). Two reverse models were computed. Job satisfaction, teachers' age and gender, school grade, and length of teaching experience served as covariates. METHODS: 466 (M(sd) = 46.2 (10.4) years) online questionnaires were completed by Italian teachers of primary (n = 204) and middle (n = 242) schools. Measures of burnout, depression, anxiety, and mentalization were administered. RESULTS: The findings corroborated our hypotheses: in all models, processing emotions served as a mediator on the relationship between depression, anxiety, and depersonalization, and on the reciprocal one. Job satisfaction positively impacted processing emotion, and negatively impacted depression and depersonalization; women teachers reported high levels of the anxious trait. CONCLUSIONS: Overall, it can be concluded that the ability to mentalize has a beneficial impact on teachers' well-being. Policymaking, clinical, and research implications were discussed.

The representation of child-parent relation: validation of the Italian version of the child-parent relationship scale (CPRS-I).

This study proposes a psychometric validation of the Italian version of the Child-Parent Relationship Scale (CPRS) developed by Pianta in 1992. Based on attachment theory, the scale assesses parents' relationship perceptions with their own child and comprises three scales: Closeness, Conflict, and Dependency. A sample of 501 parents (188 fathers and 313 mothers) completed 30 items of the Italian version of the Child-Parent Relationship Scale (CPRS-I) online, but only 437 answered 85% of the entire protocol; hence, the analyses only focused on 437 participants. The first analysis of the original theoretical model revealed poor fit, item loadings, and internal consistency. Therefore, a follow-up analysis was conducted. Exploratory and confirmatory analyses with a split sample (EFA = 218; CFA = 219) confirmed the original three-factor structure of the Italian sample, although some items were eliminated. The validity and reliability of the Italian version of the CPRS-I were also verified by correlating the above three factors with measures of adult attachment styles and children's internalizing and externalizing behaviors. The CPRS-I showed significant correlations with all tested constructs, in line with those found by Driscoll and Pianta for the short form of the scale. Our results confirm that the CPRS-I has the same structure as the original scale; therefore, it can be a useful tool for assessing parents' perceptions of their relationship with their children. The implications for educational and clinical settings are also discussed.

Prognostic Relevance of Multi-Antigenic Myeloma-Specific T-Cell Assay in Patients with Monoclonal Gammopathies.

Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients' HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies.

Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia.

The clinical relevance of angiopoietin-2 (Ang2) in chronic lymphocytic leukemia (CLL) was previously suggested by the association between high Ang2, and shorter progression-free survival reported in small series of patients. Here, we evaluated Ang2 glycoprotein levels in plasma samples collected from a multicentric cohort of CLL patients (n = 316) using an enzyme-linked immunosorbent assay method, and we investigated its prognostic role in relation to time to first treatment (TTFT) and overall survival. Based on a cutoff equal to 2459 pg/mL, we divided our cohort in 2 subsets (high and low Ang2) composing 100 (31.6%) and 216 (68.4%) patients, respectively. High Ang2 was predictive of reduced TTFT (P < .001) and overall survival (P = .002). Multivariate analysis confirmed that high Ang2 was an independent prognosticator for TTFT (hazard ratio = 1.739; 95% confidence interval, 1.059-2.857; P = .029). Significant associations were found between high Ang2 and advanced Binet stages (P < .001), high beta(2)-microglobulin (P < .001), unmutated variable region of immunoglobulin heavy chain gene status (P < .001), high CD38 and zeta-chain-associated protein kinase 70 expression (P < .001 and P = .003), and intermediate/high cytogenetic risk (P = .005). Moreover, Ang2 added prognostic power to other conventional prognosticators and helped to refine prognosis among CLL subsets with both high and low vascular endothelial growth factor plasma levels. Ang2 plasma level may be a useful independent prognosticator for CLL.

Physical contact with endothelial cells through ß1- and ß2- integrins rescues chronic lymphocytic leukemia cells from spontaneous and drug-induced apoptosis and induces a peculiar gene expression profile in leukemic cells.

BACKGROUND: Chronic lymphocytic leukemia B cells display prolonged survival in vivo, but when cultured in vitro rapidly undergo spontaneous apoptosis. We hypothesize that interactions with endothelial cells in infiltrated tissues and during recirculation may have a pathogenic role in chronic lymphocytic leukemia. DESIGN AND METHODS: We evaluated apoptosis of leukemic cells after co-culture on a monolayer of human umbilical vein endothelial cells with addition of fludarabine and antibodies that block adhesion. Then, we compared microarray-based gene expression profiles between leukemic cells at baseline and after co-culture. RESULTS: We found that the endothelial layer protected leukemic cells from apoptosis inducing a 2-fold mean decrement in apoptotic cells after 2 days of co-culture. Moreover, the endothelial layer decreased the sensitivity of chronic lymphocytic leukemia B cells to fludarabine-induced apoptosis. Physical contact with endothelium mediated by both ß(1)- and ß(2)- integrins is essential for the survival advantage of leukemic cells. In particular, blocking CD106 on endothelial cells or CD18 on leukemic B cells led to the almost complete abrogation of the survival advantage (>70% inhibition of viability). However, a reduction of apoptosis was also measured in leukemic cells cultured in conditioned medium collected after 2 days of co-culture, implying that survival is partially mediated by soluble factors. Overall, the contact with endothelial cells modulated 1,944 genes in chronic lymphocytic leukemia B cells, establishing a peculiar gene expression profile: up-regulation of angiogenesis-related genes, an increase of genes involved in TGFß and Wnt signaling pathways, secretion of cytokines recruiting stromal cells and macrophages and up-regulation of anti-apoptotic molecules such as Bcl2 and Survivin. CONCLUSIONS: Our study supports the notion that endothelial cells are major players in the chronic lymphocytic leukemia microenvironment. Adhesion to endothelium strongly supports survival, protects from drug-induced apoptosis and extensively modifies the gene expression profile of leukemic cells.

Children's representations of the COVID-19 lockdown and pandemic through drawings.

The COVID-19 pandemic and the measures to face it have placed children and their caregivers in front of many challenges that could represent sources of stress. This work aims to explore the point of view of children through drawing, as a spontaneous means of expression, relating it to parents' perceptions of children's difficulties, strengths, and mentalization skills. The sample consists of 18 children (mean age = 8.22, SD = 1.79). Parents were asked to complete: a socio-demographic questionnaire with information on the impact of COVID-19 on the family, the Strengths and Difficulties Questionnaire, and the Everyday Mindreading Scale. Children were asked to draw three moments: "Before" the pandemic, "During" the lockdown, and "After," when the COVID-19 will be passed. The drawings were coded by constructing a content and expressive analysis grid, adapting coding systems found in the literature. Data were collected at the beginning of the summer of 2020, just after the first lockdown period (from March to May 2020 in Italy). The results of the present work are in line with previous studies that reported experiences of wellbeing and tranquility of children in time spent at home with family during the pandemic. From the drawings emerges that children feel sufficiently able to master the situation, as reflected by including themselves in drawings and providing many details of the house in "During" drawings. The literature also reports a feeling of sadness/loneliness caused by the lack of friends, an element that we also find in the tendency to represent friends significantly more in the drawings concerning the future. Some contents of drawings (inclusion of friends, relatives, and parents) appeared associated with emotional, interpersonal, and mentalizing abilities of children, as perceived by parents. Exploring children's representations of a stressful event like the pandemic through drawings allows to focus both on their difficulties and on their resources, with useful implications for the educational support.

BTK Inhibitors Impair Platelet-Mediated Antifungal Activity.

In recent years, the introduction of new drugs targeting Bruton's tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were initially considered less immunosuppressive than chemoimmunotherapy, an increasing number of reports have described the occurrence of unexpected opportunistic fungal infections, in particular invasive aspergillosis (IA). BTK represents a crucial molecule in several signaling pathways depending on different immune receptors. Based on a variety of specific off-target effects on innate immunity, namely on neutrophils, monocytes, pulmonary macrophages, and nurse-like cells, ibrutinib has been proposed as a new host factor for the definition of probable invasive pulmonary mold disease. The role of platelets in the control of fungal growth, through granule-dependent mechanisms, was described in vitro almost two decades ago and is, so far, neglected by experts in the field of clinical management of IA. In the present study, we confirm the antifungal role of platelets, and we show, for the first time, that the exposure to BTK inhibitors impairs several immune functions of platelets in response to Aspergillus fumigatus, i.e., the ability to adhere to conidia, activation (as indicated by reduced expression of P-selectin), and direct killing activity. In conclusion, our experimental data suggest that antiplatelet effects of BTK inhibitors may contribute to an increased risk for IA in CLL patients.

Human Adipose Mesenchymal Stromal/Stem Cells Improve Fat Transplantation Performance.

The resorption rate of autologous fat transfer (AFT) is 40-60% of the implanted tissue, requiring new surgical strategies for tissue reconstruction. We previously demonstrated in a rabbit model that AFT may be empowered by adipose-derived mesenchymal stromal/stem cells (AD-MSCs), which improve graft persistence by exerting proangiogenic/anti-inflammatory effects. However, their fate after implantation requires more investigation. We report a xenograft model of adipose tissue engineering in which NOD/SCID mice underwent AFT with/without human autologous AD-MSCs and were monitored for 180 days (d). The effect of AD-MSCs on AFT grafting was also monitored by evaluating the expression of CD31 and F4/80 markers. Green fluorescent protein-positive AD-MSCs (AD-MSC-GFP) were detected in fibroblastoid cells 7 days after transplantation and in mature adipocytes at 60 days, indicating both persistence and differentiation of the implanted cells. This evidence also correlated with the persistence of a higher graft weight in AFT-AD-MSC compared to AFT alone treated mice. An observation up to 180 d revealed a lower resorption rate and reduced lipidic cyst formation in the AFT-AD-MSC group, suggesting a long-term action of AD-MSCs in support of AFT performance and an anti-inflammatory/proangiogenic activity. Together, these data indicate the protective role of adipose progenitors in autologous AFT tissue resorption.

Mapping levels of theory of mind in Alzheimer's disease: a preliminary study.

BACKGROUND: Research on Theory of Mind (ToM), the ability to understand behaviour based on mental state representation, has shifted towards a life span perspective in typical and atypical conditions (dementia). OBJECTIVES: The aim of this study is to investigate the presence and the features of ToM decay in early Alzheimer's disease (AD) patients compared to healthy controls adopting a neurodevelopmental stance. METHOD: Sixteen AD patients and 16 healthy controls were submitted to an increasing complexity ToM battery, tapping ToM precursors, standard first- and second-order false beliefs and advanced ToM tasks (Eyes Test and strange stories). RESULTS: The results underline a similar pattern of increasing difficulty of the tasks that explore ToM abilities in both the groups. They also confirm the presence of a strong gap in performance between the CTR and the AD groups, especially in the more complex ToM tasks, whereas there is no significant difference between the two groups in the first level of reasoning about beliefs (first-order false belief). The impairment in specific cognitive functions (i.e. memory and executive functions) seems to correlate with the decline in the most complex mentalistic abilities. CONCLUSION: This study identifies a specific pattern of deterioration in ToM abilities in AD patients, following backwards developmental steps typical of the acquisition of mentalizing abilities, where the most complex ToM levels are impaired, whereas the intermediate and the simplest ones are preserved.

Maternal Psychological Distress and Children's Internalizing/Externalizing Problems during the COVID-19 Pandemic: The Moderating Role Played by Hypermentalization.

In order to explore the psychological impact of the COVID-19 outbreak on the caregiver-child relationship, we investigated the interplay among COVID-19 exposure and children's internalizing/externalizing problems during the Italian lockdown, hypothesizing a mediation effect played by maternal distress. Additionally, we included maternal reflective functioning (i.e., hypermentalization) as a moderator factor among this interplay. A total of 305 Italian mothers of children aged 6-13 years (M = 10.3; SD = 2.4) filled in an online survey. Findings revealed an indirect effect of maternal COVID-19 exposure on children's anxious/depressed (k2 = 0.46) and attention problems (k2 = 0.32) via maternal distress. Hypermentalization moderated the impact of maternal COVID-19 exposure on children's anxious/depressed problems (ß = -1.08, p = 0.04). Hypermentalization moderated both the relation between maternal distress and children's aggressive behaviors (ß = 12.226; p < 0.001) and between maternal distress and children's attention problems (ß = 5.617, p < 0.001). We found pivotal significant effects of maternal hypermentalization on children's anxious/depressed and attention problems, indicating that the higher the mother's hypermentalization was, the higher the children's problems were. Our results broaden what we knew on the role of maternal reflective and emotional functioning on children's emotional/behavioral adjustment during stressful situations.

Correction: The Mentalized Affectivity Scale (MAS): Development and validation of the Italian version.

[This corrects the article DOI: 10.1371/journal.pone.0249272.].

The Mentalized Affectivity Scale (MAS): Development and validation of the Italian version.

This study proposes a psychometric validation of the Italian version of the Mentalized Affectivity Scale (MAS) developed by Greenberg and colleagues in 2017. The mentalized affectivity construct integrates mentalization ability in the process of emotional regulation. An adult sample (N = 506) completed the 60-items MAS online version. In contrast to the three-factor structure of the original version, the Italian context confirmatory and exploratory factor analyses with splitted sample (CFA = 258; EFA = 248) revealed a five-factor structure. The hierarchically structured MAS factors are: Emotional Processing (being able to process emotion in situations); Expressing Emotions (talking and knowing emotions); Identifying Emotions (awareness of emotions); Control Processing (to control emotional reactions and expression), and Autobiographical Memory (related to childhood experiences). We also verified the convergent validity and reliability of the Italian version of the MAS by correlating the above five factors with measures of emotion regulation and reflective functioning. Moreover, we analyzed the relationships among the factors of the MAS, personality measures and well-being indexes, such as life satisfaction and self-efficacy: The new 35-item MAS scale showed robust correlations with all the tested constructs. Our results confirm that the MAS is a useful measure to assess mentalized affectivity, with the Italian version showing a more complex structure than the original English one, thus enriching the literature about mentalization.