Differences in perceived online communication and disclosing e-motions among adolescents and young adults: The role of specific social media features and social anxiety.

INTRODUCTION: Social media are widely used by adolescents and young adults as a mean to maintain interpersonal relationships. Recent studies have found that young individuals with high levels of social anxiety feel more confident in communicating online. However, little is known about the role of perceived social media characteristics that could minimize the distress they experienced in face-to-face interactions. In this study, we rely on the tenets of the Transformation Framework, according to which social media, with its own features, may transform social relationships, including disclosing emotions and communicating with others online, in ways that may differ across individuals with or without specific vulnerability (e.g., social anxiety). Therefore, this cross-sectional study aims at examining the contribution of three specific social media features (i.e., asynchronicity, cue absence, and visualness) in explaining perceived breadth and depth of online communication, both directly and via e-motional processes (i.e., expression and facilitating use of e-motions), across groups of individuals with high versus low levels of social anxiety. METHODS: Participants were 1046 Italian adolescents and young adults (61.4% females; Mage = 17.9, SD = 3.23) who completed an anonymous self-report questionnaire between 2021 and 2022. Participants with very high scores on social anxiety (above the 90th percentile; socially anxious), were distinguished from all others (socially nonanxious) and a multigroup analysis (MGA) was run to compare the pattern of associations across the two different groups. RESULTS AND CONCLUSION: Results from the MGA showed significant differences between the two groups, partially confirming our hypotheses. Specifically, among socially anxious individuals, perceived cue absence was found to benefit perceived breadth and depth of online communication, and asynchronicity to enhance online emotional processes; conversely, these associations were negative in the group of socially nonanxious. Thus, these findings underly the contribution of social media in explaining youngsters' online experiences and support the potential beneficial role of some social media features for those more socially vulnerable.

New Dominant-Negative IL6ST Variants Expand the Immunological and Clinical Spectrum of GP130-Dependent Hyper-IgE Syndrome.

Patients with autosomal dominant (AD) hyper-IgE syndrome (HIES) suffer from a constellation of manifestations including recurrent bacterial and fungal infections, severe atopy, and skeletal abnormalities. This condition is typically caused by monoallelic dominant-negative (DN) STAT3 variants. In 2020, we described 12 patients from eight kindreds with DN IL6ST variants resulting in a new form of AD HIES. These variants encoded truncated GP130 receptors, with intact extracellular and transmembrane domains, but lacking the intracellular recycling motif and the four STAT3-binding residues, resulting in an inability to recycle and activate STAT3. We report here two new DN variants of IL6ST in three unrelated families with HIES-AD. The biochemical and clinical impacts of these variants are different from those of the previously reported variants. The p.(Ser731Valfs*8) variant, identified in seven patients from two families, lacks the recycling motif and all the STAT3-binding residues, but its levels on the cell surface are only slightly increased and it underlies mild biological phenotypes with variable clinical expressivity. The p.(Arg768*) variant, identified in a single patient, lacks the recycling motif and the three most distal STAT3-binding residues. This variant accumulates at the cell surface and underlies severe biological and clinical phenotypes. The p.(Ser731Valfs*8) variant shows that a DN GP130 expressed at near normal levels on the cell surface can underlie heterogeneous clinical presentations, ranging from mild to severe. The p.(Arg768*) variant demonstrates that a truncated GP130 protein retaining one STAT3-binding residue can underlie severe HIES.

Friendship quality in adolescence: the role of social media features, online social support and e-motions.

The last decade has seen a growing interest in understanding what role social media play in adolescent experiences, including friendship relationships. However, little is known about the associations of specific characteristics of social media and individual factors with friendship quality. This study was designed in line with the tenets of the so-called Transformation Framework (Nesi et al., 2018) with the aim of testing whether and how social media features, online social support, and online expressions of emotions play a role in adolescents' friendship quality. Participants were 744 Italian adolescents (64.5% females) with an average age of 15.9 years (SD = 1.31). First, a path analysis was conducted to test the hypothesized model on the whole sample of adolescents. Finally, two multi-group analyses (MGA) were conducted to analyze differences across gender groups (female vs. male) and group of social media users (problematic vs. non-problematic). Path analysis yielded a complex pattern of associations, in which different perceived social media features were significantly associated with different dimensions of friendship quality, both directly and indirectly via perceived online social support and the tendency to express e-motions on social media. Moreover, MGAs confirmed significant differences among both genders and social media users. The findings provide support for the importance of considering social media as a social context with its own characteristics for the study of adolescents' peer experiences, by taking into consideration that the hypothesized role of social media in supporting friendship relations during adolescence may depend on individual factors. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03564-3.

Longitudinal associations of social-cognitive and moral correlates with defending in bullying.

Defending in bullying is a complex, yet important behavior that is likely associated with individual characteristics and group factors that operate simultaneously in the classroom microsystem. However, little research has longitudinally analyzed the role of multiple promoting factors at both the individual and classroom level. Drawing on the social-ecological theory and social-cognitive theory, the present study examined the prospective associations between Fall defending self-efficacy, moral disengagement, moral identity, and moral distress and Spring defending behavior. Participants were 1163 adolescents (48.7% females; Mage = 13.6, SD = 1.1) attending 67 classrooms in Italian public schools. Defending showed moderate stability over one school year. At the individual level, multilevel analyses showed that T1 self-efficacy for all students, and moral distress for male students, positively predicted T2 defending. Moreover, high moral disengagement negatively predicted T2 defending only when students also reported high levels of moral identity. At the class-level, T1 class defending and class moral identity explained between-class variability in T2 defending. The findings have multiple implications for interventions that aim to increase defending behavior.

Longitudinal Links of Individual and Collective Morality with Adolescents' Peer Aggression.

Adolescents' aggressive behavior has been often linked to biases in morality. However, limited knowledge is available regarding the relative strength of different moral correlates, both at the individual and class-level, in predicting different types of aggressive behavior over time. To address this gap, the present study tested the prospective associations of moral identity and moral disengagement with reactive and proactive aggression in a short-term longitudinal study. The sample consisted of 1158 Italian adolescents (48.7% females; Mage = 13.6 years, SD = 1.1). Participants completed self-report measures of moral identity, moral disengagement, perceived collective moral disengagement in the fall, and reactive and proactive aggression in the fall and in the spring. Multivariate multilevel analysis indicated that, at the individual level, after controlling for the stability of aggressive behavior, T2 (Time 2) reactive aggression was higher for students who reported lower moral identity and higher moral disengagement at T1 (Time 1). For proactive aggression, a significant interaction effect indicated that the negative association between T1 moral identity and T2 aggression was apparent only at high levels of T1 moral disengagement. Moreover, proactive aggression was significantly predicted by higher perceived collective moral disengagement. At the class-level, T1 collective moral disengagement helped explain between-class variability of T2 reactive and proactive aggressive behavior. How these results expand previous research on morality and aggressive behavior and their potential implications for prevention and intervention programs is discussed.

Immune deficiency, autoimmune disease and intellectual disability: A pleiotropic disorder caused by biallelic variants in the TPP2 gene.

Four individuals from two families presented with a multisystemic condition of suspected genetic origin that was diagnosed only after genome analysis. The main phenotypic features were immune system dysregulation (severe immunodeficiency with autoimmunity) and intellectual disability. The four individuals were found to be homozygous for a 4.4 Kb deletion removing exons 20-23 (NM_003291.4) of the TPP2 gene, predicting a frameshift with premature termination of the protein. The deletion was located on a shared chromosome 13 haplotype indicating a Swiss founder mutation. Tripeptidyl peptidase 2 (TPP2) is a protease involved in HLA/antigen complex processing and amino acid homeostasis. Biallelic variants in TPP2 have been described in 10 individuals with variable features including immune deficiency, autoimmune cytopenias, and intellectual disability or chronic sterile brain inflammation mimicking multiple sclerosis. Our observations further delineate this severe condition not yet included in the OMIM catalog. Timely recognition of TPP2 deficiency is crucial since (1) immune surveillance is needed and hematopoietic stem cell transplantation may be necessary, and (2) for provision of genetic counselling. Additionally, enzyme replacement therapy, as already established for TPP1 deficiency, might be an option in the future.

Social norms and e-motions in problematic social media use among adolescents.

INTRODUCTION: Being constantly connected on social media is a "way of being" among adolescents. However, social media use can become "problematic" for some users and only a few studies have explored the concurrent contribution of social context and emotion regulation to problematic social media use. The current study aimed to test: (i) the influence of friends (i.e., their social media use and group norms about social media use); and (ii) the effects of difficulties in emotion regulation and so-called "e-motions" on adolescents' problematic social media use. METHODS: A cross-sectional study was conducted in Italian secondary schools. An online questionnaire was administered to 761 adolescents (44.5% females; Mage = 15.49 years; SDage = 1.03). RESULTS: Path analysis showed that social norms were directly associated with problematic social media use and friends' social media use was associated with the frequency of social media use, which, in turn, was associated with problematic use. Difficulties in emotion regulation were directly and indirectly linked to problematic social media use via frequency of use and facilitating use of e-motions. CONCLUSIONS: These findings provide support for the importance of both peer influence and emotion regulation in this context. Social norms and emotion regulation should be considered in prevention programs addressing problematic social media use in adolescents.

[Transient hypogammaglobulinemia of infancy]. / Hypogammaglobulinémie transitoire de l'enfant.

Transient hypogammaglobulinemia of infancy is characterized as a reduction of one or more classes of immunoglobulins with a response to vaccines and normal subpopulations of lymphocytes B presenting in the first years of life. The diagnosis is made a posteriori, once the levels of immunoglobulins are normalized, in general between 2 and 4 years of age. Clinical presentation varies : the child may be either asymptomatic or present with recurrent infections, atopy and / or auto-immunity. There are no clinical or immunological features that distinguish this condition from a common variable immunodeficiency (CVID). Because of the risk of severe infections, it is necessary a follow up by a paediatric immunologist. Depending on the presentation and evolution, a prophylaxis with antibiotics or a substitution with immunoglobulins might be indicated.

L'hypogammaglobulinémie transitoire de l'enfant (HTE) est caractérisée par une réduction d'une ou plusieurs classes d'immunoglobulines (Ig) avec réponse vaccinale et sous-populations lymphocytaires dans la norme, se présentant dans les premières années de vie. Le diagnostic se fait a posteriori une fois que les niveaux d'immunoglobulines se sont normalisés, généralement entre 2 et 4 ans. Le tableau clinique peut être très variable : l'enfant peut être asymptomatique, présenter des infections récurrentes, des allergies et / ou de l'auto-immunité. Aucune caractéristique clinique ou immunologique ne permet de distinguer l'HTE d'une immunodéficience type commune variable (CVID en anglais) et, devant le risque d'infection grave, un suivi clinique et immunologique est nécessaire. Selon l'évolution, une antibioprophylaxie ou une thérapie substitutive en immunoglobulines peuvent être indiquées.

A matter of life and death: substance-caused and substance-related fatalities in Ibiza in 2015.

OBJECTIVES AND METHODS: In the framework of the EU-funded project "EU-Madness," we collected and analysed all the reports of fatalities directly or indirectly related to substances of abuse registered in Ibiza from January to September 2015, in order to analyse the characteristics of the sample, the identified substances, and the nature of deaths associated with their consumption. RESULTS: A significant increase of substance-caused deaths with respect to the previous 4 years has been highlighted. Most of the subjects were young males, more than half were not Spanish. Males prevailed also amongst the victims of traffic accidents and suicides. The most commonly involved substances included MDMA, alcohol, cocaine, THC, opiates and prescription drugs. CONCLUSIONS: Although the use of NPS is rapidly increasing in Europe, according to the results from our sample, alcohol and well-known stimulants (MDMA and cocaine) are still the substances of abuse mainly involved in the cases of substance-caused and substance-related fatalities. The significant increase of fatalities in Ibiza in the last 5 years is an issue that must be taken into account and should be better investigated, as other theories besides NPS-increased diffusion should be proposed, and therefore, targeted prevention strategies should be designed.

IL-17 receptor A and adenosine deaminase 2 deficiency in siblings with recurrent infections and chronic inflammation.

BACKGROUND: Data on patients affected by chronic mucocutaneous candidiasis underscore the preponderant role of IL-17 receptor A (IL-17RA) in preserving mucocutaneous immunity. Little is known about the role of adenosine deaminase (ADA) 2 in regulation of immune responses, although recent reports linked ADA2 deficiency with inflammation and vasculitis. OBJECTIVE: We sought to investigate the mechanisms of chronic inflammation and vasculitis in a child lacking IL-17RA and ADA2 to identify therapeutic targets. METHODS: We report a family with 2 siblings who have had recurrent mucocutaneous infections with Candida albicans and Staphylococcus aureus and chronic inflammatory disease and vasculitis since early childhood, which were refractory to classical treatments. Array-based comparative genomic hybridization analysis showed that both siblings are homozygous for a 770-kb deletion on chr22q11.1 encompassing both IL17RA and cat eye critical region 1 (CECR1). Immunologic studies were carried out by means of flow cytometry, ELISA, and RIA. RESULTS: As expected, in the affected child we found a lack of IL-17RA expression, which implies a severe malfunction in the IL-17 signaling pathway, conferring susceptibility to recurrent mucocutaneous infections. Surprisingly, we detected an in vitro and in vivo upregulation of proinflammatory cytokines, notably IL-1ß and TNF-α, which is consistent with the persistent systemic inflammation. CONCLUSIONS: This work emphasizes the utility of whole-genome analyses combined with immunologic investigation in patients with unresolved immunodeficiency. This approach is likely to provide an insight into immunologic pathways and mechanisms of disease. It also provides molecular evidence for more targeted therapies. In addition, our report further corroborates a potential role of ADA2 in modulating immunity and inflammation.

A variable degree of autoimmunity in the pedigree of a patient with type 1 diabetes homozygous for the PTPN22 1858T variant.

We investigated whether the PTPN22 C1858T polymorphism is associated with the autoimmune conditions present in the family of a child affected by type 1 diabetes (T1D) carrying the TT genotype (index patient) and the potential immunological effect of the variant. We found that nine family members carried the CT genotype and five suffered from autoimmunity. Interestingly, anti-ZnT8 antibodies were detected in T1D patients and in three healthy relatives. In the TT patient, we showed diminished T-cell proliferation and reduced interleukin-2 (IL-2) and interferon-gamma (IFN-γ) production. A marked reduction of IL-2 was also observed for all CT relatives with autoimmunity and a lack of IFN-γ production was observed for the younger brother of the index patient, heterozygous for the polymorphism. In this family, the C1858T variant might confer a high risk of autoimmunity. Moreover, our data confirm that impaired IL-2 production upon T-cell receptor stimulation is associated with autoimmunity in the carriers of the polymorphism. This study might prompt to extend the panel of risk markers in relatives of subjects affected by T1D.

Correlation of Der p 2 T-cell responses with clinical characteristics of children allergic to house dust mite.

BACKGROUND: An understanding of the mechanisms responsible for the development and maintenance of allergic inflammation and their clinical implications is needed to develop specific and successful treatment for allergy. OBJECTIVES: To characterize in vitro T-cell responses to Der p 2, one of the major allergens of house dust mite (HDM), and investigate potential correlations between clinical and laboratory parameters. METHODS: Forty-two patients monosensitized to HDM and 10 age-matched, healthy children were studied. Dendritic cells pulsed with Der p 2 were used to stimulate autologous CD14(-) cells. Der p 2-specific T-cell activation markers, proliferation, and cytokine production profiles were examined. RESULTS: Der p 2-specific T-cell activation markers, proliferation, and T(H)2 cytokine production were significantly higher in HDM patients compared with healthy controls. Moreover, a significant correlation between proliferation and T(H)2 cytokine production was observed. Within the allergic group, skin reaction to HDM was significantly stronger in patients with a Der p 2-specific T-cell response. Levels of HDM-specific IgE directly correlated with interleukin 5 and interleukin 13 levels and with skin prick test results and, ultimately, with the patient's family history of allergy. Furthermore, the presence of atopic march correlated with T-cell proliferation. CONCLUSION: We found that, in HDM patients, Der p 2-specific T(H)2 responses, promoted by autologous dendritic cells in vitro, correlate with clinical parameters.

Mycobacterium avium subsp. paratuberculosis in an Italian cohort of type 1 diabetes pediatric patients.

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne's disease in ruminants. Recent studies have linked MAP to type 1 diabetes (T1D) in the Sardinian population. The aim of this study was to investigate the prevalence of MAP infection in a T1D cohort from continental Italy compared with healthy control subjects. 247 T1D subjects and 110 healthy controls were tested for the presence of MAP. MAP DNA was detected using IS900-specific polymerase chain reaction (PCR). The presence of antibodies towards a MAP antigen, heparin binding hemoagglutinin (HBHA), was detected by ELISA. We demonstrated a higher MAP DNA prevalence in plasma samples from T1D patients and a stronger immune response towards MAP HBHA, compared with healthy control subjects. Moreover, in the recent onset patients, we observed an association between anti-MAP antibodies and HLA DQ2 (DQA1 0201/DQB1 0202). These findings taken together support the hypothesis of MAP as an environmental risk factor for the development of T1D in genetically predisposed subjects, probably involving a mechanism of molecular mimicry between MAP antigens and pancreatic islet ß-cells.

Genotypes of p53 codon 72 correlate with age at onset of type 1 diabetes in a sex-specific manner.

In type 1 diabetes mellitus (T1D) p53 pathways are up-regulated and there is an increased susceptibility to apoptosis. The hypothesis is that p53 codon 72 polymorphism could be associated with T1D. A total of 286 children with T1D and a control sample of 730 subjects were studied. p53 codon 72 polymorphism was analysed by polymerase chain reaction. A large increase of p53 *Arg/*Arg was observed in T1D patients with age at onset < 6 years. A strong linear correlation between *Arg/*Arg genotype and age at onset was observed in females. The involvement of the *Arg/*Arg genotype in apoptosis suggests that during the autoimmune process leading to T1D, genetic factors that favor apoptosis may contribute to the onset of overt disease.

Happy air®, a successful school-based asthma educational and interventional program for primary school children.

BACKGROUND: To investigate whether an active partnership between schools, parents, and pediatricians can improve the management of asthma and quality of life of children with asthma. METHODS: A comprehensive asthma program (Happy Air®), based on a strong family-physician-school relationship, was carried out over a period of 3 years in six primary schools (2765 children). This program provides educational intervention to families, school staff, and students, as well as the administration of written questionnaires to identify children with asthma, asthma diagnosis and management, and, last but not least, extracurricular activities to improve respiratory and psychological conditions. Quality of life of children and parents, at the beginning and end of the program, was assessed using PedsQL™ 4.0 (Pediatric Quality of Life Inventory) measurement model. RESULT: Asthma was diagnosed in 135 children, of which 37 (27%) were diagnosed de novo. In all children, both single item and total clinical asthma scores showed a significant increase (p < .001) at the end of the Happy Air® program. The average scores of both the total PedsQL™ 4.0 and the four Scales were significantly increased (p < .001). CONCLUSION: Happy Air® is a model for a strategy of education- and school-based intervention for children with asthma and their families. This multi-action program for diagnosis, clinical follow-up, education, self-management, and quality-of-life control aims to minimize the socioeconomic burden of asthma disease.

Ligation of CD46 to CD40 inhibits CD40 signaling in B cells.

CD40 induces B cells to switch to IgE in the presence of IL-4 and up-regulates their expression of the low-affinity receptor for IgE, CD23, which promotes the immune response to allergen complexed with IgE antibody. CD40 binds to CD40L and to the C4b-binding protein (C4BP) using distinct sites. CD46 is a receptor for the product of activated complement C4b. Some microbial antigens bind both C4BP and CD46, potentially bridging CD40 to CD46. In addition, immune complexes containing both C4b and C4BP may cross-link CD40 to CD46. We demonstrate that cross-linking CD46 to CD40 on B cells inhibits CD40-mediated up-regulation of surface CD23 expression and induction of IL-4-dependent IgE isotype switching. This was associated with inhibition of induction of Cε germ line transcripts and of activation-induced cytidine deaminase mRNA expression. Furthermore, co-ligation of CD46 to CD40 blocked CD40-mediated NF-κB activation. These observations suggest that complement components may play an important role in regulating CD40 activation of B cells and the allergic response.