Recurrent aphthous ulcer (RAU) is a prevalent inflammatory disorder of the oral mucosa, characterized by a persistent "vicious cycle" of excessive oxidative stress, dysregulated immune responses, and impaired tissue regeneration. Effective clinical management remains challenging due to the dynamic and hydrated oral environment, which severely limits drug retention and multi-target therapeutic efficacy. Herein, we developed a multifunctional, sprayable hydrogel (PDS Gel) using a hierarchical "oxygen-limited initiation - oxygen-controlled progression" crosslinking strategy, integrating polygalacturonic acid (PGA), dopamine (DA), and salidroside-derived carbon dots (Sal-CDs). The PDS Gel achieves rapid in situ solidification and exhibits certain mucoadhesive properties, allowing attachment to the wet mucosal surface shortly after spraying. Mechanistically, the hydrogel exhibits potent reactive oxygen species (ROS) scavenging capacity and intrinsic antibacterial activity, effectively remodeling the pathological wound microenvironment. Crucially, PDS Gel promotes macrophage polarization from a pro-inflammatory M1 phenotype toward a pro-regenerative M2 phenotype, thereby suppressing excessive inflammatory cascades. Simultaneously, it restores fibroblast-mediated extracellular matrix (ECM) remodeling and enhances endothelial cell-driven angiogenesis. In vivo evaluations using both oral mucosal and full-thickness skin defect models demonstrate that PDS Gel significantly accelerates wound closure, facilitates epithelial reconstruction, and promotes orderly collagen deposition. Collectively, this self-oxidatively crosslinked immunomodulatory hydrogel provides a promising biomaterial paradigm for the precision therapy of RAU and other complex mucosal lesions.

Two-dimensional transition-metal dichalcogenides (TMDCs) are promising atomically thin semiconductors for next-generation electronics and optoelectronics. However, wafer-scale epitaxy of tungsten-based TMDCs is limited by the chemical inactivity of conventional oxide precursors, which restricts the formation and incorporation of growth species. Here we introduce a solid-liquid-equilibrium molten precursor formed from mixed WO3/Na2WO4 that is proposed to generate reactive WO4 growth units and stabilize the tungsten supply. The resulting WS2 grows through sustained lateral propagation, producing crystallographically aligned monolayer wafers with narrow excitonic linewidths ascribed to suppressed disorder. First-principles calculations show that the molten precursor shifts the rate-limiting step from oxide conversion to edge incorporation, while sodium-mediated attachment lowers the propagation barrier. This work establishes precursor-state engineering as a general route to overcome reaction-limited regimes in tungsten-based two-dimensional TMDCs epitaxy.

Maltreated children are at risk of exhibiting attachment disorders: The reactive attachment disorder (RAD) and the disinhibited social engagement disorder (DSED). Determining overall proportions for these disorders, however, is difficult. Assessment methods have varied across studies and over time due to a shift in diagnostic criteria from the Diagnostic and Statistical Manual of mental disorders - 4th Edition (DSM-IV) to the DSM-5. This study examines the overall proportion of RAD-DSED combined (34 studies with 47 independent samples, 8994 participants), RAD (16 studies with 19 independent samples, 1,924 participants), and DSED (16 studies with 21 independent samples, 2,018 participants). Inclusion criteria were all empirical English studies reporting on at least one RAD or DSED classification/diagnosis in children 9 months to 18 years old. Moderators included child age and sex, sample type, measure type, nosological system type, year of publication, study geographical region, and study quality. Random-effects meta-analyses with logit transformation of event proportions were conducted. Publication bias was not tested, given that symmetry assumptions do not apply to proportion data. Results set the overall proportions of attachment disorders in at-risk samples (RAD-DSED combined) at 18.4% [13.4%, 24.9%], 9.6% for RAD [6.6%, 13.7%], and 20.1% for DSED [12.2%, 24.7%]. Some RAD-DSED combined, RAD, and DSED proportions varied according to types of measures, nosological systems, and geographical region of study. Results indicate a decline in RAD proportions since the advent of the DSM-5 in 2013 (from 8.4% [6.5%, 10.9%] to 4.6% [1.4%, 5.6%]), and the DSM-5 algorithm for RAD is markedly more restrictive than that of the Research Diagnosis Criteria (RDC).

INTRODUCTION: The application of physical restraints in child and youth mental health settings remains controversial. Physical restraints are control interventions involving the use of a physical device or manual holding to restrict a young person’s movement. Although their use is permitted to manage risky behaviours, physical restraints can cause severe physical and psychological harm in children and youth. Existing literature on restraint use focuses on children and youth in inpatient settings, while research on its use in community health settings remains limited. METHODS: The current study aims to examine patterns and risk factors associated with the use of physical restraints among children and youth in both inpatient and community health settings. Data for this study were drawn from the interRAI Child and Youth Mental Health (ChYMH) assessment instruments (including those with developmental disabilities; ChYMH-DD), implemented by trained professionals as part of standard clinical practice. The sample comprised of 32,422 children and youth aged 4–18 receiving mental health services in Ontario between 2012 and 2022, across community and inpatient settings. This study employed a retrospective secondary analysis of assessment data. Logistic regression analysis was used to identify factors associated with physical restraint use. RESULTS: In our sample, males and younger children (4–11) experienced the most physical restraint. Results indicated that children with a diagnosis of autism (ASD), reactive attachment disorder, schizophrenia and other psychotic disorders, and substance use disorder experienced higher rates of physical restraint than those without a diagnosis. Furthermore, externalizing symptoms, internalizing symptoms, risk of suicide and self harm, high caregiver distress, dependent cognitive skills, and living with a nonrelative were associated with physical restraint use. CONCLUSIONS: Findings provide researchers and clinicians with important insights into risk factors for physical restraint among vulnerable children and youth, which can be used to inform care planning and the development of targeted prevention and early intervention programs. This research highlights the importance of identifying trauma, providing trauma-informed care, and using a standardized assessment-to-intervention approach across service sectors to reduce the use of physical restraints in child and youth mental health settings.

The developmental origins of reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) continue to be poorly understood. This cross-sectional study reports on the rates of RAD and DSED behaviours in a clinical sample of children presenting for Fetal Alcohol Spectrum Disorder (FASD) assessment (N = 123). It examines whether RAD and DSED behaviours, assessed by diagnostic interview with carers, are better explained by maltreatment (timing/type) or neurodevelopmental inhibitory-control deficits, assessed using the BRIEF-2, adjusting for age, sex and variables related to care history. There were high rates of DSED and relative low rates of RAD behaviours in this sample. Neglect past 24 months of age significantly predicted the presence of DSED behaviours related to affectionate behaviour and lack of reticence with strangers, whereas neglect and removal before 24 months did not impact these behaviours. Poor inhibitory control significantly predicted most DSED behaviours, and a RAD behaviour related to dysregulated negative affect. The overlap between poor inhibitory control, which was unrelated to maltreatment exposure in this sample, and DSED and RAD behaviours highlights the risk of diagnostic confusion when assessing for these disorders in children with suspected FASD. However, the findings also emphasise that even in the presence of poor inhibitory control owing to alcohol exposure, co-occurring exposure to prolonged neglect (past 24 months) may still contribute to the presentation of DSED behaviour. Implications for diagnosis and support are discussed. Future work should determine the non-inhibitory control related mechanisms contributing to DSED and RAD in children with prenatal adversity.

Adverse Childhood Experiences (ACEs), particularly those related to caregiving, can compromise the attachment bond that children establish with their primary caregivers. This study aimed to understand, through a systematic review, the relationship between ACEs that occurred in early life and the symptoms of Reactive Attachment Disorder (RAD) during adolescence. Using the PRISMA methodology, a search was conducted in the Web of Contents databases Science, ProQuest Central, PubMed and Scopus. The search yielded 1,443 results, of which only 8 met the inclusion criteria. The results show that there is a relationship between ACEs and a greater presence of RAD symptoms, as well as other mental health problems in adolescents. Likewise, those adolescents who are under some protective measure and have experienced ACEs, present more symptoms associated with RAD. It can be concluded that ACEs have negative consequences on establishing secure bonds, leading to more significant development of RAD and its maintenance during adolescence. The results can help to propose prevention and intervention strategies in vulnerable groups.

Adverse childhood experiences are a risk factor for attachment disorders. While several neuroimaging studies have shown changes in functional networks in children who have experienced institutional care, the results are inconsistent. Furthermore, no research has been conducted on how structured residential care, such as Japan's small-group family-style care, influences attachment-related symptoms and functional connectivity. This study compared attachment-related symptoms (reactive attachment disorder [RAD] and disinhibited social engagement disorder [DSED] symptoms) between youth aged 9-18 years raised in Japanese small-group residential care (RC; n = 31) and those raised in birth families but not in RC (NRC; n = 37). Group differences in resting-state functional connectivity were also analyzed using multivariate pattern analysis (MVPA) on functional magnetic resonance imaging (fMRI) data. MVPA revealed group differences in whole-brain functional connectivity patterns from the right occipital pole and the left lingual gyrus (LLG). Functional connectivity between the LLG and the frontal medial cortex (FMC) was reduced in RC youth. LLG-FMC connectivity was positively correlated with RAD scores, while longer duration of stay in RC was negatively correlated with RAD symptoms. This study highlights caregiving environment's influence on attachment-related symptoms and functional connectivity, higher levels of RAD and DSED symptoms and reduced LLG-FMC functional connectivity in the RC group. However, this study further demonstrated not only the association between longer stays in family-like RC and the reduction of RAD symptoms but also changes in the connectivity. These findings suggest that stable, high-quality care may have the potential to mitigate adverse developmental outcomes.

Background: Stress-related disorders, including PTSD, acute stress disorders, adjustment disorder, and attachment disorders, arise from complex interactions between genetic susceptibility and environmental stressors. While early environmental factors play a central role in the development of these disorders, there is growing evidence that genetic predisposition also contributes to individual differences in vulnerability and resilience. This narrative review examines current evidence on genetic predisposition and resilience mechanisms in stress-related psychopathology during developmental age. Methods: A literature search was performed using PubMed, Cochrane, MedRxiv, and Medline databases, focusing on studies published between 2010 and 2025, written in English, in the pediatric and adolescent population. Priority was given to original research articles and high-impact reviews. Studies were selected based on relevance to the genetic mechanisms underlying vulnerability and resilience to stress. 71 of 317 were selected. Two hundred forty-six articles were excluded due to a lack of relevance to the topic or because they included an adult population. Results: Polymorphisms and epigenetic modifications in genes involved in hypothalamus-pituitary-adrenal axis (FKBP5, NR3C1, ADCYAP1R1 and ACE), serotoninergic (SLC6A4 and HTR2A), noradrenergic and dopaminergic system (COMT and MAOA), BDNF, estrogen receptor and excitatory amino acid transporters are associated with increased risk of psychopathology following early trauma, but are also implicated in the development of resilience. Conclusions: Genetic factors influence both vulnerability and resilience to stress-related disorders. However, further studies based on the role of genetics are needed to advance precision and personalized medicine, which is still largely underexplored to this day in the field of stress-induced disorders.

Attachment, Personality Disorders and Depression in Adolescence Depressive disorders are particularly common in child and adolescent psychiatric settings. There are high comorbidity rates, however, research on comorbid personality disorders in adolescent age groups remains limited. Attachment-related dynamics play a significant role in the development of both depression and personality disorders and they represent important indicators of therapeutic outcomes. The present study shows our latest findings on attachment patterns and personality pathology in an adolescent inpatient psychiatric sample with depression. More than half of the adolescents were classified with an unresolved attachment pattern, and one-third met the criteria for a personality disorder. Furthermore, young people with depression showed elevated levels of identity diffusion. Therapeutic approaches that address attachment- related aspects and personality pathology may offer an effective treatment option for adolescents with depression.

Due to adverse circumstances in institutional care settings, institutionalized children are at risk of developing insecure attachment types and attachment disorders. The current study examined the role of institutionalization on attachment by comparing children residing in institutions with children in foster care and never-institutionalized children living in Türkiye. Further, the moderating role of children's temperamental characteristics (i.e., frustration and perceptual sensitivity) between the care groups and attachment was investigated. In total, 103 children (18-39 months old; 37 residing in institutions, 29 in foster care families, and 37 never-institutionalized children living with their biological families), and their caregivers participated. Attachment types were assessed via an observation-based measurement tool. Attachment disorders were assessed via interviews with caregivers. Temperamental characteristics were measured by a caregiver-reported questionnaire. The results indicated that children in institutions had less secure, more avoidant, and disorganized attachment types than those in foster care and never-institutionalized children. Furthermore, children with low perceptual sensitivity displayed more avoidant attachment if they stayed in institutions compared to their peers in foster care. Being in foster care and having high levels of perceptual sensitivity negatively predicted Reactive Attachment Disorder. The findings indicate important implications for future studies and social policies.

The site selective modification of proteins and peptides is an important venture when it comes to the study of biological systems, such as in the determination of viable pharmacological targets and in the understanding of biomolecular mechanisms. In this paper we report on the development of novel bifunctional probes that allow for the unambiguous site-specific labelling of short peptides for spectroscopic measurements as demonstration of our future intentions to introduce these as functional labels for the study of protein dynamincs in situ. The symmetrical nature and bifunctional attachments of these probes to their targets significantly reduces their orientational disorder (i.e. 'dye diffusion'), improving the accuracy and interpretation of established methods to study protein dynamics such as fluorescence polarization and Foerster Resonance Energy Transfer (FRET) measurements. In addition to solving a problem which has led to previous probes giving convoluted data owing to atropisomeric diastereoisomerism upon binding, we also introduce bio-orthogonal attachment groups that circumvent some of the drawbacks associated with the traditional labelling chemistries of thiol-reactive groups. These novel probes will be useful tools for future bulk and single-molecule spectroscopic experiments.