Beyond the cortico-centric models of cognition: the role of subcortical functioning in neurodevelopmental disorders

The main aim of the present opinion article is to discuss and argue how the classic cortico-centricmodel of neurodevelopmental disorders is not exhaustive of the possible explanation of thesedisorders. The alternative proposal presented here is to include the cortico-subcortical networkmodel to explain them

Theory of Mind in deaf adults

Purpose: The present study analyzed the social-cognitive and social-perceptual components of Theory of Mind (ToM) comparing three groups of deaf adults to three matched hearing groups. The influence of verbal IQ was also investigated. Methods: The participants were 15 native signers, 15 late signers, 17 oral deaf adults paired by gender, age and mental age to 47 hearing adults. All participants completed the assessment of the two components of ToM and of the verbal IQ. Results: Late signers and oral deaf adults showed lower scores then hearing peers both in the social-perceptual and social-cognitive components of ToM. Native signers showed lower scores then hearing peers in the social-perceptual component. Verbal IQ was the predictor of the social-cognitive component for late signers and oral deaf adults, while it was not significant for the social-perceptual component. Conclusions: The findings yielded support for the two components of TOM and contributed to the extent of the existing literature on ToM in deafness

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

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

Acoustic stimulation time-locked to the beginning of sleep apnea events reduces oxygen desaturations: a pilot-study.

We aimed to determine whether bone-conducted acoustic stimulation could prematurely terminate sleep apnea events, thereby decreasing amplitude and duration of subsequent oxygen desaturation. As oxygen desaturation has been linked to cardiovascular consequences, we postulate this could be a viable therapy in some cases. Eight patients with severe Obstructive Sleep Apnea (2 women, 45 [20-68] y.o. Apnea-Hypopnea Index: 77.7 ± 22.3/h) underwent polysomnography at the Lausanne University Sleep Center. Short acoustic stimulations were administered by bone conduction every second event of sleep apnea. Sounds were remotely administered using a Dreem® headband worn by patients while undergoing nocturnal polysomnography. Amplitude (%) and duration(s) of oxygen desaturations following terminated apneas were compared to that of non-stimulated previous and subsequent events. 549 stimulations (68.6 ± 38 sounds per patient) in N1 (16.2%), N2 (69.9%), N3 (4.2%), and REM(9.6%) were conducted. Compared to the previous and subsequent non-stimulated apnea, stimulations reduced event duration by 21.4% (-3.4 ± 7.2 s, p < 0.0001) while oxygen desaturation amplitude and duration were reduced by 30.4% (mean absolute difference ± SD: -1.9 ± 2.8%, p < 0.0001), and 39.6% (-5.7 ± 9.2 s, p < 0.0001) respectively. For these variables, each patient showed a significant improvement following acoustic stimulation. Sound-associated discomfort was rated 1.14 ± 1.53 on an 8 points scale (8 = worst) and only 6.8% of emitted sounds were perceived by the patients, suggesting a well-tolerated intervention. Bone-conducted sound stimuli decreased apnea events duration as well as duration and amplitude of associated oxygen desaturations. Stimulations were well tolerated and rarely perceived by patients. This therapeutic approach deserves further investigation, with monitoring of effects on sleep quality, daytime function/sleepiness and cardiovascular parameters

Immunogenic cell death induced by chemotherapy and immune tolerance mechanisms in acute myeloid leukemia

Sia nei tumori solidi che nelle neoplasie ematologiche, è stato dimostrato che alcuni agenti chemioterapici, come le antracicline, sono altamente immunogenici e determinano, attraverso le cellule dendritiche (DCs), un’efficiente attivazione della risposta antitumorale mediata dalle cellule T. Tale processo, caratterizzato dalla traslocazione della calreticulina e delle HSPs 70/90 sulla superficie cellulare delle cellule tumorali e dal rilascio di HMGB1 e di ATP, è detto morte cellulare immunogenica (ICD). Oltra alla ICD, però, la chemioterapia genera fenomeni infiammatori nel microambiente tumorale e attiva pathway immunosoppressivi a carico delle DCs, che potrebbero alterare la risposta immunitaria. Scopo del presente studio è stato caratterizzare la ICD indotta da antracicline nella leucemia acuta mieloide (LAM) e valutare l’induzione di pathway inibitori, come l’enzima indoleamina-2,3-diossigenasi (IDO1). In vitro, ex vivo ed in vivo abbiamo dimostrato che il trattamento con antracicline induce ICD anche nella LAM. Nei pazienti sottoposti a chemioterapia è stata riscontrata una risposta anti-leucemica caratterizzata dalla produzione di IFN- nei linfociti CD4+ e CD8+, capaci di uccidere i blasti autologhi pur mostrando un fenotipo exhausted, ma anche l’espansione di una popolazione di linfociti T regolatori. La ICD infatti determina la maturazione delle DCs, che attivano efficacemente linfociti T antigene-specifici ma, allo stesso tempo, esprimendo elevati livelli di IDO1, inducono linfociti T regolatori che limitano la risposta anti-leucemica. Questi risultati sono stati confermati nel modello murino leucemico dove, a seguito della chemioterapia, l’infiltrato tumorale è arricchito di DCs, mature esprimenti IDO1, ma anche di linfociti T caratterizzati da fenotipo exhausted. I nostri dati confermano che la ICD, attiva anche nella LAM, determina una risposta immunitaria efficace nei confronti della malattia ma anche l’attivazione di pathway inibitori nelle DCs che alterano tale risposta. La combinazione della chemioterapia con inibitori di IDO1 rappresenterebbe un approccio interessante per potenziare l'effetto immunogenico della chemioterapia e la risposta anti-leucemica.Recently, both in solid tumors and haematological malignancies, it has been shown that some chemotherapeutic agents, such as daunorubicin, are highly immunogenic and activate the immune response via cross-priming of anti-tumor T cells by dendritic cells (DCs). Such process, known as immunogenic cell death (ICD), is characterized by tumor cells modifications, such as cell surface translocation of calreticulin and heat shock proteins, extracellular release of ATP and pro-inflammatory factor HMGB1. Alongside with ICD, chemotherapy is known to induce inflammatory modifications within tumor microenvironment, which may also elicit immunosuppressive pathways. In particular, DCs may be driven to acquire tolerogenic features, which may ultimately hamper anti-tumor T-cells. Aim of this study is to characterize ICD in acute myeloid leukemia (AML) and to evaluate the involvement of some DC-related inhibitory pathways, such as indoleamine-2,3-dioxygenase 1 (IDO1) expression. In vitro, ex vivo and in vivo we demonstrated that daunorubicin treatment induced ICD in AML. Ex vivo, T-cell monitoring of daunorubicin-treated AML patients displayed an increase in leukemia-specific IFN--producing CD4+ and CD8+ T cells, which were capable to kill autologous blasts but showed an exhausted phenotype. We also observed the expansion of regulatory T cells (Tregs). ICD, in fact, induced maturation of DCs which efficiently activate antigen-specific T lymphocytes but simultaneously express high levels of IDO1, inducing a population of Tregs which inhibit the anti-leukemia response. These results were confirmed in leukemic murine model where daunorubicin treatment resulted in increased maturation status of tumor infiltrating DCs expressing IDO1, but also in an increased infiltration of exhausted T lymphocytes. Our data confirm that ICD is active in AML and results in an immunological response against AML but also in the induction of inhibitory pathway. The combination of chemotherapy with IDO1 inhibitors represents an interesting approach to enhance the immunogenic effect of chemotherapy and anti-leukemic immune response

PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response.

In the last years, dendritic cells (DC) have been evaluated for antitumor vaccination. Although DC-based vaccines have raised great expectations, their clinical translation has been largely disappointing. For these results, several explanations have been proposed. In particular, the concomitant expression by DCs of tolerogenic pathways, such as the immunosuppressive agent indoleamine 2,3-dioxygenase-1 (IDO1), has been demonstrated. The aim of this study is to evaluate both the stimulatory and the tolerogenic feature of monocyte-derived DCs (Mo-DCs) after maturation with PGE2. In particular, the role of IDO1 expression in PGE2-matured Mo-DCs has been addressed. Here we show that PGE2, which is required for full maturation of DCs, is one mediator of DC tolerance by enhancing IDO1. PGE2-mediated expression of IDO1 results in the production of kynurenine, in the generation of Tregs, and in the inhibition of either the allogeneic or the autologous antigen-specific stimulatory capacity of DCs. When pulsed with leukemic lysates and matured with PGE2, DCs are impaired in the induction of IFN-γ secreting CD4(+) and CD8(+) T cells due to IDO1 upregulation. Moreover, the inhibition of IDO1 enhances the antileukemic response. Overall, these results point toward the use of IDO1 inhibitors to enhance the vaccination capacity of DCs, matured with PGE2

Disability as a job resource: The role of job crafting and organizational citizenship behaviours. Towards an approach to value diversity in organizations

The number of employment opportunities afforded to people with disabilities in Italy is still not entirely satisfactory. Managerial policies should build a more favourable context, full of stimuli, support and backing for the promotion of good disability management practices within both private and public organizations. The aim of this study was to investigate how disability understood as a resource can positively influence the organizational climate and, consequently, the enactment of supportive and proactive behaviors, using the Job Demands-Resources model (JD-R) as a starting paradigm. Analyses were performed on 129 school educators in May 2021, who answered a structured questionnaire comprising several constructs, such as the perception of disability as a resource (2 items), job crafting (9 items) and extra-role behaviours (4 items). The mean age of the respondents was 51.6 years; most of them were female, married or cohabiting, and had a university degree. The study was performed through a non-parametric approach (PLS-SEM) and validated through bootstrap. Analyses showed that the relationship between disability as a resource and extra-role behaviors was partially mediated by the effect of job crafting. Results highlighted that workers with a predisposition to consider their colleagues with disabilities as a tool for growth are more likely to implement those behaviors that can improve the quality of organizational life and individual well-being, such as those oriented to proactivity and those aimed at expressing support, voluntary actions, and professional development even when this is not immediately required by the role